SCPHA
2014 Pharmacy Workbook
Live Pharmacy Board Review
Table of Contents
1. KEY LABS
2. SIDE EFFECTS
3. ANTIEPILEPTIC DRUGS (AED’s)
4. ANTIEPRESSANTS
5. NEUROLEPTICS
6. PAIN
7. GOUT
8. CHRONIC OBSTRUCTIVE PULMONARY DISEASE
9. ASTHMA
10. PEPTIC ULCER AND GERD
11. DIABETES
12. HYPERTENSION
13. ONCOLOGY
14. HIV
15. ANGINA PECTORIS
16. HYPERLIPIDEMIA
17. ANTIBIOTICS
18. HEART FAILURE
19. ANTITHROMBOTIC DRUGS
20. COGNITIVE LOSS AND DEMENTIA
21. PHARMACY MATH
22. STATISTICS
1
Pharmacy is an ever-changing science. As new research and clinical experience broaden our knowledge, changes in treatment and drug
therapy are required. This guide has been checked in efforts to provide information that is complete and in accord with the standards
accepted at the time of writing. Readers are encouraged to confirm the information contained herein with other sources. For example, and
in particular, readers are advised to check the product information sheet included in the package of each drug to be certain that the
information contained in this work is accurate and that changes have not been made in the recommended dose, contraindications for
administration, or any characteristic of the agent.
This review guide / workbook is intended to serve the user as a reference and not as a complete drug information resource. It does not
include information on every therapeutic agent available or concept that may be encountered on the exam. This guide is designed for review
of key concepts in a live teaching format and not for reference for any patient or pharmaceutical care or individual study without live
component. The guide is designed to be used in conjunction with other information (e.g. 4 years of pharmacy school training and pertinent
notes / materials; package insert of respective agents) and is not designed to be solely relied upon by any user. The user of this data hereby
and forever releases authors and individuals involved in development of this data from any and all liability of any kind that might arise out
of use of this guide.
2
KEY LABS
SIDE EFFECTS
3
ANTIEPILEPTIC DRUGS (AED’s)



Epilepsy: Periodic attacks of disturbed cerebral function (seizures) that may or may not be
accompanied by convulsive movements, loss of consciousness and abnormal behavior.
The pathophysiology of a seizure is due to an unstable cell membrane in the gray matter of the
brain.
o The cause of the unstable cell membrane linked to 3 causes: 1) abnormality in potassium
conductance, 2) abnormality in voltage-sensitive ion channels, or 3) deficiency in membrane
ATPases linked to ion transport.
o Excitatory neurotransmitters (glutamate, aspartate, acetylcholine, norepinephrine) enhance
the propagation of seizures; while inhibitory neurotransmitters (GABA, dopamine) decrease
the propagation of seizure activity in the brain.
o The spread can be local (partial seizure) or throughout the entire brain (generalized seizure).
Types
o Partial: More difficult to treat; requires higher blood levels than generalized.
 Simple (Jacksonian, focal): Localized to single cerebral hemisphere (not associated
with LOC).
 Complex (psychomotor, temporal lobe): spread of focal discharge to other cerebral
hemisphere. Characterized by visual, auditory and olfactory disturbances with
somatic pain. Associated with LOC.
o Generalized (results in LOC).
 Tonic Clonic (Grand Mal): convulsions (muscle contraction and jerking).
 Myoclonic: brief shock-like contraction of a muscle group.
 Clonic seizures—jerking motion while tonic seizures involve a sustained muscle
contraction.
 Atonic: sudden loss of muscle tone known as “drop attacks.”
 Absence (Petit Mal): Rhythmic movement of eyelids and mouth.
TREATMENT

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Goal: elimination of seizures with no drug side effects.
Optimal quality of life requires balancing seizures, side effects, and life issues (e.g. driving, safety).
Initial therapy is initiated with one AED; 70% of patients controlled on monotherapy.
Combination AED therapy is achieved by combining seizure medications with different MOA.
Switching AEDs requires titration process; abrupt discontinuation of an AED may lead to
breakthrough seizures.
Prolonged use of AEDs that cause CYP450 enzyme induction and valproate may increase the risk of
osteoporosis.
Enzyme-inducing AEDs may decrease serum concentrations of estrogen / progestin resulting in oral
contraceptive failure.
o Levetiracetam and valproate do not affect serum concentrations of oral contraceptives.
AEDs should be used as monotherapy at the lowest dose in pregnant women.
4

Generics of AEDs are available.
o Meta-analysis found no difference in seizure control.
o However, switching between generic products can alter serum concentrations.
MEDICATIONS
1. Phenobarbital (Luminal): Modulate Na Channels.
2. Primidone (Mysoline): Modulate ___ Channels.
3. Phenytoin (Dilantin): Modulate Na Channels.
4. Carbamazepine (Tegretol): Modulate Na Channels.
5. Ethosuximide (Zarontin): Modulate Ca Channels.
6. Valproic acid (Depakene) / Divalproex (Depakote): Modulate Na Channels.
7. Felbamate (Felbatol): Inhibit glutamate Channels.
5
8. Gabapentin (Neurontin): Modulate Ca Channels & enhance GABA activity.
9. Lamotrigine (Lamictal): Modulate Na Channels.
10. Topiramate (Topamax): Modulate Na Channels; inhibit glutamate activity; enhance GABA.
11. Levetiracetam (Keppra): Unknown.
6
Drug Interaction Properties with Antiepileptic Drugs
Enzyme
Substrate
Inducers
CYP 1A2
Carbamazepine
Carbamazepine
Inhibitors
Phenytoin
Phenobarbital
CYP 2C9
Phenobarbital
Carbamazepine
Phenytoin
Phenytoin
Carbamazepine
Phenobarbital
Valproic acid
Valproic acid
CYP 2C19
Phenobarbital
Felbamate
Phenytoin
Topiramate
Valproic acid
Zonisamide
CYP 2D6
Zonisamide
Carbamazepine
CYP 3A4
Carbamazepine
Carbamazepine
Phenytoin
Phenobarbital
Uridine diphosphate
glucuronyl-transferase
Lamotrigine
Lamotrigine
Carbamazepine
Phenobarbital
Phenytoin
7
Valproic acid
Brand/Generic Names and Formulations of AEDs
Generic
Brand
Formulations
Sodium Channel Modulators
Carbamazepine
Tegretol,
Tablet
Tegretol XR
Chewable tablet
Epitol
Extended release tablet
Equitro
Extended release capsule
Suspension
Lamotrigine
Lamictal
Tablet
Chewable tablet
Disintegrating tablet
Oxcarbazepine
Trileptal
Tablet
Suspension
Valproic acid
Depacon
Softgel capsule
Depakene
Solution
Stavzor
Divalproex
Depakote
Delayed release capsule
Depakote ER
Extended release tablet
Delayed release/enteric coated tablet
Phenytoin
Dilantin
Capsule
Phenytek
Extended release capsule
Chewable tablet
8
Suspension
IV solution for injection
Fosphenytoin
Cerebyx
IV/IM solution for injection
Phenobarbital
Luminal
Tablet
Elixir
IV solution for injection
Calcium Channel Modulators
Ethosuximide
Zarontin
Liquid-filled capsule Syrup
Pregabalin
Lyrica
Capsule
GABA Modulators
Clonazepam
Klonopin
Tablet
Klonopin Wafers
Disintegrating tablet
Glutamate Modulators
Felbamate
Felbatol
Tablet Suspension
Combination Modulators
Gabapentin
Neurontin
Capsule
Tablet
Solution
Topiramate
Topamax
Capsule/sprinkles Tablet
Zonisamide
Zonegran
Capsule
Unknown Mechanism of Action
Levetiracetam
Keppra
Tablet
Keppra XR
Extended release tablet
IV solution for injection Solution
9
Additional AED Medications:
1) Clobazam (Onfi) is a benzodiazepine utilized for adjunctive treatment of Lennox-Gastaut
syndrome in patients two years of age and greater.
a. Lennox-Gastaut syndrome is a severe form of epilepsy and usually begins before 4 years
of age. Seizure types vary and includes tonic (stiffening of the body, upward deviation of
the eyes, dilation of the pupils, and altered respiratory patterns), atonic (brief loss of
muscle tone and consciousness, causing abrupt falls), atypical absence (staring spells),
and myoclonic (sudden muscle jerks). There may be periods of frequent seizures mixed
with brief, relatively seizure-free periods. Most children with Lennox-Gastaut syndrome
experience impaired intellectual functioning or information processing, along with
developmental delays, and behavioral disturbances. Lennox-Gastaut syndrome can be
caused by brain malformations, perinatal asphyxia, severe head injury, central nervous
system infection and inherited degenerative or metabolic conditions.
b. Treatment for Lennox-Gastaut syndrome includes clobazam and anti-epileptic
medications such as valproate, lamotrigine, felbamate, or topiramate. There is usually
no single antiepileptic medication that will control seizures.
2) Ezogabine (Potiga) acts through potassium channels and is an adjunctive treatment for partial
epilepsy in adults. Unique effect – QT interval prolongation.
3) Lacosamide (Vimpat) inactivates voltage dependent sodium channels and is add-on therapy for
adults with partial epilepsy. CYP450 2C19 substrate and inhibitor; PR interval increase possible
(watch out for beta blockers and calcium channel blockers).
4) Rufinamide (Banzel) is for adjunctive treatment of Lennox-Gastaut syndrome in patients 4 years
of age and greater. Shortens QT interval (watch out for digoxin). Mild inducer of CYP450 3A4.
5) Vigabatrin (Sabril) is used for infatile spasms and add-on for complex partial epilepsy. Restricted
distribution program because of concerns about retinal toxicity and visual field loss.
6) Zonisamide (Zonegran) is for adjunctive treatment of partial seizures in adults with epilepsy.
Mild carbonic anhydrase inhibitor; therefore, can cause metabolic acidosis which increases the
risk renal stones. Remember pneumonic for metabolic acidosis and anion gap (MUDPILES).
10
AED Assessment
1. A female patient presents to the pharmacotherapy clinic with migraine headaches that are impacting
her career and family life. She is seeking input about the management of the headaches. She has a past
medical history of partial epilepsy, hypertension, and reflux. Medications include gabapentin, lisinopril,
and pantoprazole. Which of the following medications may be effective in managing partial epilepsy and
migraine headaches?
a. Clobazam
b. Pregabalin
c. Topiramate
d. Clonazepam
2. XB is a 37 year-old patient presenting to the neurology clinic for new onset seizures. XB recently had
multiple seizures consisting of a loss of consciousness with rapid eye movement. His past medical
history is significant for allergic rhinitis and a bulging disk in lower back obtained from a new exercise
program. Medications include nasal corticosteroid. Which of the following would be a potential choice
for the management of this type of epilepsy? Select all that apply.
a. Discontinue the nasal corticosteroid as this may cause seizures.
b. Phenytoin
c. Ethosuximide
d. Valproic acid
e. Phenobarbital
3. BV is a 26 year-old epidemiology graduate student. She has a past medical history of partial epilepsy.
Medications include multivitamin and phenytoin. She presents to the student health center for a
prescription for an oral contraceptive. What should be done with the epilepsy management in order to
prevent drug interactions with the oral contraceptive? Select all that apply.
a. Discontinue phenytoin
b. Start carbamazepine
c. Start Topiramate
d. Start Levetiracetam
11
4. Select the formulations that are available for oral phenytoin. Select all that apply.
a. Capsules
b. Suspension
c. Intravenous
d. Chewable tablets
5. Place the following AED’s in order of their target serum concentration. Use the lowest number within
the therapeutic range and order from lowest to highest. Phenobarbital, carbamazepine, valproic acid,
ethosuximide.
a. Phenobarbital<carbamazepine<valproic acid=ethosuximide.
b. Carbamazepine<phenobarbital<valproic acid=ethosuximide.
c. Carbamazepine=valproic acid<ethosuximide<phenobarbital.
d. Ethosuximide<phenobarbital<carbamazepine<valproic acid.
12
ANTIEPRESSANTS
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Major depressive disorder (MDD) is diagnosed when an individual experiences one or more major
depressive episodes without a history of manic, mixed, or hypomanic episodes.
An MDD episode is defined by criteria listed in the Diagnostic and Statistical Manual of Mental
Disorders.
o The diagnosis of MDD requires the presence of at least five depressive symptoms present
every day that cause clinically significant effects and the symptoms must last for a minimum
of 2 weeks.
Individuals with MDD experience significant and pervasive symptoms that affect mood, thinking,
physical health, work, and relationships.
o Suicide may be a result of MDD that has not been diagnosed and treated adequately.
The exact cause of MDD is unknown; appears multifactorial.
MDD patients present with a combination of emotional, physical, and cognitive systems.
TREATMENT
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The goals of treatment are to:
o reduce the symptoms of acute depression;
o facilitate the patient’s return to a level of functioning before the onset of illness;
o prevent further episodes of depression;
o prevention of suicide attempts.
Management options for depression may include medications, cognitive behavior therapy, and
electroconvulsive therapy (ECT).
Antidepressants can be classified in several ways, including classification by chemical structure and
the mechanism of antidepressant activity.
Antidepressants cause pharmacodynamic (e.g. additive pharmacologic effects) and pharmacokinetic
(e.g. changes in drug levels) interactions with other medications.
o The pharmacodynamic interactions involve receptor blockade.
Antidepressants have a response rate of 60% to 80%.
o May induce remission in 30%.
o Antidepressants do not produce a clinical response immediately.
o Improvement in physical symptoms (sleep, appetite, energy) can occur within the first week
of treatment.
o Improvement of emotional symptoms of depression will take at least 2 to 4 weeks and up to
6 to 8 weeks for full effects.
Depression with psychotic features requires addition of neuroleptic or electroconvulsive therapy
(ECT).
Augmentation therapy with antipsychotic medications may be utilized when antidepressant did not
produce desired response.
o Quetiapine and aripirazole are approved for adjunctive MDD treatment.
13
o
Olanzapine / fluoxetine approved as fixed-dose combination pill for treatment-resistant
depression.
MEDICATIONS
1) MAO Inhibitors
2) TCA’s
3) Tetracyclics
4) SSRI’s
5) Misc
a. Bupropion
14
6) SNRI’s

Serotonin Syndrome

Pregnancy and Depression:
o Risks of congenital malformations are low with SSRIs. There is a self-limited neonatal
behavioral syndrome reported. Paroxetine is classified as category D – increased risk of
cardiovascular and other malformations.
o Limited data with SNRIs.
15
ANTIDEPRESSANT Assessment
1. BG is a 34 year-old patient presenting for follow-up of mood changes. She has not been sleeping,
gaining weight, and noticed significant changes is mood. She is diagnosed with MDD. She has a negative
past medical history and is not taking any medications. Which of the following medication classes could
be considered first line treatment options for BG’s MDD? Select all that apply.
a. SNRIs
b. MAOIs
c. TCAs
d. SSRIs
e. Mirtazapine
2. A female patient presents to your pharmacy to pick up a new prescription for an oral contraceptive.
She is new to your pharmacy and you ask her about other medications. She states her other medication
is paroxetine. She has been taking paroxetine for the past 9 months. Three months later she picks up her
prescription for paroxetine; however, you notice she has not refilled her oral contraceptive within the
last month. She states that she is considering becoming pregnant. Which of the following counseling
points should you discuss with the patient? Select all that apply.
a. Paroxetine is classified as a pregnancy category D during pregnancy.
b. She should call her provider to discuss alternative antidepressant management prior to becoming
pregnant.
c. Paroxetine is okay to take during the 1st and 2nd trimester of pregnancy, but should be discontinued
prior to 3rd trimester.
d. Paroxetine is not absorbed with hormonal changes during pregnancy and the dose should be
increased if she becomes pregnant.
3. Which of the following antidepressants is not expected to cause sexual side effects? Select all that
apply.
a. Paroxetine
b. Bupropion
c. Nortriptyline
d. Desvenlafaxine
16
NEUROLEPTICS

Etiology of schizophrenia is unknown but alteration of neurotransmitters (e.g. dopamine) has a
significant role in the development of schizophrenia.

Schizophrenia has various types of symptoms: Positive, negative, and cognitive symptoms.
o
Positive symptoms – excess or added of normal functions to normal functions.

o
Negative symptoms - loss of normal functions or qualities from an individual’s personality.

o
Delusion and hallucinations are common examples of positive symptoms.
Lack of initiative, anhedonia, flat affect, withdrawal, insomnia.
Negative symptoms more difficult to assess; because negative symptoms are associated
with other psychiatric disorders.

Diagnostic and Statistical Manual of Mental Disorders provides criteria for schizophrenia diagnosis.
TREATMENT

Goal: decrease symptoms, improve quality of life, and improve patient functioning, minimize
adverse effects.

Treatment options for schizophrenia include non-pharmacolgic and pharmacologic therapy.

Classes of antipsychotics are:

o
first-generation antipsychotics (FGAs) or typical;
o
second-generation antipsychotics (SGAs) or atypical.
FGAs & SGAs are effective for positive symptoms.
o

SGAs are more likely to improve negative symptoms
FGAs have high-affinity dopamine-2 (D2) receptor antagonists.
o
Not considered as first-line therapy for schizophrenia due to the safety and tolerability
concerns.

SGAs are D2 receptor antagonists; however the affinity for the D2 receptor is less compared to FGAs.
o

SGAs exhibit greater affinity toward serotonin 5-HT2 compared to D2 receptor affinity.
Efficacy:
o
Clozapine more effective for: psychotic symptoms, non-responders, decrease suicide risk.
o
Meta analysis: Olanzapine over aripiprazole, quetiapine, risperidone, and ziprasidone.
17

Side effects (Class wide):
o
General
o
EPS
o
TD
o
Dystonia
o
Akathisia
o
NMS
MEDICATIONS
1) Typical
a. Phenothiazines
18
b. Non-phenothiazines
2) Atypical
19
NEUROLEPTIC Assessment
1. BV is presents with symptoms of schizophrenia to the Emergency Department. He is brought by his
care giver. BV is presenting with positive signs of schizophrenia. Which of the following represent
positive schizophrenia signs? Select all that apply.
a. Apathy
b. Delusions
c. Hallucinations
d. Blunted affect
2. Which of the following neuroleptics would be appropriate first-line options manage his signs? Select
all that apply.
a. Risperidone
b. Haloperidol
c. Clozapine
d. Olanzapine
3. TU is a patient presenting to the primary care clinic for follow-up of schizophrenia. He is receiving
olanzapine 10 mg daily. Which of the following labs should be monitored?
a. Platelets
b. Blood sugar
c. Hemoglobin
d. Potassium
20
4. A patient with newly diagnosed schizophrenia is evaluated by the medical team during rounds. She
has exhibited positive and negative symptoms and meets DSM criteria. She has been stabilized and is to
start chronic treatment to prevent a relapse. She has been counseled on the effects of the medications
and would like to have a medication that can minimize weight gain. Which of the following medications
will treat the patients’ symptoms and minimize weight gain?
a. Haloperidol
b. Ziprasidone
c. Olanzapine
d. Quetiapine
5. Which of the following neuroleptic medications will have a significant effect (increase) of prolactin
levels? Select all that apply.
a. Risperidone
b. Aripiprazole
c. Metronidazole
d. Quetiapine
e. Voriconazole
21
PAIN
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

Pain can be acute or chronic.
Chronic pain: 1) nociceptive; 2) neuropathic.
o Nociceptive: treated with non-opioid or opioid.
o Neuropathic: treated with adjuvant medicines (antidepressants & antiepileptics).
Combining different types of analgesics may provide an additive effect.
NON-OPIOID ANALGESICS


Maximum analgesic effect of acetaminophen & aspirin occur with single doses between 650 and
1300 mg.
o NSAIDs may have higher analgesic ceiling.
Tolerance does not develop to non-opioid analgesics.
MEDICATIONS
1) Salicylates
2) APAP
a. Acetaminophen has central (spinal cord) prostaglandin inhibition similar to NSAIDs.
b. The dosing of acetaminophen is similar to aspirin (eg, 325-650 mg q 4-6 hours as needed for
pain), and should not exceed 4 grams per day.
3) Non-selective NSAIDs
a. NSAIDs exhibit highly individual responses with respect to efficacy and side effects
b. NSAIDs have two key pharmacologic properties and they are:
i. Anti-inflammatory: peripheral prostaglandin inhibition
ii. Analgesia: central inhibition of prostaglandins/other neuroactive chemicals
c. The anti-inflammatory duration (but not analgesic duration of action) correlates to serum
half-life.
d. NSAID drug interactions reduce or increase the effect of certain medications.
i. NSAIDs reduce the effects of ACE inhibitors, beta-blockers, loop diuretics, and
thiazide diuretics,
ii. increase the effects of anticoagulants, cyclosporine (nephrotoxicity), digoxin,
phenytoin, lithium, methotrexate, and probenecid.
4) Selective COX-2 Inhibitors
22
OPIOIDS

Opioids divided into:
o Partial agonists.
o


Full agonists.
o Mixed agonist / antagonist.
Full agonists have no ceiling except as limited by side effects.
Class side effects:
MEDICATIONS
1) Morphine
2) Oxycodone
3) Oxymorphone
4) Hydromorphone
5) Fentanyl
6) Methadone
23
7) Meperidine
Additional Agents

Systemic local anesthetics prolong nerve depolarization via sodium channels in the nerve
membranes. Examples include lidocaine and mexiletine.
o
o
•
Capsaicin—Topical 0.025% and 0.075% used for diabetic and other neuropathies.
o
•
Lidocaine—Regional nerve blocks and local anesthesia applications. May need to be repeated or infused via a regional nerve
catheter.
Mexiletine—Oral congener of lidocaine used for neuropathy, neuralgia, and sympathetic pain syndromes.
Alters function of pain-sensitive nerve endings (nociceptors) through substance-P depletion as well as alter the activities of the
nociceptors.
Lidocaine 5% patches (Lidoderm)—Approved for the treatment of postherpetic neuralgia.
o
o
Analgesic effect due to decrease in sensory activities of the pain receptors through local anesthetic effects.
Tachyphylaxis can occur with continuous use; therefore, patients require a 12-hour break between the patch changes daily.
• Skeletal muscle relaxants—Cyclobenzaprine has tricyclic structure and is primarily used for
musculoskeletal spasms.

Baclofen and benzodiazepines are GABA agonists.

Tizanidine, a congener of clonidine, has antinociceptive (pain relieving) properties. These agents are
used for spasms from spinal origin such as nerve root impingement or spinal cord compression and
irritation.
24
PAIN Assessment
1. UV presents to the pharmacy with an injury occurred during a popular home exercise DVD routine.
She attempted to keep up, but injured herself. She is in mild to moderate pain. Which of the following
are considered first-line initial treatment for mild-moderate pain? Select all that apply.
a. Ketorolac
b. Morphine
c. Misoprostol
d. Acetaminophen
2. XI is a 74 year-old retired pharmacy professor. XI plays golf every day until recently, he twisted his
knee while playing with his grandson. He has a past medical history of peptic ulcer disease (2 years ago),
reflux, hypertension, and coronary artery disease. Select the past medical history for XI that places him
at an increased risk of gastrointestinal bleeding from non-selective NSAIDs.
a. Peptic ulcer disease
b. Reflux
c. Hypertension
d. Coronary artery disease
3. Select the morphine formulation that has a maximum daily dose.
a. MS Contin
b. Demerol
c. Avinza
d. Kadian
25
PAIN – Rheumatoid


Disease modifying anti-rheumatic drugs (DMARDs) are used early in treatment.
DMARDs
o Achieve clinical remission
o Prevent damage to joints
o Do not have immediate analgesic effect
MEDICATIONS
1) Methotrexate ( Rheumatrex)
2) Lefluonamide (Arava)
3) Hydroxychloroquine
4) Sulfasalazine (Azulfidine)
26
DRUGS FOR PAIN – Rheumatoid: Nonbiologic DMARD
Generic Name
Trade Name
Dosage Range
Administration Schedule
Routes of Administration
Methotrexate
Rheumatrex,
Trexall
Initial: 7.5 mg
Once weekly
po, IM, SQ, IV
1-2 doses/d
po
Once daily
po
2-3 divided doses/d
po
Maximum: 20 mg
Leflunomide
Arava
Dose (load): 100 mg/d × 3 d
Maintenance: 20 mg/d
Hydroxychloroquin
Plaquenil
Initial: 400-600 mg × 4-12 wk
Maintenance: 200-400 mg
Sulfasalazine
Azulfidine
Initial: 0.5-1 g
Maintenance: 2-3 g
Maximum: 3 g/d
Gold sodium
thiomalate
Myochrysine
25-50 mg
Every 2-4 wk
IM
Auranofin
Ridaura
3-6 mg
1-2 doses/d
po
2-3 doses/d
po
Maximum: 9 mg/d
D-Penicillamine
Cuprimine
Initial: 125-250 mg/d
Maintenance: 500-1500 mg
Cyclophosphamide
Cytoxan
1-2 mg/kg
Once daily
po, IV
Azathioprine
Imuran
Initial: 1 mg/kg
1-2 doses/d
po, IV
Maintenance: 1-2.5 mg/kg
Cyclosporine
Neoral
2.5-5 mg/kg
Once daily
po, IV
Minocycline
Minocin
100-200 mg
2 doses daily
po
27
DRUGS FOR PAIN – Rheumatoid: Biologic DMARD
Routes of
Administration
Generic
Brand
Dosage Range
Administration Schedule
Infliximab
Remicade
3 mg/kg
Weeks 0, 2, and 6, and then every
8 wk
IV
Etanercept
Enbrel
25 mg twice weekly or 50 mg once weekly
1-2 doses/wk
SQ
Adalimumab
Humira
40 mg
Every 14 d
SQ
Abatacept
Orencia
Weight based: <60 kg = 500 mg
Weeks 0, 2, and 4, and then every
4 wk
IV
Repeat in 14 d, then discontinue
IV
Once daily
SQ
60-100 kg = 750 mg >100 kg = 1000 mg
Rituximab
Rituxan
1000 mg IV infusion: oqnitial: 50 mg/h,
may Increase every 30 min to max 400
mg/h
Subsequent: 100 mg/h, may increase every
30 min to max 400 mg/h
Anakinra
Kineret
100 mg
28
GOUT



Syndrome characterized by elevated uric acid; formation and deposition of monosodium urate
crystals into joints and uric acid urolithiasis.
Features:
o Affects lower extremity joints
o Fast & sudden
o Can be severe
o Causes: stress, trauma, alcohol, infection, surgery, rapid lowering of UA, medications
Reduce modifiable risk factors:
o Avoid purine rich food (e.g. red meat), avoid alcohol, and keep hydrated.
o Avoid (if possible) medications that cause hyperuricemia:
 Niacin, thiazides, low-dose asa, pyrazinamide, ethambutol, cyclosporine, cytotoxic
medications
Pharmacologic Options for Patients With Acute Gout
Drug Class
Examples
Typical Dose
Comments
NSAIDs
Indomethacin
(Indocin)
50 mg po tid, then taper and
discontinue once response is
achieved
Any NSAID at anti-inflammatory dosing is effective
Naproxen (Naprosyn)
750 mg po initially, then 250 mg po
tid until attack has subsided
Caution in patients with a history of GI bleeding or
ulcers
Sulindac (Clinoril)
200 mg bid × 7 d
Colcrys
1.2 mg at first sign of flare, then 0.6
mg every hour; maximum 1.8 mg po
over a 1 h period
Colchicine
Caution in patients with renal or hepatic insufficiency
Best used if within 24 h of the attack
Avoid intravenous use; intravenous formulation no
longer manufactured
Most common adverse effects—nausea, vomiting,
diarrhoea
Rare but serious adverse effects: myelosuppression,
neuromyopathy
Caution in patients with renal or hepatic insufficiency
Potential drug interactions with erythromycin,
simvastatin, and cyclosporine can increase risk of
colchicine-induced toxic effects
Corticosteroids
Prednisone
40-60 mg po daily × 3 d, then
decrease by 10 mg every 3 d until
discontinuation
Useful for patients in whom NSAIDs and colchicine are
contraindicated or in polyarticular flares
Triamcinolone
acetonide
60 mg IM × 1 dose
Caution in patients subject to hyperglycemia Intraarticular therapy may be treatment of choice if only
one or two accessible joints are involved
(Kenalog)
Methylprednisolone
(Depo-Medrol)
10-40 mg × 1 dose by intra-articular
injection
29
Pharmacologic Options for Urate-Lowering Therapy in Patients with Chronic Gout
Generic Name (Trade Name)
Typical Dose
Comments
Allopurinol (Zyloprim)
100-300 mg po daily
Adjust dose for renal insufficiency
May precipitate acute gout attack
Adjust dose based on SUA levels
Can cause rare life-threatening hypersensitivity reaction
Can be used to treat both urate overproduction and renal
urate underexcretion
Febuxostat (Uloric)
40-80 mg po daily
Avoid in patients with severe hepatic impairment
Probenecid (Benemid)
250-500 mg po bid
Adjust dose based on SUA levels
May precipitate acute gout attack
Modifies renal excretion of other drugs; monitor for drug
interactions
Maintain adequate hydration
Colchicine (Colcrys)
CrCl = 50 mL/min: 0.6 mg po bid;
Avoid IV use; IV formulation no longer manufactured
CrCl 35-49 mL/min:0.6 mg po daily;
Most common adverse effects—nausea, vomiting,
diarrhoea
CrCl 10-34 mL/min: 0.6 mg po every 2-3
d;
Rare but serious adverse effects: myelosuppression,
neuromyopathy
CrCl < 10 mL/min: Avoid use
Caution in patients with renal or hepatic insufficiency
Potential drug interactions with erythromycin,
simvastatin, and cyclosporine can increase risk of
colchicine-induced toxic effects
30
GOUT Assessment
1. Which of the following is the generic name for Colcrys?
a. probenacid
b. colchicine
c. sulindac
d. febuxostat
2. A patient is picking up a new prescription for colchicine. Which of the following are the appropriate
counseling points to discuss with the patient?
a. The patient should be counseled on gastrointestinal side effects of nausea, vomiting, diarrhea, and
abdominal pain.
b. The patient should be counseled on possibility of a rash.
c. The patient should be counseled on signs and symptoms of bleeding.
d. The patient should be counseled on close monitoring of blood glucose levels.
3. The target serum uric acid level when treating gout is typically:
a. ≤ 6 mg/dL
b. ≤ 7 mg/dL
c. ≤ 8 mg/dL
d. ≤ 9 mg/dL
31
CHRONIC OBSTRUCTIVE PULMONARY DISEASE






COPD is a preventable chronic disease of the airways that is characterized by gradual, progressive
loss of lung function.
COPD is characterized by airflow limitation that is not fully reversible.
Emphysema is an abnormal permanent enlargement of the airspaces distal to the terminal
bronchioles, accompanied by destruction of their walls and without obvious fibrosis.
Chronic bronchitis is inflammation of the bronchioles with mucus hypersecretion and chronic
productive cough when all other causes of cough have been ruled out.
The medications available for COPD are effective for reducing or relieving symptoms, improving
exercise tolerance, reducing the number and severity of exacerbations, and improving the quality of
life.
No medications have been shown to slow the rate of decline in lung function
ASTHMA



The major characteristics of asthma are airway inflammation and bronchial hyper-responsiveness
which cause variable degree of airflow obstruction.
Asthma medications are classified into two broad categories of quick relief and long-term control.
Independent of severity, all persons with asthma should have a quick relief medication readily
available.
COPD and ASTHMA KEY CONCEPTS

Pulmonary Function Tests
MEDICATIONS
1) Beta agonists
2) Anticholinergics
3) Corticosteroids
a. Inhaled
b. Systemic
32
4) Methylxanthines
5) Leukotriene inhibitors
33
COPD and ASTHMA Assessment
1. CK is a patient with obstructive lung disease and presents to your pharmacy for a prescription for
albuterol meter dose inhaler to be administered as needed. Which of the following should be monitored
while the patient receives the medication?
a. Achilles rupture
b. Seizures
c. Hyponatremia
d. Heart palpitations
2. Select the side effects that may occur with high theophylline concentrations. Select all that apply.
a. Vomiting
b. Seizures
c. Arrhythmias
d. Glaucoma
3. Select the inhaler utilized in the management of lung disease that contains a medication that may
cause oral candidiasis if a patient does not rinse mouth after administration. Select all that apply.
a. Symbicort
b. Singulair
c. Dulera
d. Advair
34
PEPTIC ULCER AND GERD MEDICATIONS
PUD






Peptic ulcers are lesions in the stomach or duodenum that extend into the gastrointestinal (GI) tract.
Lesions develop in response to damage by gastric acid and pepsin.
Gastric ulcers can occur anywhere in the stomach, but most are located on the lesser curvature.
In contrast, duodenal ulcers occur in the first part of the duodenum.
PUD is commonly divided into three forms:
1) H. pylori induced,
2) nonsteroidal anti-inflammatory drug (NSAID) induced,
 Damage from NSAIDs can occur by two mechanisms:
 direct irritation of the gastric epithelium
 systemic inhibition of prostaglandin (cyclooxygenase-1 [COX-1] and
cyclooxygenase-2 [COX-2]) synthesis
3) stress related mucosal damage (SRMD)
 superficial lesions that form in the mucosal layer of the stomach within hours of
major stressful event (trauma, burns, surgery, organ failure, or sepsis).
 common cause of gastrointestinal bleeding in the intensive care unit.
Testing for H. pylori:
1) Tests available to evaluate for H. pylori include: urea breath test; stool antigen test;
serology.
2) Sensitivity of urea-based test and the stool test is reduced by use of proton pump inhibitors,
bismuth containing products, or antibiotics. Patients should not take these medications for
at least two weeks before testing.
GERD




Abnormal reflux of gastric contents into the esophagus is the cause of GERD.
Caused by:
o Transient lower esophageal sphincter (LES) relaxation;
o Reduced lower esophageal sphincter tone;
o Delayed gastric emptying;
o Hormonal changes in pregnancy.
Abnormal defense mechanisms may promote the development of gastroesophageal reflux:
o anatomic factors (hiatal hernia),
o reduced esophageal clearance,
o delayed gastric emptying,
o inadequate mucus secretion,
o decreased salivary buffering.
Lifestyle Modifications
o Avoid laying down 2-3 hours after a meal;
o Elevating head of bed;
35

o Weight loss
GERD in pregnancy
o Progesterone mediated decrease in LES tone
o Treatment: antacids or sucralfate
 Avoid antiacids with sodium bicarbonate because of risk of maternal or fetal
alkalosis.
MEDICATIONS
1) H2 antagonists
2) Sucralfate
3) Proton pump inhibitors
4) Prostaglandins
36
PUD and GERD Assessment
1. UY is a patient with recurrent peptic ulcer disease. She has been evaluated and treated for H. pylori
even though serology test have been negative. She is to remain on suppressive therapy with a proton
pump inhibitor indefinitely. Which of the following are possible long-term side effects associated with
proton pump inhibitors. Select all that apply.
a. Clostridium difficile associated diarrhea (CDAD)
b. Vitamin B12 deficiency
c. Dose related diarrhea
d. Cognitive impairment
2. A 73 year-old male has recently received a drug-eluting stent for management of his coronary heart
disease and acute coronary syndrome. He was recently diagnosed with peptic ulcer disease and his
provider would like to use a proton pump inhibitor because he feels the patient is frail and would not
survive a gastrointestinal bleed. Which of the following would you recommend?
a. Esomeprazole
b. Metronidazole
c. Omeprazole
d. Pantoprazole
3. PM is a 44 year-old patient with a past medical history significant for irritable bowel syndrome (IBS).
She has recently developed severe heartburn and will start lifestyle modifications and antacid therapy as
needed. Her IBS is predominantly diarrhea. Which of the following antacid(s) would you recommend to
help manage the patients heartburn, but not exacerbate the IBS predominant symptom.
a. Aluminum containing antacids
b. Magnesium containing antacids
c. Sucralfate
d. Misoprostol
37
4. RT is a 54 year-old patient that presents to his pharmacy. He is experiencing acid indigestion issues
and recently started on a new medication. Which of the following medications can turn the tongue and
stool black?
a. Pantoprazole
b. Clarithromycin
c. Tetracycline
d. Bismuth subsalicylate
5. QZ is a patient with a diagnosis of erosive esophagitis. She has a past medical history of hypertension,
depression, acute coronary syndrome, and diabetes. Medications include lisinopril, sertraline,
clopidogrel, metoprolol tartrate, and metformin. Which of the following would you recommend to treat
the erosive esophagitis?
a. Sucralfate
b. Proton pump inhibitor
c. H2 Antagonist
d. Misoprostol
38
PUD and GERD Supplemental Material
Drug Regimens to Eradicate H. pylori
PPI or H2RA
Antibiotic 1
Antibiotic 2
Bismuth
Clarithromycin-based triple
therapy
PPI bid or esomeprazole once
daily
Clarithromycin 500 mg bid Amoxicillin 1000 mg bid or
metronidazole 500 mg bid
Bismuth quadruple therapy
H2RA or PPI bid or esomeprazole Metronidazole 250 mg qid Tetracycline 500 mg qid or
once daily
amoxicillin 500 mg qid
Duration
14 d
Bismuth subsalicylate
525 mg qid
10-14 d
Prepackaged Products
Prevpac
Lansoprazole 30 mg bid
Clarithromycin 500 mg bid Amoxicillin 1000 mg bid
Helidac (metronidazole,
tetracycline and bismuth)
PPI or H2RA
Metronidazol 250 mg qid
Pylera (metronidazole,
tetracycline and bismuth)
Omeprazole 20 mg bid for 10 d Metronidazole 125 mg qid Tetracycline 125 mg qid
Tetracycline 500 mg qid
10-14 d
Bismuth subsalicylate
525 mg qid
14 d
Bismuth subcitrate 140 10 d
mg qid
Treatment Options for GERD
Therapeutic Category
Generic Name
Brand Name
Standard Dose
Antacids
Combination of aluminum hydroxide,
magnesium hydroxide, and simethicone
Maalox or Mylanta
30 mL with meals and at bedtime C
Proton pump inhibitors
Omeprazole
Prilosec
20-40 mg daily
C
Lansoprazole
Prevacid
15-30 mg daily
B
Rabeprazole
Aciphex
20 mg daily
B
Pantoprazole
Protonix
40 mg daily
B
Esomeprazole
Nexium
20-40 mg daily
B
Cimetidine
Tagamet
400 mg bid
B
Famotidine
Pepcid
20 mg bid
B
Nizatidine
Axid
150 mg bid
B
Rantidine
Zantac
150 mg bid
B
Gastric protectants
Sucralfate
Carafate
1 g four times per day
B
Promotility agents
Metoclopramide
Reglan
10 mg four times per day
B
Bethanechol
Urecholine
25 mg four times per day
C
Baclofen
Lioresal
5-10 mg tid
C
H2-receptor antagonists
39
Pregnancy Category
DIABETES







There are two major types of diabetes: type 1 (T1DM) and type 2 (T2DM).
o Other subclasses have been identified: gestational diabetes (GDM) and secondary diabetes
associated with hormonal syndromes, medications, diseases of the pancreas.
Diabetes is characterized by hyperglycemia due to defects in insulin action, insulin secretion or both.
Key differences between T1DM and T2DM are the pathophysiology, etiology of hyperglycemia, and
clinical presentation.
T1DM
o Cellular-mediated autoimmune process causes destruction of pancreatic β-cells resulting in
an absolute deficiency of insulin.
o Due to the lack of insulin, glucose is not able to be used as energy.
o Onset of symptoms leading to the diagnosis of T1DM is abrupt
o Classic symptoms of polydipsia, polyuria, polyphagia, and weight loss or ketoacidosis due to
lipolysis.
T2DM
o Impaired insulin secretion and insulin resistance at sites such as the liver, muscles, and
adipocytes.
o Able to produce insulin, but the amount may not be sufficient to keep up with the body’s
glucose metabolism, or the insulin that is produced may not work appropriately.
Agents for T1DM are insulin and amylin analogs.
Agents for T2DM are oral antihyperglycemic agents, GLP-1 receptor agonists, or pramlintide with or
without insulin therapy.
40
COMPLICATIONS
MEDICATIONS
1) Insulin
2) Sulfonylureas
3) Biguanides
4) Alpha-glucosidase Inhibitors
5) TZDs
6) Meglitinides
41
7) GLP-1 Receptor Antagonist (Exenatide, Byetta; Liraglutide, Victoza)
8) DPP-4 Inhibitors (Sitagliptin, Saxagliptin, Linagliptin, Alogliptin)
9) SGLT2 Inhibitors (Canagliflozin, Invokana; Dapagliflozin, Farxiga)
42
Prevention and Management of Complications
Goals
Screening/Diagnosis
Treatment
Screening: Measure BP at every visit
LSM
Macrovascular Complications
Hypertensiona
SBP <130 mm Hg
ACEi or ARB in addition to LSM
DBP <80 mm Hg
Diagnosis: >130 mm Hg/>80 mm Hg
on confirmed separate days
Thiazide diuretic may be added if BP is
not controlled with LSM and ACEi or
ARB if CrCl >30 mL/min or loop diuretic
if CrCl <30mL/min
Multiple antihypertensive therapies are
usually required to attain goal BP
Review special populations to make sure
no contraindications or unwanted side
effects occur
Hyperlipidemiab
TC <200 mg/dL
TG <150 mg/dL
HDL-C >50 mg/dL in
women
Screening: Yearly fasting lipid panel
for most patients. In patients with lowrisk lipid profiles (LDL-C <100
mg/dL, HDL-C >50 mg/dL, and TG
<150 mg/dL) at least every 2 y
HDL-C >40 mg/dL in men
Statin therapy regardless of baseline
LDL-C levels for patients with diabetes
who have overt CVD or are without
CVD, but are over the age of 40 and have
one or more other CVD risk factorsc
LDL-C <100 mg/dL in
patients without overt
CVD
LDL-C <70 mg/dL in
patients with overt CVD or
patients with DM and
other uncontrolled risk
factors (optional)
Antiplatelet therapy
To be on therapy if no
contraindications or
specific population
concerns are present
LSM focusing on reduced saturated fats,
trans fats, and cholesterol intake in
addition to physical activity
Review special populations to make sure
no contraindications or unwanted side
effects occur
Screening: Advised to assess each visit
for antiplatelet therapy
Patients with a Framingham score
calculation > 10%, males > 50 y old, and
females >60 ys old with at least one
additional risk factor of HTN, smoking,
dyslipidemia, family history of CVD, or
albuminuria should start aspirin therapy
of 75-162 mg daily for primary
cardiovascular prevention in T1DM and
T2DM
Aspirin therapy is recommended at the
dosage of 75-162 mg daily for secondary
prevention in those with a history of CVD
In the presence of a documented aspirin
allergy, clopidogrel therapy may be used
Review special populations to make sure
no contraindications or unwanted side
effects occur
Smoking cessation
Complete cessation
Screening: Advised to assess smoking
status at each visit
Include smoking cessation counseling
and forms of treatment for cessation
Screening: Obtain annual test to assess
excretion of urine albumin in patients
with T1DM with duration of diabetes
≥5 y and in all T2DM at diagnosis
ACEi or ARBs should be used in
nonpregnant patients with diabetes who
have micro- or macroalbuminuria
Screening:
Laser photocoagulation may be an option
Microvascular Complications
Nephropathy
Reduce the risk or slow the
progression leading to
chronic kidney disease or
dialysis
Achieve BP and glucose
goals
Retinopathy
Reduce the risk or slow
progression leading to
blindness or other
complications
43
1. All adults and children of ages 10 y
or older with T1DM within 5 y
after diagnosis
Achieve BP and glucose
goals
2. All patients with T2DM shortly after
diagnosis of diabetes Further
follow-up examinations should be
performed yearlyd
3. Women with preexisting diabetes
who are planning pregnancy or
become pregnant should have an
examination within the first
trimester
Neuropathy
Foot care
Dental care
Reduce the risk or slow
progression leading to
distal symmetric
polyneuropathy (DPN)
Screening:
Medical relief of symptoms related to
DPN and autonomic neuropathies are
recommended: TCA (amitriptyline,
nortriptyline, imipramine),
anticonvulsants (gabapentin,
carbamazepine, pregabalin,e duloxetinee)
or capsaicin cream
Obtain glucose goals
1. Assess annually using simple
clinical tests (pinprick sensation,
vibration perception [128-Hz
tuning fork], and 10-g
monofilament pressure sensation at
the distal plantar region of both
great toes and metatarsal joints for
DPN
Surgical options
2. At diagnosis for T2DM and 5 y after
diagnosis for T1DM, patients
should be screened for
cardiovascular autonomic
neuropathy
Smoking cessation
Reduce the risk of
infection or amputation
Screening: All patients with diabetes
should have an annual comprehensive
foot examination/inspection which
includes screening recommendations
for neuropathies
Provide education to patients
Achieve glucose goals
Initial screening for PAD is
recommended
Smoking cessation
Reduce the risk of
infection or gingival
disorders
Screening: Yearly to twice yearly
Preventative measures
Achieve glucose goals
Good oral hygiene
Infectious Disease
Influenza vaccination
Reduce the risk of
infection or death
Screening: Identify those who have not
received the vaccine It is important to
start talking with patients about this in
the summer and throughout influenza
season
Provide influenza vaccine yearly during
influenza season
Pneumococcal
vaccination
Reduce the risk of
infection or death
Screening: Identify those who have not
received the vaccine
Provide vaccine twice throughout the
lifetime.
Revaccinate patients who are >65 y of
age and received initial dose ≥5 y ago and
were <65 y of age at that time
a
Diagnostic blood pressure is lower in patients with diabetes than in those without diabetes.
If drug-treated patients are not able to obtain LDL-C goal, it is recommended to target a reduction in LDL-C by about 30% to 40% from
baseline.
c
Statin therapy may be considered in addition to LSM for low-risk patients if LDL-C is above 100 mg/dL or in those with multiple CVD risk
factors.
d
Less frequent examination may be appropriate following one or more normal eye examination.
e
FDA-approved treatment for painful diabetic neuropathy.
b
44
Pharmacokinetic Profile of Insulins
Insulin
Trade Name (Manufacturer)
Onset (h)
Peak (h)
Duration (h)
Comments
NovoLog (Novo Nordisk)
≤0.25
0.5-1.5
3-4
• Bolus-type insulin
Rapid-Acting
Insulin aspart
• Route of administration: SC, IV, CSII
• Available in insulin-delivery devices (pens)
• Concentration: U-100
• Formulations:
1. NovoLog
2. NovoLog 70/30 (insulin aspart protamine/aspart)
• Mix only with NPH (inject immediately after mixing)
• Unopened refrigerated vial/device: good until expiration
date
• Opened vial/device: good for 28 d regardless of
refrigeration (once device is open, should not be refrigerated)
• Pregnancy category B
• Lactation: unknown if excreted in human milk
Insulin lispro
Humalog (Eli Lilly)
≤0.25
0.5-1.5
3-4
• Bolus-type insulin
• Route of administration: SC, IV, CSII
• Available in insulin-delivery devices (pens)
• Concentration: U-100
• Formulations:
1. Humalog
2. Humalog 50/50 (insulin lispro protamine/lispro)
3. Humalog 75/25 (insulin lispro protamine/lispro)
• Mix only with NPH (inject immediately after mixing)
• Unopened refrigerated vial/device: good until expiration
date
• Opened vial/device: good for 28 d regardless of
refrigeration (once device is open, should not be refrigerated)
• Pregnancy category B
• Lactation: unknown if excreted in human milk
Insulin glulisine
Apidra (Sanofi-aventis)
≤0.25
0.5-1.75
1-3
• Bolus-type insulin
• Administered: SC, IV, CSII
45
• Available in insulin-delivery device (pens)
• Concentration: U-100
• Mix only with NPH (inject immediately after mixing)
• Unopened refrigerated vial/device: good until expiration
date
• Opened vial/device: good for 28 d regardless refrigeration
(once opened pens should not be refrigerated)
• Pregnancy category C
• Lactation: unknown if excreted in human milk
Short-Acting
Regular
Humulin R (Eli Lilly)Novolin R
(Novo Nordisk)
0.5-1
2-3
3-6
• Bolus-type insulin
• Administered: SC, IV, CSII
• Available in insulin-delivery device (pens):
• Concentration: U-100 and U-500 (only Humulin R)
• Formulations:
1. Humulin R
2. Humulin 70/30 (insulin isophane suspension/regular)
3. Novolin R
4. Novolin 70/30 (insulin isophane suspension/regular)
• Mix only with NPH (may store mixture for <7 d)
• Unopened refrigerated vial/device: good until expiration
date
• Opened vial/device: see individual package inserts (once
opened pens should not be refrigerated)
• Pregnancy category: B
• Lactation: unknown if excreted in human milk
Intermediate-Acting
NPH
Humulin N (Eli Lilly)Novolin N
(Novo Nordisk)
1-4
4-10
10-16
• Basal-type insulin
• Administered: SC
• Available in insulin-delivery device (pens)
• Formulation:
1. Humulin N
2. Humulin 70/30 (insulin isophane suspension/regular)
3. Novolin N
46
4. Novolin 70/30 (insulin isophane suspension/regular)
• Concentration: U-100 and U-500 (only Humulin R)
• Mix only with short-rapid acting insulin.
• Unopened refrigerated vial/device: good until expiration
date
• Opened vial/device: see individual package inserts (once
opened pens should not be refrigerated)
• Pregnancy category B
• Lactation: unknown if excreted in human milk
Long-Acting
Insulin glargine
Lantus (Sanofi-aventis)
1.5
None
20-24
• Basal-type insulin
• Administered: SC
• Available in insulin-delivery device (pens)
• Concentration: U-100
• Do not mix with any other insulins/solutions
• Unopened refrigerated vial/device: good until expiration
date
• Opened vial/device: good for 28 d regardless of
refrigeration (once opened pens should not be refrigerated)
• Pregnancy category C
• Lactation: unknown if excreted in human milk
Insulin detemir
Levemir (Novo Nordisk)
1.5
Relatively none
12-24
• Basal-type insulin
• Administered: SC
• Available in insulin-delivery device (pens)
• Concentration: U-100
• Do not mix with any other insulins/solutions
• Unopened refrigerated vial/device: good until expiration
date
• Opened vial/device: good for up to 42 d regardless of
refrigeration (once opened pens should not be refrigerated)
• Pregnancy category C
• Lactation: unknown if excreted in human milk
Abbreviations: CSII, continuous subcutaneous insulin infusion; IV, intravenously; SC, subcutaneously.
47
Diabetes Assessment
1) TY is a 44 year-old patient presenting for a follow-up appointment at the pharmacotherapy
clinic. TY is being followed for increased blood sugars. His blood sugar today continues to be
high despite several months of attempted lifestyle modifications. The PharmD is going to
inititate pharmacologic therapy to control his blood sugar and hemoglobin A1c levels. Which of
the following medications is preferred for first line treatment of type 2 diabetes?
a. Saxagliptin
b. Nateglinide
c. Glipizide
d. Metformin
2) RT is a 51 year-old patient with type 2 diabetes mellitus. He is going to be started on an oral
anti-diabetic medication because lifestyle modifications did not achieve glycemic goals. What
percentage does most oral antihyperglycemic medications lower glycated hemoglobin?
a. 0.5-1.5%
b. 1.5-2%
c. 2-2.5%
d. 2-3%
3) Which of the following diabetes medications is available in an extended release formulation?
Select all that apply.
a. Liraglutide
b. Exenatide
c. Acarbose
d. Metformin
e. Glipizide
4) Which of the following is a common side effect of Glucophage?
a. Weight gain
b. Diarrhea
c. Lactic acidosis
d. Pancreatitis
48
HYPERTENSION





Blood pressure is the mathematical product of peripheral vascular resistance (PVR) and cardiac
output (CO)
Hypertension is the result of increased CO and/or increased PVR.
Majority of patients with hypertension have essential hypertension because their BP is elevated for
unknown reasons.
o Fewer than 10% of patients have secondary hypertension.
o Secondary Causes:
Hypertension is diagnosed when the average of two or more BP measurements are elevated at two
or more clinical encounters.
Lifestyle factors have been associated with the development of hypertension, including excess body
weight; excess dietary sodium intake; reduced physical activity; inadequate intake of fruits,
vegetables, and potassium; smoking; and excess alcohol intake.
o Dietary Approaches to Stop Hypertension (DASH) eating plan was devised to aid in the
prevention and treatment of hypertension.
 Recommendations include a high intake of fruits, vegetables, and low-fat dairy
products along with a reduced content of dietary cholesterol, saturated fat, and
total fat.
 The diet is also rich in potassium and calcium and low in sodium.
 The preferred intake of dietary sodium is no more than 100 mmol/d (2.4 g of
sodium).
TREATMENT





Guidelines recommend a thiazide-type diuretic, a calcium channel blocker, ACEi, or ARB as initial
therapy for the general population.
For black patients, a thiazide-type diuretic or calcium channel blocker is recommended for initial
therapy; except for those with chronic kidney disease or heart failure (ACEi or ARB is
recommended).
Beta blockers are no longer recommended for initial therapy except for patients with compelling
indications.
If blood pressure is more than 20 mm Hg over goal, consider use of two agents.
Guidelines recommend a BP goal of 140/90.
o For patients 60 years of age and greater without diabetes or chronic kidney disease, one
guideline recommends 150/90 mm Hg as the BP goal.
49
MEDICATIONS
1) Compelling Indications
2) Diuretics
3) Beta Blockers
4) Centrally Acting Anti-Adrenergic Agents
5) Peripherally Acting Anti-Adrenergic Agents
50
6) Calcium Channel Blockers
7) Direct Vasodilators
8) Alpha-1 Adrenergic Blockers
9) ACE Inhibitors
10) ARBs
11) Direct Renin Inhibitors
51
Hypertension Assessment
1. A 62 year old white man with newly diagnosed hypertension presents to your pharmacy clinic.
Lifestyle modifications did not get the patient to goal. Which of the following would you recommend for
initial treatment of hypertension for this patient? Past medical history is significant for hypertension and
allergic rhinitis. Medications include loratidine 10 mg daily as needed for seasonal allergies.
a. Thiazide type diuretic
b. Aliskiren
c. Atenolol
d. Clonidine
2. A 64 year-old black man with newly diagnosed hypertension presents to your pharmacy clinic.
Lifestyle modifications improved his blood pressure; however, the patient did not reach goal. Which of
the following would you recommend for initial treatment of hypertension for this patient? Past medical
history is significant for hypertension and allergic rhinitis. Medications include loratidine 10 mg daily as
needed for seasonal allergies.
a.
b.
c.
d.
Indapamide
Aliskiren
Nebivolol
Isosorbide / hydralazine (Bidil)
3. A 64 year old black man with newly diagnosed hypertension presents to your pharmacy clinic.
Lifestyle modifications did not get the patient to goal. Which of the following would you recommend for
initial treatment of hypertension for this patient? Past medical history is significant for hypertension and
diabetes. Medications include metformin.
a. Chlorthalidone
b. Lisinopril
c. Metoporolol succinate
d. Isosorbide / hydralazine (Bidil)
52
4. Which of the following antihypertensive medications may be recommended as initial therapy in a
patient with a past medical history significant for hypertension and reflux disease? Select all that apply.
a. Thiazide-type diuretic
b. ACE inhibitor
c. ARB
d. Beta Blocker
5. JD was started on a new medication for her blood pressure. About a week later she noticed a
persistent cough. Which of the following medications could be the cause? Select all that apply.
a. Maxzide
b. Bystolic
c. Vasotec
d. Diovan
e. Catapres
6. A patient presents to the emergency room (ER) with signs and symptoms of hyperkalemia. Electrolyte
testing reveals serum potassium of 6.7 mmol/L. Which agents could cause or exacerbate the electrolyte
abnormality? Select all that apply.
a. Bumex
b. Mavik
c. Dyrenium
d. Aldactone
e. Cozaar
53
ONCOLOGY

Class Wide Effects
MEDICATIONS
Alkylating Agents
1) Busulfan (Myleran)
2) Cyclophosphamide (Cytoxan)
3) Ifosfamide (Ifex)
Platinum Analogues
1) Carboplatin (Paraplatin)
2) Cisplatin (Platinol)
Anthracyclines
1) Dounorubicin (Cerbidine)
2) Doxorubicin (Adrimycin)
3) Idarubicin (Idamycin)
Antibiotics
1) Bleomycin
2) Dactinomycin (Cosmegen)
54
Antimetabolites
1) Methotrexate (Amethopterin)
2) Cytarabine (Cytosar)
3) Fluorouracil (Adrucil)
Vinca Plant Alkaloids
1) Vincristine (Oncovin)
2) Vinblastine (Velban)
Taxanes
1) Paclitaxel (Taxol)
2) Docetaxel (Taxotere)
Camptothecins
1) Irinotecan (Camptosar)

Mucositis
o Medications

Emetogenic Potential
o High
o
Moderate
55
o

Low
CHEMO MAN
56
ONCOLOGY SUPPLEMENT









Modern medical science has led to significant improvement in the survival and quality of life for
clients with neoplastic (neoplasm) conditions (benign or malignant tumors).
Neoplasm (sometimes called tumor or cancer) is an abnormal mass of tissue, the growth of which
exceeds and is uncoordinated with that of normal tissues and persists after cessation of the stimuli
which evoked the change.
Key feature of cancer is unregulated cell division and growth, secondary to the loss of normal
control mechanisms that govern cell survival, proliferation, and differentiation.
Benign tumors are limited to the tissue of origin and do not invade surrounding tissue.
Malignant tumors can invade local tissues and undergo distant spread (metastasis).
Malignant tumors (often referred as cancer) are predominantly of three types and are divided based
on the tissue type of origin.
o Carcinomas (of epithelial origin), the sarcomas (of connective tissue origin, mesenchymal
origin) or leukemia’s (of hematological origin).
 The first two types are referred to as solid tumors.
Treatment is customized to individual client’s based on their tumor burden, concurrent medical
problems, Karnofsky performance status, organ function (e.g. kidney, liver, cardiac function) and
patient expected treatment outcomes.
Effectiveness of antineoplastic treatment are measured by reduction of tumor size, decrease or
reversal in tumor progression, reduction of tumor related symptoms, improvement in quality of life
and prolongation of survival.
The National Comprehensive Cancer Network (NCCN) (www.nccn.org) publishes free updated
standardized NCCN Clinical Practice Guidelines in Oncology for the management of various types of
cancers.
PHARMAGOLOGIC PROPERTIES OF ANTINEOPLASTIC DRUGS



Nomenclature: The term antineoplastic chemotherapy describes a type of antineoplastic therapy
that uses pharmacological agents to treat cancer.
Other modalities of antineoplastic therapy include surgery and radiotherapy.
o Surgery and radiation may be used alone or in combination with chemotherapy.
o Key difference between surgery and radiation and chemotherapy is that surgery and
radiation therapy is almost always localized therapy, while chemotherapy is systemic
therapy.
o If a cancer is detected early and is localized to a specific area of the body the main
treatment will generally be local non-pharmacological modalities (surgery or radiotherapy).
o However, if the cancer is detected later or is suspected to have spread, then systemic
chemotherapy is utilized, either alone or as adjuvant to surgery and radiotherapy.
Antineoplastic chemotherapy can be classified into three major groups:
57
a) Adjuvant chemotherapy: chemotherapy given after local treatment (e.g. surgery or
radiotherapy) because of concern of residual disease not removed by the local treatment
b) Neoadjuvant chemotherapy: chemotherapy given prior to main treatment, with an aim to
reduce the size or extent of local cancer thus improving success of local main treatment
c) Primary induction chemotherapy: chemotherapy is the main modality of treatment and is used
in clients with advanced or metastasized disease that do not have suitable local treatment
options











Goals of Therapy: The goal of chemotherapy is to selectively kill or suppress cancer cells and to
achieve this with minimal or no damage to normal cells.
Treatment damage cells (normal and neoplastic) leads to adverse effects.
The cardinal feature of the cancer cells is to proliferate (divide or reproduce) and chemotherapeutic
agents act by damaging proliferating cells.
As chemotherapeutic agents damage proliferating cancer cells, they may cause collateral damage to
normal non-cancerous proliferating cells in the body such as in the hair follicles, intestinal epithelial
lining, or bone marrow.
Cell cycle: As our body grows from an early embryonic stage to adult stage, our embryonic stem
cells undergo controlled and regulated cell cycle division with proliferation to ultimately form
differentiated cells that have lost their ability to divide.
However, certain cells called committed adult stem cells lie dormant in various tissues and activate
their ability to divide in response to bodily demands.
These committed stem cells serve the physiological function of cell replenishment and repair.
In the presence of a cancer causing condition, such as a carcinogen or a mutation, such stem cells
(and rarely an adult cell) may enter cell division cycle in an uncontrolled fashion leading to cancer.
The chemotherapeutic agents that specifically target cells that are moving through the various
stages of cell division are called Cell cycle specific drugs
Chemotherapeutic agents that can target cancer cells whether they are cycling through cell cycle or
resting in G0 phase are called cell cycle non-specific drugs.
Generally, it is easier to kill cells when they are metabolically active, i.e. when they are cycling
through cell cycle.
CHEMOTHERAPY REGIMEN PRINCIPLES




Principles of chemotherapy regimen are similar to the principles of antimicrobial therapy.
In both the goal is to achieve suppression / eradication of disease using optimal dosing and
scheduling.
Another goal is to minimize host toxicity and adverse events prevent the development of drug
resistance.
Dosing: Optimal chemotherapy dosing and schedule is based on knowledge of mechanism of action
and detailed experimental evidence.
58
o


Most chemotherapeutic agents have a narrow therapeutic range and it is critical to ensure
that the dose is within the recommended therapeutic window to ensure damage to cancer
cells and minimal effects to normal cells.
o Achieving sub-therapeutic dosage may not kill cancer cells and lead to development of
resistance, while achieving supra-therapeutic dosage may cause collateral damage to
normal cells.
o Most chemotherapy doses are measured in milligrams per kilogram of body weight or per
meters squared of body surface area.
o Other factors that influence dosing include the patient’s ability to metabolize and/or excrete
drug (e.g. kidney or liver disease), age, comorbidities, and drug interactions.
Cycles and intermittent chemotherapy administration: Cancer cells originate from normal host cells
and share metabolic and biologic components of normal cells.
o Damage to shared components will lead to collateral damage to normal cells.
o Thus it is important to identify differentiating factors that provide selective survival benefit
to normal cells over cancer cells.
o One such differentiating factor is that, in most cases, normal cells such as bone marrow tend
to recover faster after a chemotherapeutic insult compared to cancer cells.
o If chemotherapy is provided intermittently, the interval between cycles may allow selective
survival benefit to normal cells compared to cancer cells.
o Duration between the cycles must be long enough to allow recovery of the most sensitive
normal cells, but not long enough to allow growth of cancer cells.
o The duration and frequency of the cycles are dependent on type of drug or cancer and are
based on expert consensus and evidence from observational and experimental science.
o Some regimens may use a single dose followed by several days or weeks without treatment.
o Others may involve several day dosing, or intermittent day dosing followed by treatment
free periods.
Multi-drug regimens: Use of combination therapy provides similar benefits in antineoplastic
chemotherapy as in antimicrobial chemotherapy.
o Using multiple drugs will lead to maximum focused damage at lower doses of individual
drugs without compromising therapeutic efficacy.
o This will reduce the adverse event profile of individual drugs.
o Secondly, combination drugs may work synergistically achieving higher kill rate then
otherwise expected.
o Further, development of resistance to multi-drug regimens is far more difficult compared to
individual drug therapy.
o This is especially true if the individual drugs target cells differently and do not have
overlapping toxicity profiles.
o There are numerous multi-drug chemotherapy regimens that are clinically utilized.
o Select examples of evidenced based multidrug regimens include:
a) Non small cell lung cancer: paclitaxel, carboplatin, and bevacizumab
b) Small cell lung cancer: Cyclophosphamide, doxorubicin, vincristine
c) Breast Cancer: Cyclophosphamide, methotrexate, fluorouracil
59






d) Hodgkin's Lymphoma: Mechlorethamine, vincristine, procarbazine,
prednisone
Routes of administration: Chemotherapy can be administered enterally (orally) or parenterally
(intravenous, sub-cutaneous, intramuscular).
Since most chemotherapeutic agents may damage skin and muscle tissue, sub-cutaneous and
intramuscular administration is almost never done.
Although intravenous administration can be done through smaller veins in the arms and hands,
access to larger more central veins through central venous catheter, such as peripherally inserted
central catheter (PICC) or Implantable Venous Access Port (Port-A-Cath) are preferred as they allow
administration of multiple drugs simultaneously, reduce the number of needle sticks by allowing
long term access, allow for frequent and longer duration of continuous infusions, and avoid damage
to skin and muscle tissues from unintended accidental leakage from smaller veins into subcutaneous
tissue.
Alternatively, local administration of chemotherapeutic agents can be performed for specific types
of cancers that are located at certain regions of the body.
Intravesical chemotherapy is administration of chemotherapeutic agent directly into the urinary
bladder for treatment of bladder cancer, while intraperitoneal chemotherapy is administration into
the peritoneal cavity of the abdomen for cancer such as ovarian cancer.
The most commonly performed local administration is intrathecal administration for central nervous
system cancers. Here the chemotherapeutic agent is administered directly into the cerebrospinal
fluid surrounding the brain and spinal cord after performing a lumbar puncture procedure. The
rationale for intrathecal therapy is that chemotherapeutic agents administered via veins may not
enter the intrathecal compartment because of restriction to flow of drug imposed by normal blood
brain barrier.
CHEMOTHERAPEUTIC AGENTS:
Alkylating agents: Alkylating agents are most effective in the G1 and S phase of cell cycles but because
of its action on G0 resting phase cells are classified as cell cycle non-specific drugs. Drugs of this class
transfer their alkyl- group into cellular components especially in the cell’s nucleus and interfere with
DNA replication process. Cyclophosphamide is the most commonly used chemotherapeutic agent in this
group with some other common drugs being chlorambucil, melphalan and busulfan.
Antimetabolites: Antimetabolites interfere with cellular metabolism required for DNA and RNA
synthesis during cell cycle, preventing progression in cell division and slowing down cell replication. They
have molecular structures that are similar to normal metabolites such as folic acid and nucleotides, and
thus get inserted into the DNA causing loss of function and damage. Common antimetabolites include 5flurouracil, methotrexate, 6-mercaptopurine and gemcitabine.
Antineoplastic antibiotics: These are compounds that were found to have anticancer activity discovered
during research for antibiotics against infection. They bind to DNA in a fashion similar to alkylating
agents and interfere with DNA replication process. The popular drugs in this group include
anthracyclines, bleomycin, and mitomycin.
60
Hormones: Certain types of cancer, such as testicular cancer, breast cancer and ovarian cancer are
sensitive to stimulation by naturally occurring body hormones such as testosterone or estrogen. Such
hormone sensitive tumors can be suppressed by using hormone antagonists or by reduce circulating
levels of endogenous hormones via feedback mechanisms by introducing synthetic hormone analogues
that have no influence on tumor growth. Examples of these agents include Flutamide, Tamoxifen and
Leuprolide.
Antimitotic agents: Antimitotic agents interfere with cell division, specifically in the M-phase of the cell
cycle. Important examples of this group include paclitaxel and vincristine.
CHEMOPROTECTANTS:
The treatment of cancer is complicated by the toxicities associated with the use of antineoplastic agents.
Certain toxicities may be life-threatening and require aggressive monitoring with early interventions to
minimize complications, while others such as mucositis, nausea and vomiting, although may not be life
threatening may be prevented or minimized leading to improved patient satisfaction and compliance.
Myelosuppression: Myelosuppression or bone marrow suppression is the most common dose-limiting
side effect of cytotoxic agents. This includes anemia, neutropenia, and thrombocytopenia. Neutrophils
(a white blood cell) are affected more than red blood cells or platelets because they have shorter life
span and proliferate rapidly. Myelosuppression, especially neutropenia usually occur within 10 to 14
days after starting chemotherapy administration. It begins to recover by about 3 to 4 weeks of the last
chemotherapy dose. With some agents this may be delayed or prolonged lasting for about 4-6 weeks.
Anemia: Anemia is the most common symptomatic hematologic complication of cancer chemotherapy,
with the common symptoms reported being fatigue and shortness of breath. The presence of fatigue in
cancer patients correlates well with the severity of the anemia. Treatment of the anemia results in
improvement in fatigue and quality of life. Recombinant human erythropoietic products (epoetin alfa
and darbepoetin alfa) are useful in the management of anemia. They increase hemoglobin and
hematocrit levels, decrease transfusion requirements and improve quality of life. The initial step in the
management of anemia includes identifying the cause of the anemia and starting appropriate therapy
(e.g. patients with low iron should receive iron supplementation). Patients should not receive an
erythropoietin product until other causes of anemia have been ruled out.
Neutropenia: Neutropenia increases the risk for infection and is defined as absolute neutrophil count
(ANC) less than 500 /mm3. The ANC is calculated by multiplying the percentage of neutrophils
(segmented plus banded neutrophils) by the total white blood cell count. The diagnosis of infection in
neutropenic patients is difficult because usual signs and symptoms are often absent. Clinicians must
treat fever in such a patient as a medical emergency and initiate antibiotics for suspected infection
unless proven otherwise. Colony stimulating factors (CSFs) are naturally occurring proteins used to
increase the neutrophils. Granulocyte colony stimulating factor (G-CSF) and granulocyte-macrophage
colony stimulating factor (GM-CSF) are examples of agents used to increase the neutrophils. G-CSF
(filgrastim) stimulates the production of neutrophils and promotes proliferation of granulocytes and
61
monocytes / macrophages. The CSFs reduce the incidence, magnitude, and duration of neutropenia
when used as preventive therapy following myelosuppressive chemotherapy regimens.
Thrombocytopenia: Chemotherapy-induced thrombocytopenia may lead to significant bleeding and are
often managed by platelet transfusions. Platelet transfusions are reserved for patients with a platelet
count less than 10,000 cells/mm3 unless they are actively bleeding. Patients with non-myeloid
malignancies who experienced thrombocytopenia with a prior chemotherapy cycle may receive
oprelvekin (IL-11). Oprelvekin decreases the need for platelet transfusions and the numbers of platelets
required for transfusions. Unfortunately, oprelvekin is associated with significant adverse reactions.
Mucositis: The gastrointestinal mucosa is composed of epithelial cells with a rapid turnover. Cells with
rapid turnover are the common sites for chemotherapy-induced toxicity. Mucositis can lead to painful
ulcerations, infection, and inability to eat, drink, or swallow. The most effective means of preventing
mucositis is through good oral hygiene. Pharmacologic management of mucositis includes:

Amifostine for mucositis caused by radiation.

Cryotherapy (e.g. ice chips) as a prophylactic measure for standard and high-dose chemotherapy
regimens.

Antimicrobial lozenges, sucralfate and chlorhexidine rinses, and magic mouthwash compound
rinses are sometimes used in clinical practices although not advocated by clinical guidelines.

Palifermin for prevention and treatment of mucositis in patients receiving high-dose
chemotherapy for stem cell transplant or leukemia induction.
Chemotherapy-induced nausea and vomiting (CINV): Nausea and vomiting are the toxicities that are
the most feared by patients who are undergoing chemotherapy. The rate of emesis varies depending
upon the patient risk factors and the drug therapy regimen. Cancer treatments are stratified into high,
moderate, low, and minimal emetogenic potential. High emetogenic antineoplastics cause emesis in
90% of cases (if no anti-emetic prophylaxis is given). The rates of emesis among moderate, low, and
minimal emetogenic antineoplastics are 30 to 90%, 10 to 30%, and less than 10% respectively. With
proper prophylaxis using antiemetic’s, the rate of emesis when receiving a highly emetogenic regimen
can be reduced to about 30%. The optimal method of managing CINV is to provide adequate
pharmacologic prophylaxis given a patient’s risk level for emesis. CINV regimens should include a
prophylactic regimen and a breakthrough antiemetic drug as needed. Management of CINV includes:

Behavior therapy (e.g. relaxation, guided imagery, and music therapy)

Antisecretory agents can be helpful in reducing gastroesophageal reflux that may trigger or
exacerbate CINV.

Antiemesis guidelines recommend corticosteroids (dexamethasone), serotonin receptor
antagonists, and NKI receptor antagonists.
62
Pharmacotherapy principles regarding the management of CINV include:

High emetogenic regimens should be managed with a triple-drug combination consisting of
dexamethasone, aprepitant, and serotonin antagonist to prevent both acute and delayed
emesis.

Moderate emetogenic regimens should be managed with dexamethasone and a serotonin
antagonist.

Low emetogenic regimens may be managed with a single antiemetic with either dexamethasone
or a dopamine antagonist (e.g. prochlorperazine, metoclopramide).

Minimal emetogenic regimens may be managed with as needed antiemetics.
Hemorrhagic Cystitis: Hemorrhagic cystitis is acute bleeding from the lining of the bladder caused by
cyclophosphamide and ifosfamide. Cyclophosphamide and ifosfamide are metabolized to acrolein
leading to the bladder toxicity. The use of preventive strategies can significantly reduce the incidence of
hemorrhagic cystitis. Management of hemorrhagic cystitis includes:

Administration of mesna: mesna binds to acrolein preventing the bladder toxicity

Hydration

Bladder irrigation
Anthracycline cardio toxicity: Anthracyclines may form free radicals and the free radicals combine with
oxygen to form superoxide which can make hydrogen peroxide. Oxygen free radical formation is a cause
of cardiac damage and may be prevented by the use of dexrazoxane.
Methotrexate Bone Marrow and Gastrointestinal Toxicity: High-dose methotrexate administration is
associated with the development of irreversible myelosuppression and gastrointestinal mucosa damage.
Leucovorin is administered to bypass the methotrexate inhibition of dihydrofolate reductase of normal
cells.
Platinum Nephrotoxicity: Cisplatin and carboplatin may cause nephrotoxicity and can be prevented by
the administration of fluids and amifostine.
63
Select Antineoplastic Agents
Antineoplastic
Alkylating Agents
Cyclophosphamide
(Cytoxan)
Busulfan (Myleran
/ Busulfex)
Cisplatin
Mechanism of
Action
Indications
Contraindications
(C);
Warnings /
Precautions (W/P)
Prevents cell
division by
cross-linking
DNA strands
and decreasing
DNA
synthesis. Cell
cycle nonspecific.
Hodgkins and
non –
hodgkins
lymphoma;
chronic and
acute
leukemia;
breast,
testicular,
endometrial,
ovarian, and
lung cancers
C: hypersensitivity to
cyclophosphamide,
pregnancy;
Reacts with
guanosine and
interferes with
DNA
replication and
transcription of
RNA.
Oral: chronic
myelogenous
leukemia
(CML);
Inhibits DNA
synthesis by
the formation
of DNA crosslinks;
covalently
binds to DNA
bases and
disrupts DNA
function
Bladder,
testicular, and
ovarian
cancer.
Intravenous:
conditioning
regimen prior
to allogeneic
cell
transportation
Has several
unlabeled
uses as well.
Adverse Effects (A)&
Interactions (I)
A: Myelosuppression;
Gastrointestinal;
Dermatologic;
Genitourinary; Endocrine
(sterility, SIADH)
W/P: Hazardous agent –
use precautions for
handling and disposal.
I: Substrate, Inhibitor, and
Dosage adjustment may be
Inducer of CYP450
needed for hepatic or renal
dysfunction, may cause
cardio toxicity (high dose)
and may potentiate
anthracycline cardiac
toxicity.
C: Hypersensitivity to
A: central nervous system
busulfan;
(insomnia, anxiety, headache,
dizziness); cardiovascular
W/P: Hazardous agent
(tachycardia, hypertension,
– use precautions for
edema, thrombosis);
handling and disposal,
dermatologic (rash, alopecia,
may cause severe
hyperpigmentation of skin);
myelosuppression,
Endocrine (hypo-magnesemia,
seizures have been
kalemia, calcemia,
reported (patients
hyperglycemia);
receiving high-dose
Gastrointestinal (nausea and
busulfan should receive
vomiting, diarrhea, mucositis,
anticonvulsant
xerostomia);Myelosuppression;
prophylaxis), may
Hepatic (increase bilirubin and
cause delayed
liver function tests, sinusoidal
pulmonary toxicity
obstruction syndrome);
(range 4 months to 10
Pulmonary (fibrosis, cough)
years), high doses
associated with
I: Substrate of CYP450 3A4
increased risk of
hepatic veno-occlusive
disease
C: hypersensitivity to
A: Neurotoxicity (peripheral
platinum containing
neuropathy), Dermatologic
products; pre-existing
(alopecia), gastrointestinal
renal dysfunction,
(nausea and vomiting – highly
myelosuppression ,or
emetogenic),
hearing impairment;
myelosuppression, hepatic
pregnancy
(increased liver function tests);
Nephro and ototoxicity
W/P: Hazardous agent
– use precautions for
handling and disposal,
cumulative renal
toxicity may be
severe, dose related
toxicities include
myelosuppression,
nausea and vomiting;
Ototoxicity is
manifested by tinnitus
or loss of high
frequency hearing;
Anaphylactic-like
reactions have been
reported and may be
managed with
epinephrine,
corticosteroids, and /
or antihistamines.
Antimetabolites
64
Dosing
Administration
400-800
mg/m2 per
treatment
course may be
repeated at 24 week
intervals
To minimize bladder
toxicity, increase normal
fluid intake during and
for 1-2 days after
dosing. Most adults
require at least 2 liters
per day. High-dose
regimens should be
accompanied by
hydration and mesna.
CML
remission: 60
mcg / kg /
day;
Intravenous busulfan
should be administered
2 hours via a central
line.
CML
maintenance:
1-4 mg/day to
maintain
white blood
cell 10,00020,000
cells/mm3
Advanced
bladder
cancer: 50-70
mg/m2 every
3-4 weeks;
Metastatic
ovarian
cancer: 75100 mg/m2
every 3-4
weeks
Patients should receive
adequate hydration prior
to and for 24 hours after
administration; maintain
urine output (>100
mL/hour) for 24 hours;
maximum rate of
infusion for patients
with heart failure is 1
mg/minute
Methotrexate
(Rheumatrex,
Trexall)
5-Fluorouracil
(Adrucil)
Irreversibly
binds to
dihydrofolate
reductase
resulting in
inhibition of
purine and
thymidylic acid
synthesis
(inhibits DNA
synthesis).
Methotrexate
(MTX) is cell
cycle specific of
the S phase.
Leukemia’s;
breast, head,
and neck
cancers;
osteosarcoma;
soft-tissue
sarcomas;
lymphomas
A pyrimidine
antimetabolite
that interferes
with DNA
synthesis by
blocking the
methylation of
deoxyuridylic
acid.
Carcinomas
of breast,
colon, head
and neck,
pancreas,
rectum, or
stomach
C: hypersensitivity to
methotrexate; severe
renal or hepatic
dysfunction; AIDS;
pre-existing
myelosuppression.
W/P: Hazardous
agent – use
precautions for
handling and
disposal; MTX has
been associated with
acute and potentially
fatal hepatotoxicity;
MTX elimination is
reduced in patients
with ascites and may
require dose
modification; May
cause renal damage;
Tumor lysis
syndrome may occur
in patients with high
tumor burden; may
cause lifethreatening
pneumonitis; may
cause
myelosuppression;
low dose mtx has
been associated with
development of
malignant
lymphomas;
diarrhea and
ulcerative stomatitis
may require
interruption of
therapy; may cause
seizures; may cause
severe and fatal
dermatologic
reactions;
concomitant
administration with
NSAIDs may cause
severe
myelosuppression or
gastrointestinal
toxicity
C: Hypersensitivity to
fluorouracil,
dihydropyrimidine
dehydrogenase
deficiency, pregnancy
W/P: Hazardous
agent – use
appropriate
precautions for
handling and
disposal; Discontinue
use in patients with
intractable vomiting,
precipitous fall in
blood counts,
stomatitis,
hemorrhage, or
myocardial ischemia
occurs;
65
A: Central nervous system
(headache, nuchal rigidity,
vomiting, fever, seizure, motor
paralysis); Dermatologic;
Endocrine (hyperuricemia);
Gastrointestinal (ulcerative
stomatitis, nausea, vomiting,
diarrhea, mucositis;
Myelosuppression; Renal failure;
Hepatotoxicity
Head and
neck cancer:
25-50 mg/m2
once weekly;
A: Central nervous system
(cerebellar syndrome –
confusion, disorientation,
headache); Dermatologic
(alopecia, rash); Cardiovascular
(angina, myocardial ischemia);
Gastrointestinal (anorexia,
diarrhea, stomatitis):
Myelosuppression; Allergic
reaction
500-600
mg/m2 every
3-4 weeks
(there are
numerous
dosing
regimens)
Lymphoma:
1 g/m2 every
3 weeks or
1.5 g/m2
every 4
weeks
Specific dosing
schemes vary for
methotrexate, but high
dose should be
followed by leucovorin
to prevent toxicity.
Intravenous bolus as a
slow push or short (515 minutes) bolus
infusion, or as a
continuous infusion;
Doses greater than
1000 mg/m2 are usually
administered as a 24hour infusion; Toxicity
may be reduced by
giving the drug as a
constant infusion
Cytarabine / Ara-C
(Cytosar)
Anthracycline /
Antibiotic
Doxorubicin
(Adriamycin)
Bleomycin
(Blenoxane)
Inhibits DNA
synthesis.
Cytarabine is
specific for the
S phase of the
cell cycle.
Leukemia’s
and
lymphomas
Inhibition of
DNA and RNA
synthesis by
intercalation
between DNA
base pairs by
inhibition of
topoisomerase II
Leukemia’s,
lymphomas,
multiple
myeloma, and
carcinoma of
the head and
neck, thyroid,
lung, breast,
stomach,
pancreas,
liver, ovary,
bladder,
prostate, and
uterus
Inhibits
synthesis of
DNA; binds to
DNA leading to
single and
double-strand
breaks
C: Hypersensitivity to
cytarabine
W/P: Hazardous
agent – use
appropriate
precautions for
handling and
disposal; Potent
myelosuppressive
agent; Use caution in
patients with renal or
hepatic dysfunction
Squamous
cell
carcinoma,
melanomas,
sarcomas,
lymphoma
C: Hypersensitivity to
doxorubicin or other
anthracyclines; recent
myocardial infarction,
severe arrhythmia,
exceeding cumulative
dose of
anthracyclines;
Baseline neutrophil
count less than
1500/mm3; severe
hepatic impairment
W/P: Hazardous
agent – use
appropriate
precautions for
handling and
disposal; Reduce
dose in patients with
impaired hepatic
function; doselimiting
myelosuppression
may occur; leukemia
has been reported
following treatment;
potent vesicant, if
extravasation
occurs, severe tissue
damage leading to
ulceration, necrosis,
and pain may occur
C: Hypersensitivity to
bleomycin, severe
pulmonary disease,
pregnancy
W/P: Hazardous
agent – use
appropriate
precautions for
handling and
disposal; Occurrence
of pulmonary
fibrosis is higher in
elderly patients,
smokers, and
patients with prior
radiation or
concurrent
oxygen;Idiosyncratic
reactions consisting
of chills,
hypotension, fever,
wheezing has been
reported in
lymphoma patients
Vinka Alkaloids
66
A: Central nervous system
(neurotoxicity); Conjunctivitis;
Myelosuppression;
Gastrointestinal
75-200
mg/m2/ day
for 5-10 days
When administering
via intravenous
infusion, infuse over 13 hours or as a
continuous infusion.
Intravenous doses
greater than 1.5 g/m2
may produce
conjunctivitis,
Dexamethasone eye
drops should be
administered at 1-2
drops every 6 hours
during and for 2-7 days
after cytarabine is
done.
A: Cardiotoxicity; Dermatologic;
Endocrine (infertility,
hyperuricemia); Gastrointestinal;
Myelosuppression
60-75
mg/m2/dose
every 21
days
Administer intravenous
push over at least 3-5
minutes, intravenous
piggyback over 15-60
minutes, or continuous
infusion
I: Substrate and inhibitor of
CYP450
A: Dermatologic (rash, peeling
of skin, hyperpigmentation,
alopecia); Gastrointestinal
(stomatitis); Pulmonary
(pulmonary fibrosis, cough)
0.25-0.5
units/kg 1-2
times per
week
Vincristine
(Vincasar)
Binds to tubulin
and inhibits
microtubule
formation
Leukemia’s,
lymphomas
C: hypersensitivity to
vincristine; for
intravenous use only
(fatal if given
intrathecally);
pregnancy;
W/P: Hazardous
agent – use
appropriate
precautions for
handling and
disposal; Vincristine
is a vesicant – avoid
extravasation;
dosage modification
required for those
with hepatic
dysfunction or
neuromuscular
disease;
Taxanes
Paclitaxel (Taxol)
Promotes
microtubule
assembly
inhibiting cell
replication
Breast, nonsmall cell
lung, head
and neck
cancers
C: Hypersensitivity to
paclitaxel;
W/P: Hazardous
agent – use
appropriate
precautions for
handling and
disposal; Severe
hypersensitivity
reactions reported;
Stop infusion and do
not re-challenge for
severe hypotension
requiring treatment or
if angioedema occurs;
Myelosuppression is
dose-limiting
toxicity, do not
administer if
baseline absolute
neutrophil count is
less than 1500
cells/mm3; caution in
patients with hepatic
dysfunction;
peripheral neuropathy
may occur, reduce
dose by 20% for
severe neuropathy;
infusion related
reactions may occur
(monitor vital signs
during infusion)
Miscellaneous
Antineoplastics
67
A: Dermatologic (alopecia,
rash); Cardiovascular (orthostatic
hypotension); Central nervous
system (headache, confusion);
Gastro
0.25-0.5
mg/m2 for 5
days every 4
weeks
Fatal if given
intrathecally;
Intravenously
administered as short
(10-15 minutes)
infusion, slow IV push
(1-2 minutes), or 24
hour continuous
infusion.Administration
of vincristine with
itraconazole has been
reported to cause
paralytic ileus,
neurogenic bladder,
absence of deep
reflexes, and severe
paralysis of lower
extremities within 10
days of starting
itraconazole
Non-small
cell lung
cancer: 135
mg/m2 over
24 hours
every 3
weeks
When administered as
sequential infusions,
taxane derivatives
should be administered
before platinum
derivatives to limit
myelosuppression;
premedication with
dexamethasone,
diphenhydramine,
cimetidine, and
ranitidine is
recommended
I: Substrate of CYP 450 system
& weak CYP 450 inhibitor
A:Myelosuppression;
Dermatologic (flushing,
alopecia); Neuropathy;
I: Substrate of the CYP 450
system and a weak CYP 450
inducer
Asparaginase
(Elspar)
Inhibits protein
synthesis by
hydrolyzing
asparaginase to
aspartic acid and
ammonia
Leukemia
C: History of serious
allergic reaction to
asparaginase or any
E. coli derived
asparaginase; history
of serious thrombosis,
pancreatitis or
hemorrhagic events
with prior
asparaginase
treatment;
6000
units/m2/dose
3 times per
week for 6-9
doses
W/P: Hazardous
agent – use
appropriate
precautions for
handling and
disposal; Monitor for
allergic reactions;
may alter hepatic
function, use caution
with pre-existing
hepatic dysfunction
Hydroxyurea
(Hydrea)
Interferes with
synthesis of
DNA during S
phase of cell
division
Melanoma,
leukemia,
ovarian, head
and neck
cancer
C: Hypersensitivity to
hydroxyurea; severe
anemia; severe
myelosuppression;
pregnancy
A:Myelosuppression;
Gastrointestinal; Dermatologic
(rash)
W/P: Hazardous
agent – use
appropriate
precautions for
handling and
disposal;
Hydroxyurea is
mutagenic and
clastogenic.
Treatment of
myeloproliferative
disorders with longterm hydroxyurea is
associated with
leukemia
Procarbazine
(Matulane)
Inhibits DNA,
RNA, and
protein synthesis
Lymphoma
C: Hypersensitivity to
procarbazine; preexisting
myelosuppression;
pregnancy;
W/P: Hazardous
agent – use
appropriate
precautions for
handling and
disposal; use caution
in pre-existing renal
or hepatic dysfunction
68
A: Myelosuppression;
Gastrointestinal (nausea.
Vomiting, diarrhea); influenza
like syndrome; disulfiram-like
reaction
I: Possesses MAO inhibitor
activity and has potential for
severe food and drug interactions
Dose should
be titrated to
patient
response and
white blood
cell counts;
usual oral
doses range
from 10-30
mg/kg/day; if
white blood
cell count
falls to less
than 2500
cells/mm3 or
platelet count
to less than
10,000
cells/mm3
therapy
should be
stopped for
at least 3
days and
resumed
when values
rise toward
normal
2-4
mg/kg/day in
single or
divided
doses for 7
days then
increase dose
to 4-6
mg/kg/day
until
response in
leukocyte
count is
obtained
(less than
4000
cells/mm3 or
platelet count
(less than
100,000
cells/mm3)
May be administered
intramuscularly,
intravenously, or
intradermal (skin test
only for allergic
reaction); Intravenous
administration
increases the risk of
allergic reactions;
Manufacturer
recommends a test dose
prior to initial
administration and
when given after an
interval of 7 days or
more; The skin test site
should be observed for
at least 1 hour for a
wheal or erythema; A
negative skin test does
not preclude the
possibility of an
allergic reaction;
Desensitization may be
performed in allergic
patients
Capsules may be
opened and emptied
into water (will not
dissolve completely)
May be given as a
single daily dose or in
2-3 divided doses
Tretinoin
(Vesanoid)
Binds to nuclear
receptors and
inhibits clonal
proliferation and
granulocyte
proliferation
Leukemia
C: Sensitivity to
parabens, vitamin A,
retinoids; pregnancy;
W/P: Hazardous
agent – use
appropriate
precautions for
handling and
disposal; About 25%
of patients with
acute promyelocytic
leukemia experience
a syndrome
characterized by
fever, dyspnea, acute
respiratory distress,
weight gain,
pulmonary
infiltrates, edema,
multi-organ failure;
during treatment,
40% develop rapidly
evolving
leukocytosis; high
risk of teratogenicity
– not to be used in
women of
childbearing
potential
69
A: Retinoic acid syndrome;
gastrointestinal; cardiovascular;
hematologic
I: Substrate of CYP 450 system;
weak inhibitor and inducer of
CYP 450 system
45
mg/m2/day in
2-3 divided
doses for up
to 30 days
Administer with meals;
do not crush capsules
Adverse Effects Associated with Antineoplastic Agents
General: Chemotherapy agents are toxic not only to cancer cells but also to various host tissues and organs. Toxicities generally occur as a
result of inhibition of host cell division. Host tissues most susceptible to chemotherapy include tissues with renewal cell populations (e.g. bone
marrow and epithelium of gastrointestinal tract and skin). The toxicities of antineoplastic agents are the most important factors limiting the use
of potentially curative doses.
Myelosuppression (Bone Marrow Suppression): Although not seen with all antineoplastics, myelosuppression is the most common doselimiting side effect of antineoplastic agents. Antineoplastics can affect any cell line, including red blood cells, neutrophils (a white blood cell),
and platelets. Decreased red blood cells can cause anemia and patients present with fatigue. Low neutrophil counts (neutropenia) increase the
risk of bacterial infections. Reduced platelets (thrombocytopenia) may cause bleeding. There are numerous antineoplastic agents and regimens
that cause myelosuppression.
Gastrointestinal: Gastrointestinal toxicities include nausea and vomiting (N&V), oral complications, and lower bowel disturbances. N&V are
common serious toxicities associated with most chemotherapy agents. While the emetogenic potential of antineoplastic agents varies, emesis
commonly occurs on the first day of treatment and may persist for several days. Complications of the oral cavity include mucositis / stomatitis,
xerostomia (dry mouth), infection, and bleeding. Approximately 40% of patients treated with antineoplastic develop oral complications.
Chemotherapy may also damage the lining of the esophagus leading to esophagitis. Lower gastrointestinal complications include malabsorption, diarrhea, or constipation.
Dermatologic: Dermatologic toxicities associated with antineoplastic agents include alopecia (hair loss), hypersensitivity reaction, extravasation
(passage / leakage of agent into tissue), and hyperpigmentation (pigment changes in skin, hair, or nails). Numerous antineoplastic agents are
associated with dermatologic reactions.
Specific Organ Toxicities: Specific organ adverse effects (e.g. neurotoxicity, nephrotoxicity) are attributed to a unique uptake of the
antineoplastic agent by the organ or a select toxicity of the agent to the organ. While there are numerous antineoplastic agents that cause
specific organ toxicities, they are not as wide spread as the general toxicities (myelosuppression, gastrointestinal, and dermatologic).
Neurotoxicity: Neurotoxicity is a central nervous system toxicity manifested by a generalized encephalopathy with symptoms of confusion,
seizures, and / or coma. Cerebral dysfunction (ataxia, coordination difficulties) and leukoencephalopathy (change in personality, dementia) may
also be seen. The antineoplastic agents most commonly associated with neurotoxicity include cytarabine and L-asparaginase. Other agents that
produce central nervous system toxicities include: methotrexate (encephalopathy, leukoencephalopathy), fluorouracil (cerebral dysfunction),
interferon (encephalopathy), fludarabine (altered mental status, blindness), and alkylating agents (encephalopathy).
Peripheral nerve toxicity:Paresthesia is numbness and tingling involving the feet, hands, or both. This nerve toxicity is associated with vincristine
and vinblastine (vinka alkaloids). Other agents that may cause peripheral nerve toxicity include cisplatin, etoposide, oxaliplatin, paclitaxel, and
docetaxel. Oxaliplatin also causes a peripheral neuropathy triggered by cold sensation.
Cranial nerve toxicity: Cranial nerve toxicity may cause trigeminal neuralgia, facial palsy, depressed corneal reflexes, and vocal cord paralysis.
Agents associated with cranial nerve toxicity include the vinka alkaloids, ifosfamide, and cisplatin. Cisplatin may also cause ototoxicity.
Autonomic neuropathy: Autonomic neuropathy is abdominal pain with or without constipation and may lead to ileus (small bowel obstruction).
The vinka alkaloids as associated with autonomic neuropathy.
Pulmonary: Pulmonary edema (fluid in the lungs) is associated with cytarabine, aldesleukin, and gemcitabine. Pulmonary fibrosis is a scarring /
thickening of the lungs and may cause shortness of breath, chest pain, and coughing. Pulmonary fibrosis is associated with bleomycin and
busulfan.
Cardiovascular: The anthracycline antibiotics (e.g. doxorubicin) cause a dose dependent cardiac toxicity (cardiomyopathy). Patients will
experience heart failure symptoms (shortness of breath and tachycardia). Electrocardiographic (EKG) changes may be seen with anthracyclines,
cisplatin, etoposide, paclitaxel, and cyclophosphamide. The EKG changes (ST segment changes, T wave flattening) may lead to arrhythmias.
Fluorouracil is associated with causing angina.
Nephrotoxicity: Platinum analogs (cisplatin and carboplatin) may damage the kidney function leading to nephrotoxicity (decrease in kidney
filtration and urine output). Oxaliplatin is not associated with nephrotoxicity.
Hepatotoxicity: Hepatotoxicity is destruction of the liver leading to jaundice, nausea, vomiting, abdominal pain, encephalopathy, and cirrhosis.
Antineoplastic agents associated with hepatotoxicity are L-asparaginase, carmustine, etoposide, mercaptopurine, and methotrexate.
Genitourinary (GU):Cyclophosphamide and ifosfamide cause a cystitis characterized by tissue edema and ulceration followed by sloughing of
epithelial cells leading to hemorrhage.
70
Chemoprotectants
Agent
Mechanism of
Action
Use
Epoetin alfa
(Epogen /
Procrit)
Induces
erythropoiesis by
stimulating the
division and
differentiation of
committed
erythroid
progenitor cells;
induces the
release of
reticulocytes from
the bone marrow
into the
bloodstream
Treatment of
anemia (elevate /
maintain red blood
cell level and
decrease need for
transfusions)
Stimulates the
production,
maturation, and
activation of
neutrophils
Stimulation of
granulocyte
production during
chemotherapyinduced
neutropenia
Filgrastim
(Neupogen) –
also referred to
as Granulocytecolony
stimulating
factor (G-CSF)
Contraindications
(C) / Warnings &
Precautions (W/P)
C: hypersensitivity
to albumin or
mammalian cellderived products;
uncontrolled
hypertension;
W/P:
Erythropoiesisstimulating agent
(ESA) increased the
risk of serious
cardiovascular
events, mortality,
and / or tumor
progression; A
shortened overall
survival and / or
increased risk of
tumor progression
or recurrence has
been reported in
studies with
breast, cervical,
head and neck,
lymphoid, and
non-small cell lung
cancer patients;
Use lowest dose
needed to avoid
red blood cell
transfusions to
decrease risk of
cardiovascular and
thrombovascular
events, dosing
should be
individualized to
maintain
hemoglobin levels
within 10-12 g/dL;
Use caution in
patients with
hypertension or
with a history of
seizures; prior to
treatment with
ESAs, correct or
exclude
deficiencies of iron,
vitamin B12, and /
or folate
C: Hypersensitivity
to filgrastim or E.
coli derived
products;
W/P: do not use 24
hours before or
after
administration of
cytotoxic
chemotherapy
because of the
potential sensitivity
of rapidly dividing
myeloid cells;
allergic-type
reactions (rash,
urticaria, wheezing,
71
Adverse Effects
(AE) & Interactions
(I)
Cardiovascular
(hypertension,
thrombotic /
vascular events);
Central nervous
system (fever,
dizziness,
insomnia,
headache, seizure);
Dermatologic
(pruritus, skin pain,
rash);
Neuromuscular
(arthralgia)
Formulation (F), Dosing
(D) & Administration (A)
Comments
F: injection;
Darbepoetin alfa
(Aranesp) is also a
erythropoiesisstimulating agent
AE: bone pain
F: injection;
D: Initial dose – 150
units/kg 3 times per week
or 40,000 units once
weekly;
A: hemoglobin levels
should not exceed 12g/dL
and should not rise
greater than 1 g/dL per 2week time period
D: Dosing should be
based on actual body
weight, even in obese
patients; 5 mcg/kg/day –
doses may be increased
by 5 mcg/kg according to
the duration and severity
of neutropenia;
A: Continue until 14 days
or the absolute
neutrophil count reaches
10,000/mm3; may be
administered undiluted
by subcutaneous
injection; may be
Pegfilgrastim
(Neulasta) is a
pegylated form of
filgrastim – this
increases the effect
of the medication
allowing for less
frequent dosing;
Sargramostim
(Leukine) is a
granulocytemacrophage colony
stimulating factor
(GM-CSF). GM-CSF
is used to shorten
the time to
neutrophil recovery
Oprelvekin
(Neumega)
Amifostine
(Ethyol)
Growth factor
which stimulates
thrombopoiesis –
increased platelet
production
Prodrug that is
metabolized to
free thiol. The free
thiol binds and
detoxifies reactive
metabolites of
cisplatin; also acts
as a scavenger of
free radicals
generated by
cisplatin or
radiation therapy
in tissues
Prevention of
severe
thrombocytopenia;
reduce the need
for platelet
transfusions
following
myelosuppressive
chemotherapy
Reduce the
cumulative renal
toxicity associated
with repeated
administration of
cisplatin; reduce
the incidence of
moderate to severe
xerostomia in
patients
undergoing
postoperative
radiation
treatment for head
and neck cancer
dyspnea,
tachycardia, and /
or hypotension)
have occurred
C: Hypersensitivity
to oprelvekin;
W/P: Allergic
reactions including
anaphylaxis have
been reported.
Permanently
discontinue in any
patient developing
an allergic
reaction; may
cause fluid
retention – use
caution in heart
failure and
hypertension
patients;
Arrhythmia,
pulmonary edema,
and cardiac arrest
have been
reported; use
caution in patients
with renal or
hepatic dysfunction
C: Hypersensitivity
to aminothiol
compounds;
W/P: Patients who
are hypotensive or
dehydrated should
not receive
amifostine;
interrupt
hypertensive
therapy for 24
hours before
treatment;
adequately hydrate
prior to treatment
and keep in a
supine position
during infusion;
monitor blood
pressure every 5
minutes during
infusion; serious
cutaneous
reactions including
Stevens-Johnson
syndrome have
been reported; it is
recommended that
antiemetic
medication be
administered prior
to and in
conjunction with
amifostine;
hypersensitivity
reactions have
been reported;
reports of clinicallyrelevant
hypocalcemia are
rare, but serum
calcium levels
should be
monitored in
72
administered by
intravenous bolus over
15-30 minutes in D5W
AE: Cardiovascular
(tachycardia,
edema, syncope,
arrhythmia);
Central nervous
system (headache,
dizziness);
Endocrine /
Metabolic (fluid
retention);
F: injection;
AE: Cardiovascular
(hypotension);
gastrointestinal
(nausea /
vomiting);
Endocrine /
metabolic
(hypocalcemia)
F: injection;
D: 50 mcg/kg once daily
for 10-21 days (until postnadir platelet count is
greater than 50,000
cells/mcL;
A: Administer
subcutaneously in the
abdomen, thigh, hip, or
upper arm;
mg/m2
D: 910
over 15
minutes once daily 30
minutes prior to cisplatin;
Xerostomia dosing: 200
mg/m2 over 3 minutes
once daily for 15-30
minutes prior to
radiation;
A: Refer to dosing
recommendations for
blood pressure. There are
specific
recommendations for
dosing dependent upon
the patient’s blood
pressure
and to reduce the
incidence of severe
and life-threatening
infections
Administer first
dose 6-24 hours
after the end of
chemotherapy;
Discontinue at least
48 hours before
beginning the next
cycle of
chemotherapy
Administer over 3
minutes (prior to
radiation therapy)
or 15 minutes (prior
to cisplatin);
administration as a
longer infusion is
associated with a
higher incidence of
side effects;
antiemetic
medication,
including
dexamethasone 20
mg intravenous and
a serotonin
receptor antagonist
is
recommendedprior
to and in
conjunction with
amifostine
Palifermin
(Kepivance)
Dexamethasone
( DexPak)
Ondansetron
(Zofran)
Recombinant
keratinocyte
growth factor that
leads to
proliferation,
differentiation and
migration of
epithelial cells in
multiple tissues
including the
tongue, buccal
mucosa,
esophagus, and
salivary gland
Decrease the
incidence and
severity of oral
mucositis
associated with
hematologic
malignancies in
patients receiving
myelotoxic therapy
Mechanism of
antiemetic activity
in unknown;
decreases
inflammation by
suppression of
neutrophil
migration and
decreased
production of
inflammatory
mediators;
suppresses normal
immune response
Antiemetic and
many other
indications
Selective 5-HT3
receptor
antagonist, both
peripherally on
vagal nerve
terminals and
centrally in the
chemoreceptor
trigger zone
patients at risk of
hypocalcemia
C: Hypersensitivity
to palifermin or E.
coli derived
proteins;
W/P: Edema,
erythema, pruritus,
rash, taste
alteration, tongue
discoloration /
thickening may
occur
C: Hypersensitivity
to dexamethasone ;
systemic fungal
infections;
W/P: Use with
caution in patients
with thyroid,
hepatic or renal
impairment,
cardiovascular
disease, diabetes,
glaucoma,
cataracts,
myasthenia gravis,
patients at risk for
osteoporosis,
patients at risk for
seizures, or
gastrointestinal
diseases
Prevention of
nausea and
vomiting
associated with
moderately to
highly emetogenic
cancer
chemotherapy
C: Hypersensitivity
to ondansetron or
5-HT3 receptor
antagonist;
W/P: Ondansetron
should be used on
a scheduled basis,
not on an as
needed (prn); use
caution on patients
with congenital
long QTc syndrome
or risk factors for
QTc prolongation
(e.g. medications
known to prolong
73
AE: Edema,
dysesthesia, rash,
pruritus,
mouth/tongue
discoloration /
thickness, cough
AE: Cardiovascular
(edema, heart
failure); central
nervous system
(euphoria,
headache,
insomnia, mood
swings, psychic
disorder);
dermatologic
(acne, alopecia,
hyper / hypopigmentation,
wound healing
impaired);
Endocrine /
metabolic (adrenal
suppression,
Cushing’s
syndrome,
diabetes, sodium
retention);
Neuromuscular
(arthropathy,
myopathy,
osteoporosis,
weakness); Ocular
(cataracts,
glaucoma);
Miscellaneous
(moon face,
abnormal fat
distribution)
I:Substrate of the
CYP 450 system;
Inducer of the
CYP450 system
AE: Central
nervous system
(headache,
drowsiness);
gastrointestinal
(constipation);
dermatologic
(rash);
I: Substrate of the
CYP450 system;
weak inhibitor of
the CYP 450
system
F: injection;
D: 60 mcg/kg/day for 3
consecutive days before
and after myelotoxic
therapy; total of 6 doses;
A: Administer by
intravenous bolus; do not
administer during or
within 24 hours of
chemotherapy (before or
after); allow solution to
reach room temperature
before administration; do
not use if at room
temperature for more
than one hour
F: elixir, injection,
solution, tablet;
D: 10-20 mg 15-30
minutes before treatment
on each treatment day;
numerous dosage
regimens exist;
A: administer oral
formulation with meals to
decrease gastrointestinal
upset
F: injection; solution;
tablet; oral disintegrating
tablet;
D: highly emetogenic
agents: 24 mg given 30
minutes prior to start of
therapy;
Moderately emetogenic
agents: 8 mg every 12
hours beginning 30
minutes before
chemotherapy;
A: Oral disintegrating
tablets – do not remove
from blister until needed;
Administer first 3
doses prior to
myelotoxic therapy,
with the 3rd dose
given 24-48 hours
before therapy
begins; the last 3
doses should be
administered after
myelotoxic therapy,
with the first of
these doses after
but on the same
day as stem cell
infusion and at least
4 days after the
most recent dose of
palifermin
May cause adrenal
suppression,
particularly in
younger children or
in patients receiving
high doses for
prolonged periods;
Withdrawal and
discontinuation
should be done
slowly and carefully
Several 5-HT3
receptor
antagonists are
available:
Granisetron (Kytril);
Palonosetron
(Aloxi); Dolasetron
(Anzemet)
QTc interval,
electrolyte
abnormalities)
Aprepitant
(Emend)
Mesna
(Mesnex)
Dexrazoxane
(Zinecard)
Leucovorin
(Folinic Acid)
Inhibits substance
p / neurokinin
1(NK1) receptor;
augments the
activity of 5-HT3
receptor
antagonist and
corticosteroid
activity
In blood, mesna is
oxidized to
dimesna which in
turn is reduced in
the kidney back to
mesna, supplying a
free thiol group
which binds to and
inactivates
acrolein, the
urotoxic
metabolite of
ifosfamide and
cyclophosphamide
Chelating agent
that interferes
with free radical
generation
A reduced form of
folic acid,
leucovorin supplies
the cofactor
blocked by
methotrexate
Prevention of acute
and delayed
nausea and
vomiting
associated with
moderately and
highly emetogenic
chemotherapy (in
combination with
other antiemetics)
Reduce the
incidence of druginduced
hemorrhagic
cystitis
Reduction of the
incidence and
severity of
cardiomyopathy
associated with
anthracyclines who
have received a
cumulative dose of
300 mg/m2 and
who would benefit
from receiving
additional therapy
anthracyclines
Antidote for folic
acid antagonists
(methotrexate) and
rescue therapy
following high-dose
methotrexate
C: Hypersensitivity
to aprepitant;
W/P: Use caution
with agents
primarily
metabolized via
CYP450 3A4; Use
caution with
hepatic
impairment; Not
intended for
treatment of
existing nausea and
vomiting or for
chronic continuous
therapy
C: Hypersensitivity
to mesna or other
thiol compounds;
W/P: Examine
morning urine
specimen for
hematuria prior to
ifosfamide or
cyclophosphamide
treatment; if
hematuria (greater
than 50 RBC/HPF)
develops, reduce
dose or discontinue
drug; allergic
reactions have
been reported;
patients should
receive adequate
hydration;
C: Hypersensitivity
to dexrazoxane;
W/P: May add to
myelosuppression
of anthracyclines;
adjust does for
renal insufficiency
AE: Central
nervous system
(fatigue, dizziness);
Gastrointestinal
(nausea,
constipation,
diarrhea);
Neuromuscular
(weakness);
I: Substrate of
CYP450 system;
inhibitor and
inducer of CYP450
system
AE: Cardiovascular
(flushing); central
nervous system
(dizziness,
headache, fever);
dermatologic
(rash);
gastrointestinal
(taste alteration)
peel backing off blister,
do not push tablet
through; using dry hands,
place tablet on tongue
and allow to dissolve.
Swallow with saliva
F: Capsule;
D: 125 mg on day 1,
followed by 80 mg on
days 2 and 3 in
combination with other
antiemetics;
A: First dose should be
given 1 hour prior to
antineoplastic therapy;
subsequent doses should
be given in the morning
F: injection, tablet;
D: Short infusion – mesna
dose is equal to 60% of
the ifosfamide dose given
in 3 divided doses (0,4, 8
hours after the start of
ifosfamide)
Continuous infusion:
Mesna dose is equal to
20%(bolus) of the
ifosfamide dose, followed
by a continuous infusion
of mesna at 40% of the
ifosfamide dose;
AE:
Myelosuppression;
dermatologic;
gastrointestinal
Aprepitant serum
concentration may
be increased when
taking with
grapefruit juice –
avoid concurrent
use
A: Oral: administer orally
in tablet formulation or
parenteral solution
diluted in water, milk,
juice, or carbonated
beverage; patients who
vomit within 2 hours after
taking oral mesnashould
repeat the dose or
receive intravenous
mesna;
Intravenous: administer
by short (15-30 minutes)
infusion or continuous
infusion)
F: Injection;
D: 10:1 ratio of
dexrazoxane:doxorubicin
(e.g. 500 mg/m2
dexrazoxane: 50 mg/m2
doxorubicin)
Mesna dosing
schedule should be
repeated each day
ifosfamide is
received. If
ifosfamide dose is
adjusted, then
mesna dose should
also be modified to
maintain the
mesna-toifosfamide ratio
Cardiac monitoring
should continue
during dexrazoxane
therapy
A: Doxorubicin should be
given within 30 minutes
after beginning the
infusion of dexrazoxane
C: Pernicious
anemia or vitamin
B12 deficient
megaloblastic
anemia’s;
AE: Dermatologic
(rash)
F: Injection, tablet;
D: Treatment of overdose
– oral 5-15 mg/day;
High-dose methotrexate
74
Leucovorin should
not be
administered
concurrently with
methotrexate. It is
usually initiated 24
W/P: When used
for treatment of
overdose
administer as soon
as possible; when
used for
methotrexate
rescue therapy
methotrexate
serum
concentrations
should be
monitored to
determine dose
and duration of
leucovorin therapy;
75
therapy – 10mg/m2 –
start 24 hours after
beginning of
methotrexate infusion –
continue every 6 hours
for 10 doses until
methotrexate level is less
than 0.05 micromole/L;
A: Due to calcium content
do not administer
intravenous solutions at a
rate greater than 160
mg/minute
hours after the start
of methotrexate.
Toxicity to normal
tissues may be
irreversible if
leucovorin is not
initiated by 40
hours after the start
of methotrexate
infusion
ONCOLOGY Assessment
1. Select the genitourinary adverse reaction associated with cyclophosphamide.
a. Cardiomyopathy
b. Myelosuppression
c. Ototoxicity
d. Hemorrhagic cystitis
2. A nurse is reviewing a patient profile and notices that the patient has an order for high-dose busulfan.
What prophylaxis medication should patients on high-dose busulfan receive?
a. Anticonvulsant
b. Fluids
c. Colony-stimulating factor
d. Leucovorin
3. A patient is receiving cisplatin for treatment of cancer. Which preventive measures may be employed
to prevent adverse effects associated with cisplatin? Select all that apply.
a. Amifostine
b. Bladder irrigation
c. Adequate hydration
d. Cytarabine
4. Select the antineoplastic that is associated with causing tinnitus.
a. Cyclophosphamide
b. Cisplatin
c. Cytarabine
d. Tetracycline
5. Select the folate antimetabolite that is associated with mucositis, fatal hepatotoxicity, pneumonitis,
and lymphomas.
a. Cytarabine
b. Hydroxyurea
c. L-asparaginase
d. Methotrexate
76
6. Select the antineoplastic that is associated with the development of pulmonary fibrosis. Select all that
apply.
a. Bleomycin
b. Busulfan
c. Cisplatin
d. Nitrofurantoin
7. A nurse is to administer vincristine 0.25 mg/m2 at 9 am. The nurse is reviewing the potential methods
of vincristine administration to ensure she is complying with approved polices. Select the method of
vincristine administration.
a. Intrathecally
b. Intravenous
c. Sublingual
d. Subcutaneous
8. Which of the following medications is a major drug interaction to a patient receiving vincristine?
a. Itraconazole
b. Azithromycin
c. Acetaminophen
d. Intravenous fluids
9. A nurse is instructing her students about proper administration of antineopalstic agents. They are
monitoring a patient receiving paclitaxel. What laboratory value must be monitored and evaluated
before administration of paclitaxel?
a. Glucose
b. Sodium
c. Amalyase
d. Neutrophils
10. Select the medication(s) that should be given to a patient before receiving paclitaxel. Select all that
apply.
a. Colony stimulating factors (e.g. Filgrastim)
b. Diphenhydramine, dexamethasone, ranitidine
c. Amifostine
d. Dexrazoxane
77
11. Select the antineoplastic that may cause a disulfiram-like reaction when a patient drinks alcohol.
a. Cisplatin
b. Methotrexate
c. Procarbazine
d. Hydroxyurea
12. The nurse documented in her progress note that her patient is having fatigue and would like for the
medical team to address her symptoms. The physician prescribed an erythropoietin stimulating agent.
The nurse reviews the patients chart to verify she does not have any contraindications. Select the
contraindication for ESAs.
a. Uncontrolled hypertension
b. Renal failure
c. Lymphomas
d. Anemia
13. Select the chemoprotectant that is associated with fluid retention.
a. Filgrastim
b. Epoetin alfa
c. Opreluekin
d. Leucovorin
14. Select the chemoprotectant that is used to prevent nephrotoxicity and xerostomia.
a. Leucovorin
b. Amifostine
c. Dexrazoxane
d. Mesna
15. Select the chemoprotectant that is associated with the development of mood swings.
a. Dexamethasone
b. Amifostine
c. Mesna
d. Leucovorin
16. Select the 5-HT3 receptor antagonist(s) that are used in the management of nausea and vomiting for
highly emetogenic antineoplastic agents. Select all that apply.
a. Ondansetron (Zofran)
b. Granisetron (Kytril)
c. Palonosetron (Aloxi)
d. Dolasetron (Anzemet)
78
17. The nurse is evaluating the anti-emetic regimen for her patient. The regimen includes: ondansetron,
dexamethasone, and aprepitant. The nurse wants to minimize interactions for her patient. What drug /
food interaction does the nurse need to evaluate that is a contraindication for aprepitant?
a. Tyramine containing foods
b. High salt content foods
c. Grapefruit juice
d. Water intake
18. Select the chemoprotectant that supplies a free thiol that binds to acrolein preventing a major
antineoplastic adverse reaction.
a. Mesna
b. Leucovorin
c. Dezrazoxane
d. Hydroxyurea
19. A patient is receiving high-dose methotrexate and the nurse is about the start administering
leucovorin rescue therapy. Select the answer that represents important information about the
administration of leucovorin.
a. Leucovorin should be administered concurrently with methotrexate
b. Leucovorin should not be administered at a rate greater than 160 mg/min
c. Leucovorin should not be given with high-dose methotrexate (only low dose)
d. Leucovorin can be given with 72 hours of methotrexate
20. Select the antineoplastic that forms oxygen free radicals and is a cause of cardiac damage and may
be prevented by the use of dexrazoxane.
a. Antimetabolites
b. Alkylating agents
c. Anthracyclines
d. Antibiotics
79
HIV




Differentiate HIV and AIDS
Resistance testing recommended when HAART started
www.aidsifo.nih.gov
Mechanism of Action
TREATMENT



Antiretroviral therapy is recommended for all HIV infected individuals to reduce the risk of disease
progression and to prevent transmission of the virus to others.
Highly active antiretroviral therapy (HAART)
o Backbone
o Base
Therapy is recommend as preferred or alternative HAART.
MEDICATIONS

NRTI’s
o Indirect inhibitors of reverse transcriptase
1) Abacavir, ABC (Ziagen)
2) Didanosione, DDI (Videx)
80
3) Emtricitabine, FTC (Emtriva)
4) Lamivudine, 3TC (Epivir)
5) Stavudine, D4T (Zerit)
6) Tenofovir, TDF (Viread)
7) Zidovudine, AZT (Retrovir)

NNRTI’s
o Direct inhibitors of reverse transcriptase.
o Resistance develops quickly is used as monotherapy or in combinations that does not
completely suppress viral replication.
o Drug interactions
1) Delaviridine, DLV (Rescriptor)
2) Efavirenz, EFV (Sustiva)
3) Etravirine, ETR (Intelence)
4) Nevirapine, NVP (Viramune)
5) Rilpivirine, RPV (Edurant)
81

Protease Inhibitors
o Prevent the cleavage of protein precursors essential for HIV mutation, infection, and
replication.
1) Atazanavir, ATV (Reyataz)
2) Darunavir, DRV (Prezista)
3) Fosamprenavir, FPV (Lexiva)
4) Indinavir, IDV (Crixivan)
5) Lopinavir / ritonavir, LPV/RTV (Kaletra)
6) Nelfinavir, NFV (Viracept)
7) Ritonavir, RTV (Norvir)
8) Saquinavir, SQV (Invirase)
9) Tipranavir, TPV (Aptivus)

Integrase Strand Transfer Inhibitors (INSTIs)
82
o
The enzyme integrase is responsible for the process that results in viral DNA insertion into
the host genome. INSTIs block this process.
1) Raltegravir, RAL (Isentress)
2) Elvitegravir, EVG (Stribild)
3) Dolutegravir (Tivicay)

CCR5 Antagonist
o Binds to the CCR5 co-receptor, preventing entry of virus into CD4 host cell.
o Patients should be screened for CCR5 tropism prior to starting treatment.
1) Maraviroc, MVC (Selzentry)

Fusion Inhibitor
1) Enfuvirtide, T20 (Fuzeon)
Pre-Exposure Prophylaxis (PrEP)



Truvada is approved for PrEP to reduce the risk of sexually acquired HIV-1 in adults at high risk.
Follow-up HIV-1 antibiody testing is recommended while taking this medication to ensure early
diagnosis.
Resistance can develop if Truvada is continued for PrEP after HIV infection has occurred.
Post-Exposure Prophylaxis (PEP)

Three or more active medications should be utilized for all occupational exposures, regardless of
severity.
83



Treatment should be started within 72 hours of exposure, but delayed treatment may still provide a
benefit.
Continue treatment for at least 4 weeks.
Follow-up HIV testing is recommended for at least 4-6 months after the exposure.
84
HIV Assessment
1. Highly active antiretroviral therapy includes a combination of a backbone regimen consisting of two
nucleoside reverse transcriptase inhibitors and the addition of which of the following (as listed as
preferred therapy by the HIV guidelines)? Select all that apply.
a. Non-nucleoside reverse transcriptase inhibitor
b. Protease inhibitor
c. Integrase strand transfer inhibitor
d. Nucleoside reverse transcriptase inhibitor
e. CCR5 Antagonist
2. A 48 year-old female was recently diagnosed with HIV-1 infection. Her infectious diseases physician
ordered several baseline tests prior to initiating highly active antiretroviral therapy. Baseline labs
included an HIV genotype, HLA-B*5701, complete blood count, HIV RNA, and CD4. Which of the
following statements are true regarding the test HLA-B*5701. Select all that apply.
a. Abacavir hypersensitivity reactions are strongly associated with the presence of the HLA-B*5701
allele.
b. Patients that screen positive for the HLA-B*5701 allele may receive therapy with abacavir IF it is active
according to the HIV genotype.
c. Abacavir hypersensitivity reactions may present with respiratory symptoms.
d. Abacavir hypersensitivity reactions may present with gastrointestinal symptoms.
3. Select the correct statement(s) about the nucleoside reverse transcriptase inhibitor lamivudine, 3TC
(Epivir). Select all that apply.
a. Has the same DNA base pair as emtricitabine.
b. Is a cytosine analog.
c. Can cause peripheral neuropathy.
d. Can cause hyperpigmentation of the palms and soles.
85
4. Which of the following HIV nucleoside reverse transcriptase inhibitors is also available in a lower-dose
formulation that is FDA approved for the treatment of chronic hepatitis B?
a. stavudine
b. tenofovir
c. lamivudine
d. zidovudine
5. A 39 year-old HIV patient has a pre-treatment viral load of 200,000 copies/ml. The patient is ready to
start treatment and has agreed with his provider to be adherent. Which of the following non-nucleoside
reverse transcriptase inhibitor-based regimens would be the best choice for this patient? The HIV
genotype demonstrates that the agents listed below do NOT have any genetic mutations. Additionally,
the back-bone for this patient will be tenofovir and emtricitabine.
a. Rilpivarine
b. Efavirenz
c. Nevirapine
d. Dolutegravir
6. Select the HIV combination regimen that is available as single tablet therapy. Select all that apply.
a. Efavirenz, emtricitabine, tenofovir
b. Lopinovir, ritonavir, emtricitabine, tenofovir
c. Rilpivarine, emtricitabine, tenofovir
d. Elvitegravir, cobicistat, emtricitabine, tenofovir
e. Darunavir, ritonavir, emtricitabine, tenofovir
86
ANGINA PECTORIS



Clinical syndrome – transient myocardial ischemia.
o Atherosclerosis
o Coronary artery spasm
Symptoms: chest pain, shortness of breath, weakness, sweating, palpitation
Approaches to therapy of angina
o Acute
 Rest, nitroglycerin, oxygen (if hospitalized)
o Chronic
 Modification of life style (diet, smoking)
 Treatment of underlying diseases (e.g. diabetes, HTN)
 Drug therapy: Nitrates, BB, CCB, ACEI
o Unstable
 Acute Coronary Syndrome
MEDICATIONS
1) Nitrates
87
HYPERLIPIDEMIA








Hyperlipidemia is a major risk factor for coronary heart disease (CHD).
o CHD is a narrowing of the small blood vessels that lead to the heart, usually a result of
atherosclerosis.
Low-density lipoprotein cholesterol (LDL-C) can provoke several components of the atherosclerotic
inflammatory response, including promoting unstable lesions concentrated with lipid-laden
macrophages.
For every 1 mg/dL change in LDL-C, the relative risk for CHD is changed in proportion by about 1%,
although this link is weaker in women and in the elderly.
Elevated triglycerides (TG) can cause acute pancreatitis and may also predict CHD.
o TG appear to have indirect atherosclerotic effects related to procoagulant properties,
adverse impact on endothelial function, and correlation with low HDL-C and small, dense
LDL-C particle formation.
High-density lipoprotein cholesterol (HDL-C) is a strong inverse predictor for CHD.
o HDL-C is involved in reverse cholesterol transport, delivering cholesterol from the cell wall
to the liver for disposal.
o HDL-C can prevent LDL-C oxidation and may also inhibit platelet aggregation and activation.
o For every 1 mg/dL increase in HDL-C, the risk of future CVD is reduced by 2% in men and 3%
in women; death from myocardial infarction or coronary disease is reduced by 6%.
Guidelines from the American College of Cardiology and American Heart Association no longer
recommend specific cholesterol targets in the treatment of hyperlipidemia.
HMG-CoA reductase inhibitors (statins) are the lipid-lowering drugs of choice for most patients with
atherosclerotic cardiovascular disease.
o They decrease the incidence of coronary events and death
Lipid lowering medications must be taken indefinitely; when they are stopped, cholesterol levels
return to pretreatment levels.
MEDICATIONS
1) Bile Acid Sequestrants
a. Cholestyramine (Questran)
b. Colestipol (Colestid)
2) Niacin (Nicotinic Acid, vitamin B3)
3) HMG-CoA Reductase Inhibitors
88
4) Fibric Acid Derivatives
a. Gemfibrozil (Lopid)
b. Fenofibrate (Tricor)
5) Fish Oil
a. Long chain, unsaturated omega 3 fatty acids
b. Present in cold-water fish and commercially available capsules
c. Decrease fasting TGs 20-50%
i. Reducing hepatic TG production
ii. Increase TG clearance
6) Red Yeast Rice
a. Fermented rice product
b. Contains natural HMG-CoA reductase inhibitors
c. Equivalent to 20-40 mg lovastatin
d. Side effects same as statins
e. Not FDA regulated.
89
DYSLIPIDEMIA Assessment
1. RE is a 58 year-old male with a past medical history of hypertension, chronic obstructive pulmonary
disease, and recently diagnosed coronary artery disease and dyslipidemia. Which of the following should
be the primary treatment for patients with atherosclerotic cardiovascular disease?
a. Bile acid sequestrant
b. Fish oil
c. Niacin
d. Statin
2. Which of the following statins are available generically and have been shown to reduce cardiovascular
risk? Select all that apply.
a. Atorvastatin
b. Pravastatin
c. Lovastatin
d. Pitavastatin
e. Rosuvastatin
3. Which of the following cholesterol medications utilized for the management of dyslipidemia has a
category X for use during pregnancy?
a. Niacin
b. Ezetimbie
c. Lovastatin
d. Gemfibrozil
4. Adverse effects of statins include which of the following? Select all that apply.
a. Myopathy
b. Unpleasant after taste
c. Flushing
d. Cholelithiasis
e. New-onset diabetes mellitus
5. Adverse effects of fish-oil supplements include which of the following? Select all that apply.
a. Dyspepsia
b. Myopathy
c. Flushing
d. Polyneuropathy
90
ANTIBIOTICS
















Antimicrobials that kill many different species of bacteria are called broad-spectrum.
Antimicrobials that kill only a few different species of bacteria are called narrow-spectrum
antimicrobials.
Empirically treating infectious diseases and monitoring therapy requires knowledge of anti-infective
properties, host factors, patient’s normal flora, differentiating infection versus colonization, and
understanding clinical presentation and diagnostic tests (microbiologic and non-microbiologic
laboratory studies).
It is important to understand the difference in antimicrobial spectrum of activity and select agent(s)
that target the pathogens most likely causing the infection.
Antimicrobial dosing regimens with the same agent may be different depending upon the infection
or pathogen.
Integration of pharmacokinetic and pharmacodynamic properties of an agent is important when
choosing antimicrobial therapy to ensure efficacy and to prevent resistance.
Pharmacokinetics (PK) refers to a mathematical method of describing in vivo drug exposure in terms
of absorption, distribution, metabolism, and elimination.
Pharmacodynamics (PD) describes the relationship between drug exposure and pharmacologic
effect of antibacterial activity or human toxicology.
Concentration-dependent PD activity occurs where higher drug concentrations are associated with
greater rate and extent of bacterial killing.
o Fluoroquinolones, aminoglycosides, and metronidazoles are examples of antimicrobials that
exhibit concentration-dependent activity.
Time-dependent activity is maximized when these antimicrobials are dosed to maintain blood
and/or tissue concentrations above the minimal inhibitory concentration (MIC) in a time-dependent
manner.
o Beta lactams and glycopeptides exhibit time-dependent activity.
Antimicrobials with a low propensity of causing adverse events or drug interactions should be
selected if possible, particularly for patients with risk factors for a particular complication.
Host factors should be considered when evaluating a patient for antimicrobial therapy. Important
host factors are: drug allergies, age, pregnancy, genetic/metabolic abnormalities, and organ
dysfunction.
Patients with a history of immediate or accelerated reactions (eg, anaphylaxis) to penicillin should
not be given cephalosporin antibiotics.
o Patients with a delayed hypersensitivity reaction (rash) to penicillin may be given
cephalosporin under close supervision.
Normal flora is bacteria that are colonized in areas of the human body. Infections arise from normal
flora (also called endogenous flora).
A gram stain is performed to identify if bacteria are present and to determine morphologic
characteristics of bacteria (such as gram-positive or negative, or shape—cocci, bacilli).
Once a pathogen is identified, susceptibility tests can be performed to various antimicrobial agents.
o The minimum inhibitory concentration (MIC) is a standard susceptibility test.
o The MIC is the lowest concentration of antimicrobial that inhibits visible bacterial growth.
o Breakpoint and MIC values determine if the organism is susceptible (S), intermediate (I), or
resistant (R) to an antimicrobial.
91
92
Antibiotic
S
S
E
H
E
93
P
Ana+
Ana-
Atypical
MEDICATIONS
1) Penicillins
a. Group 1: Penicillin
b. Group 2: Antistaph / Penicillinase Penicillins
c. Group 3: Aminopenicillins
d. Group 4: Extended spectrum
2) Cephalosporins
a. 1st generation
b. 2nd generation
c. 3rd generation
d. 4th generation
e. 5th generation
3) Carbapenems
4) Monobactams
5) Vancomycin
94
6) Aminoglycosides
7) Quinolones
8) Linezolid
9) Macrolides
10) Tetracyclines
11) Clindamycin
12) SMZ / TMP
13) Metronidazole
95
Types of Infections
1) Skin and soft tissue infections


Caused by Staphylococcus aureus and Streptococcus pyogenes.
Staphylococcus aureus may be methicillin resistant (MRSA).
2) Bone and joint infections

Staphylococcus aureus and coagulase negative Staphylococci are most common causes.
3) Acute sinusitis



Viral
Symptoms greater than 10 days without improvement or severe symtpoms (eg fever)
greater than 3 days consider antibiotics
Bacterial causes include Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella
catarrhalis.
4) Acute Exacerbation of Chronic Bronchitis (AECB)


Viral
Bacterial causes include Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella
catarrhalis.
5) Acute Pharyngitis

Group A Streptococcus
6) Pneumonia


Community bacterial causes include Streptococcus pneumoniae, Haemophilus influenzae,
Moraxella catarrhalis, and atypicals.
Healthcare bacterial causes include Enterics, Pseudomonas, and Acinetobacter.
7) Urinary Tract Infections


Community – Enterics
Hospital – Enterics and Pseudomonas
8) Prostatitis

Enterics
9) Intra-abdominal Infections

Enterics and Bacteroides fragilis
10) Meningitis
96


Streptococcus pneumoniae, Neisseria meningitides
Group B Streptococcus in neonatal meningitis
11) Endocarditis

Staphylococcus aureus and Streptococcus species
97
ANTIBIOTIC Assessment
1. HP is a high-school wrestler that has developed a skin infection (cellulitis). He is not taking any
medications and has a negative past medical history. The final diagnosis is an uncomplicated cellulitis.
What bacterial organism would be likely to cause the infection? Select all that apply.
a. Streptococcus pyogenes
b. Proteus mirabilis
c. Staphylococcus aureus
d. Enterics
2. HP’s cellulitis was initially treated with cephalexin and it has not responded. His pain is severe and
there are red streaks extending several inches past the initial site. He is being admitted to the hospital
for parenteral antibiotic therapy. Which of the following antibiotics could be used as monotherapy to
treat the complicated cellulitis? Select all that apply.
a. Linezolid
b. Daptomycin
c. Vancomycin
d. Meropenem
e. Ceftaroline
3. TL is a 23 year-old pharmacy student studying for the Naplex exam. He has developed the sniffles and
they are distracting his studies. He goes to the student health center and is diagnosed with an acute
sinusitis. TL has no fever and has had the symptoms for 2 days. Which of the following should be
recommended to manage TL’s sinus infection?
a. Clarithromycin
b. Doxycycline
c. Time
d. Amoxicillin
98
HEART FAILURE









Heart failure (HF) is a syndrome of reduced cardiac output (CO) compromising the metabolic
needs of bodily organs and tissues.
Heart failure may result from dilation of the left ventricle and a subsequent reduction in left
ventricular function (dilated cardiomyopathy or systolic dysfunction).
o Alternatively, HF may result from hypertrophy and subsequent underfilling of the left
ventricle (hypertrophic cardiomyopathy, diastolic dysfunction, or HF with preserved
ejection fraction).
Progressive HF often severely limits exercise capacity, and mortality is most commonly
associated with sudden cardiac death (SCD) or pump failure.
Chronic HF may be managed with lifestyle modifications, medications, and implantable devices
to delay progression and reduce mortality.
Medical management aims at disrupting the neurohormonal pathways that are associated with
the disease.
o Key targets include the sympathetic nervous system (SNS) and the renin angiotensin
aldosterone (RAA) system.
Disease severity is determined by evaluating functional capacity or structural heart changes.
The New York Heart Association (NYHA) uses exercise tolerance and ability to perform activities
of daily living.
o Patients may be classified as NYHA class I if there are no symptoms or restrictions in
activity,
o class II or III if there are symptoms with moderate or mild physical activity, respectively,
o class IV if symptoms are present at rest.
o The NYHA classification system allows a patient’s current state of HF health to be
assessed at a particular point in time.
o A patient may shift between classes as disease control improves or declines.
ACC/AHA developed a staging system based on risk factors for HF and structural determinants.
patients are categorized as being at risk of developing HF (stage A), having structural heart
disease but no symptoms (stage B), developing HF signs and symptoms (stage C), and having
end-stage disease despite maximal medical therapy (stage D).
MEDICATIONS
1) Medications that may precipitate / exacerbate HF
2) Diuretics
a. Loops
99
b. HCTZ
c. K+ sparing
3) BiDil
4) ACEI
5) ARB
6) Beta Blockers
7) Inotropic Agents
100
HEART FAILURE SUPPLEMENT
Drugs That May Precipitate or Exacerbate Heart Failure
Negative Inotropic Effect
Antiarrhythmics (e g, disopyramide, flecainide, propafenone, and others)
Beta-blockers (e g, propranolol, metoprolol, atenolol, and others)
Calcium channel blockers (e g, verapamil, diltiazem)
Itraconazole
Terbinafine
Cardiotoxic
Doxorubicin
Daunomycin
Cyclophosphamide
Trastuzumab
Imatinib
Ethanol
Amphetamines (e g, cocaine, methamphetamine)
Sodium and Water Retention
Nonsteroidal anti-inflammatory drugs
Cyclooxygenase-2 inhibitors
Rosiglitazone and pioglitazone
Glucocorticoids
Androgens and estrogens
Salicylates (high dose)
Sodium-containing drugs (e g, piperacillin sodium)
101
Dosing and Monitoring for Neurohormonal Blocking Agents
Initial Daily Dose
Target or Maximum Daily
Dose
Monitoring
Captopril
6.25 mg three times daily
50 mg three times daily
BP
Enalapril
2.5 mg twice daily
10-20 mg twice daily
Fosinopril
5-10 mg once daily
40 mg once daily
Lisinopril
2.5-5 mg once daily
20-40 mg once daily
Electrolytes (K+, BUN, SCr) at
baseline, 2 wk, and after
dose titration, CBC
periodically Adverse efects:
cough, angioedema
Perindopril
2 mg once daily
8-16 mg once daily
Quinopril
5 mg twice daily
20 mg twice daily
Ramipril
1.25-2.5 mg once daily
10 mg once daily
Trandolapril
1 mg once daily
4 mg once daily
Drug
ACE Inhibitors
Angiotensin Receptor Blockers
Candesartan
4-8 mg once daily
32 mg once daily
BP
Losartan
25-50 mg once daily
50-100 mg once daily
Valsartan
20-40 mg twice daily
160 mg twice daily
Electrolytes (K+, BUN, SCr) at
baseline, 2 weeks, and after
dose titration, CBC
periodically
Adverse effects: cough,
angioedema
Aldosterone Antagonists
Spironolactone
12.5-25 mg once daily
25 mg once daily or twice daily
BP
Eplerenone
25 mg once daily
50 mg once daily
Electrolytes (K+) at baseline
and within 1 wk of initiation
and dose titration
Adverse effects:
gynecomastia or breast
tenderness, menstrual
changes, hirsutism
Beta-Blockers
102
Bisoprolol
1.25 mg once daily
10 mg once daily
Carvedilol
3.125 mg twice daily
25 mg bid (50 mg twice daily
for patients > 85 kg or 187 lb)
Metoprolol
succinate
12.5-25 mg once daily
200 mg once daily
BP, HR baseline and after
each dose titration, ECG
Adverse effects: worsening
HF symptoms (edema, SOB,
fatigue), depression, sexual
dysfunction
Intravenous Diuretics Used to Treat Heart Failure-Related Fluid Retention
Onset of Action
(min)
Duration of
Action (h)
Relative
Potency
Intermittent Bolus
Dosing (mg)
Continuous Infusion
Dosing
(Bolus/Infusion)
Furosemide
2-5
6
40
20-200+
20-40/2.5-20
Torsemide
<10
6-12
20
10-100
20/2-10
Bumetanide
2-3
4-6
0.5
1-10
1-4/0.5-1
Ethacrynic acid
5-15
2-7
0.5-1 mg/kg/dose up to
100 mg/dose
Hemodynamic Effects of Commonly Used Intravenous Agents for Treatment of Acute or
Severe Heart Failure
Drug
CO
PCWP
Diuretics
↑/↓/0
↓
Nitroglycerin
↑
↓↓
Nitroprusside
↑
Nesiritide
SVR
BP
HR
↓
0
↓
↓↓
↑/0
↓↓↓
↓↓↓
↓↓↓
↑
↑
↓↓
↓↓
↓↓
0
Dobutamine
↑↑
↓/0
↓/0
↓/0
↑↑
Milrinone
↑↑
↓↓
↓
↓
↑
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Doses and Monitoring of Commonly Used Hemodynamic Medications
Drug
Dose
Monitoring Variablesa
Dobutamine
2.5-20 μg/kg/min
BP, HR urinary output and function, ECG
Milrinone
0.1-0.75 μg/kg/min
BP, HR, urinary output and function, ECG,
changes in ischemic symptoms (eg, chest
pain), electrolytes
Nitroprusside
0.25-3 μg/kg/min
BP, HR, liver and kidney function, blood
cyanide and/or thiocyanate concentrations
if toxicity suspected (nausea, vomiting,
altered mental function)
Nitroglycerin
5-200+ μg/kg/min
BP, HR, ECG, changes in ischemic
symptoms
Nesiritide
Bolus: 2 μg/kg Infusion: 0.01 BP, HR, urinary output and kidney
μg/kg/min
function, blood BNP concentrations
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HEART FAILURE Assessment
1. DS is a 63 year-old presenting to the pharmacotherapy clinic. He has a past medical history of
diabetes, myocardial infarction, chronic obstructive pulmonary disease, secondary hypertension –
bilateral renal artery stenosis, and reflux. He has been diagnosed with systolic heart failure (HRrEF).
Which of the following comorbidities would preclude use of an ACEi for DS?
a. Cough from COPD
b. Hypertension
c. Myocardial infarction
d. Bilateral renal artery stenosis
e. Diabetes
2. HF has been initiated on an aldosterone antagonist for the management of systolic heart failure
(HFrEF). He has been on an ACEi and BB for the past year and is on target doses. Which of the following
aldosterone antagonists is preferred therapy?
a. Amiloride
b. Triamterene
c. Cytarabine
d. Spironolactone
3. HF was initiated on the aldosterone antagonist. Which electrolyte should be monitored?
a. Sodium
b. Potassium
c. Magnesium
d. Phosphate
105
ANTITHROMBOTIC DRUGS




Arterial thrombi are platelet aggregates held together by fibrin.
Antiplatelet drugs are drugs of choice for prevention and treatment of arterial thrombosis
o Anticoagulant drugs are also effective and their effects can add to those of antiplatelet
drugs.
Venous thrombi are composed of fibrin and trapped red blood cells, with relatively few platelets.
Anticoagulants are agents of choice for prevention and treatment of venous thromboembolism and
for prevention of cardioembolic events in patients with atrial fibrillation.
MEDICATIONS
Antiplatelet Drugs

Primary & secondary prevention and treatment of acute coronary syndromes (ACS); which includes:
o Unstable angina / non ST-elevation myocardial infarction;
o ST-elevation myocardial infarction;
o Percutaneous coronary intervention.
1) Aspirin
2) Dipyridamole (Persantine)
3) Thienopyridines
a. Clopidogrel (Plavix)
b. Prasugrel (Effient)
c. Ticlopidine (Ticlid)
4) Ticagrelor (Brilinta)
5) Glycoprotein IIB / IIIa (GPIIB / IIIa) receptor antagonists
a. Abciximab (ReoPro)
106
b. Eptifibatide (Integrelin)
c. Tirofiban (Aggrastat)
Parenteral Anticogulants
1) Heparin
2) Low Molecular Weight Heparins
3) Fondaparinux (Arixtra)
Direct Thrombin Inhibitors

Direct thrombin inhibitors inhibit clot-bound as well as circulating thrombin.
1) Bivalirudin (Angiomax)
2) Desirudin (Iprivask)
Oral Anticoagulants
1) Warfarin (Coumadin)
2) Dabigatran (Pradaxa)
107
3) Rivaroxaban (Xarelto)
4) Apixaban (Eliquis)
108
ANTITHROMBOTIC Assessment
1. Which medication would result in a major drug interaction if used concurrently with warfarin?
a. Lisinopril
b. Metoprolol
c. Lanoxin
d. Fluconazole
2. TE is a 29-year-old pregnant woman with an acute DVT. She takes no other medications and has no
significant past medical history. Which agent is the best choice for the initial treatment of her DVT?
a. Enoxaparin
b. Aspirin
c. Warfarin
d. Dabigatran
3. Select the appropriate routes of administration for unfractionated heparin. Select all that apply.
a. Intravenous
b. Subcutaneous
c. Intramuscular
d. Oral
e. Intrathecal
4. Which of the following anticoagulants have no available reversal agent? Select all that apply.
a. Rivaroxaban
b. Dabigatran etexilate mesylate
c. Warfarin
d. Apixaban
e. Heparin
109
COGNITIVE LOSS and DEMENTIA




Alzheimer’s disease (AD) is the most common cause of dementia, but cognitive loss is also
associated with Parkinson’s disease, dementia with Lewy bodies, and vascular dementia.
AD is a non-reversible, progressive dementia manifested by gradual deterioration in cognition &
behavioral disturbances.
AD pathophysiology includes neurofibrillary tangles and neuritic plaques made of various
proteins resulting in a shortage of acetylcholine (Ach).
o Cognitive loss (subsequently memory) is associated with depletion of Ach.
Acetylcholinesterase inhibitors (AchI) increase the concentration of Ach & have beneficial
effects on dementia symptoms.
o AchI may cause adverse dose related cholinergic effects (nausea, vomiting, and
diarrhea). Task: compare and contrast cholinergic and anticholinergic side effects.
 Bradycardia and syncope are also adverse effects.
o Concurrent use with anticholinergic medications may decrease the activity of AchI.

Donepezil tablet (Aricept, Aricpet ODT, and generics)
o Mild, moderate, severe AD dementia
 Some effects on other types of dementia
o Metabolized by CYP450 2D6 and 3A4 (minor substrate for both).
o 5 mg daily; may titrate up to 10 mg daily.
 23 mg tablet available for non-responders but has more side effects

Galantamine (Razadyne, Razadyne ER, and generics)
o Mild, moderate AD dementia
 Some effects on other types of dementia
o Minor substrate of CYP450 2D6 and 3A4
o Administer with food; tablet / solution breakfast or dinner; capsule (breakfast)
o Initial dose 8 mg daily (4 mg twice daily for immediate release; 8 mg daily for extended)
 Max dose 24 mg; 16 mg max dose for hepatic or renal dysfunction
 Treatment interruption for > 3 days – restart at initial dose

Rivastigmine (Excelon, Excelon Patch, generics)
o Mild, moderate AD or Parkinson’s dementia; patch is approved for severe AD
o Metabolized via hydrolysis and excreted in urine
o Initial dose is 1.5 mg twice daily with food; max 12 mg; Patch 4.6 mg / 24 hours
 Treatment interruption for several days; re-start at initial dose
o Formulations – solution, capsule, patch
o Administer with meals; swallow capsule whole
110

Memantine (Namenda) – solution / tablet
o Moderate, severe AD dementia
o NMDA receptor antagonist; may be used concurrently with AchI
o Initial dose is 5 mg once daily; max dose 20 mg (10 mg twice daily)
 Once daily ER formulation 7 mg titrated up to 28 mg
 Severe renal impairment max dose is IR 5 mg twice daily; ER 14 mg daily
o Side effects – central nervous system (dizziness, confusion, insomnia, hallucinations,
delusions)
o Drug Interactions – Amantadine (also a NMDA antagonist)

Antipsychotics
o Utilized to treat agitation / behavioral symptoms; NOT FDA APPROVED
o 2nd generation preferred over 1st generation neuroleptics (less EPS side effects)

Ginkgo Biloba
o Dietary supplement
o Not effective in preventing or treating dementia or cognitive decline
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Cognitive Loss and Dementia Assessment
1.
TI is a 73 year old male with a diagnosis of AD, hypertension, depression, and overactive bladder. Current
medications include donepezil, lisinopril, imipramine, and oxybutynin. Over the counter medications
include as needed diphenhydramine and acetaminophen. Select the medication(s) that may decrease the
activity of the Alzheimer’s disease medication. (Select all that apply).
a. Lisinopril
b. Imipramine
c. Oxybutynin
d. Diphenhydramine
2.
TP presents to your pharmacy to ask questions about his new medication. He was just diagnosed with
dementia. Several of his questions pertain to medication use and dementia. What is the most common
cause of dementia?
a. Vascular dementia
b. Dementia with Lewy bodies
c. Parksinson’s disease
d. Alzheimer’s disease
3.
Select the statements that are true about acetylcholinesterase inhibitors. Select all that apply.
a. They are all substrates of the CYP450 system
b. They are all inhibitors of the CYP450 system
c. They increase concentrations of acetylcholine
d. They have a drug interaction with anticholinergic medications
e. They improve symptoms of dementia
4.
A patient presents to the pharmacotherapy clinic taking rivastigmine 3 mg orally twice daily. She has been
experiencing a significant amount of gastrointestinal side effects. Select the counseling points that should
be discussed with the patient. Select all that apply.
a. Changing to the rivastigmine transdermal patch may decrease gastrointestinal side effects
b. Changing to the donepezil ODT may decrease the gastrointestinal side effect
c. Quickly increasing the dose to target dose will decrease side effect
d. Changing to extended release galantamine may decrease the gastrointestinal side effect
5.
Select the dementia medication that may be affected by CYP450 2D6 inhibitors. Select all that apply.
a. Rivastigmine
b. Donepezil
c. Galantamine
d. Memantine
112
PHARMACY MATH
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
How many grams of dextrose are required to prepare 3000 ml of a 5% w/v solution?
How many fluid ounces are in 3.5 L?
How many fluid ounces are contained in 1 gallon?
How many 2 fluid ounce bottles may be filled from 4 gallons of cough syrup?
How many grams of a chemical remain in a 1 oz bottle after 40 ml are removed?
A medication forms a calcium complex in bone forming tissue in infants in doses of 0.11 g/lb of
body weight every 6 hours. Express this in terms of milligrams per kilogram of body weight.
The dimensions of a transdermal patch are 4.1 by 4.4 cm. Express these dimensions in
corresponding inches.
A pharmacist attempted to weigh 100 mg of codeine sulfate on a balance with a sensitivity of 5
mg. Calculate the potential error in terms of percentage.
A pharmacist weighed 525 mg of a medication on a balance of dubious accuracy. When checked
on a balance of greater accuracy, the weight was found to be 485 mg. Calculate the percentage
error.
Using a graduated cylinder, a pharmacist measured 30 ml of a liquid. On subsequent
examination using a narrow guage burette, it was determined that the pharmacist actually
measured 32 ml. What was the percentage error?
What is the percentage strength of an injection that contains 50 mg of pentobarbital sodium in
each milliliter of solution?
Neupogen contains 300 mcg of filgrastim in each milliliter of injection. Calculate the percent
concentration of filgrastim in the product.
If an injection contains 0.5 % w/v of diltiazem hydrochloride, calculate the number of milligrams
of the drug in 25 ml of injection.
How many grams of potassium permangate should be used in the following prescription?
Rx
Potassium permangate 0.03% w/v
Purified water ad
250 ml
15. A pharmacist adds 5 ml of a 20% w/v solution of potassium iodide t0 500 ml of D5W for
parenteral infusion. What is the percentage strength of potassium iodide in the infusion
solution?
16. Rx
Misoprostol 100 mcg tablets
10 tablets
Lidocaine hydrochloride 1g
Glycerin qs ad
100 ml
Calculate the percent strength of misoprostol in the prescription.
17. How many liters of a 2% w/v iodine tincture can be made from 123 g of iodine?
18. An injectable contains 2 mg of a drug per milliliter of solution. What is the ratio strength and the
corresponding percentage strength of the solution?
113
19. How many milliliters of a 1:400 w/v stock solution should be used to make 4 L of a 0.05% w/v
solution?
20. How many ml of a 1% w/v stock solution of a red dye should be used in preparing 4,000 ml of a
mouth wash that is to contain 1:20,000 w/v of the red dye as a coloring agent?
21. In what proportion should 20% benzocaine ointment be mixed with an ointment base to
produce a 2.5% benzocaine ointment?
22. A pharmacist wants to use two lots of ichthammol ointment containing 50% and 5%
ichthammol. In what proportion should they be mixed to prepare a 10% ichthammol ointment?
23. What is the concentration, in milligrams per milliliter, of a solution containing 23.5 mEq of
sodium chloride per milliliter? (molecular weight of NaCl 58.5)
24. Determine the concentration: 300 g of active ingredient mixed with 400 g of inert powder.
25. Determine the concentration: 230 mg of medication contained in 30 ml of mixture.
26. You want to make 500 ml of a 6% dextrose solution using dextrose 10%. How much dextrose
10% must you use to dilute with sterile water?
27. How much water must be added to 1L of acetic acid 1:200 solution to make a solution of 1:500
acetic acid?
28. How much 70% v/v isopropyl alcohol will be prepared by diluting 5 gallons of concentrated
(100% v/v) isopropyl alcohol?
29. The patient is to take 40 mEq of potassium in the form of potassium chloride solution. How
many milligrams does this represent? MW=75
30. Potassium chloride solution is available as 10% and 20% concentrations. How much potassium in
milliequivalent / tablespoonful do these concentrations provide? MW=75
31. How many milliequivalents are contained in a 300 mg capsule of lithium carbonate? MW=74
PHARMACY MATH SUPPLEMENT
Units of Measure






Pharmaceutical calculations involve four different systems of measure: the International System of
Units (SI), formerly known as the metric system, apothecaries’, avoirdupois’, and household.
SI is an international decimalized system of measurement that uses the following units: gram, liter,
and meter.
SI is a decimal system, in the sense that all multiples and submultiples of the base units are factors
of powers of ten of the unit.
Examples of the SI system include:
o Mega: 106
o Kilo = 103
o Deci = 10−1
o Centi = 10−2
o Milli = 10−3
o Micro = 10−6
o Nano = 10−9
o Pico = 10−12
The apothecaries’ system is a traditional system of measurement using drams (liquids) and grains
(solids) and is occasionally found in prescriptions.
For example, a prescribed medicine being sold in four ounce (℥ iv) bottles or five grains (V gr.) of
aspirin.
114




The system consists of two basic units, grains for solids and minims for liquids. The avoirdupois
system is a system of weights or mass commonly used in the United States for measuring body
weight and in selling products.
The avoirdupois ounce equals 437.5 grains. Sixteen ounces (7000 grains) corresponds to 1 pound
(lb).
A common household unit of measure includes the teaspoon and tablespoon.
A teaspoon is equivalent to 5 mL and a tablespoon is equivalent to 3 teaspoons.
Number Systems
Pharmaceutical calculations utilize two systems of numbers, Arabic and Roman. The Arabic system is
more commonly used; however, the Roman system is occasionally utilized. The Roman numeral system
uses letters to represent quantities and amounts. Common examples of Roman numerals include:
• ss = ½
•I=1
•V=5
• X = 10
• L = 50
• C = 100
• D = 500
• M = 1000
Roman numerals may be grouped together to express different quantities. To interpret these numbers,
addition and subtraction may be needed. Key issues for Roman numerals include:
• When a numeral is repeated or a smaller numeral follows a larger one, the values are added together.
• ii = 2 (1 + 1 = 2)
• CXIII = 113 (100 + 10 + 1+ 1 + 1 = 113)
• When a smaller numeral comes before a larger numeral, subtract the smaller value.
• IV = 4 (5 − 1 = 4)
• IX = 9 (10 − 1 = 9)
• Numerals are never repeated more than three times in a sequence.
• III = 3
• IV = 4
• When a smaller numeral comes between two larger numerals, subtract the smaller numeral from the
numeral following.
115
• XIV = 14 (10 − 1+5 = 14)
• XIX = 19 (10 + 10 − 1) = 19
The Arabic system is a decimal system. The decimal point serves as the anchor. Each place to the left of
the decimal signals a 10-fold increase and each place to the right signals a 10-fold decrease.
Percentage and Ratio Strengths
Medications are administered as dosage forms that contain active and inactive ingredients; however,
the amount of the active ingredient in a preparation needs to be expressed. A preparation may be a
solution, but may also refer to a powder mixture, ointment, etc. There are several ways to do this and
they include: (1) amount per individual dosage form (capsule, tablet); (2) concentration per dosing
volume; (3) percent; (4) ratio strength; (4) parts per million.
Percentage specifies the number of active parts per 100 parts (eg, the number of parts of solute in 100
total parts of solution). In pharmacy, this is expressed in three ways:
• Percent weight-in-weight: % (w/w) = grams of ingredient in 100 grams of product; assumed for
mixtures of solids and semisolids
• Percent volume-in-volume: % (v/v) = milliliters of ingredient in 100 milliliters of product; assumed for
solutions of liquids in liquids
• Percent weight-in-volume: % (w/v) = grams of ingredient in 100 milliliters of product; assumed for
solutions, or suspensions of solids in liquids, or gases in liquids
Note: In performing calculations, percentages may be changed to a decimal fraction by eliminating the
% sign and dividing the numerator by 100.
0.05% = 0.05/100 or 0.0005
In reverse, a concentration expressed as a decimal can be converted to a % by multiplying by 100.
0.50 × 100 = 50%
Ratio and proportions are frequently encountered calculations in pharmacy. Ratio strength expresses
concentration in terms of parts of active ingredient related to parts of the whole. When expressing a
ratio strength, the numerator is preferably set as 1. It is written with a colon between the numbers. The
expression 1:2 means there is 1 part in a total of 2 parts. A ratio of 1:100 means there is 1 part of a drug
to 100 parts of a mixture or preparation.
Example: 5 ounces of drug A mixed with water to make 20 ounces of mixture is 5:20 or 1:4. The ratio
may be written as 1:4 or as a fraction ¼.
A proportion is the expression of two ratios which are equal. It is usually written in one of two ways: two
equal fractions (a/b = c/d) or using a colon (a:b = c:d).
Parts per million is a special case of ratio strength used to express very dilute solution concentrations.
Instead of fixing the numerator as 1, you fix the denominator as 1,000,000. Parts per notation is used to
denote relative proportions in measured quantities; particularly in low-value (high-ratio) proportions.
116
ppm (parts per million) represents the number of parts of solute in 106 parts of solution
ppb (parts per billion) represents the number of parts of solute in 109 parts of solution
ppt (parts per trillion) represents the number of parts of solute in 1012 parts of solution
Preparations of Solutions—Dilution, Concentration, and Alligation
Dilution
Medications are often prepared by pharmaceutical manufacturers with adult usage as the primary
intent. Pharmacists will encounter clinical situations in which patients are children or small in stature
requiring the medication to be diluted.
Example: An aminoglycoside antibiotic injection is available as a 10 mg/mL preparation and the infant is
to receive 4 mg. Volumes <1 mL are considered too small to measure accurately. Therefore, you must
dilute the preparation. Prepare the dilution to a final concentration of 1 mg/mL. How much medication
and how much diluent will you need if the aminoglycoside comes as 10 mg/mL in a 1 mL vial, and the
entire contents of the vial are to be used?
1 mg 10 mg

x  10 mL (total volume of the preparation)
1 mL x mL
• 10 mL − 1 mL (aminoglycoside) = 9 mL diluent Solution will then be 10 mg/10 mL (1 mg/mL).
1 mg 4 mg

x  4 mL of solution will contain 4 mg of aminoglycoside
1 mL x mL
Concentration
A solution is a mixture of two or more substances. Solutions exist in three states: gas, liquid, or solid. A
solution may exist in which the components are: (1) both liquids (a mixed drink); (2) a gas in a liquid
(soda water); (3) solid in a liquid (salt water). In a solution, the substance dissolved in the liquid is the
solute and the liquid is the solvent. If both substances are liquids, the component with the least amount
is the solute. Concentration may be defined as follows:
Concentration = Quantity of solute/Quantity of preparation
Examples:
• A 9% solution means there are 9 parts of the drug in 100 parts of solution.
• When the drug is a liquid, 1:50 means 1 mL of drug in 50 mL of solution.
• When the drug is a solid or in dry form, 1:50 means 1 g of drug in 50 mL of solution.
Powder Volume
A medication in a solid or dry form has a weight that is taken into account when preparing solutions or
suspensions; however, when this solid or dry powder is added to the diluent, it also occupies a certain
volume of space. When dealing with dry pharmaceuticals, this space is called powder volume. Powder
volume is equivalent to the difference between the final volume and the volume of diluent added.
117
Example: QP is a cystic fibrosis patient prescribed a broad-spectrum antibiotic to treat a Pseudomonas
aeruginosa infection. You are to reconstitute a dry powder that is 500 mg. The label states that you are
to add 9.3 mL and the resultant solution will be 50 mg/mL. What is the powder volume?
500 mg 50 mg

x  10 mL
x mL
1 mL
10 mL is the final volume. You added 9.3 mL, therefore the difference (10 mL − 9.3 mL = 0.7 mL) is the
powder volume.
The same calculations may be made to determine powder volume for both dry powders intended for
oral use and those intended for parenteral solution.
Alligation
The mixing of solutions or solids possessing different percentage strengths presents a calculation
problem which may be solved using an arithmetic method called alligation. In setting up an alligation
formula, you must express the strength of each component as a percentage. Then you will determine
how many parts of each different percent strength product you will need to create the final desired
concentration of your product. Finally, you will be able to calculate the exact quantity of each beginning
product you will need to create the final product. Alligation involves changing the percentages to parts
and by using ratio and proportion, solving for the unknown amount of each initial product.
Example: Prepare 500 mL of dextrose 7.5% using dextrose 5% and dextrose 50%. How many milliliter of
each solution will be needed?
Cross subtract smaller number from larger number:
Step 1:
45 parts
2.5 parts

x  27.78 mL D50W
500 mL x mL D50W
Step 2:
45 parts 42.5 parts

 472.22 mL D5W
500 mL x mL D5W
Step 3: Check to see if the two volumes of the two ingredients are equal to the total required volume
472.22 mL + 27.78 mL = 500 mL
Step 4: Another method to check your answer involves comparing the grams of dextrose of the three
solutions. The grams of dextrose from the resultant 7.5% solution should equal the sum of the grams
from the 50% and 5% solution.
(a) 500 mL total solution × 0.075 (7.5% solution was the desired final concentration) = 37.5 g of dextrose
is the amount made in the solution. When we compare the grams of dextrose contributed by the D50W
and the D5W, it should equal the 37.5 g.
(b) 27.78 mL × 0.50 (D50W) = 13.89 g of dextrose.
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(c) 472.22 mL × 0.05 (D5W) = 23.61 g of dextrose.
(d) 13.89 g + 23.61 g = 37.5 g of dextrose
Other Units of Measure
Density and Specific Gravity
Density describes the relationship between the mass of a substance and the volume it occupies.
Density 
Mass
Volume
Utilization of density allows conversion from a volume measure to a weight measure or vice versa and is
usually expressed as grams per cubic centimeter or g/mL.
The specific gravity (sp gr) is a ratio of the weight of a material to the weight of the same volume of
standard material. For liquids, the standard material is water, which has a density of 1 g/mL. Specific
gravity is unit-less, because it is equal to the density divided by density of standard material; therefore,
the units cancel out.
Specific gravity 
Weight of substance
Weight of equal volume of water
Thus,
Weight of substance = Volume of substance × Specific gravity
or,
g = mL × sp gr
Examples:
• Water is the volume of standard material. It weighs 100 g/100 mL or a specific gravity of 1. Therefore,
everything is compared to it.
• If the weight of 100 mL of a 50% solution of dextrose is 117 g, what is the specific gravity of the
dextrose solution?
• 117 g (weight of the dextrose solution)/100 g (weight of a 100 mL of water) = 1.17 specific gravity
• If a liquid has a specific gravity of 0.75. What is the weight of 150 mL?
• g = mL × sp gr
• g = 150 × 0.75 = 112.5 g
Milliequivalents
A milliequivalent (mEq) describes the ability of an inorganic molecule to dissociate in a liquid and is a
measurement of the chemical activity of an electrolyte based on its valence. The equivalent weight of an
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ion is the atomic weight of the ion divided by the absolute value of its valence. Thus the equivalent
weight of ferric ion, Fe3+ (atomic weight 55.9, valence 3) is 18.6. A milliequivalent is one-thousandth of
an equivalent weight (eg, there are 1000 milliequivalent weights in 1 equivalent weight). For a molecule,
the equivalent weight is obtained from the gram molecular weight (formula weight) divided by the total
cation or the total anion charge.
Examples: Most electrolytes are measured by the milliequivalent method (the measure of the ion’s
combining power). The valence of an ion determines how many other ions it must combine with to form
a stable compound. The valence is important, but not the positive or negative charge.
• Water (H2O): Hydrogen has a valence of 1 and oxygen has a valance of 2. It takes two hydrogen ions to
form a stable compound with 1 oxygen ion.
• Molecular weight, formula weight, and atomic weights are just numbers with no units attached.
• The atomic weight (with the unit of grams attached) and the valence determine the equivalent weight.
• Equivalent weight (in grams) = atomic weight/valence.
• Sodium has an atomic weight of 22.99 and a valence of 1.
• 1 equivalent weight of sodium = 22.99/1 = 22.99 g or 23 g.
• The milliequivalent (mEq) weight is one-thousandth the equivalent weight. The milliequivalent formula
is similar to the equivalent weight formula; however, mEq weight is expressed in milligrams.
• Milliequivalent weight (in mg) = atomic weight/valence.
• Sodium has an atomic weight of 22.99 and a valence of 1.
• 1 mEq weight of sodium = 22.99/1 valence = 22.99 mg or 23 mg.
• The mEq weight may be used to convert between mg and mEq using the equation:
• mg = mEq × molecular weight (atomic weight)/ valence or
• mEq = mg × valence/molecular weight (atomic weight)
• Sodium has an atomic weight of 23 and a valence of 1. How many mEq are present in 115 mg of
sodium?
Using the equation above: mEq  mg 
•
Valence
Atomic weight
• mEq = 115 × 1/23
• mEq = 5, so 115 mg of Na is equivalent to 5 mEq of Na
• Or solving by proportion:
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115 mg sodium 23 mg sodium (atomic weight)

x mEq
1 mEq
 5 mEq in 115 mg sodium
Moles and Millimoles
A mole = the molecular weight of a substance in grams.
A millimole (mmol) = the molecular weight or formula weight of a substance in milligrams. A one molar
solution contains 1 g of molecular weight (1 GMW = 1 mole = weight in grams of Avogadro’s number of
particles) per liter of solution. The molarity expresses the number of moles per liter. The millimolarity
(millimoles/liter) is 1/1000 times the molarity of a solution.
Examples: Magnesium has an atomic weight of 24. What is the weight of 1 millimole (mmol)?
1 mmol = 24/1000 = 0.024 g or 24 mg
Milliosmoles
Osmotic concentration is a measure of the total number of particles in solution and is expressed in
milliosmoles (mOsmol). Thus the number of milliosmoles is based on the total number of cations and
total number of anions. The milliosmolarity of a solution is the number of milliosmoles per liter of
solution (mOsm/L):
mOsmol/L 
Weight of substance (g/L)  number of species 1000
Molecular weight (g)
Number of species = number of ionic species on complete dissociation (dextrose = 1; NaCl = 2, MgCl2 =
3).
The total osmolarity of a solution is the sum of the osmolarities of the solute components of the
solution. When calculating osmolarities in the absence of other information, assume that salts (eg, NaCl)
dissociate completely. Be aware of the difference between osmolarity (milliosmoles of solute per liter of
solution) and osmolarity (milliosmoles of solute per kilogram of solvent).
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STATISTICS
1. Absolute risk reduction: Absolute difference between control and treatment groups.
2. Case-control study: Selects patients who have the outcome of interest (cases) and compares to
individuals without the outcome (controls).
3. Clinical significance: Results that are important to clinical care.
4. Cohort: A group of patients / study subjects.
5. Cohort Study: Study consisting of two groups (e.g. two cohorts). One cohort receives treatment A and
one cohort receives treatment B. The cohorts are observed over time to see which develops the
outcome of interest.
6. Confidence Interval: A 95% confidence interval is often interpreted as indicating a range within which
we can be 95% certain that the true effect lies. This statement is a loose interpretation, but is useful as
a rough guide. The strictly-correct interpretation of a confidence interval is based on the hypothetical
notion of considering the results that would be obtained if the study were repeated many times. If a
study were repeated infinitely often, and on each occasion a 95% confidence interval calculated, then
95% of these intervals would contain the true effect.
7. Confounder: A factor in the study that affects the relationship of the groups being evaluated.
8. Effectiveness: How well an intervention works in everyday real world use.
9. Efficacy: How well an intervention works in ideal circumstances.
10. Intention to Treat: Includes all patients that were randomized.
11. Meta-analysis: Combination of several studies to answer a research question.
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12. Null hypothesis: No difference between groups.
13. Observational study: Epidemiologic study. No intervention.
14. Odds Ratio: Odds of exposure in cases divided odds of exposure in controls. Odds ratio of 1 indicates
exposure to the drug is equally likely. Greater than 1, the risk of exposure is greater in cases. Less than 1,
risk of exposure is smaller in cases.
15. p-value: Level of statistical significance. A value <0.05 means that the probability that the result is
due to chance is less than 1 in 20.
16. Power: Ability of the study to detect significant difference between treatment groups.
17. Relative Risk:
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AED Answers: 1) c; 2) c, d; 3) a, d; 4) a, b, d; 5) b.
ANTIDEPRESSANT Answers: 1) a, d, e; 2) a, b; 3) b
NEUROLEPTIC Answers: 1) b, c; 2) a, b, d; 3) b; 4) b; 5) a
PAIN Answers: 1) d; 2) a; 3) c
GOUT Answers: 1) b; 2) a; 3) a
COPD and ASTHMA Answers: 1) d; a, b, c; 3) a, c, d
PUD and GERD Answers: 1) a,b; 2) d; 3) a; 4) d; 5) b
DIABETES Answers: 1) d; 2) a; 3) d, e; 4) b
HYPERTENSION Answers: 1) a; 2) a; 3) b; 4) a; 5) c, e; 6) b, c, d, e.
ONCOLOGY Answers: 1) d; 2) a; 3) a, b, c; 4) b; 5) d; 6) a, b; 7) b; 8) a; 9) d; 10) b; 11) c; 12) a; 13) c; 14) b;
15) a; 16) a, b, c, d; 17) c; 18) a; 19) b; 20) c
HIV Answers: 1) a, b, c; 2) a, c, d; 3) a, b, d; 4) c; 5) b; 6) a, c, d
DYSLIPIDEMIA Assessment: 1) d; 2) a, b, c; 3) c; 4) a, e; 5) a
ANTIBIOTIC Answers: 1) a, c; 2) a, b, c, e; 3) c
HEART FAILIRE Answers: 1) d; 2) d; 3) b
ANTITHROMBOTIC Answers: 1) d; 2) a; 3) a, b; 4) a, b, d
Cognitive Answers: 1) b, c, d; 2) d; 3) c, d, e; 4) a; 5) b, c
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