The Endocrine System
 A “communication”
system for the body
 Major components of
the endocrine system
are:
 Hypothalamus
 Pituitary gland
1
The Endocrine System (cont.)
 Secondary components of the endocrine system
are:
 Thyroid
 Parathyroid
 Pancreas
 Adrenal glands
 Gonads
 The pituitary gland controls the secondary
components of the endocrine system
 During pregnancy, the placenta also acts as an
endocrine gland
2
The Hypothalamus and Pituitary
Gland
 Hypothalamus
 Part of the brainstem
 Controls the activity of the pituitary gland
 Pituitary gland
 About the size of a large pea
 Called the “master gland” because it controls many other
glands
 Composed of anterior and posterior lobes
 Each lobe contains a number of hormones
 Hormones—chemical substances that regulate certain
bodily functions
 Steroids—slow acting, long lasting, and usually end in the
suffix “-rone” (examples: testosterone, progesterone)
 Peptides and amines—made of proteins, fast acting, and
short lived (examples: insulin, ADH)
3
Female Sex Hormones
 Estrogen—responsible for:
 Development of secondary sex characteristics
 Formation of osteoblasts
 Inhibition of osteoclasts
 Bone loss
 Progesterone—prepares lining of uterus for
implantation of fertilized egg
 Replacement female hormones may be derived
from animal, plant, or lab-modified sources
4
 Female hormones Drug Products
 MOA: replaces estradiol in females
 Indications: menopausal Sx, prevent osteoporosis,
Generic
Brand
Indications
Conjugated Estrogens
Premarin ®
Hormone
replacement
Ethinyl Estradiol
Estinyl®
Hormone
replacement
5
Oral Contraceptives
 Drugs that contain high doses of estradiol and/or progestins
 MOA: high levels of hormones “tricks” the body to think its pregnant





and ovulation don’t occurs
Indication: Birth control, vaginal bleeding control, endometriosis
Federal law mandates that the patient package insert be dispensed with
Rx to patient in retail
OC are contraindicated in women with a history of TE disorders,
strokes and breast cancer
DepoProvera is an IM injection used for birth control that lasts for 3
months
Levonorgestrel is available as Plan B, or Next Step.
 Take 1 tab as soon as possible after sex and 1 tablet 12 hours later
Generic
Brand (dose forms)
Ethinyl estradiolnorgestimate
Ortho Tri Cyclen (tablet)
EE- norgestrel
Lo-Ovral
EE-norethindrone
Loestrin, Ortho Novum
EE-etonogestrel
NuvaRing (vaginal ring)
EE-norelgestromin
Ortho Evra (patch)
Male Sex Hormone Drug Products
 MOA: replaces testosterone levels in men
 Indications: hormone replacement therapy, treatment
of anemia in cancer patient (no used for this anymore)
 Contraindications: history of liver disease, and
prostate cancer
Generic
Brand(s)
Testosterone
Androgel®, Androderm® and as testosterone
cypionate (IM injection)
Nandrolone
Durabolin ®
Fluoxymesterone
Halotestin®
Oxymetholone
Anadrol®
Side effects: weight gain, muscle hypertrophy, viriziling effects,
priapism, hepatitis and blood filled cysts in liver (oral more than IM),
long term use results in sexual problems, gynecomastia
Because of abuse in sports, federal schedule 3
7
Erectile Dysfunction Agents
 Enzyme inhibitors of phosphodiesterase IV
 Vasodilation of the penile blood vessels
 Contraindicated in men taking nitrates for chest pain
 Nitroglycerin
 Isosorbide
Generic
Brand
Sildenafil
Viagra
Tadalafil
Cialis
Vardenafil
Levitra
8
Diabetes Mellitus
 A disorder of carbohydrate metabolism
 Type I DM
 Genetic factors involved
 Environmental factors (i.e. Coxsackie virus)
 Involves destruction of pancreas by the immune system
 Begins as children and young adults
 Patients are described as insulinopenic (i.e pancreas
secretes almost no insulin)
 Patients are described as thin
 Blood abnormalities includes high blood glucose, high
triglycerides level (VLDL), high blood levels of ketone
 Physical signs are extreme thirst, nocturia, hypertension
and possible kidney disease.
9
 Type II Diabetes Mellitus
 Genetic factors involved
 Environmental factors involved
 Involves the resistance of the body to the hormone,
Insulin.
 Also described as Insulin resistance syndrome
 Signs and symptoms include those of Type I DM
 Metabolic Syndrome or Syndrome X






Independent risk factor for cardiovascular disease
Seen in men and women
Biochemically marked by high blood glucose, cholesterol,
trigycerides
BMI>25
Hypertension of greater than 130 mmHg systolic
Waistline of more than 40 in in men; 35 in in women
10
Therapy of Diabetes
 Insulin
 Regular insulin or short acting insulin


Humulin R or Novolin R
Humalog or Novolog
 Intermediate acting insulin
 Humulin N or Novolin N
 Mixture of intermediate acting /regular insulin
 Humulin 70/30 or Novolin 70/30
 Novolog 70/30
 Long acting insulin
 Lantus ® (insulin glargine)
 In general, insulin is the first line of therapy in type I
DM
 In type II DM, oral drugs are tried first, ultimately
insulin is required in this class of people as well
11
Insulin Products
http://pixgood.com/novolog-logo.html
http://www.lantus.com/considering/lantus-solostar-features/lantussolostar-pen
http://www.diabeteshealth.com/
12
 In general the dose of insulin in type I DM is about 0.5
units/kg of body weight which half of this dose given
as long acting insulin and the other half is given as
bolus dose with meals
 Type II DM patients are initiated on long acting or
intermediate acting Insulin at bedtime. The dose is
titrated according to fasting blood glucose and is
determined by the patient’s endocrinologist
13
Oral Drugs for Diabetes Mellitus
 Type I DM patients can not be treated with most of these
drugs
 Used in Type II DM
 Sulfonyureas
 Increases insulin secretion from the pancreas
 Should be given with food
 Avoid Alcohol
 Glipizide (Glucotrol®)
 Glyburide (Diabeta®)
 Tolbutamide (Orinase®)
 Glimepiride (Amaryl®)
 Biguanides
 Inhibits hepatic gluconeogenesis during fasting

Metformin (Glucophage®)
 Caution: with people with kidney disease can result in a fatal
reaction called Lactic acidosis
14
 Meglitinides
 Similar to sulfonylureas
 Taken before a meal


Repaglinide (Prandin®)
Nateglinide (Starlix®)
 Thiazolidinediones
 Also known as the glitazones
 Increases insulin sensitivity in adipose tissue and muscles


Pioglitazone (Actos®)
Rosiglitazone (Avandia®)
 Basically good drugs but since 2010, both drugs have been
implicated in serious adverse medical events
 After November 2011, Avandia and all avandia products are
restricted in distribution to the FDA REMS program
 www.fda.gov/Drugs/DrugSafety/ucm255005
15
Novel New Drugs
 dipeptidyl peptidase- 4 inhibitors
 Blocks an enzyme in the kidney called dipeptidyl
peptidase- 4
 Blockade of this enzyme allows a hormone called
glucagon like peptide I or GLP1 to last longer
 GLP1 helps augment insulin release in response to a
sugar rich meal
 Onglyza ®(saxagliptin)
 Januvia ® (sitagliptin)
 Incretin Mimetics (GLP like)
 Exenatide (Byetta®)
 Liraglutide (Victoza®)


Injectable hormones
GLP-1 agonists
16
Thyroid Disease
 Thyroid gland is responsible for secreting thyroid
hormone, T4.
 T4 basically controls metabolic functions in the body
 More T4 equals a higher basal metabolic rate
 Less T4 equals a lower basal metabolic rate
 Hypothyroidism is a condition where thyroid gland does
not secrete adequate T4
 Condition products slow BMR, slow heart rate, electrolyte
abnormalities, lipid disorders
 Tx: Levothyroxine (synthroid ®, Levoxyl ®)
 Hyperthyroidism is a condition of to much T4
 Can produce a dangerous heart condition called Atrial
Fibrillation
 Tx: Methimazole (Tapazole®), Propylthiouracil (PTU)
 SSKI (super saturated potassium iodide) used in the
emergency tx of “thyroid storm”
17
Corticosteroids
 Adrenal gland naturally produces cortisol and other “corticosteroids”
 These hormones are very important in priming the body to deal with
stress. They control artery’s and heart’s sensivity to norepinephrine,
blood pressure, water clearance by the kidney and many others
 A loss of cortisol secretion by the adrenal gland produces “adrenal
crisis” which is a medical emergency
 Drugs should not be stopped abruptly
Generic
Brand
Prednisone
Deltasone
Methylprednisolone
Medrol (oral)
Solu Medrol (IV)
Dexamethasone
Decadron
Hydrocortisone
Hytone (topical)
Solucortef (IV)
Severe side effects: immune suppression, osteoporosis,
elevated blood glucose, cataracts, growth suppression in
children
With Inhalation products like Advair® tell patients to rinse
mouth after the dose
18
The Nervous System
 Divided into central nervous system (CNS) and
peripheral nervous system (PNS)
 Central nervous system
 Includes brain and spinal cord
 Controls all nervous system functions
 Control may be direct or indirect
 Peripheral nervous system
 Includes all other nerves and sensory organs
 Controlled by central nervous system
 Divided into somatic and autonomic nervous systems
19
Functions of the Nervous System
 Sensory (afferent)
 Sends impulses from other parts of body toward the
CNS
 Senses external changes or conditions in the
environment, such as cold or heat
 Senses internal changes in the body, such as decrease in
potassium or calcium
 Integrative
 Processes perceived information about the sensory
changes
 Interprets or explains changes in external/internal
environments
20
Functions of the Nervous System
(cont.)
 Motor (efferent)
 Sends impulses away from the CNS to other parts of the
body
 Allows and controls body movement
 Causes glands to secrete hormones or other chemicals
into the bloodstream
21
Sympathetic Nervous System
 Governed by the neurotransmitter norepinephrine
 Prepares body for energetic tasks, stressful situations,
and the “fight or flight” response
 Stimulates heart, lungs, and blood vessels
 Decreases activity of gastrointestinal and
genitourinary functions
22
Parasympathetic Nervous System





Governed by the neurotransmitter acetylcholine
Activates body for sleep in nonstressful periods
Effects the “rest and relaxation” response
Decreases activity of heart, lungs, and blood vessels
Increases activity of gastrointestinal and genitourinary
functions
23
Neuron
 Smallest unit of the
nervous system
 Brain is composed of
approximately 100
billion neurons
 Highly differentiated
from other cells
24
Neurotransmitters
 Released at the end of the neuron
 Synapse is the space between two different
neurons
 Neurons transfer information by crossing
synapses
 Neurotransmitters travel across the synapse to
reach a receiving neuron
 Attach to special structures called receptors
 Communicate with and control glands, organs,
and muscles
25
Central Nervous System Drugs
 Sedatives and Tranquiller: Drugs that cause depression of
the reticular activating system in the brain. Differences in
mechanisms of action.
 Examples are
 barbiturates: Phenobarbital (Luminal®)
 Benziodiazepines: Chlordiazepoxide (Librium®), Diazepam




(Valium®), Lorazepam (Ativan®), Alprazolam (Xanax®)
BDZ were developed in the 1960’s with the advent of librium®.
BDZ are safer than barbiturates. Both dangerous with alcohol
consumption.
Used in anxiety disorder, panic disorder, GAD, sleep disorders
Control Substance: CIV
Miscellanous agents in the class are zolpidem (Ambien®),
zaleplon (Sonata®)
CNS Depressants
 Benzodiazepines and Barbiturates
 MOA: binds to GABA receptors in brain
 Indications: sedation for anxiety and pre op use
 Main Side Effect: drowiness, Dependence (CIV)
Generic
Brand
Lorazepam
Ativan
Clonazepam
Klonopin
Alprazolam
Xanax
Midazolam
Versed
Zolpidem (not a
BDZ)
Ambien
Primidone
Mysoline
Depression
 Symptoms include feelings of despair, lack of energy,
inability to concentrate
 Related to decreases in concentration of the
neurotransmitters
 Treated with drugs that:
 Block the reuptake of neurotransmitters
 TCA (tricyclic antidepressents)
 Nortripyline (Pamelor®), Amitripyline (Elavil®)
 Dangerous in overdose
 Doses over 1 gram can be fatal
 SSRI
 Fluoxetine (Prozac®)
 Paroxetine (Paxil®)
 Sertraline (Zoloft®)
 Citalopram (Lexapro)
 SNRI
 Duloxetine (Cymbalta®)
 Safer in overdose than TCA’s
28
 Interfere with the breakdown of the monoamines within
the synaptic cleft
 MAOI






Used in the 50 and 60’s
Very dangerous in overdose
Many drug interactions especially with hypoglycemic drugs
and antihypertensive drugs
Drug food interactions with foods with high tyramine content
like cheeses, wine, chocolates, etc
Phenelzine (Nardil®)
Tranylcypromine (Parnate®)
 Used now only a last ditch effort to treat SSRI resistant
depression
29
Psychosis
 State in which a person is out of touch with reality
 One cause may be an increase in dopamine
 Treated with antipsychotic drugs that attach to the dopamine D2
receptor
 Treated with dopamine receptor antagonists
Generic
Brand
Haloperidol
Haldol ®
Chlorpromazine
Thorazine®
Fluphenazine
Prolixin®
Thioridazine
Mellaril ®
Major side effects: Abnormal heart arrhthymias,
hypotension, sedation, Extrapyramidal symptoms
(Parkinson’s like) movement disorders
30
Second Generation Antipsychotics
 The previous list of Antipsychotics had major side effects of





hypotension, sedation, weight gain, erectile dysfunction, cardiac
arrhythmias (Long QT) and EPS (Extra pyramidal Symptoms)
EPS is a movement disorder that is similar to Parkinson’s disease
Second generation drugs were developed to avoid EPS
A major side effects to these drugs are: risk of drug induced diabetes
and weight gain.
Ziprasidone has the risk of cardiac arrhythmias (long QT)
Clozapine has the risk of fatal blood condition called agranulocytosis
 (Very low white blood cell count)
 FDA REMS requires registries set up to monitor this risk
Generic
Brand
Olanzapine
Zyprexa
Clozapine
Clozaril
Quetiapine
Seroquel
Risperidone
Risperdal
Ziprasidone
Geodon
31
Parkinson’s Disease
 Degenerating neurons in the basal ganglia of the brain
characterizes this disease
 These neurons are dopaminergic and secrete
dopamine as a neurotransmitter
 These neurons coordinate with neurons in the motor
cortex to help initiate movement
 Signs and symptoms
 Resting tremor: shaking limbs and hands at rest which goes
away with movement (first sign noticed by family or patient)
 Gait imbalances: patient has problems initiating movement
and may show signs of bradykinesia and muscle rigidity often
called dystonia
 Weak and achy muscle in the face progresses to slurring
speech
 Autonomic disregulation (low blood pressure)
32
Treatment of PD
 Dopaminergic drugs
 Used to “replace” dopamine in the brain
 Taken orally
 Sinemet® Carbidopa/Levodopa



Levodopa is converted to dopamine in the brain
Dramatically improves symptoms
Often effective for several years before drug resistance sets in
 Dopaminergic type drugs

Ergot alkaloid drugs that act at dopamine receptor
 Bromocriptine (Parlodel)
 Cabergoline (Dostinex®)
 Ropinirole (Requip®)
33
Antiepileptics
 Indications: Drugs used to treat seizures. Off label
use: Neuropathic pain
 MOA: Many of the drugs block the sodium ion
channel in nerves.
 Main Side effects: Drugs in this group are known
to cause birth defects
 Levetiracetam is a known cause of SJS
 Topiramate can cause kidney stones
 For emergency tx: use diazepam or phenytoin IV
Generic
Brand
Phenytoin
Dilantin
Valproic Acid
Divalproex Sodium
Depakene
Depakote
Carbamazepine
Tegretol
Gabapentin
Neurotin
Oxcarbazepine
Trileptal
Levetiracetam
Keppra
Topiramate
Topamax
Phenytoin, Valproic acid, Levetiracetam and Diazepam are available as
IV injections
Drugs used to treat Alzheimer
Disease
 Alzheimer disease is a degenerative neurological
disease of primarily cholinergic neurons
 Results in loss of memory, personality changes and
complete loss of language skills
Generic
Brand
Donepezil
Aricept
Memantine
Namenda
Rivastigmine
Exelon
 Drugs used to treat ADHD in children and adults
 Mixed amphetamine salts: Adderall® XR
 Other agents: Methylphenidate (Ritalin® Concerta ®,
Focalin ®)
 Atomoxetine (Strattera ®)
 Lisadexamfetamine (Vyvanse ®)
 Dextroamphetamine (Dexedrine ®)
 All the above drugs are controlled substances except
Atomoxetine
The Immune System
 Consists of two types
 Humoral Immunity
 Cell mediated Immunity
 Humoral Immunity
 Involves blood proteins
 Is recruited when physical barriers like the skin are breached
 Complement proteins are proteins in the blood that recognize
bacterial cells and other microorganisms.

They basically open holes in those cells and allow osmosis of water to
lyze and kill them
 Antibodies
 These are proteins that are secreted by an activated B lymphocyte
called a plasma cell.
 Antibodies are highly specific for the bacteria, fungi, protozoa that
they target
38
 Cell Mediated Immunity
 Immune reactions that are carried out by cells




Macrophages are cells that engulf and “swallow” invader cell,
bacteria and particles
Neutrophils are cells that destroy invaders by engulfing these
invaders
B lymphocytes are cells that make antibodies to an given antigen (a
marker on an invader)
T lymphocytes are cells that orchestrate and guide the immune
response
 CD4 or helper T cells help B cells make antibodies and are very
important in the immune response. They are the targets for the
HIV virus
 CD8 cells are cells that recognize viral infected cells are carry out
an attack on these cells. They kill these cells to spare the host
organism.
 NK Cells are cells that are similar to CD8 cells. These cells are
important in cancer.
39
Pathogens
 Bacteria are unicellular organisms that are know to be
the simplest form of life. They grow and divide and
require nutrition. Most bacteria are harmless but
some are virulent pathogens to humans.
 Broadly speaking bacteria are divided into gram positive
and gram negative depending a their cell wall chemistry
 Bacteria are aerobic and some are anaerobic
 Some are defined as fastidious and non fastidious
(which means that some require a special growth
medium) Brucella requires blood agar
 Some are intracellular parasites (they live inside the cell)

Examples are chlamydia and Brucella and Rickettsia
40
Serious Bacterial Infections
 Bacterial Meningitis
 Caused by Neisseria Meningitidis, Streptococcus,
Streptococcus species
 Mortality is high even with treatment
 Flesh Eating Disease
 Called Necrotizing Fasciitis
 Commonly caused by a strain of bacteria called Group A
Streptococcus or Streptococcus pyogenes
 Since the late 1990’s MRSA is the second leading cause
 Infection begins in the skin (subcutaneous tissue)
 Spread is very fast to the connective tissue called the fascia,
which is the coating to muscle cells
 Infection is by contact with contaminated sewage and water
contaminated with bacteria
 Streptococcal exotoxin activates T cells to produce massive
damage to muscle and skin
 IV high dose antibiotics are required
41
Antibiotic mechanism of action
 Penicillin and Cephalosporins: drugs inhibit the




formation of the bacterial cell wall. Bacteria swell and
die. Drugs are bactericidal
Macrolides: inhibits bacterial ribosomes and protein
synthesis. Example includes erythromycin (E-Mycin®)
and azithromycin (Zithromax®). Bactericidal or
Bacteriostatic.
Tetracyclines: Bacteriostatic by inhibiting protein
synthesis.
Fluroquinolones: Bactericidal. Binds to DNA gyrase
Aminoglycosides: (Gentamicin) Bactericidal by several
mechanisms
 Penicillins and Cephalosporins are classified as Beta Lactam
antibiotics.
 Very important antibiotics
 Treats a wide variety of bacterial infections
 Penicillins are several classes
Class
Example
Brand name
Natural Penicillin Penicillin G
Pfizerpen (IV
form)
Veetids (tablets)
Aminopenicillin
Ampicillin
Omnipen
Ureidopenicillin
Piperacillin/Tazo
bactam
Zosyn
Penicillinase
resistance
penicillins
Nafcillin
Nafcil
Aminopenicillin Amoxicillin +
+ Beta Lactamase Clavulanate
Inhibitor
Potassium
Augmentin
 Main Side Effects of penicllins/cephalosporins
 Nausea/Vomiting
 Diarrhea
 Type I hypersensivity
 Cephalosporins
 Chemically similar to penicillins (Beta lactam)
 Four generations
 Excellent antibiotics
 Similar side effects
Generation
Generic
Brand
First
Cephalexin
Keflex (oral only)
Cefazolin
Ancef (IV)
Cefaclor
Ceclor (oral only)
Cefuroxime
Ceftin (oral
suspension)
Zinacef (IV)
Ceftriaxone
Rocephin (IV only)
Cefdinir
Omnicef (oral
only)
Fourth
Cefipime
Maxipime (IV only)
Carbapenems
Meropenem
Imipenemcilastatin
Merrem (IV only)
Primaxin (IV only)
Second
Third
Third and fourth generations are used to treat meningitis and
hospital acquired infections and pneumonias
Fluoroquinolones
 Must take oral forms of these drugs separate from antacids (Maalox) by





1-2 hours
Many drug interactions
Advised to limit the consumption of caffeine while on these drugs
(ciprofloxacin more than others)
Used for URIs and UTI and GI tract infections
Fluoroquinolones are contraindicated in pregnant patients and patient
younger than 18 years old
Cipro ® comes in IV, oral tablets, opthalmic and oral suspension
Generic
Brand
Ciprofloxacin
Cipro
Levofloxacin
Levaquin
Moxifloxacin
Avelox
Lomefloxacin
Maxaquin
Tetracyclines
 Broad spectrum antibiotic class
 Effective for use in certain infections
 Chlamydia and gonorrheal infections
 Lyme Disease
 Rocky Mountain Spotted Fever
 Contraindicated in pregnant women and young children < 8 years old
 CAUTION: never use expired tetracycline products. Toxin produces serious
kidney damage
 CAUTION: advise patient to wear protective clothing. Drugs are
photosensitive chemicals
Generic
Brand
Doxycycline hyclate
Vibramycin
Doxycycline
Monohydrate
Monodox
Minocycline
Minocin
Macrolides and Ketolides
 Commonly used to treat UTI like walking pneumonia and chronic




bronchitis
Notorious for GI side effects
Contraindicated in patient with hepatic dysfunction and QTc
prolongation (a EKG cardiac abnormality that can lead to VF and
death)
Patient should take macrolides with food
CYP450 inhibitors- many drug interactions
Generic
Brand
Azithromycin
Zithromax
Clarithromycin
Biaxin
Erythromycin base
E-Mycin
Erythromycin
ethylsuccinate
EES
Telithromycin
Ketek
Aminoglycosides
 Used to treat severe life threatening infections
 IV formulations of AG are toxic to the kidney and to
cranial nerve VIII causing hearing loss (ototoxicity)
 Requires monitoring of renal function and blood levels
of these drugs
Generic
Brand
Gentamicin
Garamycin
Amikacin
Amakin
Tobramycin
Nebcin
Miscellaneous Antibiotics
Generic
Brand
Indication(s)
Adverse
Reactions
Vancomycin
Vancocin
Meningitis,
Pneumonia,
MRSA
Renal toxicity
Clindamycin
Cleocin
URI, Acne, female Increased risk of
genital infections, C. Difficile Colitis
dental
prophylaxis for
pen allergic
patients
Metronidazole
Flagyl
GI tract
infections and
protozoal
infections
Severe reaction
when taken with
alcohol
Linezolid
Zyvox
Meningitis,
Pneumonia,
MRSA
Reaction with
MAOI
antidepressants
Viral Infections
 Virus are non living things who primary reason for
existence is to make more copies of themselves
 Infect various cells. Each virus may have its own
preference called a virus’ trophism
 Antibiotics can not be used to treat these infections
 Antiviral Drugs



Acyclovir
Gancyclovir
Ribavirin
 These drugs usually acted on a viral DNA or RNA
polymerase blocking its action
51
Antiviral Drugs
 Most viral infections are self limiting
 Severe case of herpes, cytomegalovirus, and Influenza
are amenable to drug therapy
Generic
Brand
Virus
Acyclovir
Zovirax
Herpes
Valacyclovir
Valtrex
Herpes
Valganciclovir
Valcyte
CMV, Herpes
Famciclovir
Famvir
Herpes
Ganciclovir
Cytovene
CMV
Penciclovir
Denavir
Cream for oral
herpes
Oseltamavir
Tamiflu
Influenza
Zanamivir
Relenza
Influenza
(Inhalation
product)
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HIV infection
 Target of HIV is the CD4 lymphocyte
 HIV also shows trophism to the macrophage and a cell
in the CNS called a microglial cell
 RNA virus that replicates inside of CD4 cell
 CD4 cells die as virus is released and starts a new
round of infection.
 Infection can not be cured; the virus spread to
macrophages which can live for years provides a life
long viral reservoir.
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Natural History of HIV infection
 Exposure to blood or bodily fluids through sexual
contact and/or use of needles
 Prodromal stage
 Initial stage of infection: about 4 weeks patient develops
signs of flu like symptoms
 Before this period no antibodies against HIV can be
deteched
 After this febrile flu like state passes, patient is said to be
seroconverted (i.e. will show detectable antibodies)
 Clinical latency
 The immune system temporarily subdue infection
 Can last between 2-10 years
 As virus replicates in CD4 cells, these cells die by
rupture, apoptosis or attack by the CD8 cell
 As CD4 levels decline, opportunistic infection sets in
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Acquired Immunodeficiency
Syndrome
 Final Stage
 Occurs when CD4 levels have fallen to less than 200
cells/microliter
 And patient has one of the following





Pneumocystic Pneumonia caused by a protozoan,
Pneumocytis Jirovecci
Esophageal candidiasis
MAC infection
Kaposi Sarcoma
Burkitt’s Lymphoma
 Patient will usually die from one of these cancers or
infections
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Drugs used in HIV infections
 Reverse transcriptase inhibitors
 Block RNA reverse transriptase (NRTI)






AZT, Zidovudine (Retrovir®)
Abacavir (Ziagen®) known as ABC
Lamivudine (Epivir®) known as 3TC Approved for both HIV
and HBV
Emtricitabine (Emtriva®) also called FTC
Tenofovir (Viread®) approved for both HIV and HBV
 Known as TDF
Didanosine (Videx ®) known as DDI
 These drugs also come in various combinations
 Combivir (AZT and Lamivudine) known as CBV
 Emtricitabine-tenofovir (Truvada)
 NNRTI
 Efavirenz (Sustiva®) also known as EFZ
 Etravirine (Intelence®)
 Delavirdine (Rescriptor®) known as DLV
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Protease Inhibitors
 Kaletra ® (lopinavir/Retrovir)
 Reyataz ®(atazanavir)
 Aptivus® (Tipranavir)
 Prezista ® (Darunavir)
 Lexiva ® (fosamprenavir)
 Viracept ® (nelfinavir)
 Norvir ® (Ritonovir)
 Inhibits viral enzyme HIV protease which assists in viral
assembly
 Norvir and Aptivus are stored in the refrigerator
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Fusion Inhibitors
 Prevent HIV from attaching to CD4 cells
 Pharmacology is very complex
 Prevents “fusion” of virus with the cell
 Drugs include:
 Enfurvirtide (Fuzeon®) a drug given by subcutaneous
injection
 Maraviroc (Selzentry®) oral drug
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