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Pharmacology for PTs

Pharmacology: Week 1 Notes
Lecture 1: Introduction
Pharmacology – “the study of drugs, therapeutics, receptors and their mechanisms”
Galen – father of pharmacy
o Theriac – herbal Jam cure all for poisons, diseases
Oswald Schmiedeberg – founder of modern Pharm
o 1838
Importance of Pharm:
848$ per person on pharmaceuticals,
45% of global pharm market
17% of peoples health care services in US
6/10 companies – pharm
What is involved in Pharmacology?
1) Pharmacotherapeutics – the study of the use of drugs to prevent, treat, or diagnose disease
2) Pharmacodynamics: what does the drug do to the body (clinical effect) and how does it do it
(mechanical effect)?
a. How does it impact us?
i. Diuretics – make us go to the bathroom?
1. How does drug make us do that?
3) Pharmacokinetics: How is the drug handled/processed by the body – absorbed, distributed, and
elimintated? - what does the body due to the drug?
1) Therapeutic Effect – intended or desired effects of the drug
2) Side Effect – Unintended effect of the drug
i.e.: Autonomic Drugs: Downregulate autonomic, side effect: decrease depression
a. Adverse Drug Reactions (ADR): unwanted, uncomfortable, or dangerous effects that a
drug may have
b. Toxic Effects: Side Effects that are potentially harmful or life-threatening
i. Dose should be reduced or Drug should be STOPPED
Prescription Drugs – require
NonPrescription – not synomous with over the counter
Don’t require physician or pharmacist
Drug Names:
Chemical Name – N-acetyl-p-aminophenol
Generic Name – Acetaminophen
Trade (Brand) Name – Given by manufacture; license lasts 20 years
Generic vs Brand Name: Same Chemical Name!
o Active Ingredients are the same
o Inactive ingredients may differ; preservatives, partcile size
o SOMETIMES altered efficacy
o Pricess are lower
Lecture # 2 : Pharmacodynamics – What the drug does to the body.
Drug Receptor Dynamics:
Drug Molecule (Ligand) = an ion, molecule, or molecular group that binds to another chemical
entity to form a larger complex
o Breaks off of the drug substance, binds to the target cell receptor
o The Affinity dictates the effectiveness of the drug
▪ Affinity = tenacity with which drug binds to receptor
Drug Response Curve:
o Ceiling Effect: no matter how much of the drug you take, you wont get more of a
o Threshold: Amount of drug needed to produce a noticable response
Four Important Values Associated with Dose Response Curve:
o Potency – how much of a medication required to get a response
▪ Curve A is more Potent because it requires LESS medication to illict the response
▪ The least amount of dosage to illict the response
o Efficacy
▪ Maximum effect is different regardless of the amount of drug you take
o Slope
▪ How Quickly the drug will work
• A is more effective/faster
o Variability
▪ How consistent the response to the medication is
• Differences in responses to the same dosage
Drug Effectiveness (Effective Dose)
o Is the dose or amount of drug that produces a therapeutic response or desired effective
in some fraction of the subjectes taking it
▪ Median Effective Dose = 50% of the population = ED50 (most Common)
▪ Minimal Effective Dose: the lowest dose level of pharmaceutical product that
provides clinically significant response in average efficacy = MED
▪ Median Toxic Dose – dose where 50% of the population deonstrates ADVERSE
▪ Minimal Toxic Dose = Smallest dosage of the drug that produces signs or
symptoms of toxicity = MTC
▪ Median lethal Dose – dose at which 50% of the population die = LD50
▪ Minimal Lethal Dose – lowest dose level of a pharmaceutical product that will
produce death of an organism
Therapeutic Index: How safe the drug is
o Compares the amount of a therapeutic agent that causes the therapeutic effect to the
amount that causes toxicity.
• ED50 and TD50 should be very far apart = Larger Therapeutic Index
Therapeutic Window: the range of dosage of a drug or of its concentration in a bodily system
that provides safe, effective therapy
o The Entire area between the therapeutic effect and toxic effect
Drug Receptors: Mechanism of Action
Ligand Gated Ion Channel
o i.e. cholinergic nicotinic receptors
Enzyme Linked Receptors
o i.e.: Insulin Receptors
G-Protein Coupled Receptors
o i.e. A and B adrenoceptors
o Ligand mechanism to call G protein to bind
o i.e.: Steroid Receptors
▪ Go through the cell, bind inside the cell
Agonists and Antagonist Drug Receptors
Agonists – Activate
Antagonists – Prevent Activation
Competitive Antagonists – Binds to specific Receptor site and once there, blocks another drug
or chemical from binding to that site
Non-Competitive Allosteric Antagonists
o Allosteric – Of or relating to the binding of a molecule at a site other than the active site
o Non Competitive – bind to a DIFFERENT site which reduces binding of the agonists by
allosteric mechanism
▪ Can be Irreversible or Temporary
Physiologic Anatagonists
o Two Agonsists acting on to different receptors causing OPPOSING Responses
▪ i.e.: Histamine and Adrenaline counter-act each other
Full or Partial alteration of receptor function
Effects of Receptors on Drug Efficacy:
o Combined effects of efficacy: Can compound on each other, or cancel out
Sensitivity of Receptors
o Decreased Sensitivity = Same Number of Receptors, Less sensitive to ligand
o Increased Sensitivity = Same number of Receptors, more sensitive to ligand
Regulation of Receptors
o Down Regulation = Decreased number of receptors through prolonged exposure and
o Up Regulation = increased number of receptors
Increased exposure to a stimulus decreases the sensitivity; meaning the receptors no longer
respond to the stimulus at the original intensity
o Build up a “tolerance”
More Information: http://tmedweb.tulane.edu/pharmwiki/doku.php/basic _principles_of_pharm
Lecture 3: Pharmacokinetics –what the body does to the drug)
4 Main Components: ADME
Routes for Delivery of Drugs:
1) Enteral – Through the GI Tract
a. Orally
b. Buccally – cheek
c. Sublingually
d. Rectally
2) Parenteral – Any route that does NOT require GI tract
a. Inhalation
b. Injection
c. Topical
d. Transdermal (ionto, phono)
1) ORAL –
a. Advantage: Easy, Convenient
b. Disadvantages: SLOWER, Incomplete absorption can occur
i. First Pass Effect : drug first passed through the LIVER via hepatic portal vein
1. Filters drug; therefore only part of the drug is circulated
a. Advantages:
ii. Absorbed directly into Superior Vena Cava
1. i.e.: Nitroglycerin (following heart attack – gets to heart FASTER)
iii. Drug Stability
iv. AVOIDS First Pass
b. Disadvantages:
i. Inconvenient
ii. Small Doses only
iii. Unpleasant taste
a. Advantages:
i. Good for those who cant take by mouth
ii. Can be given to unconcious person
b. Disadvantages
i. Not as well absorbed
ii. Irritate Tissue
iii. Uncomfortable
1) Intravenous – into vein
a. Advantages:
i. Rapid
ii. Direct to circulation
iii. NO first Pass
iv. Complete Absorption
b. Disadvantages
i. Infection
ii. Harder Administration
2) Inhalation/Intranasal
a. Advantages;
i. Directly to Pulmonary System
ii. Limited systemic effect
iii. No First pass
iv. Easy to administer
b. Disadvantages
i. Localized Effects
ii. Limited Medications
3) Injection
a. Intramuscular or Intra-Joint
b. Advantages
i. Compared with IV duration; action is LONGER
ii. Greater Concentration of meds can be delivered
iii. No First Pass
iv. Practical outside hospital
c. Disadvnatages
i. Onset of response is slower than IV
4) Topical (Transdermal)
a. Advantages –
i. Low Risk of Side Effects
ii. No First pass effect
iii. Easy to obtain
b. Disadvantages
i. Local Effects Only
ii. Not Well Absorbed into deeper layers
Absorption: How it get into the blood stream to be distributed
“processs of moving the drug from site of administration to site of activity”
All drugs (except IV) must pass through a membrane before gaining access to blood
o GI lining
o Blood Vessel Membrane
Ways Drugs are Absorbed:
1) Simple Passive Diffusion: Passive movement of solute from a high concentration to low
a. Most Common
2) Filtration : movement of water and solute molecules across the cell membrane due to
hydrostatic pressure generated by cardiovascular system
a. Water Pressures (not concentrations)
3) Facilitated Diffusion: movement of molecues across cell membrane via special transport
a. “piggy backing” on other molecules
4) Active transport: movement of material from area of lower concentration to area of higher
a. Requires energy to “move up stream”
5) Pinocytosis/Endocytosis
a. Small particles suspended in extracellular fluid are brought into the cell through an
invagination of the cell membrane, resulting in a suspension of the particles within a
small vesicle inside the cell
i. Engulf particles
Bioavailability – (subcategory of Absorption) = the fraction of an administered dose of UNCHANGED drug
Amount of drug that actually reaches circulation to be effective
o First Pass can influence this
▪ Penicillin Oral = 30% Bioavailability
▪ Penicillin IM = 90%+ Bioavailability
Coating on the Drugs to improve bioavailability
Enteric-Coated = not broken down in stomach, improved absorption
Factors that Affect Drug Absorption
Aqueous Solubility – Rate of dissolution governs the rate of absorption
o Drugs in Solid Form absorb Slower than those in Liquid form
Concentration: Higher concentration of drugs will improve simple diffusion passive transport
Area of Absorption: Larger area of absorption (Lungs) results in faster absorption
o Improved surface area
Vascularity of the Absorbing Area
o Increased Blood Flow Increases drug absorption
Drug Metabolism: the breakdown of drugs; determines the duration and intensity of a drug’s
pharmacologic action
Distribution: The process by which a drug reversibly leaves the blood stream and enters the interstitium
and/or the cells or tissues
(http://howmed.net/pharmacology/distribution-of-drugs/ )
Factors Affecting Drug Distribution: RELATED TO THE DRUG
1) Lipid Solubility = The Greater the lipid solubility, the more the distribution
2) Molecular Size = Larger size, less the distribution
3) Degree of Ionization = drugs are trapped when present in the ionized form; depending upon the
pH of the medium
a. If drugs are highly polarized; the drug is unable to pass freely
4) Cellular Binding = different drugs have different affinity for different cells. All cells do not bind
the same drugs
5) Duration of Action = action prolonged by presence of BOUND form
Factors Affecting Drug Distribution: RELATED TO THE BODY
1) Vascularity – Drug will go to areas quickest with greatest blood flow
a. Brain, Heart, Kidney…. Before Fat, Cartilage, Bone
2) Transport Mechanisms
3) Blood Barriers – Different blood barriers exist (Blood Brain or Placental barrier)
4) Plasma Binding Proteins – If bound to plasma (less free drug for target site)
5) Free and Bound Forms of Drugs
6) Drug Interactions – if a number of drugs are simultaneously diven, or drugs interact with
endogenous substances, one drug can be displaced by another
7) Disease States: different diseases affect the distribution of drugs
8) Drug Reservoirs: Drugs are stored and are released slowly
a. Bone, Liver, Fat
9) Volume of Distribution – volume in the body into which a drug distributes
Free and Bound Forms of Drugs
When a drug enters the body, it exists in
1) Free Form – Metabolized and excreted because they
can cross the glomerular membrane
a. Free Forms of drugs are therapeutically
b. Ready for use
2) Bound Form – act as a reservior. They are NOT
metabolized or ecreted and do not have therapeutic
or toxic effect
a. Encapsulated
When free form is used up, the drug is released from the reserviors
Elimination: Excretory Organs
Main Excretory Organs = Kidney
Secondary Organs:
o Liver
o Lungs
o Skin
o Salivary Glands
o Lacrimal Glands
Elimination Pathways:
o Hair
o Urine
o Tears
o Perspiration
o Saliva
o Respiration
o Milk
o Feces
o Bile
Drug Clearance and Volume of Distribution:
[Drug Arterial Blood] - [Drug Venous Blood] = Amount of Drug Eliminated
Clearance = SPEED at which the drug is eliminated from Blood Plasma
Volume of Distribution = amount of drug distributed throughout the body’s fluid volume.
Plasma Half Life = the time require for the blood or plasma concentration of the drug to fall to
half of its original level
Biological Half-Life = The time it takes for the biological processes to reduce amount in body by
50% of its initial value
Half Life Can vary from person to person based on
o Weight
o Gender
o Age
o Health
Half Life is Important because:
Tells us how long the drug will be in our body
Effects of a drug typically begin to taper off as the first half-life point is reached.
o Most cases: 90-95% of drugs is eliminated in four cycles (4 Half-Lifes)
o If a drugs half life is 10 hours, it will take 40 hours for approximately 95% of the drug to
be eliminated from the plasma
▪ 10 x 4 half-lifes = 40 hours
Lecture 4: Musculoskeletal System
Analgesics, Anti-Inflammatories, Muscle Relaxants
How drugs work to reduce pain and WHY do we have pain ?
Limit damage
Promote Healing
Protective and Survival Based Response
Nociception and Pain are NOT the same thing
Nociception is the mechanisms employed by the body to warn of tissue damage
o Is transmitted up to the brain
Pain is the perception and processing of the signals
Not all pain is a result of nociception
Process of Nociception:
Synapses at several points before reaching the brain
Each of these points allow the potential to stop or alter its further propagation
o At the Tissue
o At the Spinal Cord – TENS (interfering with pain signals)
o At the Brain
Pain as an indicator of tissue healing:
Inflammatory process can cause pain but is necessary for healing
Reducing inflammation can Reduce pain, but inflammation is important!
1) Helps limit Mobility/ Protects area
2) Brings in cells to prevent infection
3) Brings in tissues to assist repair process
Neurotransmitters that are activated with Inflammation; activate Nociceptors to signal damage/healing
needed in a certain area:
Substance P
Excitatory vs Inhibitory Neurotransmitters:
Not all pain is the same!
Acute Pain and Chronic are Different
o Physiologically different
▪ Chronic not fully dependent on Nociception
▪ More dependent on cognitive changes
Lecture 5: Opioids:
“Pain Crisis, Not Opioid Crisis”
Pain viewed as “the 5th Vital Sign”
o Pts focus more on Pain
Current Pharmacological Treatment of Pain
380 Medications to treat pain
o Two Main Categories
▪ Prescription – Chronic Pain
▪ Non-Prescription – Acute Pain
o Types:
Opioids: Oldest and Strongest Pain Reliever
Three Types:
o Occurring in Nature
o Synthetically Derived
o Endogenous
Method Of Action:
o Receptors : in THE CNS
▪ Mu- Brain, Spinal Cord
▪ Delta- Brain, Spinal Cord
▪ Kappa- Brain only
o Decrease Neuronal Transmitter Release & Decreasing Nociceptive Impulse Propagation
o Elevate the Nerve Pain Threshold and Decreasing Transmission of impulse to the brain
How do the Opioid Receptors Work?
o Mu- receptors also on the POST SYNAPTIC TERMINAL
o Presynaptic Nerve Terminal:
▪ Opioid Ligand binds to Mu, Delta, Kappa receptors causing:
• Inhibition of Ca2+ Channels by activation? of G-Coupled Ca channels
• Block of release of pain neurotransmitters like Glutamate and
Substance-P via G-protein coupled receptors
o Postsynaptic Nerve Terminal HYPERPOLARIZATION by Opening POTASSIUM K+ Channels
in Brain and Spinal Cord
▪ Opioid Ligands bind to Mu receptor in post-synaptic, opening K+ Channels
Does not allow post-synaptic neuron to repolarize; stays active, so can’t fire a secondary impulse
A. Occurring in Nature:
• Poppy Seed; activates G protein, decreases pain
o Morphine, Heroin, Codeine
B. Synthetic and Semi-Synthetic Opioid Meds:
1) Semi-Synthetic
a. Hydromorphine
b. Oxycodone (Oxycontin, Percocet)
c. Hydrocodone (Vicodin)
d. Buprenorphine
e. Pentazocine
2) Fully Synthetic
Propoxyphene (Darvocet)
C. Endogenous – Naturally Occurring in our Adrenal Medulla and Gut
a. Enkephalins – morphine like NT found in brain/adrenal glands
b. Dynorphins – class of opioid peptide that arise from precursor protein prodynorphin
c. Endorphins – morphine like NT found in the brain and pituitary gland
Mu Receptors are the most active
Opioids Affect the CNS, not the tissues as well:
Duration of Effect:
Long Acting Opioids vs. Short Acting Opioids
Strength of Opioids:
Milder Opioids vs Stronger Opioids
Adverse Effects:
Breaking Opioid Addiction:
Use other medications to BLOCK the side-effects of drugs
o Methadone – minimize effects of withdrawal
o Buprenorphine – minimize the effects of opioid withdrawal and block effects of
o Naltrexone – minimize withdrawal and block effects of euphoria
o Naloxone – reverse the overdose because they have stronger affinity for the opioid
receptors, knocking off the receptors for a short time.
Lecture 6: Non-Steroidal Anti-Inflammatory
What are NSAIDS?
Reduce Pain
Reduce Fever
Decrease Inflammation
Types of NSAIDS
24 on the market
o Newer substances classified on mechanism of action
Therapeutic Classification:
o Aspirin
o Paracetamol
o Indomethacin
o Ibuprofen
o Naproxen
o Aspirin
1) Chemical Based Classifications
a. Salicylates – Aspirins
b. Propionic Acid
i. Ibuprofen
ii. Naprozen
c. Phenyl Acetic Acids
d. Oxicams
e. Pyrazolone Derivative
f. Fenamates
g. Para-Aminophenol Derivative
h. Preferential COX-2 Inhibitors
i. Selective COX-2 Inhibitors
2) Mechanism of Action Based Classification
a. Non-Selective Cox Inhibitors
i. Aspirin
ii. Indomethacin
iii. Ibuprofen
iv. Naproxen
b. Semi-Selective Cox Inhibitors
i. Indomethacin
ii. Piroxicam
iii. Sulindac
c. Cox-2 Selective Inhibitors
i. Celecoxip
ii. Etoricoxib
iii. Meloxicam
How do NSAIDS work?
By Deterring Prostaglandin Production
o These chemicals are produced by cells to promote pain, fever and inflammation
▪ Enzymes that produce prostaglandins are called Cyclooxygenases (COX)
• TWO TYPES of COX Enzymes
o COX-1
o COX-2
• Both Enzymes Produce Prostaglandins
• NSAIDS BLOCK COX enzymes and reduce production of prostaglandins
COX 1 Produces Prostaglandin 1 an 2 => Stomach Mucosa, Platelets
COX 2 Produces prostaglandin 3 and 4 => Pain and Inflammations
COX 2 ONLY drugs are the best for not causing other issues (stomach issues)
Adverse Effects:
NSAIDS administered Orally – subject to first pass
Acetaminophen – Tylenol
Not an NSAID
Miscellaneous analgesic for mild to moderate pain and fever
May inhibit COX enzymes, but without the anti-inflammatory effect
Does not cause stomach issues
Acute Pain: Nociceptive Pain = NSAIDS/Acetominophen
Chronic Pain: Neuropathic & Sensory Hypersensitivity = Opioids
Clinical Pearls:
1) Aspirin – ONLY NSAID that inhibits Clotting of Blood for Prolonged period of time – 4 to 7 days
a. Used for tx of Heart Attacks and Stroke
2) Ketorolac – Toradol – very potent NSAID and is used for treating severe pain that normally
would be managed with narcotics
a. Can cause ulcers.
b. Should not be used for more than 5 days
3) Celecoxib (Celebrex); blocks COX-2 but has little effect on COX-1.
a. Subclassified as COX 2 Inhibitor
b. Causes few ulcers and less bleeding
4) If goal is to reduce pain, but allow inflammation, use Acetaminophen!
A word about Marijuana – How does it work
CBN – Cannabinols
CBDs – Cannabidiol
THC – Tetrahydrocannabinol
THC = Binds to CB Receptors CB1 and CB2 in Brain and Body
o Binding of THC prevents activity of these CB receptors
o Prevents activation of the neuron
CBD does not bind to CB receptors. Instead, it enhances the
effects of THC and CBN
CB Receptors are a form of G-Protein
o When active, they facilitate activity in the neuron
Delivery of Medical Marijuana
Smoking –
o Advantage: quick relief from pain, nausea, easy dosage, cheap
o Drawbacks: possible lung irritation
o Advantages: Precisely manage dosage, long relief
o Drawbacks: takes longer to kick in; 30 min – several hours
o Advantages: get effects of drug without a high, good at localized pain relief
o Drawbacks: not effective for some conditions
▪ Epilepsy
▪ Glaucoma
o Advantages: protects lungs
o Drawbacks: same as smoking
Tinctures: Mouth Spray
o Small dosage but prevents lung irritation
o Longer to take effect
o Same effect as edibles but without stomach issues, quicker absorption
o No First Pass
Adverse Effects of Marijuana
Clinical Considerations:
Marijuana use is growing as an alternative to opioids for pain management
In Clinic, CBD oils are used by patients
Use by clinicians dependent upon state laws
Because Marijuana impacts hippocampus, cerebellum and amygdala, there is a potential it can
help prevent formation of chronic pain
Lecture 7 – Corticosteroids
Are steroid hormones made by body or synthesized.
Synthetic – resemble cortisol
How do they work?
Decrease Inflammation
o By Decreasing the production of chemicals that cause inflammation
Reduce the activity of the immune system
o Reduce T Cell activity
How are they classified? TWO CLASSES:
1) Glucocorticoids
a. Cortisol
b. Dexamethasone
c. Cortisone
e. Methylprednisolone
f. Triamcinolone
2) Mineralocorticoids
a. Aldosterone
b. Fludrocortisone
A) How do they work?: They act by binding to glucocorticoid receptors that cause coupled
o Can Activate ANTI-INFLAMMATORY pathway
o Can Activate REPRESSION of INLAMMATORY pathway resulting in less inflammation
B) Effects of Glucocorticoids
1) Immune Effects:
a. Up-Regulate the expression of anti-inflammatory proteins
b. Down-regulate the expression of pro-inflammatory proteins
c. Glucocorticoids are also shown to play a role in the development and homeostasis
of T Lymphocytes
d. SUPPRESSIVE on immune system
i. Inhibit phospholipase
ii. Inhibit COX
1. Prevent Inflammation
2) Metabolic
a. Cortisol stimulates several processes that collectively serve to increase and maintain
normal concentrations of glucose in blood.
a. These hormones are involved in retention of SODIUM
i. When retained; increases fluid retention
1. Good when BP needs to be increased
b. They are synthesized in the zona glomerulosa of the adrenal cortex
c. Aldosterone acts on the Kidneys to provide active reabsorption of sodium and an
associated passive reabsorption of water and the active secretion of potassium
Global Effects of Corticosteroids:
1) Structural Cells
a. Decreases Epithelial Cells
b. Decreases leaking in endothelial cells
c. Decreases mucous secretions
2) Inflammatory Cells
a. Decreases the number of eosinophils
b. Decrease cytokines; T-Lymphocytes
c. Decreases Mast Cells
d. Decrease Macrophages
e. Decrease Dendritic
Results in decreased healing, decreased protection
How are CS Administered?
By Injection
Side Effects of Corticosteroids:
Central Obesity
o Cushings – misfiring in pituitary gland
▪ Moon face
▪ Belly fat
▪ Emotional differences
▪ Skin ulcers
▪ Osteoporosis
Growth Retardation in childhood
Susceptibility to infections
Increased Risk of Thombosis
Coronary Heart Disease
Lengthened Wound Healing
Gastric Ulcer
Atrophy of Skin
Excessive Hair Growth
Glaucoma and Cataracts
Anabolic Steroids – completely different than corticosteroids!
Testosterone and drugs to stimulate testosterone
o Increase protein in cells, especially muscle cells, and affect sexual characteristics such as
hair growth
Similar to sex hormones more than corticosteroids
o Orally
o Injected
o Inhaled
o Topical
o Nasal
o IV
Usually derivatives of testosterone
Side Effects
Difference between NSAIDs and Corticosteroids: Both Designed to decrease inflammation
CS don’t affect pain, just inflammation
Lecture 8: Muscle Relaxants:
Are a group of meds commonly used to treat two different conditions:
1) Spasticity – from upper motor neuron syndromes
2) Muscular Spasms or Cramps – for peripheral musculoskeletal conditions
Classes of Muscle Relaxants:
a. 2 Million Americans prescribed to muscle relaxants
i. 300,000 are 60 years +
1) Acute – muscle spasms
2) Chronic Antispasmodics – treat muscle spasms
3) Chronic Antispasticity – treat neurological muscle spasticity
1. Antispasmodics
a. Used to relieve muscle spasms in musculoskeletal rehabilitation
b. Exact cause of muscle spasms may vary, but most commonly due to:
i. Overuse
ii. Muscle fatigue
iii. Dehydration
iv. Electrolyte Abnormalities
c. Special form of muscle spasms = Dystonia
i. Abnormal transmission of chemicals in the brain
1. Torticollis
2. Acute Antispasmotics
a. Primarily act as Brain and Spinal Cord
b. Might block neuronal impulses in the spinal cord
i. Reduces alpha motor neuron excitability
c. Yellow Mustard reduces spasms!
Should only use them for 2-3 weeks at a time.
Side Effects:
Reddish-Purple or orange urine
Lowered BP upon standing
3. Chronic Antispastics –
a. Two types of motor neurons regulate skeletal muscle excitability
i. UMNs – cerebral
ii. LMNs – periphery
b. Lesions in LMNs
i. Decreased activity
c. Lesions in UMNs
i. Increased activity
ii. Spasiticity may occur b/c of excessive stimulation or lack of inhibition of alpha
motor neurons
1. Causes:
a. MS, CP, SCI, TBI, Post Stroke
Types of Antispastic Drugs:
Reduce muscle tone by acting on CNS or Skeletal Muscle
Act on CNS:
Benzodiazepines (Valium)
Act on Periphery
Botulinum toxin
Side Effects:
Muscle Weakness
4. Chronic Antispasmodics – Neurological
a. Increased activity of the muscle caused by increased neural activity at the muscles
b. Antispasmodic drugs thought to cause SEDATIVE effect at the muscle preventing nerves
from sending pain signals to the brain
Work by facilitating GABA activity at the spinal cord
▪ Act Pre and Post Synaptically to inhibit spinal reflexes
▪ Presynaptic Activation of GABA = Hyperpolarization and decrease of Ca2+ influx
which reduces glutamate release, leading to a decrease in alpha motor neuron
▪ Postsynaptic Activation of GABA = Increases K+ conductance in the IA afferent
neuron terminals, hyperpolarizing the membrane and enhancing presynaptic
Work Peripherally:
▪ Neuromuscular Blocking Agents
• Non-Depolarizing Blocking Agents
o Blocks Ach Receptors or Ion channels
▪ Blocks Calcium release channels in the sarcoplasmic
▪ RESULT: No muscle Contraction
• Depolarizing Blocking Agent
o Activating Ach receptors and causing persistent depolarization
at the motor end plate
▪ Hyperpolarization = prevents repolarization
Clinical Implications:
Schedule Therapy when sedation is less
Discuss weakness with the physician
Focus therapy on reducing the structural or biomechanical problem that leads to the occurance
of the muscle spasm
Monitor muscle weakness and fatigue
Be cognizant of potential drowsiness and dizziness
Lecture 9: Anti-Rheumatics – Disease Modifying Anti-Rheumatic Drugs = DMARDs
Rheumatic Diseases present a BROAD class of disorders, but commonly surround inflammation
Inflammation that affects
o Joints
o Tendons
o Ligaments
o Muscles
o Bones
o Organs
Types of Rheumatic Diseases
o Osteoarthritis
o Rheumatoid Arthritis
o Lupus
o Psoriatic Arthritis
o Sjogren’s Syndrome
o Gout
o Scleroderma
o Infectious Arthritis
o Polymyalgia Rheumatica
o Crohn’s Disease
DMARDs act to slow the progress of the disease
o Not just modify inflammation like NSAIDs
DMARDs: Classification
1) Synthetic – sDMARD – 2 subcategories
1) Conventional Synthetic – csDMARD
a. Methotrexate
b. Sulfasalazine
c. Leflunomide
d. Hydroxycholoroquine
e. Gold Salts
2) Targeted Synthetic – tsDMARDs
a. Drugs that were developed to target a particular molecular structure
2) Biosimilar – bsDMARD
a. bsDMARD drugs that have the same primary, secondary and tertiary structure as the
Common DMARD meds:
Mild RA
Moderate to Severe RA
Biologics – Injectable Drugs
They work by blocking specific inflammatory pathways made by immune cells
Prescribes when DMARDs are not enough to treat RA symptoms
Arent recommend for people with compromised immune systems or an infection
Most Common:
o Abatacept – Orencia
o Rituximab – Rituxan
o Tocilixiumab – Actemra
o Anakinra – Kineret
o Adalimumab – Humira
o Etranercept – Enbrel
o Infliximab – Remicade
o Certolizumab pegol – Cimzia
o Golimumab – Simponi
How do DMARDs work?
Main goal: Block Inflammation
o Prevent joint and tissue damage
o Treat the symptoms by slowly modifiying the disease
o Suppress the body’s immune and inflammatory responses
o Inhibit T Cells and B Cells of your immune system by suppressing white blood cell overactivity result in less inflammation
Adverse Response
o Upset stomach
o Nausea
o Diarrhea
o Infection
o Hair Loss
o Fatigue
o Liver Damage
Clinical Implications of DMARDS
Very powerful drugs, that take several weeks (6 – 8 weeks) to reach maximum efficacy
o To get the benefits as quickly as possible, DMARDs will usually be prescribed within 1 – 3
months of diagnosing you with RA
▪ Window where RA is more treatable before permanent damage to the joints
Increased Risk of Heart disease – 50%
Week 2: Lecture 1 Autonomic Nervous System
Three Divisions:
1) Sympathetic Nervous System – Survival mechanism
2) Parasympathetic Nervous System –
a. (Vagal/Parasympathetic) system is typically more active
3) Enteric System – uses parasympathetic and sympathetic nervous system to regulate the gut
Function of the ANS: designed to regulate our body’s homeostasis (done at a subconscious level)
1) Sympathetic Nervous System –
a. Adrenergic – release Norepinephrine
b. Preganglion is cholinergic (Acetylcholine)
c. Postganglionic is adrenergic (Norepinephrine)
2) Parasympathetic Nervous System
a. Cholinergic Fibers – release acetylcholine
i. Both Pre and Postganglionic fibers are cholinergic
ANS Receptors:
Adrenergic System:
Stimulated by Norepineprhine
▪ Alpha
▪ Beta
o Stimulated by Dopamine
▪ D
Cholinergic System
▪ Stimulated by Acetylcholine
• N Nicotinic
• M Muscarinic
Receptor Sensitivity:
Up Regulation - When levels of a particular hormone are low, Cells become MORE sensitive to it
o Absence of a hormone triggers increase in number of hormone receptors
Down Regulation
o When Levels of a particular hormone are high, cells become less sensitive to it
o Presence of hormone triggers decrease in number of hormone receptors
Pharmacological Modulation of ANS:
Drugs can mimic or block the actions of chemical transmitters and can selectively modify many
ANS functions
Modifying any step in the ANS process may increase or decrease the amount of
neurotransmitter reacting with appropriate receptors
Drugs affecting the parasympathetic nervous system: CHOLINERGIC
Involve two receptors: 1) Nicotinic and 2) Muscarinic
Agonists that mimic the effects of acetylcholine are called: CHOLINOMIMETICS
Antagonists that inhibit acetylcholine at muscarinic or nicotinic receptors are defined as
Drug affecting the sympathetic Nervous system:
Involve 3 Receptors: alpha, Beta, Delta
Agonists that mimic alpha, beta, delta receptors are called: SMYPATHOMIMETICS
Antagonists that inhibit alpha, beta, delta are defined as SYMPATHOLYTICS
Week 2: Lecture 2: Parasympathetic Nervous System: Cholinomimetics and Anticholinergics
Cholinomimetics: Agonists that Mimic the effects of Acetylcholine of PNS
Function to
o Decrease HR
o Decrease Heart Force
o Bronchial Muscle contraction
o Pupil Constriction
o Increased digestion
o Relaxed Sphincter
o Increase Urine Secretion
o Oral
o Glaucoma
o Hypotonic Bladder
o Myasthenia Gravis
o Dementia
o Hypertension
o Acetylcholine
o Bethanechol
o Carbachol
o Cevimeline
o Pilocaprine
Adverse Effects:
o Bradycardia
o Bronchospasms
o Intestinal Cramps
o Diarrhea
o Hypersalivatoin
o Blurred Vision
Anticholinergics: Antagonists that INHIBIT acetylcholine at muscarinic or nicotinic receptors of PNS
o Increased HR
o Increased Heart Fore
o Bronchial Muscle Relaxation
o Pupil Dilation
o Decreased food motility
o Contracted Sphincter
o Decreased urine secretion
o Orally
o Parkinson’s
o Bronchospasms
o Motion Sickness
o Incontinence
o Surgery Relaxant
o Antimuscarinic Anticholinergic
▪ Atropine
▪ Belladona alkaloid
▪ Clindinium
▪ Cyclopentolate
▪ Dicyclomine
▪ Flavozate
▪ Oxybutynin
o Cholinerase Inhibitors
▪ Ambenomium
▪ Demecarium
▪ Donepezil
▪ Echothiphate
▪ Edrophonium
▪ Galantamine
▪ Exelon
▪ Cognex
Adverse Effects
o Dilated pupuls
o Decreased sailvation
o Decreased gut mobility
o Increased heart rate
o Dysrhythmias
o Restlessness
o Irritability
o Hallucinations
Week 2: Lecture 3: The Sympathetic Nervous System - Sympathomimetics and Sympatholytics
Sympathomimetics – agonists that mimic alpha, beta, delta receptors are defined as sympathomimetics
o Increase heart rate
o Increased heart force
o Bronchial Muscle relaxation
o Pupil dilation
o Decreased food motility
o Contracted Sphincter
o Decreased urine Secretion
o Orally
o Inhaler
Clinical Uses
o Anaphylatic Shock
o Narcolepsy
o Attention deficit disorder
o Weight reduction
o Allergies
o Glaucoma
o Acute Heart Failure
o Shock
o Orthostatic hypotension
o Asthma and Bronchoconstriction
o Urinary Incontinence
1) Alpha Receptor Agonist
a. Methoxamine
b. Phenylephrine
c. Oxymetazoline
d. Tetrahydrozoline
e. Xylometazoline
Alpha – metyldopa
2) Beta Receptor Agonist
a. Amphetamine
b. Isoproterenol
c. Dopamine
d. Dobutamine
e. Epinephrine
f. Norepinephrine
Adverse Effects:
o Digestive Tract – Nausea, Vomit, Appetite change, heartburn, diarrhea, stomach pain,
dry mouth, indigestion, constipation, mouth fungal infection, mouth or throat irritation,
GI distress, Belching, gas
o Nervous System – vertigo, dizziness, tension, tremor, drowsy, weak, fatigue, nervous,
sleeplessnesss, aggression, unstable emotions, nightmares, shakiness,
o Circulatory System - change in HR, BP, Chest pain, discomfort, pounding in the chest,
irregular pulse
o Skin - flushing, pallor, sweating, haves, rash, pain, eczema, skin inflation
o Respiratory System – breathing problems, bronchospasm, infections, congestion,
sneezing, HA, Hoarsenss, sneezing
o Other – muscle cramps, stiffness, sorenss, bed tast, tooth pain
Sympatholytics: Antagonists that inhibit alpha, beta, delta receptors
o Decreased HR
o Decreased Heart Force
o Bronchial Muscle Contraction
o Pupil constriction
o Increased digestion
o Relaxed sphincter
o Increased urine secretion
o Orally
Clinical Use
o Raynauds Syndrome
o Surgery
o Hypertension
o Urinary hesitancy
o Urinary retention
1) Alpha Receptor Antagonist
a. Cardura
b. Phenoxybenzamine
c. Phentolamine
d. Prazosin
e. Flomax
2) Beta Receptor Antagonists
a. Acebutolol
b. Atenolol
c. Carteolol
d. Propanolol
Adverse Effects:
o CNS: Dizzy, Paresthesias, Insomnia, Depression, fatigue, vertigo
o CV: Arrhythmias, Hypotension, Heart Failure, Pulmonary Edema, CVA
o Respiratory: Bronchospasms, cough, rhinitis, bronchial obstruction
o GI: Nausea, Vomiting, Diarrhea, Anorexia, Flatulence
o GU: Decreased Libido, impotence, dysuria, Peyronie Disease
o OtherS: decreased exercise tolerance, hypoglycemia, rash
o Abrupt Withdrawal:
▪ MI, Stoke, Arrhymias, increased sensitivity to catecholamines when receptor
sites have been blocked
Clinical Considerations:
Clinicians should always check BP, HR, Respiration prior to tx
Exercises should pregress at a slower rate,
Beware of dizziness, dyspnea, orthostatic hypotension
Week 2: Lecture 4: The Cardiovascular System – Hypertension
Heart Failure
Blood Disorders
Hypertension is the most common cardiovascular disease
In people over 60 years old, it is most commonly prescribed medication
Blood pressure is regulated by the ANS; sympathetic branch
Blood Pressure Regulation: Two Ways
1) Through Nerves – Quick Response
2) Through Hormones – Slower Response
These Mechanisms Target:
1) Reduction of Peripheral Vascular Resistance
2) Reduction in Cardiac Output
1. BP Regulation by Nerves:
• Short Term Responses:
o Baroreflexes by ANS + Humoral Renin-Angiotensin-Aldosterone System =
▪ Coordinate Control and Maintenance of BP
o Baroreceptor Activation Inhibits Discharge of Tonically Active Sympathetic neurons
in the Vasomotor center of the medulla
o Conversely, reduction in stretch results in reduction of baroreceptor activity
o Increase in outflow acts through nerve endings to constrict the arterioles, which
increase peripheral vascular resistance. The sympathetic outflow also increased
Cardiac Output
o The ANS Receptors (Para and Symp) regulated cardiac and BP response for short
term regulation
2. BP Regulation by Hormones
• Long Term Control
a. Kidney is primarily is primarily responsible for long term BP control
i. Through hormones
b. Process includes:
i. Renin
ii. Angiotensin
iii. Aldosterone
iv. Vasopressin
c. Regulation of BP In HTN patients differs from healthy patients in that the baroreceptors
and the renal blood volume-pressure control systems appear to be set at a higher level
of BP
d. All antihypertensive drugs act by interfering with these normal mechanisms
How to Reduce Blood Pressure: 2 Factors:
1) Reducing Peripheral Vascular Resistance
2) Decreasing Cardiac Output
1. Reducing Peripheral Vascular Resistance:
a. Inhibition of Sympathetic Tone – via Sympatholytics
b. Inhibition of vascular smooth muscle contraction – Via Vasodilators
c. Inihibition of Angiotensin II formation: (Renin Inhibitors and Ace Inhibitors) +
Angiotensin Receptor Antagonists
d. Reduction of Blood Volume – Diuretics
2. Reducing Cardiac Output:
a. Inhibition of Sympathetic Input – via sympatholytics
b. Increase Parasympathetic Input – via Cholinomimetics
c. Decrease Heart Rate and Stroke Volume
d. Decrease Cardiac Output
Antihypertensives: Drug Classes
Angiotensin Inhibitors
1. Diuretics
A) Thiazides and Congeners – Act Directly on Kidneys to promote diuresis by inhibiting Na/Cl
cotransporter located in the distal convoluted tubule of a nephron in the kidney
a. Lozol
b. Microzide
c. Thalitone
d. Diuril
e. Enduron
B) Loop Diuretics – inhibit Na-K-Cl transporter in ascending loop of Henle
a. Bumex
b. Edecrin
c. Lazix
d. Demadex
C) Potassium Sparing – interfere with the Na-K exchange in distal convoluted tubule of the
kidneys or as an antagonist at the aldosterone receptor
a. Inspra
b. Midamore
c. Aldactone
2. Sympatholytics
a. Centrally acting antiadrenergic = inhibit CNS alpha-adrenergic receptors and decreases
sympathetic stimulation of blood vessels and Heart
b. Alpha Adrenergic blockers: prevent stimulation of alpha-adrenergic receptors at the
nerve endings of the sympathetic nervous system
i. Polythiazide
ii. Deserpidine
c. Beta Adrenergic Blockers = bind to beta-adenoreceptors and prevent the binding of
norepinephrine and epinephrine at these receptors preventing sympathetic stimulation
of the heart
i. Acebutolol
ii. Atenolol
iii. Metoprolol
iv. Propanolol
3. Vasodilators: Nitric Oxide releasers, Potassium Channel Openers, Calcium Channel Blockers, D1
Dopamine Receptor antagonists
4. Angiotensin Inhibitors – ACE
Administration of Anti-Hypertensive Meds:
Adverse Reactions:
Cardiac Arrythmias
Orthostatic hypotension
Depressed HR and Contractility
Clinical Considerations
Exercise is one of the key nonpharmacological mechanisms for controlling HTN
Other non-pharm therapies include low-sodium, low-fat diets, weight reduction, cessation of
smoking, and moderate alcohol intake
Avoid Whirlpools and quick changes in position
Week 2 : Lecture 5 Angina
Angina – Chest by caused by heart disease
Angina “to strangle”
Angina Pectoralis full name
Caused by: MOI:
Heart muscle needs constant supply of O2
Coronary Arteries are responsible for blood to the heart
Heart muscle has increased demand = need more O2
Symptoms of angina occur when blood supply to heart muscle is reduces
Coronary Arteries are narrowed or blocked by plaque or clots
Most common cause of angina is CAD
Classes of Pharmacological Treatment:
o Orally
o Sublingual or Buccal
o Injection
o IV
Anti-Angina Classes of Drugs
o Nitrates
o Calcium Antagonists
Beta Blockers
Types of Drugs:
1) Nitrates:
a. Relax Smooth Muscles within the blood vessels = vasodilation
b. Vein Dilation
c. Decreased venous return
d. Acts through release of nitric oxide
i. Isosorbide Dinitrate
ii. Nitroglycerine
2) Calcium antagonists
a. Inhibit calcium transfer into cells thereby inhibiting contraction of vascular smooth
b. Relaxation of cardiac vascular smooth muscle
c. Reduced Contractility of heart
d. Reduce BP
e. Reduce Vasospasm
i. Dilitiazem
ii. Nifedipine
iii. Verapamil
3) Beta Blockers
a. Slow the heart, Reducing how hard it has to work
b. Used prophylactically
c. Reduced HR, Reduced Contractility
d. Decreased BP
i. Atenolol
ii. Propranolol
4) Ranolazine
a. The exact way it exerts its antianginal effect is not known but may be through inhibition
of ion channels during cardiac repolarization
Goal of Drug use for Angina:
1) Increase supply or decrease demand so that O2 Delivery is sufficient
2) For Vasospastic or Variant Angina
a. Main Goal = Relax Coronary Artery Spasm
i. Nitrates and Calcium blockers
3) For Exertional Angina
a. Main Goal = Reduce Cardiac Work
i. Use nitrates and beta blockers
Adverse Effects
Sleep Disturbances
Swelling in feet, ankles, legs
Low Heart Rate
Low BP
Impotence Sexually
Clinical Considerations:
Orthostatic Hypotension
Possible Bronchoconstriciton
Cant use HR response as guide to exercise intensity
Angina is a medical emergency: if patients experience what you think to be angina; Call 911
If patients have a history of angina, exercise is to not contraindicated but care must be taken to
monitor symptoms and responses to treatment
Angina and chest pain can often mimic musculoskeletal symptoms
Week 2: Lecture 6 – Cardiovascular System Heart Failure
What is Heart Failure?
o MI = permanent damage to heart muscle
o CHF: flow of blood from the heart (Cardiac Output) Decreases, or fluid backs-up behind
the failing ventricle or both
o Heart unable to pump sufficient blood to tissues; it backs up into the lungs and or
▪ Systolic Failure = decreased contractility
• i.e; against hypertensive resistance
▪ Diastolic Failure = stiffness and decreased diastolic volume
• i.e; myopathy
Symptoms of Heart Failure:
o Tachycardic
o Weight gain
o Peripheral edema
o Lung Congestion
o Fatigue
Sympathetic System and Renin-Angiotensin Response to Heart Failure
Pharmacologic Treatment for Heart Failure:
Acute Heart Failure: Diuretics Plus Positive Inotrope
Chronic Heart Failure: Diuretics plus ACE inhibitors (+ positive inotrope if systolic failure)
Classes of Pharmacological Treatment:
Administered: Orally, but can be IV, Injection, Sublingual
o Diuretics – decrease Preload
o Aldosterone Inhibiotrs – Decrease Afterload
o ACE Inhibitors – decrease pre and afterload
o Angiotensin II receptor blockers (ARBs)
o Beta Blockers – decreased heart rate, BP, Cardiac Load
o Calcium Channel Blockers
o Cholesterol Lowering Drugs
Types of Drugs
1) Diuretics:
a. Aldosterone Inhibitors
i. Blocks the effects of aldosterone
ii. Aldosterone increases Na+ reabsorption by the kidneys, salivary glands,
sweat glands and clon
iii. Act as diuretics to decrease fluid build up
1. Eplerenone
2. Spironolactone
2) Ace Inhibitors
a. Cause Vasodilation to lower BP and decrease Peripheral Vascular resistance
b. Effective for control of BP, CHF, HTN, Stroke Prevention, Diabetes related kidney
i. Captopril
ii. Lisinopril
3) Positive Inotropes
a. Affect Contraction of the Heart Muscle
b. Divided in to
i. positive = stimulate and increase the force of contraction of heart
ii. negative = weaken force of muscular contractions, decrease how hard heart
has to work
c. Given for conditions associated with low Cardiac Output, like CHF
d. Inhibit Na/K+ Pump and increase Ca+ in SR and Myocardial cells
e. Improves myocardial force of contraction
f. Improve Blood Flow to kidney, improve kidney function
i. Decrease renin, vasoconstrctions
ii. Decrease salt and water retention
Digotoxin, Dobutamine, Milrinone
4) Vasodilators – Nitrates
a. Used in case of Acute Heart Failure
b. Produce Vasodilation to decrease afterload
c. Allows the heart to cope with workload
Nitroglycerine, Imbur, Dilatrate
5) Angiotensin II Receptor Blockers
a. Prevent Angiotensin from binding to receptors on blood vessels
i. Leads to Vasodilation and reduction of BP
b. Often used with ACE inhibitors as they have similar effects
c. Decreases Sodium Concentration
Irbesaratan, Candesartan, Losartan
6) Beta Blockers
a. Blocks NT for norepinephrine and epinephrine from binding to B1-adrenergic
receptors are located commonly in the heart and kidney
b. Decreases sympathetic activity
c. Decrease HR
d. Lowers peripheral resistance
i. Propranolol
ii. Penbutolol
iii. Acebitolol
7) Calcium Channel Blockers
a. Disruptus the movement of calcium thru calcium channels into Heart Muscle Cells
b. Decreases Heart Contraction
c. Calcium channel blockers slow electrical conduction thru the heart and thereby
correct cardiac arrythmias
d. Decrease Peripheral Vascular Resistance
Verapamil, Lovastatin, Dilitiazem, Amlodipine
8) Cholesterol Lowering Drugs
a. Decrease Peripheral vascular resistance
b. Lowers plaque build up in vessels
Crestor, Rosuvastatin, Lipitor, Niacin
Adverse Effects:
Extreme thirst
Dry Mouth
Peeing less
Dark-Colored Urine
Heavy Bleeding during your period
Red or Brown Pee
Tar-like stools
Bleeding from your gums or nose that doesn’t stop right away
Red things you cough up
Severe HA or Stomachache
Cuts that wont stop bleeding
A bump on the head or serious fall
Clinical Considerations
Monitor Heart Rate and BP
Medication will affect exercise tolerance
May cause dizziness and lightheadedness
Week 2: Lecture 7: Cardiovascular System – Cardiac Arrhythmias
General Info:
2% of population has cardiac arrythmias
o Athletes – runners
80% of patient with MI have arrhythmias
A cardiac arrhythmia is any abnormal heart rate or rhythm
Cause minor symptoms to death
Different rhythm disturbances need different treatments
Arrhythmias can reduce Cardiac Output
Classifying Cardiac Arrhythmias:
1) By Rate:
a. Bradycardia – below 60 bpm
b. Tachycardia – above 100 bpm
2) By Mechanism:
a. Automaticity b. Triggered
c. Re-Entry
A) Automaticity – Cardiac Muscle cell firing an impulse with SA node initiation
a. Problems occur when other parts of the heart generate impulse
i. May be due to increased sympathetic activity
B) Triggered Activity – occur when problems at the level of the ion channel (of individual heart
cells) result in abnormal propagation of electrical activity and lead to sustained abnormal
C) Re-entry – occurs when a propagating impulse fails to die out after normal activation of the
heart and persists to re-excite the heart after the refractory period has ended
a. Action potential does not allow for repolarization
i. Examples: A Fib, A Flutter, AV nodule rentry, AV reentry involving a bypass tract,
and ventricular fibrillation
Symptoms Associated with Cardiac Arrythmias:
Can cause a wide variety of symptoms
o Palpitations – racing, skipping, fluttering sensation in your chest
o Dizziness or Lightheadedness
o Fainting
o Low Blood Pressure
Video :
o Chest Pain
o Shortness of Breath
o Fatigue
o Heart Failure – heart cant pump enough oxygenated blood through the body
o Cardiac Arrest
o Difficulty feeding (in infants)
Types of Arrythmias:
o Palpitations – electrical signal does not originate from the sinus node
o Supraventricular Tachycardia – rapid heartbeat involving atria
o A-Fib: Ineffective contractions of atria caused by rapid irregular signals from multiple
sites in the upper half of the heart
o Atrial Flutter: extremely rapid beating of the atria (240 bpm)
o Paroxysmal Supraventricular Tachycardia: rapid heartbeat caused by extra electrical
pathway in the heart
o Ventricular Tachycardia: rapid inefficient contractions of the ventricle
o Bradycardia: slow heartbeat due to a failing sinus node or blockage in the electrical
o Congenital abnormality of the heart’s electrical system
o Inherited heart disease
o Acquired condition – scar tissue may set the stage for V-Tach
o Changes over time
Classification of Pharamacological Treatment of Anti-Arrhythmic Medication
Vaughn Williams Classification
Classes of Drugs:
o Class I: Sodium Channel Blockers
▪ Block the fast Na+ channel, which depresses depolarization, which prolongs the
action potential duration by slowing conduction at Phase 0
• Atrial Fib and Flutter
o Class II: Beta Adrenoreceptor Blockers
▪ By slowing down the conduction of electrical activity within the heart, they slow
down the heart beat when there is too much sympathetic tone
o Class III: Potassium Channel Blockers
▪ Used to prolong depolarization, since these agents do not affect sodium
channels, conduction velocity is not decreased at Phase 0
▪ Used for A Fib and Tachycardia
o Class IV: Calcium Channel Blockers
▪ By slowing down the conduction of electrical activity within the heart, they slow
down the heart beat
▪ For AV node arrhythmias
o Other
Types of Drugs:
1. Class I: Sodium Channel Blockers
a. Quinidine
b. Procainamide
c. Phenytoin
d. Flecainide
e. Disopyramide
2. Class II: Beta Adrenoreceptor Blockers
a. Propranolol
b. Metoprolol
3. Class III: Potassium channel blockers
a. Amiodarone
b. Dofetilde
c. Sotalol
4. Class IV: Calcium Channel Blockers
a. Diltiazem
b. Verapamil
Adverse Effects:
Seizures and Confusion
Mental Changes
Unwanted heart changes
Nausea and Dry mouth
Diarrhea or Constipation
Bone Marrow Damage
Vision and Hearing Changes
Breathing Problems, such as wheezing
Fatigue and Lightheadedness
Livery, Kidney and Lung Problems
Nerve and Muscle Damage
Thyroid Change
Clinical Consideration
1) Since the meds control heart activity, exercise should be closely monitored
2) Fatigue and lightheadedness are common side effects so monitor duration and intensity of
3) Orthostatic Hypotension should also be monitored when changing positions
Week 2: Lecture 8 – Cardiovascular System – Blood Disorders
Blood Disorders – when a person has a blood disorder we look at 2 things:
1) Nutrients and Growth Factors affecting formation of blood cells and platelets
1. Hematopoiesis
2) Drugs used in the control of blood clotting (hemostasis)
1. Health of the Blood = Hematopoiesis = the production of circulating erythrocytes, platelets,
leukocytes from stem cells
a. 200 billion new blood cells per day are produced
i. Most Produced in growth cells
b. Requires a constant supply of essential nutrients and hematopoietic
i. Iron
ii. Vitamin B12
iii. Folic Acid
iv. Hematopoietic Growth Factors
1. Proteins that regulate the proliferation and differentiation of
hematopoietic cells
Without these, we have less energy, fatigue more easily
c. Blood Cell Formation: classified based on the blood component stimulated
i. Erythrocyte factors are divided into nutrients:
1. Iron
2. Vitamins
3. Erythropoietin – growth factor that stimulates erythrocyte formation
Anemia = Deficiency of Oxygen Carrying Erythrocytes
Symptoms –
o Pallor
o Fatigue
o Dizziness
o Exertional Dyspnea
o Tachycardia
Causes are due to insufficient supply of:
o Iron
o Vitamin B 12
o Folic Acid
Treatment: to treat it, we have to determine what is causing it:
1) Blood Loss – what is the source of the blood loss?
a. Menstrual Cycle
b. Internal Bleeding
2) Decreased Red Blood Cell Production… need to replace:
a. Iron
b. B12
c. Folic Acid
Adverse Effects of too much of these:
Stomach Ache
2. Hemostasis – spontaneous arrest of bleeding from a damaged blood vessel
Disorders of Hemostasis:
A. Excessive Clotting – thrombosis
B. Excessive Bleeding – bleeding diathesis
Bleeding Disorders
a. Inability to stop bleeding if injured
b. Inadequate Blood Clotting May Result from:
i. Vitamin K Deficiency
ii. Genetically determined errors of clotting factor synthesis
iii. Drug Induced Conditions
iv. Thrombocytopenia
“ Coagulation Disorders”
Hemostasis in healthy individual –Appropriate hemostasis requires normal function of:
1) Coagulation Cascade – a series of proteolytic reactions that produce active
proteases and ultimately generate thrombin, which converts fibrinogen to fibrin, a
key structural component of a fibrous clot
2) Platelets – decrease of platelets = Thrombocytopenia
Mechanisms of NORMAL CLOTTING:
1) Vascular Endothelial Cells is not thrombogenic, and circulating blood platelets
and clotting factors do not normally adhere to it
2) When endothelial damage exposed the underlying tissue, platelets in the
vicinity immediately undergo a reaction that causes them to stick to the
exposed collagen, called Platelet Aggregation
3) Consequently, the coagulation cascade is activated
4) The platelet plug quickly arrests bleeding but must be reinforce by fibrin for
long-term effectiveness
1) Hemophilia – Hereditary Bleeding Disorder cause by lack of clotting factors
1. Hemophilia A – most common (83%) due to a deficiency of factor VIII 8
2. Hemophilia B – due to a deficiency of factor IX 9
3. Hemophilia C – due to deficiency of factor XI 11
2) Von Willebrand Syndrome – an inherited condition that results when the blood
lacks functioning “von Willebrand factor”, a protein that helps the blood to clot
3) Deficiency in clotting protein; factor VIII
Clotting Pathways:
Hemophilia and Von Willebrand Disease:
Blood Disorders – when people Clot TOO much: “Thrombophilia” i.e. DVT
Thrombophilia – excessive clotting disorders with the tendency to develop blood clots in
parts of the body such as deep veins in the legs
1) Also known as a Hypercoagulable Disorder:
1. DVT
2. Arterial Thrombosis
Hemostasis – Bleeding and Clotting Drugs:
Drugs used for altered hemostasis can be divided
1) Those that inhibit thrombosis – used to prevent or dissolve blood clots are
divided into 3 classes that describe their mechanisms of action
Used for those who have evidence of a pathologic thrombus or are at risk
for thrombotic vascular occlusion
a. Myocardial infarction
b. Acute coronary syndromes
c. Atrial Fib
d. Ischemic Stroke
e. DVT
2) Anticoagulants – blood thinners
• Increase time for a clot to form
• Uses:
o A Fib
o Joint Replacement
o Ischemic Stroke
o MI
• Drugs:
o Coumadin
o Heparin
o Warfarin
2. Antiplatelets agents – reduces the ability for the platelets to stick
together and inhibit the formation of clots
• Uses:
o Arterial Thrombosis
o Facilitate Clotting in patients with excessive bleeding
o MI
o Stent Thrombosis
o Ischemic Stroke
• 3 Types:
1) Glycoprotein Platelet inhibitors
a. Abcixmab
b. Eptifbatide
c. Tirofiban
2) Platelet Aggregation Inhibitors
a. Aspirin
b. Cangrelor
c. Cilostazol
3) Protease activated receptor 1 antagonist
a. Vorapaxar
3. Thrombolytics – break up clots by activating fibrinolysis and converting
plasminogen to plasmin which lyses the clot
• Uses:
o Ischemic Stroke
o MI
o PE
• Drugs:
o Alteplase
o Urokinase
o Reteplase
3) Those that facilitate clotting – drugs to prevent excessive bleeding are divided
into three classes
1. Replacement of clotting factors
2. Vitamin K supplementation (required for manufacture of clotting)
3. Drugs that inhibit plasmin (an enzyme that degrades blood clots)
Adverse Effects:
1) Anticoagulant
a. Excessive Bleeding
b. Diarrhea or Constipation
c. HA
d. Dizziness
e. Rashes
f. Hair loss
g. Jaundice
2) Antiplatelet
a. Cardiac Failure
b. Anaphylaxis
c. Stroke
d. Heart Attack
e. Anaphylaxis
f. Dyspnea
3) Thrombolytics
a. Excessive Bleeding
Cardiac Problems
Thrombus Formation
Intracranial Hemorrhage
Clinical Considerations:
Watch Cardiovascular Responsiveness during activity
Use RPE for exercise prescription
Watch for falls and wounds, the patient will not stop bleeding
Watch for clot formation and know how to screen for DVTs
Watch for Orthostatic hypotension with movements
How to Reduce Blood Pressure: 2 Factors:
3) Reducing Peripheral Vascular Resistance
4) Decreasing Cardiac Output
3. Reducing Peripheral Vascular Resistance:
a. Inhibition of Sympathetic Tone – via Sympatholytics
b. Inhibition of vascular smooth muscle contraction – Via Vasodilators
c. Inihibition of Angiotensin II formation: (Renin Inhibitors and Ace Inhibitors) +
Angiotensin Receptor Antagonists
d. Reduction of Blood Volume – Diuretics
4. Reducing Cardiac Output:
a. Inhibition of Sympathetic Input – via sympatholytics
b. Increase Parasympathetic Input – via Cholinomimetics
c. Decrease Heart Rate and Stroke Volume
d. Decrease Cardiac Output
Week 3: Lecture 1: Intro to CNS
Intro: Drugs acting on CNS were first to be discovered
• They are amoung the most commonly used
What does CNS medications include?
• Neurological Conditions – Parkinsons
• Psychiatric Conditions – Depression
• Pain
• Nausea
Mechanism of Action: How do they work?
• Nearly all drugs with CNS effects act on specific receptors that modulate synaptic transmission
o Voltage gated channels
o Ligand gated channels
• It does so by directly affecting receptor transmission
• Can also be done by affecting second messenger systems
Effects of CNS medications:
Nearly all drugs that are in this category, affect either:
1) Presynaptic (effect on neurotransmitters)
a. Synthesis
b. Storage
c. Metabolism
d. Release
2) Post Synaptic
a. Increased activation – agonists
b. Decreased activation – antagonists or inhibitors
Summary of Mechanisms: steps a drug can alter synaptic transmission
Why CNS drugs are important:
These drugs allow us to understand CNS function
o What happens during convulsions
o How do we store long term memory?
▪ Long Term Potentiation: Neurons that fire together repeatedly = learning
Revealed hypothesis on how these meds work
How vast is the human brain?
100 billion interconnected neurons
Each neuron may be connected to up to 10,000 other neurons, passing signals to each other via
as many as 1,000 trillion synaptic connections
Size of the CNS:
Human Brain’s memory vary from 1 to 1,000 terabytes
Neurons never divide or die off
o Unless stroke, brain injury, medications cause damage
Do not regrow
Anatomy and Function of CNS:
Brain and SC
Processing afferent input and sending efferent input
Clinical Implications:
Drugs affecting the CNS can have both beneficial and adverse effects on function
1) Drugs can improve movement
2) Drugs can also decrease a persons function
a. Cognitively – impair thinking and memory
b. Physiologically – decrease movement and strength, affect coordination and balance
Week 3: Lecture 2: Sedative and Hypnotics
Sedative – to calm ; used to reduce anxiety
Hypnotic – to induce sleep
Sedation or Hypnosis – all drugs in this class can be used either as a sedative OR hypnotic depending on
dosage or half life
How are these drugs classified?
1) Benzodiazepines
2) Barbiturates
3) Other Newer classes
Dose Response Curve:
Because the effects of the drugs are dose dependent, the therapeutic interaction and dose response
profiles of medications are important
Barbiturates and Benzodiazepine drugs have initial profiles that are similar
But with increase dosages, the barbiturates are more dangerous drugs because overdoes cause
anesthesia and coma/death
• Benzodiazepines have a larger margin of safety because greater dosage is required to place
people in states of anesthesia or coma
Other Factors that effect the potency of the meds:
• Half Life –
o The longer the drug stays in the system, the
more chance that additional dosages will
build up in the system before it is cleared
o This results in increased drug effects
o Great variability in half lives in this class
o Some have half lifes of 1 hour and other are 6
Lipid Solubility
• plays a role in how fast a medication enters the system
• Most Sedative drugs are lipid soluble meaning they are quickly absorbed into the body for use
and physiological effects
• This is because most sedative drugs are taken orally and must pass through the stomach and GI
To Know:
1) All sedative-hypnotic drugs cross the placental barrier
a. Can cause depression of neonatal vital function
b. Detectable in breast milk
c. Can cause depressant effects in nursing infants
d. In the elderly and in patients with liver disorders,
clearing of the meds may take longer (longer half life),
therefore drugs may accumulate in the system and
increase the sedative effects of the drugs
Overall Mechanism of Action:
Benzodiazepines, the barbiturates,
zolpidem and newer hypnotics, and
many other drugs bind to molecular
components of GABA
o A receptor present in neuronal
membranes in the CNS
This receptor complex, which functions
as a chloride ion channel, is activated
by the inhibitory neurotransmitter
o GABA is the major inhibitor NT
in the CNS
Benzodiazepines – Mechanisms
1) Potentiate GABAergic inhibition at all level of the neuraxis, including the spinal cord,
hypothalamus, hippocampus, substantia nigra, cerebellar cortex, and cerebral cortex
2) Receptors for benzodiazepines form part of the GABA receptor-chloride ion channel molecular
a. Increase the efficiency of GABAergic synaptic inhibition
b. The enhancement in chloride ion conductance induced by the interaction of
benzodiazepines with GABA-A receptors taking the form of an increase in the frequency
of channel-opening events
Clinical Uses:
• Relief of Anxiety
• For Insomnia
• For sedation and amnesia before medical and surgical procedures
• Treatment of Epilepsy and Seizure states
• For muscle relaxation in specific neuromuscular disorders
Drug Name, Onset, Duration:
--Barbiturates – used when Benzodiazepines don’t work as effectively. Act on a different mechanism:
Facilitate the actions of GABA at multiple sites in the CNS
They appear to increase the duration of the GABA-gated chloride channel openings
These effects involve a binding site or sites distinct from the benzodiazepine binding sites
Barbiturates are less selective in their actions: More generalized effect
• They also depress actions of excitatory NTs (like glutamic acid)
• Also exert non-synaptic membrane effects in parallel with their effects
These multiple sites of action of barbiturates may be the basis for their ability to induce full surgical
Types of Barbiturates: Chemical Name, Brand Name, Half Life
Barbiturates vs Benzodiazepines:
Other Medications – Mechanisms
In contrast to benzodiazepines, Zolpidem and other newer Hypnotics bind more selectively
because these drugs only interact with GABA A receptor isoforms that contain alpha 1 subunits
“Other” Types:
Adverse Effects:
• Sedation
• Musculoskeletal and other somatic effects
• Effects interfering with Rehab
• Decreased arousal or alertness
• Motor Control Dysfunction
• Weakness, increased response time, altered central processing
• Impaired fnctional ability
• Can cause dependencey
• Can build a tolerance to meds
Clinical Implications:
• Schedule Therapy when drugs levels are the lowest in the system if excessive hangover/sedative
effects are problematic
• Note: Newer hypnotics do not produce excessive hangover effects
• Also: for chronic anxiety conditions, antidepressants that are nonsedating like the selective
serotonin reuptake inhibitors may be more appropriate drugs
Week 3: Lecture 3: Seizures
Definition: a finite episode of brain dysfunction resulting from abnormal transient dischange of cerebral
• Types of Seizures:
• Tumor
• Head Trauma
• Congenital Abnormalities
• Genetic Factors
Epilepsy = recurrent seizures. 1:100 people have epilepsy
• Second most common neurological disorder (CVA is # 1)
• 500,000 have undiagnosed epilepsy
• Even though 80% are controllable ‘
Classification of Epilepsy drugs:
• Based on Seizure Type & Mechanism of Action
Types of Seizures:
Generalized Seizures
Focal Seizures:
Seizure Drug Classifications:
Effective antiseizure drugs have selective depressant actions on the abnormal neuronal
In most seizure disorders, the choice of medication depends on the empiric seizure classification
Drug Mechanisms of Action:
Drugs used to treat epilepsy generally inhibit the firing of cerebral neurons by either:
1) Increasing the inhibitory effects of GABA
2) Decreasing the effects of the excitatory amino acids glutamate and aspartate
3) By altering the movement of sodium and calcium ions across neuronal membranes
Drugs useful for partial and clonic-tonic seizures
1) Barbiturates – at one point, were considered the safest antiseizure meds
a. Safer because only taken when you have a seizure, so less chronic adverse effects
b. However, Less sedating medications have replaced barbituates
c. Are considered the drug of choice for seizures in infants
d. Facilitate and prolong the inhibitory effects of gamma-aminobutyric acid
e. At therapeutically relevant concentrations, they increase the duration of GABAmediated chloride channel openings and may block the excitatory transmitter glutamate
i. At high concentration, sodium channels may also be blocked
2) Hydantoins
a. Includes: Phenytoin, Ethotoin, Mephenytoin, fosphenytoin
b. Phenytoin is the oldest nonesedative antiseizure drug, introduced in 1938
i. One of the most effective drugs for tonic clonic seizures and partial seizures
ii. At therapeutic concentrations, the major action of phenytoin is to block sodium
channels and inhibit repetitive action potentials
c. This drug class may also decrease neuronal excitability by altered the conductance of
potassium and calcium across the nerve membrane.
a. Facilitates the inhibitory effects of GABA and their anti-seizure action is probably
mediated through this mechanism presynaptically to decrease synaptic transmission
b. These effects probably account for its anticonvulsant properties
a. Carbamezepine is considered a drug of choice for partial seizures and is often used for
treatment of generalized tonic-clonic seizures
b. One important clinical advantage of these drugs is that they are not sedative in the
usual therapeutic ranges.
a. Felbamate is an adjunct antiseizure agent with severe adverse effects that ultimately
limit its clinical use
b. Although its exact mechanism of action is unknown, evidence suggests blockade of Nmethyl-D-aspartate receptor via the glycine-binding site
c. Effective in some patient with partial seizures and myoclonic seizures, its propensity to
cause aplastic anemia and severe hepatotoxicity at unexpectedly high rates
diminishes its use
a. Amino acid derivative originally planned as a spasmolytic; found to be more effective as
an antiseizure drug
b. Although it has a close structural relationship to GABA, it appears to NOT act on GABA
c. Gabapentin is effective as an adjunct against partial seizures and generalized tonicclonic seizures
d. It has also been found effective in the treatment of neuropathic pain
a. An adjunct drug that produces a voltage-and use-dependent inhibition of presynaptic
sodium channels that results in suppression of rapidly firing neurons
b. Its efficacy is primary generalized absence seizures may involve actions on voltageactivated calcium channels
c. Lamotrigine is useful in the treatment of partial seizures and against absence of
myoclonic seizures in children
a. An inhibitor of GABA uptake in both neurons and glia, thus prolonging the inhibitory
action of synaptically released GABA in the synaptic cleft
b. Tiagabine is indicated for the adjunctive treatment of partial seizures, although some
patients appear to do well with tiagabine monotherapy
c. The drug is generally well tolerated
a. Mechanism of action probably involves:
i. Blockage of voltage dependent sodium channels
ii. The drug appears to potentiate the inhibitory effects of GABA, acting at a site
different from benzodiazepine and barbiturate sites
iii. Blocks excitatory amino acid receptors
b. All three of these actions likely contributes to topiramate’s anticonvulsant effect
c. Topiramate is effective as an adjunct against partial and generalized tonic-clonic
10) Vigabatrin
a. Irreversible inhibitor of GABA amino-transferase, the enzyme responsible for the
degradation of GABA
b. Acts be increasing the amount of GABA released at synaptic sites, thereby enhancing
inhibitory effects
c. Vigabatrin may also potentiate GABA by inhibiting the GABA reuptake transporter
d. Vigabatrin is useful in the treatment of partial seizures and tonic-clonic seizures as an
alternative agent
11) Succinimides
a. The class drugs includes
i. Ethosuximide
ii. Phensuximide
iii. Methsuximide
b. Drugs increase seizure threshold and limit the spread of electrical activity in the brain by
reducing low-threshold calcium currents
12) Valproic Acid
a. Originally introduced as a primary agent in the treatment of generalized (absence)
seizures, but has proved to also be effective against partial seizures, generalized tonicclonic seizures, and myoclonic seizures
b. The drug probably owes its broad spectrum of action to more than one molecular
c. Action against partial seizures may be a consequence of the drug’s effect on sodium
currents, blocking sustained high frequency firing of neurons
d. Blockage of NMDA receptor-mediated excitation may also be important
e. Also at high concentraions, has been shown to increase membrane potassium
conductance, thereby hyperpolarizing the resting membrane potential
f. Valproic acid is used as a primary agent in the treatment of absence seizures, partial
seizures, generalized tonic-clonic seizures, and myoclonic seizures
What medication to use?
Choice based on established efficacy in:
1) The specific seizure state that has been diagnosed
2) The prior responsiveness of the patient
3) Anticipated Toxicity of the drug
Treatment may involve a combination of drugs
Adverse Effects of Seizure Meds:
Clinical Considerations:
Teratogenicity is a concern for pregnant women taking antiseizure medication
Children born of women taking anticonvulsant drugs have an increased risk of congenital
Spina bifida has been specifically linked to the use of valproic acid and carbamazepine
Children taking antiseizure medications should be closely monitored for hepatotoxicity
This risk is greatest for children younger than 2 years but can also occur in patients of any age taking
multiple antiseizure drugs
If withdrawal from antiseizure drugs is contemplated, it should be accomplished gradually to avoid
increased seizure frequency and severity
Week 3: Lecture 4: General Anesthetics
General Anesthesia – analgesia, unconsciousness, amnesia, skeletal muscle relaxation, inhibition of
sensory and autonomic reflexes
Act as CNS depressants with action that can be induced and terminated more rapidly than
those of conventional sedative-hypnotics
Ideal anesthetic drug would induce anesthesia smoothly and rapidly while allowing for
prompt recovery after its administration is discontinued
Drug would also possess a wide margin of safety and be devoid of adverse effects
Practically used via a combination of IV and Inhaled drugs = “Balanced Anesthesia”
o Takes advantage of their individual favorable properties
o Attempts to minimize adverse reactions
Classification: Based on method of induction:
1) Inhaled
2) Intravenous ‘
Drug Choice:
• The anesthetic technique will vary depending on the proposed type of diagnostic therapeutic, or
surgical intervention
A) For minor procedures, conscious sedation is used, employing oral or parenteral sedatives,
often in conjunction with local anesthetics
These techniques provide profound analgesia, but with retention of the patient’s
ability to maintain a patent airway and to respond to verbal commands
B) For more extensive surgical procedures, anesthesia frequently includes the use of
preoperative drugs, induction of anesthesia with IV meds, maintenance of anesthesia with
combination of inhaled and IV anesthetic drugs
o Monitoring of vital signs is standard method of assessing the depth of anesthesia
during surgery
Stages of Anesthesia:
Stage 1: Analgesia (Loss of Pain Sensation)
• Patient has decreased awareness of pain
• Sometimes have amnesia
• Consciousness impaired by not lost
Stage 2: Disinhibition (Combative Behavior)
• Patient appears to be delirious and excited
• Reflexes enahcnes and respiration is irregular
o Retching
o Vomiting
o Incontinence
• Efforts made to limit the duration and severity of this stage
o To re-establish regular breathing
Stage 3: Surgical Anesthesia
• Patient is unconscious and has no pain reflexes
• Respiration is very regular
• Blood Pressure is maintained
Stage 4: Medullary Depression (Medullary Paralysis) – DEATH
• Patient develops severe respiratory and cardiovascular depression that requires mechanical and
pharamacologic support
• Without full circulatory and respiratory support, death rapidly ensures
Mechanism of Action: Inhaled
• Most inhaled anesthetics, barbiturates, benzodiazepines, atomidates, and propofol : Facilitate
GABA mediated inhibition of GABA-A receptors
• May also act via antagonism of the excitatory neurotransmitter glutamic acid at the N-methyl-Daspartate (NMDA) receptor
• CNS neurons in different regions of the brain have different sensitivities to general anesthetics
o Inhibition in pain pathways occurs BEFORE inhibition of neurons in the brain stem and
mid brain reticular formation (arousal and alertness)
Speed of Induction is dependent on:
1) Solubility – the more rapidly a drug equilibrates with the blood, the more quickly the drug
passes into the brain to produce anesthetic effects
a. Nitrous oxide equilibrates more rapidly than halothane and therefore takes effect more
2) Inspired gas partial pressure: a high partial pressure of the gas in the lungs results in more rapid
achievement of anesthetic levels in the blood anesthesia
a. A high initial inspired anesthetic concentration will increase the rate of induction of
anesthesia by increasing the rate of transfer into the blood
3) Ventilation Rate: The greater the ventilation, the more rapid is the rise of alveolar and blood
partial pressure of the agent and the onset of anesthesia
a. High ventilation can be achieved by mechanical or assisted ventilation via an
endotracheal tube
4) Pulmonary Blood Flow –
a. at high pulmonary blood flows, the gas partial pressure in the blood rises at a slower
rate because a larger volume of blood is exposed to the anesthetic gas in the lungs;
thus, the onset of anesthesia is delayed
b. at low rates, the rate of rise of arterial tension of inhaled anesthetics is increased and
onset of anesthesia is faster
c. In circulatory shock, this effect may accelerate the rate of onset of anesthesia with
agents of high blood solubility
5) Arteriovenous concentration gradient
a. Uptake of soluble anesthetics into highly perfused tissues may decrease gas tension in
mixed venous blood
b. The greater the different in anesthetic tensions between arterial and venous blood, the
more has been taken up by viscera, muscle, etc. and the more time it will take to
achieve equilibrium with brain tissue.
Termination of inhaled anesthetic actions:
• Inhaled Anesthetics are primarily terminated by redistribution of the drug from the brain to the
blood and elimination of the drug through the lungs
• Some volatile liquids such as halothane and methoxyflurane are also eliminated in part by
metabolism in the liver
Group 1 Drugs: General Anesthetics
Group 2 Drugs: General Anesthetics
Group 3 Drugs: General Anesthetics
Most Commonly Used General Anesthetics
Nitrous Oxide
1) Intravenous:
• In the last 20 years, there has been increasing use of intravenous drugs in anesthesia, both as
adjuncts to inhaled anesthetics and in techniques that do not include inhaled anesthetics
• IV Agents: Do NOT require specialized vaporizer equipment for their delivery or expensive
facilities for the recovery and disposal of exhaled gases.
• Intravenous drugs have an onset of anesthetic action faster than the fastest of the inhaled
gaseous agents
• Recovery is sufficiently rapid with many IV drugs to permit short ambulatory outpatient surgical
2) Barbiturates
• Generally have high lipid solubility which promotes rapid entry into the brain and results in
surgical anesthesia in one circulation time = FASTER
• These drugs are used for induction of anesthesia and for short surgical procedures
• Liver metabolism is required for elimination from the body
3) Benzodiazepines
• Slower onset of CNS effects with a longer duration of action
• Patients may experience severe postoperative respiratory depression
o Can use flumazenil to accelerate recovery
• Prolonged sedation is often problematic during recovery
4) Etomidate
• Affords rapid induction with minimal change in cardiac function or respiratory rate and it
has a short duration of action
• The drug is not analgesic, and its primary advantage is in anesthesia for patients with limited
cardiac or respiratory reserve
5) Ketamine
• This drug produces a state of dissociative anesthesia in which the patient remains conscious
but has marked catatonia, analgesia and amnesia
• Ketamine is a chemical congener of the psychotomimetic agent phencyclidine – PCP
• The drug is the only IV anesthetic that is a CARDIOVASCULAR STIMULANT, and this action
may lead to an increase in ICP
• In most patient, ketamine decreases the respiratory rate
• Because of the high incidence of postoperative psychic phenomena associated with its use,
ketamine is not commonly used in general surgery in the US.
o Useful for poor-risk geriatric patient and in unstable patients
▪ Cardiogenic or septic shock
6) Opioid
a. Morphine and fentanyl are used with other CNS depressants
i. Like Nitrous oxide and Benzodiazepines
b. Especially valuable in high risk patients who might not survive a full general anesthetic
7) Propofol
a. Most commonly used IV anesthetic
b. Produces anesthesia as rapidly as the IV barbiturates and recovery is more rapid
c. Propofol has antiemetic actions
i. Recovery is not delayed after prolonged infusion
d. It is used for induction and maintanence of anesthesia in balanced anestheria and as a
primary anesthetic in outpatient surgery
Adverse Effects of General Anesthersia
Increased Intracranial Pressure
Decreased arterial flow
Decreased cardiac output
Peripheral vasodilation
Ventricular Arrhythmias
Increased arterial CO2 tension
Muscle Weakness
Respiratory Compromise
Altered Mental status
Sore Throat
Muscle Pain
Clinical Considerations:
Time: Usually passage of time will allow for the effects of the anesthesia to wear off
Contact Physician if any adverse effects continue for prolonged period of time
Week 3: Lecture 5: Local Anesthesia
Local Anesthesia result when sensory transmission fomr a local area of the body to the CNS is BLOCKED
Local Anesthetics Constitute a group of chemically similar agents that block the Na Channels of excitable
Restricted to Localized area because they are applied topically or by injection
Even if drugs given in the vicinity of the spinal cord, it is still considered a form of local
anesthesia because only a specific level of the cord impulse is blocked
Localized Surgical Procedures
Labor and Delivery
Various Surgical Procedures
Frozen Shoulder joint manipulations
Spinal Anesthesia
Temporary autonomic blockade
Short term pain relief
o Tendonitis
o Cancer
o Minor Skin injuries or irritations
Mechanism of Action of Local Anesthetics:
a. Local anesthetics block voltage-dependent Na Channels and reduce influx of sodium
a. Ions, thereby prevent depolarization of the membrane and block conduction of
the action potential
b. Local Anesthetics access receptors on the channels from the cytoplasm or the
c. Because the drug molecule must cross the lipid membrane to reach the
cytoplasm the more lipid-soluble (nonionized, uncharged) form reaches
effective intracellular concentrations more rapidly than does the ionized form
d. ONCE inside the axon, the ionized charged form of the drug is the more
effective blocking entity
e. Thus, both the nonionized and the ionized forms of the drug play important
roles, the first in reaching the receptor site and the second in causing the effect
f. The affinity of the receptor site within the sodium channel for the local
anesthetic is a function of the state of the channel, whether resting, open, or
inactivated, and therefore is both voltage and time dependent
g. More rapidly firing nerve fibers are usually blocked before more slowly firing
h. Local Anesthetic binds to the receptor site on the Na Channel, and the channel
maintains the blocked position
i. By blocking a sufficient number of channels, the anesthetic prevent action
potential propagation along the affected portion of the nerve axon
j. Other ions can influence local anesthetic action: High Concentration K+
k. Note: Co-Administration of a vasoconstrictor slows down the removal of the
drug to reduce potential CNS toxicity
The sensitivity of various types of nerve fibers to local anesthetics depend on:
o Fiber Diameter
o Myelination
o Physiologic Firing Rate
o Anatomic Location
In general, smaller fibers are blocked MORE EASILY than larger fibers, and myelinated fibers are
blocked MORE EASILY than unmyelinated fibers.
Fibers located in the periphery of a thick nerve bundle are blocked sooner than those in the core
because they are exposed earlier to higher concentration of the anesthetic
o Activated pain fibers rapidly, therefore, pain sensation appears to be blocked by LOWER
concentrations of local anesthetics
▪ Smaller Dosage
How are local anesthetics administered?
Intrathecally – spine
Types of Local Anesthetics: Amides vs Esters:
Esters = Plasma and tissue esterases
Amides: Liver
Adverse Effects:
Decreased Cardiac Output
Decreased HR
Inability to feel sensations such as pain, deep pressure, light touch, heat and cold
Possible Motor impairment
Clinical Considerations:
Time – advise physician if effects are prolonged
Potentiation of Functional Outcomes Secondary to drug therapy -local anesthetic relief of pain
may allow increased function without sedation
Week 3: Lecture 6: Parkinson’s and Other Movement Disorders
The major Movement disorders include:
o Parkinsons
o Huntingtons
o Wilsons
o Tourettes
Types of abnormal movements:
o Athetosis
o Ballismus
o Chorea
o Dyskinesia
o Tics
o Tremor
Parkinson’s: Pathogenesis
Slow, progress degeneration of dopaminergic neurons in the Basal Ganglia and associated
Resulting clinical signs and symptoms d/t an imbalance in neuro-transmitter function because of
this neuronal degeneration
o Rigidity
o Akinesia
o Flat Facies
o Tremor at rest
Parkinson’s: Therapeutic Strategy:
Restore Dopamine activity in the brain
o Difficult to find drug regimens that don’t involve serious adverse effects
Increase activity of dopamine already available
Parkinson’s Drug Classifications:
Classified by Target Element
Levodopa Mechanism of Action:
Dopamine does not cross the blood-brain barrier and thus has no therapeutic effect in
Parkinson’s disease if given as such
o L-dopa is transported across the BBB into the brain where it is rapidly converted to
dopamine by L-amino acid decarboxylase
o To prevent premature conversion of levodopa to dopamine in peripheral tissue,
levodopa is usually given WITH a DOPA decarboxylase inhibitor such as Carbidopa which
does not cross the BBB and thus prevents the conversion of levodopa to dopamine in
peripheral tissues
Neuroprotective Drugs: drugs that potentially slow the progression of Parkinson
Antipoptotic Agents
Glutamate antagonists
Intraparenchymally administered glia-derived neurotrophic factor
Coenzyme Q10
Anti-inflammatory drugs
Note: The efficacy of these agents remains to be established
Clinical Considerations – Levodopa:
Levodopa – can ameliorate all clinical features of Parkinson’s disease, but is particularly effective
in relieving bradykinesia and its associated disabilities
The best results of levodopa are obtained in the First Few years of treatment
Early initiation of treatment with levodopa lowers the mortality rate
Responsiveness to the drug usually decrease with time
Some patients also begin to develop adverse effects at dosages previously well tolerated, which
may be caused by selective denervation-induced or drug-induced super-sensitivitiy
Debilitating effects of such response fluctuations on daily activities can sometimes be reduced
by including dopamine agonists in the drug regimen
Adverse Effects: Levodopa
Most adverse effects are dose dependent
o Anorexia
o Nausea
o Postural Hypotension
o Tachycardia
o Hypertension
o Dyskinesias
Dopamine Agonist Receptors:
Used in combination with levodopa and with anticholinergic drugs
o Also for people who cannot tolerate levodopa
Dopamine agonists act directly on dopamine receptors and may have a beneficial effect additive
to that of levodopa
o Increase functional activity of dopamine NT pathways
Monoamine Oxidase Inhibitors:
Selegiline is a partially selective inhibitor of monoamine oxidase (MAO) type B, the enzyme
isoform that metabolizes dopamine in preference to norepinephrine and serotonin
Selegiline retards the breakdown of dopamine and thus may increase brain dopamine levels,
both endogenous or those provided by levodopa treatment
At higher doses, it is less selective and inhibits both MAO-A and MAO-B, producing effects like
those of the antidepressant MAO inhibitors
Selegiline is used as an adjunct to levodopa in Parkinson’s disease and has also been used as the
sole agent in newly diagnosed patients but has only a minor therapeutic of Parkinson’s disease
when given alone
An antiviral agent, was by chance found to have antiParkinson’s disease properties
Amantadine inhibits the N-methyl-D-aspartic acid receptor-mediated stimulation of
acetylcholine release
Amantadine may enhance dopaminergic neurotransmission by increasing synthesis or release of
dopamine or by inhibiting dopamine re-uptake
Amantadine has limited by favorable influence on the bradykinesia, rigidity, and tremor of
Parkinson’s disease
It is less potent than levodopa and usually effective for only a few weeks
Catechol-O-Methyltransferase Inhibitors
Entacapone and tolcapone are selective inhibitors of COMT, the enzyme that converts levodopa
to 3-O-methyldopa
Inhibiton of dopa decarboxylase (by carbidopa) is associated with compensatory activation of
other pathways of levodopa metabolism, especially COMT
Increased plasma levels of 3OmD are associated with poor therapeutic response to levodopa,
partly because the compound competes with levodopa for active transport into the CNS
Such selective COMT inhibitors prolong the action of levodopa by increasing the amount
transported into the brain and diminishing its peripheral concentration
These agents may be helpful in patients receiving levodopa who have developed response
fluctuations, improving response and prolonging “on” time
Acetylcholine-Blocking Drugs
These drugs decrease the excitatory actions of cholinergic neurons on cells in the striatum by
blocking muscarinic receptors
Use as an adjunct to levodopa
Antimuscarinic drugs may improve the tremor and rigidity of Parkinson’s diease in 50% of
patient but have little effect on bradykinesia
Other Movement Disorders:
Huntington’s Disease
Tourette’s Syndrome
Wilson’s Disease
A) Huntington’s Disease
a. Progressive Chorea and Dementia
b. Loss of GABA transmitter functions and enhance Dopaminergic activity
c. Cholinergic deficit because choline acetyltransferase is decreased in the basal ganglia of
patients with this disease
d. Drug therapy involves
i. Dopamine-Depleting Drugs
ii. Dopamine Receptor Antagonists
B) Tourette’s Syndrome
a. Unknown cause
b. Tics, Violent or repetitive movements and loud, obscene, or hostile vocalizations
c. The disease often occurs in adolescence or young adulthood and may, if severe, have a
significant impact on the patient’s life
i. Haloperidol – D2 Receptor Blocker
1. IF this drug is not successful:
a. Pimozide
b. Carbamazepine
c. Clonazepam
d. Clonidine
C) Wilson’s Disease
a. Recessively inherited disorder of copper metabolism
b. Characterized by deposits of copper salts in liver and other tissue, brain
i. Chelating agents, penicillamine, trientine
Clinical Considerations:
Severe Orthostatic Hypotension
Therapy Occuring during off time of medication
Aggressive therapeutic rehabilitation intervention to maximize potential
Coordinate rehabilitative therapy with the peak effects of drug therapy for maximum benefit
o Increase movement velocity
o Increase muscle strength
o Possible reduction in tremor
o Possible reduction in rigidity
Week 3: Lecture 7 – Antidepressants
Major Depression: One of the most common forms of mental illness in the U.S. with as many as 6% of
the population depressed
An estimated 10% of people become depressed during their lifetime
Symptoms of Depression:
Intense Feelings of Sadness and Despair
Sleep Disturbances
Somatic Complaints
Suicidal Thoughts
Physiology of Depression:
Norepinephrine and Serotonin are NT that function to express mood
o Functional decrease in the activity of these amines is thought to result in depression
o Functional increase in activity of these amines results in mood elevation
Included Disorders:
Panic Disorders
Chronic Pain
Tricyclic Antidperessants
Monoamine oxidase inhibitors
Selective serotonin reuptake inhibitors
Mechanism of Action:
Antidepressants cause potentiation of the neurotransmitter actions of norepinephrine,
serotonin, or both
Long-term use of tricyclics and MAOIs, but not SSRIs, lead to downregulation of B-adrenergic
1) Tricyclic Antidepressants
• Were the first successful antidepressants
• Are structurally related to the phenothiazine antipsychotics and share certain of their
pharmacologic effects
• The acute effect of tricyclic drugs is to inhibit the reuptake mechanisms (SERT, and NET)
responsible for the termination of the synaptic actions of NE and 5-HT in the brain
• Presumably results in potentiation of their NT actions at postsynaptic receptors
2) Heterocyclic Antidepressants
These drugs have varied structures and include second-generation antidepressants
o Amoxapine, bupropion, maprotiline, and newer, third generation drugs
The Pharmacokinetics of most of these agents are similar to those of the TCAs.
Some 2nd gen drug inhibit reuptake of NE, other have more effect on 5-HT reuptake
3rd Generation drug: Venlafaxine, although not tricyclic, is a potent inhibitor of the 5-HT
transport and, at higher doses, of the NE transporter as well
Mirtazapine has a unique action: It increases amine release from nerve endings by antagonism
of presynaptic alpha-2 adrenoceptors involved in feedback inhibition
3) Monoamine Oxidase Inhibitors:
MAOIs are structurally related to amphetamines and are orally active
They inhibit both MAO-A, which metabolizes NE, 5-HT, and tyramine, and MAO-B, which
metabolizes dopamine
Tranylcypromine is the fastest in onset of effect but has a shorter duration of action than other
MAOIs (2-3 weeks)
It is prudent to assume that the drug effect will persist from 7 days to 2 or 3 weeks after
discontinuance of the drug
MAOIs increase brain amine levels by interfering with their metabolism in the nerve endings,
resulting in an increase in the vesicular stores of NE and 5-HT
When neuronal activity discharges the vesicles, increase amounts of amines are released,
presumably enhancing their actions
4) Selective Serotonin Reuptake Inhibitors
a. Fluoxetine is the prototype of a group of drug that are SSRIs
b. They are designed to inhibit serotoin reuptake
c. All of them require hepatic metabolism and have longer half-lives of 18-24 horus
d. The acute effect is a highly selective action on 5-HT transporters
e. They block the reuptake of other amine neurotransmitters
f. Because of their selectivity, they produce fewer and less troublesome adverse effects
than nonselective antidepressant drugs
Adverse Effects of Antidepressants
Clinical Considerations for Antidepressants:
Orthostatic hypotension
• Compressive garments
• Tilt table
• Allow patient’s BP time to adjust to postural changes
• Monitor response to exercise
In many cases, antidepressant medications can help with overall functional outcomes at both the
activity and participation levels owing to their psychologic effects
Week 3: Lecture 8: Anti-Psychotics
General Information:
• Number of patient requiring hospitalization in mental institutions has markedly decreased since
the first neuroleptic drugs
o Reserpine and Chlorpomazine were found to be useful in the early 1950s
o Because of the positive effects of drug therapy on the symptoms of the disease,
psychiatric philosophy has shifted to a more biologic basis
• PTs may encounter patients taking antipsychotic medications in several settings
• The term psychosis denotes a variety of mental disorders
• Antipsychotic agents are used in schizophrenia and other psychoses and agitated states
• Schizophrenia is not cured by drug therapy
• Symptoms may be ameliorated by antipsychotic drugs
• Protracted therapy is often needed and can result in severe toxicity
Is a particular kind of psychosis characterized mainly by marked thinking disturbance
Pathogenesis of schizophrenia is unknown, although a genetic predisposition has been proposed
The molecular basis of the disease is also unclear, but evidence suggests there is a link with
abnormalities of amine neurotransmitter function, especially that of dopamine
For this reason, drug therapy for schizophrenia is directed at this group of NTs and their
Therapeutic Goals of Medication:
Primary use: reduce some of the positive symptoms of schizophrenia
o Hyperactivity
o Bizarre ideation
o Hallucinations
o Delusions
Beneficial effects may take weeks to develop
Newer atypical drugs also improve some of the negative symptoms of schizophrenia
o Emotional blunting
o Social Withdrawal
Older drugs are still used;
o Low cost
Mechanism of Action:
The mechanism of action of antipsychotic agents is based on the dopamine hypothesis of
o Proposes that the disorder is caused by a relative excess of functional activity of the
neurotransmitter dopamine in specific neuronal tracts in the brain
o Based on the observations that many antipsychotic drugs block brain dopamine
receptors (especially D2 receptors) and dopamine agonist drugs exacerbate
o An increased density of dopamine receptors has been detected in certain brain regions
of untreated patients diagnosed with schizophrenia
Anti-psychotic drugs:
The Major Chemical Subgroups of Older Antipsychotic Drugs are:
o Phenothiazines
o Thioxanthenes
o Butyrophenones
Newer Drugs (second-generation or atypical drugs) vary in their chemical structure but are all
effective in schizophrenia. Are more expensive. They include:
o Clozapine
o Loxapine
o Olanzapine
o Risperidone
o Quetiapine
o Ziprasidone
o Aripiprazole
The majority of the drugs target dopamine, but also serotonin is targeted as well
The antipsychotic drugs are well absorbed when given orally and, because they are lipid soluble,
readily enter the CNS
These drugs require metabolism by liver enzymes before elimination and have long plasma halflives that permit once daily dosing
Adverse Effects:
Weight gait
Sexual Problems
Dry Mouth
Blurred Vision
Low BP
Low WBC count
Bipolar Affective Disorder: (Manic-Depressive) frequently diagnosed and characterized by cyclic attacks
of mania with many symptoms of paranoid schizophrenia alternating with periods of severe depression
Bi-Polar Disorder:
Episodes of mood swings characteristic of this condition are generally unrelated to life events
Although the exact biologic disturbance has not been identified, a preponderance of
catecholamine-realted activity is thought to be present during the MANIC PHASE
Bipolar disorder has as strong FAMILIAL component, and genetic studies have identified at least
three possible linkages to different chromosomes
Drugs that increase this activity then to exacerbate mania, whereas those that reduce activity of
dopamine, norepinephrine, acetylcholine and glutamate relieve mania
Bipolar Disorder – Medications
Lithium: Antimanic drug; better defied as “mood-stabilizing agent”
Carbamazepine: recognized as effective in some manic-depressive patients despite not being
formally approved for such use
Valproic acid: recently approved for the treatment of mania, and is being evaluated as a mood
Atypical antipsychotics beginning with olanzapine are being investigated and approved as
antimanic agents and potential mood stabilizers
Mechanisms of Lithium:
Management of Lithium:
Pharmacological Management of Bipolar:
Adverse Effects: Lithium:
➢ Any Marked Changes in mental behavior such as confusion or withdrawal or bizarre motor
movements may indicate drug toxicity
➢ Thyroid enlargement may occur, but thyroid dysfunction is rare
➢ Reversible nephrogenic diabetes insipidus occurs commonly at therapeutic drug levels
➢ Edema is a frequent adverse effect of lithium therapy and may be related to some effect of
lithium on sodium retention
Clinical Considerations: Anti Psychotics
Orthostatic Hypotension
Balance and posture problems
Tardive Dyskinesia
Orthostatic Hypotension
Compressive garments
Tilt table
Allow sufficient time for BP changes
Monitor response to exercise
In many cases, these meds can help with functional outcomes at both the activity and
participation levels
Week 4 – Lecture: 1 Endocrine System Part 1
This section includes:
General Information:
The endocrine system integrates major organ systems with each other and the
nervous systems
The endogenous ligands that the endocrine system uses to perform this
integrative task are called hormones
Hormones are released from specialized cells, circulate in the blood, and
regulate physiologic processes in one or more target organs
The endocrine system provides many useful therapeutic targets and many drugs
either mimic or block the effects of naturally occurring hormones
This section will focus on drugs that regulate several related endocrine systems:
1) The hypothalamic-pituitary endocrine system, which exerts control over many
integrative functions and other endocrine tissues and interacts directly with the
nervous system
2) The thyroid gland, an essential regulator of growth, development, and normal
function of many organ systems
3) The gonadal system, which regulates the development and function of
reproductive tissues
Hypothalamus Pituitary Adrenal Axis:
HPA Axis:
o Hypothalamus
o Pituitary Gland
o Adrenal Gland
Hormones released by the Pituitary:
Hypothalamic and pituitary hormones, and there synthetic analogs, have
pharmacologic applications in three areas:
1) Replacement therapy for hormone deficiency states
2) Antagonist therapy for diseases resulting from excessive production of, or
response to, pituitary hormones
3) Diagnostic tools for performing stimulation tests
Growth Hormone-releasing hormone:
Growth hormone-releasing hormone (GHRH) is a hypothalamic hormone that
stimulates the release of growth hormone (GH) from the anterior pituitary
GH (also known as somatotropin) is an important regulator of growth in children
and tissue maintenance in adults
Two short synthetic peptides with activity similar to GHRH are available for
clinical use
In normal individuals, theses peptides produce a rapid increase in plasma GH
Somatostatin (somatotropin releases-inhibiting hormone, SRIF) is found in the
pancreas and other parts of the GI system as well as in the central nervous
This hormone inhibits the release of a number of
hormones including GH, glucagon, insulin, and
Because of its short duration of action, somatostatin
itself is of no clinical values
Octreotide, a synthetic somatostatin analog with a
longer duration of action, is used to reduce
symptoms caused by certain tumors that produce
excessive concentrations of hormones
Tumors that are partially responsive to octreotide’s
inhibitory effects include GH-secreting tumors that
cause acromegaly, carcinoid tumors, gastrinoma,
and glucagonoma
Thyrotropin-Releasing Hormone
Thyrotropin-releasing hormone (TRH) stimulates thyrotropin (thyroidstimulating hormone, TSH) release from the anterior pituitary
TRH also increases prolactin production by the anterior pituitary, but has no
effect on the release of GH or adrencorticotropin (ACTH)
TRH has been used in diagnostic testing of thyroid dysfunction
Corticotropin Releasing Hormone:
Corticotropin-releasing hormone (CRH) stimulates
secretion of both ACTH and the closely related
peptide Beta-endorphin from the anterior pituitary
Gonadotropin Releasing Hormones:
Gonadotropin-releasing hormone (GnRH) coordinates
reproductive function in males and females by
regulating release of two gonadotropins – luteinizing
hormone (LH) and follicle-stimulating hormone (FSH) –
from the anterior pituitary
Steady dosage of GnRH agonists is used to suppress
gonadotropin secretion in patients with prostatic
carcinoma or other gonadal steroid sensitive tumors,
endometriosis, or precocious puberty
GnRH agonists are also used to suppress endogenous
gonadotropin release in women undergoing controlled
ovarian hyperstimulation and in assisted reproduction
technology such as in vitro fertilization
There GnRH antagonists may also be effective in
disorders that are currently treated with GnRH agonists,
including endometriosis, uterine fibroids, and prostatic
Prolactin Inhibiting Hormone:
Dopamine (also called prolactin-inhibiting
hormone, PIH) is the primary physiologic regulator
of prolactin release
Acting through D2 dopamine receptors, dopamine
inhibits prolactin release
Dopamine itself is not used to treat
Bromocriptine all other orally active ergot
derivatives such as pergolide as used to reduce
prolactin secretion from normal glands as well as
Anterior Pituitary Hormones:
Growth Hormone (Somatotropin)
Recombinant forms of human GH are somatropin and somatrem; the latter is somatotropin with
an extra methionine added to the protein
Recombinant growth hormone is used to treat:
o GH deficiency in children and adults
o Turner’s syndrome treated with GH frequently achieve increased final adult height
o Growth in children with failure to thrive secondary to chronic renal failure or HIV
o Adults with acquired immune deficiency syndrome (AIDS)-associated wasting
Thyroid Stimulating Hormone:
In thyroid cells, thyroid stimulating hormone TSH increases uptake and production of thyroid
TSH has been used as a diagnostic tool to distinguish primary from secondary hypothyroidism
Adrenocorticotropin Hormone
Adrenocorticotropic hormone (ACTH) is made in the pituitary gland in
response to the release of another hormone, called corticotropinreleasing hormone (CRH), by the hypothalamus which leads to
production of cortisol in the adrenal glands
During stress, when cortisol levels increase, ACTH levels fall
Both ACTH and cortisol levels change throughout the day. ACTH is
normally highest in the early morning (between 6 am and 8 am) and
lowest in the evening (between 6 pm and 11 pm)
The thyroid gland secretes two types of hormones
o The first is calcitonin, a peptide that is important in calcium metabolism and bone
o The second type of thyroid hormone consists of two iodine-containing hormone
thyroxine (T4) and triiodothyronine (T3), development, and metabolism
The actions of thyroid hormones include normal growth and development of the nervous
skeletal, and reproductive systems and regulation of metabolism of fats, carbs, proteins, and
Clinical Use:
Thyroid hormone therapy can be accomplished with either T4 or T3.
o Synthetic T4 (levothyroxine) is usually the first choice
T3 acts more quickly, but has a shorter half-life and is more expensive
Adverse Effects:
o Toxicity due to excessive suppkementation of thyroid hormones is expressed as
o Older patients, those with cardiovascular disease, and those with long-standing
hypothyroidism are highly sensitive to the stimulatory effects of T4 on the heart, and
this sensitivity should be considered in the rehabilitation processes associated with
these patients
Thyroid Meds:
T4 only meds: synthetics
o Levothroid, Levoxyl, Synthroid, Unithroid
T3 only medications: synthetics
o Liothyronine, Cytomel
T4/T3 combos: synthetic
o Liotrix, Euthroid, Thyrolar
T4/T3 medications (bioidentical/natural)
o Armour, Nature-thyroid, Westhroid, Desiccated Thyroid
Anti-Thyroid Drugs – Thiamides
Propylthioruacil (PTU) and methimazole are small sulfur-containing molecules that inhibit
thyroid hormone production
The thioamides can be taken orally and are effective in most patients with uncomplicated
The thioamides can be taken orally and are effective in most patients with uncomplicated
Because synthesis (rather than release) of thyroid hormone is inhibited, the onset of activity of
these drugs is usually slow, often requiring 3 to 4 weeks for full effect
However, high-dose PTU also inhibits the conversion of T4 to T3.
o PTU is less likely than methimazole to cross the placenta and enter breast milk, but it
should be used cautiously in pregnant and nursing women:
Most Common Toxic Effect: Skin Rash
Iodide Salts and Iodine:
Iodide salts inhibit thyroid hormone release, possibly by inhibiting thyroglobulin proteolysis
These salts also decrease the size and vascularity of the hyperplastic thyroid gland
Because iodide salts inhibit release as well as synthesis of thyroid hormones, their onset of
action occurs relatively rapidly – within 2 to 7 days
However, their effects are transient; the thyroid gland “escapes” from the iodide block after
several weeks of treatment
Iodide salts are used to manage severe hyperthyroidism, a “thyroid storm”
o Life threatening sudden acute exacerbation of all of the symptoms of hyperthyroidism
o Prepare patients for surgical resection of a hyperactive thyroid
Radioactive Iodine and Iodinated Radiocontrast Media:
Radioactive Iodine is taken up and concentrated in the thyroid gland severely can be given
without endangering other tissues
Unlike the thioamides and iodide salts, an effective dose of 131l can produce a permanent cure
of hyperthyroidism without surgery. 131l should not be used in pregnant or nursing women
Certain iodinated radiocontrast media, such as ipodate, effectively suppress the conversion of
T4 to T3 in the liver, kidney and other peripheral tissues
Inhibition of hormone release from the thyroid may also play a part
Ipodate is useful for rapidly reducing T3 concentrations in hyperthyroidism
Clinical Implications:
1) Thyroid Hormones:
a. Exercise intolerance associated with both hyper-thyroidism and hypo-thyroidism
b. Intolerance to tmeprature
c. Hypothyroidism: Cold Intolerance
d. Hyperthyroidism: Heat intolerance
2) Estrogens and Progesterone receptor agonist
a. DVT
b. MI
c. HTN
d. Decreased capacity to participate in aerobic conditioning due to thyroid dysfunction
e. Increased risk for embolic event during therapy
f. Increased risk of MI during therapy
Week 4: Lecture 2: Endocrine Part 2
Gonadal Hormones and Inhibitors:
The gonadal hormones include the steroids of the ovary
o Estrogen
o Progesterone
And the Testes:
o Testosterone
Drugs with mixed effects demonstrate agonist effects in some tissues and antagonist effects in
other tissues
Synthetic Androgens, all of which have anabolic activity, are also available for clinical use
Ovarian Hormones:
The ovary is the primary source of sex
hormones in women during childbearing years
o Between Puberty and Menopause
During each menstrual cycle, in response to
FSH and LH from the anterior pituitary, a
follicle in the ovary matures, secretes
increasing amounts of estrogen, releases an
ovum, and finally transforms into a
progesterone-secreting corpus luteum
o If the ovum is not fertilized and
implanted, the corpus luteum
o The uterine endometrium, which
proliferated as a result of stimulation
by estrogen, is shed as a part of the
menstrual flow, and the cycle repeats
Follicle-Stimulating Hormone
FSH stimulates gametogenesis and follicle development in women and spermatogenesis in men
o These products are used in combination with other drugs to treat infertility in both
Luteinizing Hormone:
In women, luteinizing hormone acts in concert with FSH to regulate:
o Gonadal Steroid Production
o Follicular Development
o Ovulation
In men, LH regulates testosterone production
A Human Chorionic gonadotropin (hCG) is almost identical to LH,
used to treat:
o Hypogonadism in men and women
o Controlled hyperstimulation and assisted reproductive
technology programs
Clinical Use – Estrogen
Estrogens are used in the treatment of hypogonadism in young females
Another use is as HRT in women with estrogen deficiency resulting from premature ovarian
failure, menopause, or surgical removal of the ovaries
HRT ameliorates hot flushes and atrophic changes in the urogenital tract
Estrogen is also effective in preventing bone loss and osteoporosis
o Increase risk of adverse cardiovascular events and breast cancer when estrogen is used
by postmenopausal women for this pharmacological effect
o Finally the estrogens are components of hormonal contraceptives
The major Ovarian Estrogen in Women is ESTRADIOL
The drug can also be administered via transdermal patch or vaginal cream
Long-acting esters of estradiol that are converted in the body to estradiol, such as estradiol
cypionate, can be administered by IM injection
Mixtures of conjugated estrogens from biologic sources are used orally for hormone
replacement therapy
Physiological Effects of Estrogen:
o Estrogen is essential for normal female sex development
o Hormone is responsible for growth of vagina, uterus, and uterine tubes during
childhood, appearance of secondary sexual characteristics, and the growth support
associated with puberty
o The hormone modifies serum protein levels and reduces bone reabsorption
o Estrogen also enhances blood coagulability and increases plasma triglyceride and high
density lipoprotein (HDL) cholesterol levels while reducing low-density lipoprotein (HDL)
cholesterol levels while reducing LDL cholersterol
Adverse Effects of Estrogen:
o In hypogonadal girls, the dose of estrogen must be adjusted carefully to prevent
premature closure of epiphyses of the long bones, resulting in short stature
o The relationship between long-term estrogen therapy and cancer continues to be
o When used alone for HRT in women with a uterus; increased risk of endometrial cancer
▪ Can be prevented by combining estrogen with a progestin
o Estrogen use by postmenopausal women is also associated with a small increase in the
risk of breast cancer, myocardial infarction and stroke
o Dose-dependent toxicities include
▪ Nausea
▪ Breast tenderness
▪ Increased risk of migraine HA
▪ Thromboembolic events
▪ Gallbladder disease
▪ Hypertriglyceridemia
Progestins – used as contraceptives either alone or in combo with estrogen
Used with estrogen to prevent estrogen-induced endometrial cancer
Progesterone is used in assisted reproductive technology programs to promote and maintain
Micronized form is ued orally for HRT and progesterone-containing vaginal creams are also
Synthetic Progestins have improved oral bioavailability
Physiological effects:
o Increases secretory changes in the endometrium and is required for the maintenance of
o Other progestins also stabilize the endometrium but do not support pregnancy
Adverse Effects:
o The toxicity of progestins is LOW
▪ However, may increase BP and decreased HDL cholesterol
o Long term use: associated with decrease in bone density and delayed resumption of
ovulation after termination of therapy
Hormonal Contraceptives:
Contain either Progestin, or a combination of estrogen and progestin
Hormonal contraceptives are available in a variety of preparations, including oral pills, longacting injections, transdermal patches, vaginal rings, and IUDs
Three types of Oral Contraceptives available:
1) Monophasic preparations are a combo of estrogen-progestin tablets that are taken
in constant dosage throughout the menstrual cycle
2) Biphasic and triphasic preparations are combination preparations in which the
progestin or estrogen dosage or both, changes during the month to more closely
mimic hormonal changes in the menstrual cycle
3) Progestin
Postcoital Contraceptives (emergency contraception/plan B) will prevent pregnancy if
administered within 72 hours after unprotected sexual intercourse
Mechanism of Action Contraceptives:
Primary Action: Inhibit Ovulation
Additional Changes in the Cervical Mucus Glands, Uterine tubes, and endometrium also
decrease the likelihood of fertilization and implantation
Progestin-only agents do not always inhibit ovulation and instead act through other mechanisms
Plan B: not well understood
o When administered before the LH surge, the inhibit ovulation
Also affect cervical mucus, tubal function, and endometrial lining
Can also be used to treat:
o estrogen deficiency in young women with primary hypogonadism after their growth has
been achieved
o Acne, Hirsutism, Dysmenorrhea, Endometriosis
Users of combination hormonal contraceptives have reduced risks of ovarian cysts, ovarian and
endometrial cancer, benign breast disease, pelvic inflammatory disease, as well as a lower
incidence of ectopic pregnancy, iron deficiency anemia, and RA
Adverse Effects of Contraceptives:
The incidence of dose-dependent toxicity has fallen since the introduction of the low-dose
combined oral contraceptives
The most notable adverse effects include thromboembolism and a potentially increased risk of
developing breast cancer at a younger age
Increased risk results in an elevated potential for MI, stroke, DVT, and PE
Evidence also suggests that the lifetime risk of breast cancer in women who are current or past
users of hormonal contraceptives is NOT affected by oral contraceptive use
o May be an earlier onset of breast cancer
Selective Estrogen Reception Modulators:
SERMS are mixed estrogen receptor ligands that act as agonists in some tissues and as partial
agonists or antagonists in other tissues
Tamoxifen is a SERM effective in treatment of hormone-responsive activation by endogenous
o acts as an agonist at endometrial estrogen receptor, causing hyperplasia and increasing
the risk of endometrial cancer
o can cause hot flushes, reflecting an antagonist effect, whereas it also increases risk of
venous thrombosis (agonist)
o In bone, has agonist effect more than antagonists estrogenic actions
▪ Prevents Osteoporosis in women who are taking the drug for breast cancer
o Prophylactic use of tamoxifen reduces the incidence of breast cancer in women who are
at very high risk
o Raloxifene:
▪ Approved for preventing osteoporosis
• Agonist effect on bone
▪ Prevention of breast cancer in high risk women
▪ Unlike tamoxifen, drug has NO estrogenic effects on endometrial tissue
▪ Adverse effects also include hot flushes and increased risk of venous thrombosis
Androgens – Testosterone
Primary use: replacement therapy in Hypogonadism
Used to stimulate RBC production in certain anemias and to promote weight gait in patients
with wasting syndrome
Adverse Effects:
Women use: menstrual irregularity and virilization
▪ Hirsutism
▪ Enlarged Clit, deeper voice
Pregnant Women use:
▪ Can cause virilization of the fetus’ external genitalia
▪ Gynecomastia
▪ Teste shrinkage
▪ Infertility
High Doses
▪ Jaundice
▪ Elevation of Liver Enzyme levels
▪ Heptaocellular carcinoma
▪ Increased lipid levels = atherosclerosis
▪ Sodium retention = HTN
Pancreas Function and Physiology
Blood Sugar Control
Secretion of Substances which aid digestions
Pancreas Hormones:
Islet of Langerhans contain 4 main types of endocrine cells
Theses 4 include:
o Glucagon-producing alpha cells
o Insulin- and amylin producing beta cells
o Somatostatin-producing delta cells
o Pancreatic polypeptide-producing cells
Of these, the insulin-producing B cells are the most numerous
Most common disease related to pancreatic function is DM
Main target tissues: Liver, Muscle, Adipose
Promotes glycogen synthesis, glycolysis, carb oxidation
o Inhibits protein breakdown
o Promotes glucose uptake in adipose tissue
Effect is to move glucose from blood into cells to boost supplies of glycogen and lipids that can
later be used to supply energy during fasting
Diabetes Mellitus
Type 1 – insulin dependent
Type 2 – non-insulin dependent
Drugs for Diebetes
o Pharmaceutical human insulin
o The available insulin formulations
provide 5 rates of onset and
durations of effects:
▪ Rapid Onset
▪ Rapid Onset with short
▪ Intermediate onset and
▪ Slow onset with peak action
▪ Combination
o Insulin preparations contain zinc
o The ratio of zinc and other substances to insulin influence the RATE of RELEASE of active
hormone from the site of administration and the duration of action
Adverse Effects of Insulin Therapy:
Diabetic patients who use insulin are subject to two types of complications
o Hypoglycemia
o Immunologic toxic effects from the development of antibodies
o Rapid development of hypoglycemia in individuals with intact hypoglycemia awareness
causes autonomic hyperactivity with both sympathetic and parasympathetic
▪ Symp: Tachycardic Palpitations, sweating, tremulousness
▪ Para: nausea, hunger
o In patients who experience frequent hypoglycemic episodes, autonomic warning signs
can be less frequent or absent
Administrate glucose or simple sugars
o Candy or IV glucose
Intramuscular injection of glucagon to raise serum glucose levels
Insulin can cause weight gain
Drugs that Effect Bone:
Calcium and Phospate are the major mineral constituents of bone
o Body carefully regulates via homeostasis
98% of the 1 to 2 kg of Calcium and 85% of the 1 kg to 2 kg of calcium and 85% of the 1 kg of
phosphorus in the human adult are found in bone
o Bone acts as principal structural support the body and provides space for blood cell
Bone Health:
Dysfunction in homeostasis of bone = increased risk of osteoporosis and fx
Avg American diet provides 600-1000mg Calcium a day
o 100 to 250 mg absorbed
▪ Duodenum and Upper Jejunum
▪ Secretion: Ileum
At a steady state: renal exertion of calcium and phosphate balances intestinal absorption
o 98% of filtered calcium
o 85% of filtered phosphate absorbed by kidneys
Endogenous Agents:
PTH – enhances both bone resorption and formation
o Excess PTH = increases bone resorption
o Low doses: increases bone formation without stimulating bone resorption
o Net Effect: raise serum calcum and reduce serum phosphate
Vitamin D: keeps your bones strong by helping your body absorb calcium and phosphorous,
raising serum levels for both
o Calcitonin – lower serum calcium and phosphate by actions on bone and kidney
▪ Inhibits osteoclastic bone resorption
o Estrogen – Estrogen and estrogen receptor modulators (Tamoxifen or Raloxifene)
prevent or delay bone loss in postmenopausal women
▪ Long term estrogen tx increases cardiovascular and cancer risks
o Glucocorticoid – alter bone mineral homeostasis by antagonizing Vitamin D-stimulated
intestinal calcium transport, stimulating renal calcium exertion, and blocking bone
▪ Chronic systemic use of glucocorticoids is a common cause of Osteoporosis in
adults and stunted skeletons development in children
Exogenous Agents:
1) Biphosphonates – compounds that reduce both resorption and formation of bone by acting on
the basic hydroxyapatite crystal structure of bone function
a. In postmenopausal women, chronic biopshoponate therapy slows osteoporosis
progression and reduces fx
b. Chronic exposure to floride ion, especially in high concentrations, may increase new
bone synthesis
i. Not clear it the bone has
normal strength
2) Fluoride – Chronic exposure to fluoride ion (especially high concentrations) may increase new
bone synthesis
a. Unclear if the bone has normal strength
b. No decrease in incidence of fractures in people with osteoporosis
Bone Disorders – Osteoporosis
Calcitonin is approved for the treatment of post-menopausal osteoporosis
o Increases bone mass and reduces fractures (only in the spine)
Bisphosphonates are efficacious inhibitors of bone resorption
o Increase bone density
o Reduce risk of fractures in hip, spine, other loctions
Despite early promise the fluoride might be useful in the prevention or treatment of
postmenopausal osteoporosis, this form of therapy remains controversial
Teriparatide (recombinant from of PTH 1-34) was recently approved for tx of osteoporosis
o Stimulates new bone formation
Drugs that effect Hyperlipidemia
Atherosclerosis is the abnormal accumulation of lipids and products resulting from inflammatory
response in the wall of arteries
o Leading cause of death in Western world
Heart attacks, angina pectoris, peripheral arterial disease, strokes
Very low density lipoprotein (VLDL)
Low-density lipoprotein (LDL)
Intermediate-density lipoprotein (IDL)
High Density Lipoprotein (HDL)
o Retrieve cholesterol from the artery wall and inhibit the oxidation of
atherogenic lipoproteins
o Low levels of HDL = independent risk factor for coronary artery diease
o High levels of HDL = protective
The risk of atherosclerotic heart disease increases with high concentrations of
atherogenic lipoproteins such as LDL and low HDL
Premature or accelerated development of atherosclerosis is strongly associated
with elevated levels of total cholesterol and LDL cholesterol
Treatment Strategies:
Cholesterol, Saturated Fats, Trans Fats = primary dietary factors that contribute to
elevated LDL levels
o Total Fat and Caloric restriction = important in the management of triglycerides
o Omega-3-fatty acids found in fish oils can induce profound lowering of triglycerides in
some patients
o Omega-6-fatty acids found in vegetable oils may increase triglycerides
Drug Classes: 5 Drugs to decrease serum concentrations of lipids in the blood and prevent or
reverse associated atherosclerosis
o HMG-CoA Reductase (Lovastatin)
o Bile Acid Sequestrants (Resins)
o Cholesterol absorption inhibitors (Ezetimibe)
o Nitrotonic Acid (Niacin)
o Fibric Acids (Fibrates)
Anti-Hyperlipidemic drugs: Effects and Side Effects
Clinical Implications:
➢ Physical Therapists need to be aware of the fact that repeated bouts of hypoglycemia may result
in blunted autonomic nervous system warning symptoms
➢ Osteoporosis:
o Have patients take bisphosphonates after or at least 1 hour prior to therapy sessions
o Have patients take calcitonin on a day when therapy is NOT scheduled
o Schedule Therapy sessions for days when SERM drugs or teriparatides are not
administered, or on a day prior to drug administration
➢ Hyperlipids:
o Several of the lipid-lowering drug classes can cause myalgia, arthralgia, and muscle
Arthralgia, myalgia, and muscle weakness may decrease patient function because of
pain and may adversely affect functional outcomes of treatment
The clinician should differentiate pain associated with exercise from that associated
with the adverse effects of these drugs
Week 4: Lecture 3: Respiratory System
General Info: Respiratory Tract Divided into two systems:
1) Upper: Nose, Sinuses, Oropharynx, Larynx
2) Lower: Trachea and lungs
The two are treated differently
Upper Respiratory System:
➢ Disorders associated with
o Infections – (most commonly uncomplicated viral rhinotracheitis)
o Seasonal Allergies – allergic rhinoconjunctivitis and rhinotracheitis
➢ For the most part, these dysfunctions are self-limiting
Mechanism of Action: Upper Respiratory
Secretion of Histamine and other mast cell mediators causes vasodilation of the nasal
o Leads to nasal congestion/runny nose
o Commonly associated with seasonal allergies and viral infections
H1 receptor antagonists (antihistamines):
o decrease mucus production and vasodilation
Nasal decongestants:
o Decrease vasodilation
o Mast cell stabilizers
Bronchial congestion with cough and excessive mucus production are also associated with viral
These manifestations may be relieved with drugs that suppress coughing or assist in clearance of
mucus from larger airways in the lungs
o Expectorants
Drugs to treat upper respiratory tract infection: H1 Blocking Antihistamines
Uses – Allergies, Motion sickness
Two Major Subgroups:
o Older First-generation agents: Typified by diphenhydramine and doxylamine
▪ Highly sedating agents w/ autonomic receptor-blocking effects
o Newer Subgroup: first generation agents is less sedating and has fewer autonomic
H1 Blockers are competitive antagonists at the H1 receptor level
These drugs have no effect on histamine release from storage sites and are more
effective if given before histamine release occurs
Structure resembles muscarinic blocker and alpha adrenocepter blockers
▪ Many of the first-gen agents are potent pharmacologic antagonists at these
autonomic receptors
Adverse Effects:
Sedation and Antimuscarinic effects such as dry mouth and blurred vision
Types of H1 Blocking Antihistamines
Uses: Allergies, Colds
Nasal Decongestants are agonists at alpha adrenoceptors and may be classified as
Systemic or Topical
Blood Vessels of the upper respiratory tract mucosa contain alpha1 and alpha2
Stimulation of these receptors decreases blood flow and thus volume of the nasal
Decongestants are all direct-acting alpha agonists and have indirect sympathomimetic
Adverse Effects – Tremors, Increased Blood Pressure, Anxiety
Antitussives and Expectorants
Use – Cough Suppressant and Mucus Removal
Natural Opioids (such as dextromethorphan)
o Suppress the cough center in the medulla oblongata
▪ Increases stimulatory threshold required to initiate the cough reflex
o Some meds assist in expectoration of respiratory mucus by stimulating respiratory tract
▪ Increased airway fluid volumes and decreased mucus viscosity
Adverse Effects: GI dysfunction, tachycardia, HTN
Lower Respiratory System:
➢ Disorders of the lower respiratory tract may be broadly classified as:
o Parenchymal infections
o Obstructive airway conditions
▪ Typically limit expiratory airflow
• Bronchial Asthma
o Chronic Obstructive Airway disorders are further subdivided into:
▪ Chronic Bronchitis
▪ Emphysema
▪ Bronchiectasis
▪ Cystic Fibrosis
➢ Obstructive Airway Disorders: Bronchial Asthmas
o Early Phase Responses occur following exposure to a trigger stimulus and a late-phase
response which begins 6 to 8 hours later
▪ Initiated by the stimulus (allergen) binding to IgE bound to mast cells in the
airway mucosa
o Subsequent release of eicosanoids and other mediators result in the initial
bronchospasm and influx of additional inflammatory cells
o Bronchospasm decreases the airway diameter and limits expiratory airflow
o Hallmark of the late-phase response is:
▪ airway inflammation with interstitial airway edema
▪ invasion of white blood cells
▪ epithelial injury with decreased mucociliary function
▪ sustained bronchoconstriction
➢ Chronic Obstructive Pulmonary Disorders: Bronchitis, Emphysema, Bronchiectasis, Cystic
Fibrosis – Common Characteristics:
Acute Bronchospasm:
➢ Early Phase Meds:
o Acute Bronchospasm can usually be treated promptly and effectively with
o Beta2 -selective agonists, muscarinic antagonists, and theophylline and its derivatives
are available for this indication
▪ Methyxathines – Xanthine
➢ Late Phase Medications:
o Late response inflammation and bronchial hyperactivity can be treated with:
▪ Corticosteroids
▪ Cromolyn
▪ Nedocromil
▪ Leukotriene antagonists
o These drugs inhibit release of mediators from mast cells and other inflammatory cells or
block their effects
o Corticosteroids:
▪ Use – Late/Severe
▪ Inhibit Phospholipase A2 and reduce Eicosanoid synthesis
▪ Excessive activity of phospholipase A2 is thought to be particularly important in
asthma because the leukotrienes that result from eicosanoid synthesis are
extremely potent bronchoconstrictors and also participate in the late
inflammatory response
▪ Reduce Release of Archidonic acid by Phospholipase A2 and inhibit the
expression of type 2 cyclooxygenase (Cox-2_
• Inducible for of Cycloxygenase
▪ Adverse Effects: Candidiasis
• Reduced with water gargling after meds
o Leukotriene Antagonists: derived from arachidonic acid (precursor of prostaglandins)
Two Families of Leukotrienes
• 1st group: Inflammation is dependent on neutrophils
o Cystic Fibrosis
o Inflammatory bowel disease
o Psoriasis
• 2 Group: Eosinophil and Mast Cell induced bronchoconstriction in
• Bind to highly selective receptors on bronchial smooth musle and other
airway tissue
• Types:
o Lipoxygenase Inhibitors
o Receptor Inhibitors
Meds for COPD:
➢ Management of COPD usually involved acute exacerbation of breathing disorders
Clinical Implications:
Antihistamines cause sedation and orthostatic hypotension
Nasal decongestants may increase BP and HA
Antitrussives can cause decreased respiratory drive
Lower Respiratory drugs may cause cardiac arrhythmias
Week 4: Lecture 4 – Chemotherapeutics
Discussing: Antibacterial and Antiviral
General Info:
➢ Antimicrobial Drugs are amount the most dramatic examples of advances in medicine
o Classified by type of infectious organism they are used to treat
➢ Antibacterials:
o Bacteria can directly damage or destroy human cells by releasing toxins and they can
compete with human cells for vital nutrients
▪ Are single-celled prokaryotes
▪ Fungi, protozoa, multicellular organism have nuclei containing genetic material
and are called eukaryotes
▪ Viruses, are not strictly cellular at all and comprise a very different form of life
▪ Bacterial deoxyribonucleic acid forms a long circular molecule called a nucleoid
Classifying Antibiotics:
➢ Most Common way to Classify antibiotics is on the basis of their site of action:
o Inhibitors of bacterial cell wall synthesis
o Inhibitors of bacterial protein synthesis
o Inhibitors of bacterial DN synthesis
➢ Some antibiotics are also:
o Bactericidial (kill bacteria)
o Bacteriostatic (inhibit bacterial growth
➢ Bacteriostatic antibiotics are successful in treating infections in patients with intact immune
systems because they prevent bacterial population from increasing
o Allow host defense mechanisms to eradicate the remaining population
Antibiotic Resistance:
➢ Mechanism:
o Production of drug-inactivating enzymes
o Changes in the structure of target receptors
Increased antibiotic efflux via drug transporters
Decreases in cell wall permeability to antibiotics
Most common cause of resistance is the use of inappropriate antibiotics for viral or
other nonsusceptible infections
Other Cause of Resistance:
▪ Use of inadequate dosage or duration of an appropriate drug
• Eliminate only the most susceptible organisms, leaving the more
resistant ones to proliferate.
Inhibitors of Cell Wall Synthesis
➢ Penicillins
➢ Cephalosporins
Clinical Implications:
➢ Many of the anti-bacterial and anti-viral meds will cause GI problems and nausea.
o Because of this, frequent trips to restroom is expected
➢ Individuals taking these meds are batting bacteria or viruses and therefore are likely to feel
fatigue and weakness
➢ Many of these drugs are contagious, so clinicians should protect themselves with flu shots or