Pharmacology Crash Course

Why do physical therapists need pharmacology?

* communication w/ pt and other healthcare providers
* recognize over-medication, adverse/side effects or under-medication and refer pts to appropriate prescriber when there are concerns
* administer certain drugs
* advice pts about potential drug effects/adverse effects, w/in scope of practice
* future prescription privileges

Drug names

* chemical structure name
* generic name based on prefix, base and suffix (what it does)
* trade name given by manufacturer
* supposed to refer to drugs by generic names

examples of drug names

chemical name - generic - trade

* acetyl salicylic acid - aspirin - bayer, ecotrin
* benobenzyl penicillin - ampicillin - rosscillin
* N-4(hydroxyphenyl) acetamide - acetaminophen - Tylenol

pharmokinetics

* how does the body affect a drug
* how drug are absorbed, metabolized, and excreted by body
* considered carefully in designing and dosing drugs

pharmacodynamics

* indication for the drug
* mechanism of action
* adverse effects and side effect
* drug - drug and drug-food or other interactions

how the drug is absorbed into the body

* route of administration
* onset

how the drug is metabolized

* distribution and bioavailability
* peak and duration
* half - life
* how drug is eliminated from body
* duration of action and half-life

administration

determined by bioavailability of drug

* protein vs lipid vs other chemical molecule
* oral
* parenteral
* IV
* intramuscular
* subcutaneous
* transdermal
* inhaled
* buccal/sublingual

oral administration

most common method of administration

advantages of oral administration

* cheap
* easy to administer
* convenient

disadvantages of oral administration

* 1st pass metabolism
* must be GI compatible
* potential for abuse

parenteral administration

administered in a manner other than through digestive tract

IV administration

into vascular compartment

advantages of IV administration

* fast
* wide distribution throughout body

disadvantages of IV administration

* little control
* requires sterility
* requires skilled provider to administer

clone

hypnotic/tranquilizer

amivir

neuraminidase inhibitor

vir

anitviral

previr

serine protease inhibitor

mab

monoclonal antibody

zumab

humanized monoclonal antibody

advantages of intramuscular administration

* moderately rapid
* administered at home for some patients

disadvantages of intramuscular administration

* absorption depends on blood supply
* concentration and bioavailability

advantages/ disadvantages of subcutaneous administration

* similar to intramuscular
* slower absorption

side effect

same as adverse effect

advantages of transdermal administration

* convenient
* cheaper
* sterility not required

disadvantages of transdermal administration

* complex pharmacokinetics and inconsistent absorption
* depends on blood supply

advantages of inhaled administration

* very rapid
* may stay local
* may be administered at home

disadvantages of inhaled administration

* may not remain local
* requires some level of skill to administer
* moderate control after administration

advantages of buccal/sublingual administration

* faster than oral
* slower than IV/inhalation
* does not requires sterilization

liver function in metabolism of drug

* orally administer drug must pass through here (1st pass)
* primary site of metabolism
* biotransformation

biotransformation

* conversion of active to inactive or vice versa
* drugs may be bio-transformed into toxic chemicals
* toxic chemicals may be detoxified
* first pass metabolism - drug must survive liver

other sites of metabolism

* skin (Vit D)
* kidney (common site)

factors that affect metabolism

* age
* liver function
* enzyme-induction
* genetics

elimination of drugs

* kidney primary site
* lungs and GI tract too

factors affecting elimination

* age
* liver and kidney
* presence of certain chemicals

age affect on elimination

older adults and children may metabolize and eliminate certain drugs more slowly

liver and kidney for elimination

dysfunction slows metabolism and elimination of some drugs (both common in elderly)

presence of certain chemicals for elimination

can increase or decrease elimination

* vit C acidifies urine
* increasing excretion of weak bases (many drugs weak base)

indications

what conditions is the drug used for

mechanism of action

determines action/indications and adverse effects

side effects or adverse effects

unintended consequences or exaggerated intended effects of the drug that are harmful, unwanted or interfere with Rx

potency

amount of drug necessary to achieve given response

* only determines size of pill
* does not tell about ability of drug to produce effect

efficacy

effectiveness of drug in producing the desired response when given at max dose

* determines true ability of drug to achieve desired effect

potency vs efficacy example 1

* opioid versus NSAID for pain
* opioid may have low potency compared to NSAID
* given at max dose opioid more efficacious

potency vs efficacy example 2

* morphine vs. carfentynyl
* carfentanyl (Wildnil) is an analogue of opioid analgesic fentanyl
* quantitative potency \~ 100x fentanyl and 10,000x morphine
* very high potency medication more likely to be intentionally or unintentionally abused or lead to fatalities or complications compared to low potency medication

therapeutic window definition

difference between ED50 of drug and LD50

* does that is lethal in half of subjects

therapeutic window characteristics

* generally applied to all medications
* larger therapeutic window = safer drug
* drugs with narrow therapeutic windows typically exhibit toxicity

therapeutic window low drug examples

* digitalis
* theophylline
* lithium
* many chemo drugs

selective toxicity definition

difference in toxicity of an antimicrobial medication to microbe vs. host

higher selective toxicity

safe/better tolerated drug (antibiotic, anti fungal)

examples of drugs with high selective toxicity

* penicillin
* unless pt has specific allergy, well tolerated

example of low selective toxicity

* vancomycin
* may cause hearing loss and nephrotoxicity possible

principles governing drug action

* drugs work through neurotransmitter and a receptor
* secondary effect is often change in neurotransmitter receptor activity
* no magic bullets
* most drugs have general effect and act on other targets besides designated target
* non specificity of drugs
* drugs used to treat different disorders

example of non specific drug

* valium
* anti-seizure
* anti-anxiety
* anesthetic
* sedative-hypnotic used for sleep
* muscle relaxer
* anti-spasticity

lock and key model

* receptors is like a lock
* only particular molecule (agonist) with certain structure can unlock it = effect of stimulation
* other molecules can bind to receptor that do not unlock it but instead block activation (antagonist)

examples of pharmacologic receptor mechanisms

* molecular interaction w/ endogenous agonist/antagonist
* neurotransmitter exogenous agonist
* neurotransmitter antagonist
* drug that block re-uptake/breakdown of NT
* drugs that facilitates neurotransmitter release

molecular interaction w/ endogenous agonist/antagonist

epinephrine

* agonize the adrenergic receptor in heart, lung, CNS

neurotransmitter exogenous agonist

bromocreptine (parlodel)

* agonize dopamine receptors

neurotransmitter antagonist

acetophenazine (thorazine)

* antagonize dopamine R’s in limbic system

drug that block reuptake/breakdown of NT

Fluoxetine (prozac)

* serotonin specific re-uptake inhibitor

drugs that facilitate neurotransmitter release

amphetamine (ritalin)

* Increase NE release and prevents re-uptake

sympathomimetics/sympatholytics

(adrenergic vs. adrenergic inhibitors)

* activation of SNS increases anxiety, HR, BP, bronchoconstriction
* anti-adrenergic drugs (sympatholytics) used in CV disease and respiratory disease

Hypertension (HTN) is often Rx with selective ________ __or__ __________ that block SNS activation of B1-adrenergic receptors in heart

B1-antagonists; blockers

* effect is lowering resting HR, lower BP, and reduced max HR and Ex tolerance

asthma and COPD often Rx with selective _________ that activate B2-adrenergic receptors in bronchiolar smooth muscles (causing bronchiole dilation, improving respiratory function

B2-agonists

* adverse effects arise due to non-specific effects on other Beta receptors

other drugs used for HTN

* diuretics
* direct vasodilators
* indirect vasodilators

diuretics for HTN

lower blood pressure by getting rid of fluid

direct vasodilators for HTN

* lower BP by dilating peripheral arteries
* alpha-1 agonists and others

indirect vasodilators for HTN

* ACE inhibitors
* block rennin-angiotensin pathway leading to vasoconstriction
* angiotensin receptor blockers (ARBs)
* nitrates (nitroglycerine and others)

other cardiovascular drugs

* anticoagulants
* anti-lipid or lipid lowering drugs
* anti-arrhythmic drugs

anticoagulants

* decrease clotting or break up clots
* Heparin, Warfarin, Aspirin, Clopdogrel

Anti-lipid or lipid lowering drugs

* statins
* block the endogenous formation of cholesterol

anti-arrhythmic drugs

* calcium channel blockers


* beta blockers

stimulants

increase alertness, attention, and energy uppers

types of stimulants

* direct sympathomimetics
* classic indirect stimulants such as amphetamines
* milder over the counter stimulants

direct sympathomimetics

* epinephrine
* dopamine

Classic indirect stimulants such as amphetamines

* dextroamphetamine (dexedrine, adderall)
* methylphenidate (ritalin, concerta)
* ephedrine - taken off market

adverse effects of stimulants

* irritability
* anxiety
* insomnia
* nausea
* weight loss

milder over the counter stimulants

* caffeine
* in Red Bull, Mountain Dew, vivarin

depressants

lower CNS activity and impair cognition

* strong analgesics
* anesthetics
* sedative hypnotics
* most anti-seizure medications
* anti-spasticity and anti-spasm medications

strong analgesics

* opioids
* non opioid pain killers

anesthetics

* opioids
* ketamine
* inhaled anesthetics
* muscle relaxers (benzodiazepines)

sedative hypnotics

* benzodiazepines
* diazepam (valium) and alprazolam (xanax)
* barbiturates
* mephobarbital (mebaral) and pentobarbital (nembutal)

cardiovascular system meds

* autonomic nervous sytem stimulants and inhibitors
* antihypertensive drugs
* lipid lowering drugs
* drugs affecting blood coagulation
* other drugs directly affect the heart

central nervous system meds

* drugs affecting mental status and alertness
* analgesics
* anesthetics
* antidepressants and antipsychotics

meds for all patients

* drugs affecting inflammation
* drugs affecting muscle tone/function
* antimicrobials
* chemotherapy

anti-spasticity and anti-spasm medications

* muscle relaxers
* baclofen

anti-spasticity medications

* treat a wide variety of neuromuscular conditions involving spasticity
* CP, SCI, TBI, MS, CVA

peripherally acting injectables that inhibit neuromuscular junction

* botox
* used to irreversibly inhibit Ach release from NMJ presynaptic nerve terminal

centrally acting anti-spasticity medications

* baclofen oral (lioresal)
* inhibits motor neurons in SC
* adverse effects: drowsiness and sedation
* baclofen intrathecal (pump delivers it to SC)
* effective and fewer SE
* administration must be monitored and may lead to complications

drugs that regulate mood, affect, cognition

* antidepressants
* serotonin-specific re-uptake inhibitors (SSRIs)
* serotonin and norepinephrine re-uptake inhibitors (SNRIs)

antidepressants

widely used in rehab and often help patients participation and engagement

serotonin-specific reuptake inhibitors

* considered 2nd generation antidepressants
* modest adverse effect profile

serotonin and norepinephrine reuptake inhibitors

* condensed 3rd generation antidepressants
* more expensive

anti-inflammatories

wide variety of subtypes given inflammation is different in different body systems and involves wide variety of pathways

general anti-inflammatories

* non steroidal anti inflammatory Drugs (NSAIDS)
* glucocorticoids
* cytokine inhibitors

non steroidal anti-inflammatory drugs

* inhibit eicosanoids, pain, and inflammation promoters derived from lipid bilayer
* Ibuprofen, aspirin, naproxen
* over the counter and well tolerated except for GI effects

glucocorticoids

* predni%%sone%% (deltasone)
* corti%%sone%%
* dexametha%%sone%%
* hydrocorti%%sone%%

users of glucocorticoids

* respiratory
* neurologic
* endocrine
* rheumatoid
* cancer
* GI disorders

cytokine inhibitors

* tumor necrosis factor-alpha inhibitors
* synthetic antibodies that bind TNF
* adalimumab (Humira), etanercept (Enbrel), golimumab (simponi)
* newer drugs that are only available as injection