Pharmacology Flashcards
Why should PTs understand pharmacology?
medications may alter clinical presentation or course of therapy
Role of PTs in pharmacology
monitor for medication adherence
educate on preventative health care
monitor for exercise-induced changes w/medication
identify rehab effects vs drug effects
Drug definition
Substance (other than food) intended to affect the structure or function of the body, includes drugs of abuse
Drug names can be…
chemical
generic
brand name
Polypharmacy
multiple definitions
1. more drugs prescribed than warranted
2. Too many pills to take, pill burden
3. more than 5 drugs a day
Why is polypharmacy a problem?
Increased risk of ADRs
Low adherence to drug therapy
Unnecessary healthcare costs (hospitals, $)
Pharmacodynamics
why you took the drug in the 1st place
effect of the drug on the body
includes cellular effects by which drugs produce systemic effects
Pharmacokinetics
effects of body on the drug
involves absorption, distribution, metabolism, excretion
Absorption
HOW do we take it?
Distribution
WHERE does it go in the body
Elimination
HOW LONG does it stay in the body?
made up of metabolism and excretion
Steps of how new drugs are developed and approved
- Science and testing on animals
- Application to FDA to test on humans
- Clinical Trials
*Phase 1 = max dose & ADRs
*Phase 2 = effect of drug on disease
*Phase 3 = placebo vs drug
Dietary Supplements
Has to meet these criteria:
1. supplement diets with vitamin, mineral, herb
2. ingestion
3. not food or meal
4. labeled at supplement
Prescription
Drug that is authorized by PCP
Over the counter drugs
available to any consumer
Risks of over the counter drugs
decreased awareness of dosages
increased drug-drug interactions
delay use of more effective meds
Enteral Absorption
via the GI tract
oral, sublingual, rectal
Parenteral Absorption
bypassing the GI system
Inhalation, Injection, Topical, Transdermal
Advantages of oral
Easy
safe–> don’t have to be sterile, and don’t reach peak plasma levels for awhile
Disadvantages of oral
must not be destroyed by acidic gastric environment
can cause GI upset
less predictable timeframe to reach effective plasma level
First Pass Effect
- Drugs are taken up from capillaries in stomach & small intestine and are transported by the hepatic portal vein to liver cells.
- Dosage has to be high enough to allow drug to survive enzymes of liver
Factors that affect the rate of GI absorption
Blood flow and intestinal motility
Gastric emptying time
Food
Buccal
between cheek and gums
Sublingual
under tongue
Sublingual and Buccal path of drugs
Oral mucosa –> veins –> superior vena cava –> heart
bypasses first-pass effect, so onset is much more rapid
Nitroglycerin
used to relieve acute anginal attacks
sublingual and buccal path of drugs
Rectal route
typically only used for treating local conditions
unconscious pts, vomiting (positive)
poor absorption, rectal irritation (negative)
Advantages of Parenteral
quantity of drug that reaches target site is more predictable than enteral routes
time frame is more predictable
no food, enzyme breakdown, GI issues
Routes of Parenteral
Inhalation
Injection
Topical
Transdermal
Inhalation
gases or aerosols
rapid entry into bloodstream
excellent for pulmonary conditions
can use nebulizer, spacer, diskus to avoid irritation
Spacer
one-way valved holding chamber for aerosolized drugs contained in MDIs
PTs should help to teach pts how to use inhalers
Injection
Can get peak drug level to target tissue quickly
easier to overdose, easy to cause infection
Methods of Injection
Intravenous
Intra-arterial
Intramuscular
Subcutaneous
Intrathecal
Intra-articular
Intravenous
can be a bolus or indwelling catheter
Intra-arterial
targets drug to certain tissues
Intramuscular
rapid, but stable drug use
Subcutaneous
injection directly in deepest skin layer, can be bolus or implanted device
Intrathecal
targets drug next to spinal cord, to enable easier bypass of blood-brain barrier
Intra-articular
injection into intra-articular space usually drugs to treat joint pain and/or inflammation
TOpical Administration
Can be applied to the skin or mucous membranes
Skin Topical Administration
drugs applied to skin, with intention of treating skin itself
generally POOR systemic absorption from skin
Mucous Membrane Topical Administration
drugs applied to mucous membranes with significant systemic absorption possible
Transdermal vs Topical
Goal is different
Drug design or modality used with it
Patches
only for transdermal use
only on intact skin
heat-dependent, avoid excessive heat
Indication
uses of the drug for a particular condition
ADRs
harmful unintended reactions to medicines that occur at doses normally used for treatment
Serious ADRs
require intervention by HCP
only had to occur once
Respiratory depression is a characteristic of all
opioids
Most common drug classes associated with ADRs
opioids
diuretics
anticoagulants
Patients that experience ADRs are more likely to be
older
female
have longer LOS
be taking larger number of medications
Incidences of ADRs increases with
more than 4 meds
Types of ADRs
Intrinsic ADR
Idiosyncratic ADR
Hypersensitivity ADR
Intrinsic ADRs
predictable based on properties of the drug
typically dose-dependent
70-80% of ADRs
Idiosyncratic ADR
unpredictable
can be due to genetic differences in metabolism
Hypersensitivity ADR
reactions usually occur after prior exposure
dose dependent
Dermatologic Toxicity
-development of cutaneous disease due to combined effects of drug and light
-NSAIDs, oral contraceptives are common offenders
Pts should decrease sun exposure between 10 AM to 4 PM and wear sun protective clothing
Ototoxicity
-damage to organs or nerves in the ear, leads to hearing and balance problems
-Lasix/diuretics are common offenders
pts risk increases with renal impairment. Tinnitus should be reported to PCP
GI Toxicity
-damage to mucosal lining of GI tract
-nausea, vomiting
-nsaids and chemotherapy are offenders
-pts with history of ulcers or older than 60 should be careful with multiple uses of NSAIDs, antiplatelet/coagulants
-report s/s of ulcers
-use lowest effective dose for shortest time
Nephrotoxicity
Damage to kidney cells or causing renal impairment
-NSAIDs, asprin, acetaminophen
pts should recognize that kidney disease is asymptomatic. identify risk factors, and encourage high-risk pts to decrease NSAID consumption
RF for kidney disease
DM
HTN
greater than 60 years old
family hx of kidney disease
Hepatotoxicity
-damage to liver cells or causing liver impairment
-acetaminophen is common offender
pt with liver disease or consume more than 3 drinks a day should avoid acetaminophen
CNS Toxicity
-observable disruption of normal brain function
-antihistamines, antidepressants are common offenders
pts are vulnerable if they are elderly; should reduce dosage and time frame. recent changes in cognition should be reported
CV toxicity
many heart medications cause problems
-antihypertensives
-antiarrhythmics
Antihypertensives
cause orthostatic hypotension
-you should perform transfers slowly
-incorporate cool-down period in exercise
-caution when exiting warm aquatherapy
Antiarrhythmics
often cause rate and rhythm disturbances
monitor vital signs and pts subjective symptoms
Common problems in older adults
polypharmacy
altered pharmacokinetics
altered pharmacodynamics
Prescribing Cascade
prescription to combat ADR of other drug
Altered pharmacodynamics causes
increased sensitivity to warfarin, benzodiazepines, opiates, NSAIDs
PIMS
potentially inappropriate medications in older adults
risks tend to outweigh the potential benefits
PTs role in managing meds
- Take complete drug hx or review inpatient charts
- be aware of changes in condition
- recognize ADRs
- Aware of drugs that impact mobility
- communicate with PCP
Considerations with reviewing pts medication list
What has changed?
Total number of medications?
How many meds in same class of drugs?
Timing of medication?
Pt characteristics impacting drug?
black box warning
strongest warning FDA requires for drugs that may cause serious or life-threatening ADRs
bioavailability
percentage of drug that actually reaches the systemic circulation
(system/administered)x100
Distribution of Drug
-movement of drug out of the systemic circulation and into interstitial/intracellular fluids
-volume distribution of a drug is not homogenous within the body
Variables that affect volume of distribution
blood flow to the tissue
drug binding to plasma proteins (albumin)
tissue permeability
drug binding within cells
Meds that easily cross all membranes…
take the longest to be eliminated
goes from blood–(brain)–viscera–muscle–fat
Why is drug storage a problem?
-decreases amount of drug that reaches target tissue
-redistribution of drug as it moves out storage may cause prolonged effects
-potential damage to tissues that are storing drug
Tissues that hold drugs for longer
adipose tissue
bone & teeth
organs, like liver and kidneys
Metabolism
chemical alteration of drug to make it inactive and more suitable for excretion from body
liver is primary organ, relies on enzymes
Liver enzyme
cytochrome P450
CYP = drug metabolizing enzyme
metabolize thousands of compounds
can be induced or inhibited by drugs, supplements, foods
Substrate
molecule upon which an enzyme acts
birth control is an example of a substrate
Inhibitor
turns a regular dose into an overdose
decreases the metabolism of a drug, which then increases the blood plasma level of drug
Inducer
Increases metabolism of drug
decrease effectiveness of drug
CYP450 Inducers
St Johns Wort
Chronic cigarette smoking
Common drug with grapefruit warning
Statins
Factors affecting drug metabolism
Age
Disease
Genetics
Drug/Supplement Interactions
Drug/Food interactions
Age and drug metabolism
-Older adults have decreased liver mass, blood flow, and CYP450 enzyme activity
-reduced clearance of drugs
-some increased intensity of drugs
Disease and Drug Metabolism
dysfunction or decreased blood flow to liver or kidney decrease metabolism
Genetics and Drug Metabolism
slight change in proteins in drug-metabolizing enzymes
Excretion
physical elimination of the drug from the body
kidney is the primary organ through glomerular filtration
GI and lungs have some roles
What affects excretion?
health of kidney
blood flow to kidney
pH of urine
degree of protein binding
Drug Elimination Rate
rate at which drug is eliminated helps determine the dose and frequency drug is prescribed
Steady State
amount of drug administered during dosing exactly replaces the amount of excreted
Half Life
amount of time required for 50% of the drug remaining n the body to be eliminated
(Volume of distribution/clearance of the drug)x.7 = half life
Why is the knowledge of the half-life of a drug helpful for a PT?
- to determine whether S/S could be the result of drug’s effect
- In pts with decreased clearance an/or increased Vd, usually increase in half life
- to monitor and emphasize adherence with dose and frequency of drug administration
Nifedipine
procardia
calcium channel blocker
Dose
just the amount
dosage
amount and frequency
What influences dosing schedule?
Half Life
Therapeutic index
Therapeutic Index
therapeutic window
rough indicator of a drug’s safety profile
TD
Toxic dose, for 50% of people
ED
effective dose for 50% of people
Distribution and Exercise
-highly variable
-changes blood flow and perfusion
-can increase serum albumin
-all causes decreased free drug that is available to bind to target cells
Metabolism and Exercise
-blood flow to liver decreases as ex increases
-may decrease metabolism and increase drug effect
-change in drug protein binding may off-set reduced metabolism
Excretion and Exercise
-decreases renal blood flow and glomerular filtration rate
-prolonged drug effect because of decreased drug elimination rate
Oral absorption and exercise
-decreased GI motility and blood flow
-decreased absorption rate, leads to delayed drug effect
Transdermal absorption and Exercise
ex increases skin temp, blood flow, tissue hydration
-may cause increase in absorption of drug
Subcutaneous and intramuscular injections and absorption
ex increases blood flow to muscles and subcutaneous tissues
-may cause increase in absorption rate
Drug receptor theory
-to produce a response, drug must combine with receptor (cell membrane or inside cell)
-physiological response happens after interaction
-receptors respond to neurotransmitters, hormones, drugs, etc
drugs are designed to interact with specific receptors
Agonist
drug binds to specific receptor and activates it, produces change in cell function. Affinity/efficacy
can either act on ion channel to change permeability, act enzymatically to influence functions, affect gene function
Antagonist
drug binds to a specific receptor and prevents an endogenous agonist from binding to the receptor. produces no change in cell function. only affinity.
Affinity
amount of attraction between drug and receptor
Selective
drug is considered selective if it binds to only 1 receptor subtype and produces a single physiologic response
no drug is perfectly selective
Example of agonist
albuterol is selective beta-2 adrenergic receptor agonist, binds to and activates beta-2 receptors and smooth muscle of bronchioles
Example of antagonist
metoprolol is a selective beta-1 adrenergic receptor antagonist, binds to beta-1 receptors on cardiac muscle cells. prevents activation by norepinephrine and epineprhine resulting in decreased HR and BP
Dose response curve
relationship between drug concentration (dose) and teh magnitude of the drug effect (response)
THerapeutic Index
estimate of drug safety, assessment of clinical efficacy compared to toxicity. the closer to 1, the more toxic the drug.
TD/ED = TI
Low therapeutic index
Patients are more likely to have ADRs at therapeutic drug concentrations
Plasma levels of drug are more likely to be monitored (you should measure INR with warfarin)
Warfarin
Plasma INR should be checked regularly.
begin daily, and then transition to 1-4 weeks depending on kidney function
remember that warfarin has lots of interactions with food, drug, supplements. it works by inhibiting the synthesis of several clotting factors
High INR
supratherapeutic
higher risk of bleeding
Low INR
subtherapeutic
higher risk of clots
Warfarin Interactions
sudden increase in vitamin K increases risk of clotting
sudden decrease in vitamin k increases risk of bleeding
Transdermal administration
drugs applied to skin when teh intended site of action is beyond the skin
drug must penetrate skin and resist breakdown by enzymes
patches, iontophoresis, phonophoresis assist in release
CYP450 Inhibitors
Grapefruit
Fluoxetine
Ciprofloxacin
