Foundations in Pharm Flashcards
4 key components of assessment of drug therapy
- indication
- effectiveness
- safety
- adherence
4 phases of pharmacokinetics (ADME)
- absorption
- distribution
- metabolism
- excretion
factors influencing PK and PD
- physiologic
- pathophysiologic
- genetic variability
- drug interactions
pharmacokinetics (definition)
the study of drug movement through the body
what the. body does to the drug
3 ways for a drug to cross a cell
- direct penetration of cell membrane
- channels and pores
- transport systems
what’s absorption in PK?
mvnt of a drug from site of administration into the blood
Factors affecting drug absorption (5)
rate of dissolution
surface area
blood flow
lipid solubility
pH
two routes of absorption
enteral vs parenteral
bioavailibility (F)
F= amount of drug absorbed/drug dosage
bioavailability is affected by (3)
- gastric empty tiem
- pH of the stomach
- speed the drugs moves through the GI tract
bioavailability of IV therapy is __
100%
bioavailability
bioavailability: ability of drug reaching the systematic circulation from the site of administration.
Bioequivalence
bioequivalence: two different drugs or different dosage forms of the same drug produce the same concentration vs drug time (generic products)
What’s the first pass effect?
drugs given orally are absorbed through GI tract and carried to liver
liver metabolizes the drug BEFORE reaching the systemic circulation, large drug inactivated, leading to decrease in therapeutic effect
administer drugs via parenteral, sublingual, transdermal, etc. e.g. nitroglycerine
distribution
mvnt of drugs form the blood to various tissues
volume of distribution
amount of drugs in the body/ plasma concentration
4 factors affecting distribution
- blood flow
- lipophilicity
- molecular size and weight
- drug protein binding
High protein-bound drugs
gradual release (blood is reservoir)
Low protein-bound drugs
immediate release
consequences of drug metabolism
- accelerated renal excretion
- drug inactivation
- increased therapeutic action
- activation of prodrugs
- increased toxicity
Enzyme inducer__ level of drug in the body
Enzyme inhibitor___ level of drug in the body
Enzyme inducer decrease
Enzyme inhibitor increase
metabolism
enzymatic alteration of drugs
3 processes of renal drug excretion
- glomerular filtration
- passive tubular reabsorption
- active tubular secretion
factors modifying renal drug excretion
- pH dependent ionization
- competition for active tubular transport
- age. (newborns have limited capacity to excrete drugs)
pharmacodynamics (definition)
what drugs do to the body and how they do it
dose-response relationships
relationship dosage size and intensity of response
affinity
the strength of attraction b/t a drug adn its receptor
intrinsic activity
the ability of a drug to activate a receptor following binding
drugs acting through simple chemical or physical interactions with other small molecules
antacids, antiseptics, osmotic laxatives
drugs acting on protein targets such as enzymes, membrane carriers, ion channels
ACE inhibiotrs, SSRIs, CCB
DI definition and types
an interaction where the efficacy or toxicity of one or more drugs is altered
drug-drug
drug-food
drug-herb
common CYP450 inducers
barbiturates
rifampin
carbamazepine
phenytoin
glucocorticoids
common CYP450 inhibitors
erythromycin
clarithromycin
paroxetine
fluoxetine
cimetidine
fluoroquinolones
ketoconazole
omeprazole
grapefruit
Top 5 CYP450 enzymes
CYP1A2,3A4, 3A5
2C9,2C19,
2D6
Drugs with high interaction potential
digoxin (lanoxin)
phenytoin (dilantin)
theophylline (TheoDur)
Warfarin (Coumadin)
cimetidine (Tagamet)
cyclosporine (Neoral)
tacrolimus (Prograf)
lithium (Carbolith)
carbamazepine (Tegretol)
rifampin
drugs requiring empiric dose adjustment
> 50% renally eliminated
active or toxic metabolites
may require incrase dosing interval or decrease dose
Enterohepatic Recirculation
Repeating cycle in which a drug is transported from the liver into the duodenum and then back to the liver
Steps in urinary excretion
- Glomerular filtration
2. Passive tubular reabsorption
3. Active tubular secretion
Nonrenal Routes of Drug excretion
Breast milk
Bile
Lungs
Sweat and saliva
What determines the dosing interval?
Drug half life
time to reach plateau
~ 4 half lives
3 Techniques for reducing fluctuations in drug levels
- Continuous infusion
- Administer a depot preparation: releases the drug slowly and steadily
- Reduce both the size of each dose and the dosing interval
Maximal efficacy
largest effect that a drug can produce
potency
amount of drug we must give to elicit an effect
-Simple Occupancy theory
○ The intensity of the response is proportional to number of receptors occupied by the drug
○ Max response occur when all receptors occupied
○ Cannot explain potency difference
-Modified occupancy theory
○ Affinity: explains potency
○ Intrinsic activity: explains maximal efficacy
two types of antagonist and there differences
Noncompetitive: irreversible bind
Competitive: reversible bind
ED50
average effective dose
standard dose
therapeutic index calculation
LD50/ED50
Drugs that induce PGP
reduced absorption, increased elimination
Idiosyncratic effects
an uncommon drug response resulting from a genetic predisposition
Paradoxical effect
opposite of the intended drug response
Iatrogenic disease
disease that occurs as the result of medical care or treatment
Tachyphylaxis
Reduction in drug responsiveness brought on by repeated dosing over a short time
E.g. transdermal nitroglycerin
Biomarkers
gene characteristics related to drug responses
factors influencing drug response
patient factors
genetics
disease factors
environmental factors
Risk factors for nephrotoxicity
preexisting renal insufficiency
age
dehydration
more than one nephrotoxic drugs
dosage administered
extended treatment duration
recent exposure to vanco or aminoglycoside
other comorbidities
Factors predicting drug removal by dialysis
low molecular weight
water-soluble
low protein binding
small volume of distribution
fundamentals of deprescribing
medication d/c plan: tapering schedule
management plan: potential symptoms of withdrawal, monitor and follow-up
use of decision-support tools and algorithms
therapeutic drug monitoring (2 ways)
- clinical response
- follow serum drug level
what kind of drugs require therapeutic drug monitoring
durgs with a defined therapeutic range adn low therapeutic index
