Foundations in Pharm Flashcards by Jennifer Zhao

4 key components of assessment of drug therapy

indication
effectiveness
safety
adherence

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4 phases of pharmacokinetics (ADME)

absorption
distribution
metabolism
excretion

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factors influencing PK and PD

physiologic
pathophysiologic
genetic variability
drug interactions

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pharmacokinetics (definition)

the study of drug movement through the body
what the. body does to the drug

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3 ways for a drug to cross a cell

direct penetration of cell membrane
channels and pores
transport systems

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what’s absorption in PK?

mvnt of a drug from site of administration into the blood

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Factors affecting drug absorption (5)

rate of dissolution
surface area
blood flow
lipid solubility
pH

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two routes of absorption

enteral vs parenteral

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bioavailibility (F)

F= amount of drug absorbed/drug dosage

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bioavailability is affected by (3)

gastric empty tiem
pH of the stomach
speed the drugs moves through the GI tract

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bioavailability of IV therapy is __

100%

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bioavailability

bioavailability: ability of drug reaching the systematic circulation from the site of administration.

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Bioequivalence

bioequivalence: two different drugs or different dosage forms of the same drug produce the same concentration vs drug time (generic products)

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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

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distribution

mvnt of drugs form the blood to various tissues

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volume of distribution

amount of drugs in the body/ plasma concentration

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4 factors affecting distribution

blood flow
lipophilicity
molecular size and weight
drug protein binding

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High protein-bound drugs

gradual release (blood is reservoir)

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Low protein-bound drugs

immediate release

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consequences of drug metabolism

accelerated renal excretion
drug inactivation
increased therapeutic action
activation of prodrugs
increased toxicity

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Enzyme inducer__ level of drug in the body
Enzyme inhibitor___ level of drug in the body

Enzyme inducer decrease
Enzyme inhibitor increase

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metabolism

enzymatic alteration of drugs

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3 processes of renal drug excretion

glomerular filtration
passive tubular reabsorption
active tubular secretion

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factors modifying renal drug excretion

pH dependent ionization
competition for active tubular transport
age. (newborns have limited capacity to excrete drugs)

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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

1. 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

1. Continuous infusion 2. Administer a depot preparation: releases the drug slowly and steadily 3. 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)

1. clinical response 2. follow serum drug level

what kind of drugs require therapeutic drug monitoring

durgs with a defined therapeutic range adn low therapeutic index