Pharmacokinetics Flashcards
Pharmacodynamics
what the drug does to the body
Pharmacokinetics
what the body does to the drug- absorption, distribution, metabolism, elimination
Pharmacogenetics
- individual variation in pharmacokinetics usually caused by a single gene
- genetic tendency
Pharmacogenomics
- variations in pharmacokinetics and dynamics, usually due to multiple genes and environment
- how predisposition is expressed
Agonist
bind to a receptor on or within a cell and produces a response
Antagonist
bind to a receptor to block or reverse the action of an agonist
Receptors
- located on cell membranes and within the cell
- enzymes, nucleic acids, membrane-bound proteins
Full agonist vs Partial agonist
- full agonist produces 100% response that completely reverses the condition (ex/ albuterol)
- partial agonist cannot produce 100% response, even at very high doses (ex/ morphine)
Competitive vs Noncompetitive antagonist
- Competitive- compete for the same binding site
- Noncompetive- binds to different site and decreases the agonist response, partially interferes
Efficacy
- Max response a drug can produce
- How well a drug produces a response/ quality of response
Potency
- amount of drug required to produce effect
- dose required for a response
Bioavailability
- fraction of drug that reaches circulation in a form that is ready to engage in a biological response
- a drug can have no effect if it is not bioavailable
How does route of administration affect bioavailability?
few roadblocks = greater bioavailability
IV => IM => PO
How does GI motility affect bioavailability?
unpredictable effect on drug absorption- increased motility can increase or decrease absorption
How do drug-drug interactions in the gut affect bioavailability?
- drugs can increase pH to effect absorption
- antacids/ bile acid binding drugs can inactivate/impair absorption
- drugs that alter GI motility can have unpredictable effects on other drugs
How do drug-drug interactions in serum affect bioavailability?
protein-binding- when drugs bind to the same protein, the drug that has less affinity for binding will have exaggerated effect, could cause toxicity
How does absorption affect bioavailability?
Absorption- the ability of the drug to reach circulation and target tissue
-circulation is key factor- poor circulation= poor absorption
What factors influence pharmacokinetics?
Nongenetic- age, organ function, concomitant therapy, drug interactions, disease state
Genetic- drug-metabolizing agents, drug transporters, drug targets (these remain stable across lifespan)
How does drug metabolism affect bioavailability?
- Drug metabolism- mechanism where administered agent is converted to a form that prepares it for elimination- converts it to water soluble form
- drugs have to have some lipophilia to act in the body and then need to be converted to hydrophilic to be eliminated
CYP450 cascade
primary mechanism of drug metabolism,
CYP450 cascade
- primary mechanism of drug metabolism
- series of oxidation-reduction reactions that prepare a drug for excretion
- responsible for significant adverse effects
- cause issues when CYP450 inhibitor or inducer are given with substrate- cause toxicity or subtherapeutics
What is the first pass effect?
- a large portion of an oral drug is metabolized during the first pass through the liver before reaching circulation, decreasing bioavailability when drug is given in active form
- drugs given as “prodrug” are activated by the liver, therefore more bioavailable
- decreased hepatic function can cause toxicity for active drugs or subtherapeutic levels for prodrugs
Drug elimination
Kidney is major route- need good renal blood flow and function
Drug dosing steady state
- goal is to maintain steady state within therapeutic window between minimally toxic concentration (MTC) and the minimally effective concentration (MEC)
- often takes 5 half-lives (doses) to achieve steady state
IM administration in pediatrics
- not an efficient mode d/t decreased muscle tissue
- erradic blood flow in illness makes absorption unpredictable
Transdermal and topical administration in pediatrics
- greater skin surface area, higher water content, and thinner stratum corneum can all increase absorption
- occlusive dressings (diapers) can decrease evaporation => increase absorption
Gastric pH in pediatrics
- neonate- very low pH in first couple days, then pH is quite high (relative achlorhydria for first month)
- gastric acidity reaches adult levels by age 3
- pH affects absorption- drugs that are weak bases are poorly absorbed in acid environment and vice-versa
Gastric motility in pediatrics
- GI transit time and peristaltic activity is prolonged during infancy
- BF infants longer transit time than formula fed
- infants have greater intestinal surface area => increased absorption
- more normal transit time @ 6-8 mnths old
Total body water in pediatrics
- higher percentage than adults (70-75%), so may need higher doses of hydrophilic drugs to achieve therapeutic blood levels
- adult levels at age 6-7
Protein binding capacity in pediatrics
- neonates- lower serum plasma protein available for binding
- basic drugs more bioavailable as they bind to glycoprotein and lipoprotein rather than albumin (acidic drugs)
- competition for binding sites between meds and endogenous substances (bilirubin) => cross BBB to cause kernicterus
Drug elimination in pediatrics
- renal blood flow reaches adult levels @ 5-12 mnths
- GFR @ adult levels at 3-5 mnths
- tubular secretion and absorption - 7-12 mnths
- longer half life d/t prolonged metabolism and slower excretion
Considerations for drugs during pregnancy
-can it cross the placenta?
may be safe to give in pregnancy but is not ok for infants
consideration for lactation
- can it cross into breast milk?
- infant circulation is responsible for metabolism and excretion
- safe for infant = safe for BFing
Drug administration in the elderly
- less water-soluble content = longer half-life
- less muscle, more fat
- decreased renal perfusion
- comorbid diseases impact metabolism and excretion
