Basic of Pharmacokinetics Flashcards
Pharmacokinetics
How drugs get absorbed, to its receptors, and how long it stays there
Absorption
The process by which a drug leaves its site of administration and reaches the blood stream
Distribution
Drug leaves the blood stream and enters the interstitial and/ or cellular fluid
Metabolism
The alteration of the chemical structure of a drug by an enzyme
Elimination
Removal of the drug from the body
SIte of action
where a drug acts in the tissues
Transfer of drugs across membranes
Passive process-diffusion along a concentration gradient by virtue of its solubility in the lipid bilayer.
Carrier-mediated membrane transport- active transport which is energy dependent, against a electrochemical gradient.
Facilitated diffusion requires no energy, down a gradient, and is carrier mediated.
1st pass metabolism
Due to portal circulation due to the blood going straight from the portal to the liver. This inactivates some drugs.
Bioavailability
Fraction of administered drug that reaches systemic circulation following administration by any route.
Drug Distribution
Based on blood flow, capillary permeability, and drug structure.
Volume of distribution
drugs with large volumes of distribution may require higher initial doses to establish a therapeutic plasma concentration
Protein Binding
drug binds to protein such as albumin (acidic drugs) or alpha1-acid glycoprotein (basic drugs) and are pharmacologically inactive when bound.
Free drugs
Can act on target site and elicit biological response
Blood/brain barrier
Decreased permeability to water-soluable or ionized molecules. Lipid-soluble substances diffused easily. Water-soluble drugs may be used purposely when it is desirable to exclude effects on the brain. The intrathecal route of administration avoids the blood brain barrier.
Primary elimination
Through a renal mechanism
Metabolism (biotransformation)
refers to the disappearance of a drug when it is changed chemically into another compound.
Prodrugs
Inactive or less active to promote absorption. Activated by metabolism.
Reactions of drug metabolism- Phase I
Cytochrome P450 System. P450 isozymes located in most cells but mainly liver and intestinal tract. Oxidation, reduction, oxygentation, dealkylation, and hydrolysis. Primarily CYP1, CYP2, CYP3 families.
Reactions of drug metabolism- Phase II
Conjugation with 2nd endogenous substrate. Glucuronidation, sulfation, glutathione conjugation, acetylation, methylation, and glycine conjugation.
Oxidation/reduction reactions
Primarily P-450 dependent oxidation (95%). Non-P450 pathways ie alcohol dehydrogenase. Monoamine oxidase (MAO) oxidation of amino containing compounds such as catecholamines and tyramine.
Conjugation
Virtually all conjugated products are pharmacologically inactive. Neonates have not fully developed this ability.
Primary mechanism of P450 induction
to induce the expression of the enzyme through increased transcription.
Competitive inhibition
Ketaconazole has a nitrogen moiety that binds to active site
Irreversible inhibition
Secobaritol alkylates and permanently inactivates P450
Drug-drug interactions
Drugs can substrate for P450 rxn
Drugs inhibit _450 activity
Cimetidine, ciprofloxacin, erythromycin, ketoconazole, OCPs, quinidine, ETOH
Drugs that induce P450 activity
Barbituates, phenytoin, steroids, isoniazid, rifampin, ETOH
Routes of Elimination
Biliary secretion and enterohepatic cycling, exhalation, sweat, and secretion into breast milk
Half-life
the time it takes for the plasma concentration or the amount of drug in the body to be reduced by 50%
1st order kinetics
Drugs catalyzed by enzymes and follows Michaelis-Menten kinetics. The rate of metabolism is directly proportional to the concentration of free drug.
Zero-order kinetics
Non-linear kinetics where a constant amount of drug is metabolized per unit time.
Steady state drug levels
when input=output. Influence of the rate of drug infusion on the steady state are plasma concentration of drug and infusion rate, clearance of drug and volume of distribution. Time required to see steady state drug concentration is 4-5 half lives.
Distribution in the Elderly
Serum albumin levels are not altered in the majority of the elderly in the absence of chronic disease or severe malnutrition.
Metabolism in the Elderly
Phase II is preferred route of administration due to decreased metabolism in the elderly
Effects of aging on kindeys
Lower GFR
Key concept in elimination
BUN and serum creatinine may not accurately reflect true renal function in the elderly.
Distribution in the Elderly
Serum albumin levels are not altered in the majority of the elderly in the absence of chronic disease or severe malnutrition.
Metabolism in the Elderly
Phase II is preferred route of administration due to decreased metabolism in the elderly
Effects of aging on kindeys
Lower GFR
Key concept in elimination
BUN and serum creatinine may not accurately reflect true renal function in the elderly.
