Pharma principles Flashcards
Define pharmacokinetics?
what the body does to the drug
Define pharmacodynamics
what the drug does to the budy
Define clearance
Volume of plasma cleared of a drug per unit time
Define half-life?
Time taken for drug concentration to decline to half its
original value.
Depends on volume of distribution and clearance
Define volume of distribution
Volume into which a drug appears to distribute.
High for lipid-soluble drugs
Low for water soluble drugs
Define 1st order kinetics
Clearance of drug is always proportional to plasma
concentration.
Define zero order kinetics plus examples?
Clearance of drug not always proportional to plasma concentration.
Saturation of metabolism → constant rate of elimination
regardless of plasma levels.
eg. phenytoin, salicylates, ethanol
Define bioavaliability?
Percentage of the dose of a drug which reaches the
systemic circulation.
Define multiple dosing? No. of half-lives to reach steady state? TO to reduce time to reach a steady state? Examples?
When a drug is administered on a multiple-dosing regimen, each successive dosage(s) are administered before the preceding doses are completely eliminated. - resulting in accumlation of the drug in plasma
~5 HLs
use of a loading dose reduces time needed to reach a steady state
eg. Phenytoin, digoxin, amiodarone, theophylline
Indications for therapeutic drug monitoring? examples of when therapeutic drug monitoring is required?
Ix lack of drug efficacy or possibility of poor compliance
Suspected toxicity
Prevention of toxicity
Aminoglycosides (essential) Vancomycin (essential) Li (essential) Phenytoin Carbamazepine Digoxin Ciclosporin Theophylline NB. Warfarin is not monitored per se, it’s the biological effect which is monitored rather than the plasma drug level.
Define first pass metabolism? Where does it occur? Examples?
Metabolism and inactivation of a drug before it reaches
the systemic circulation.
Occurs in gut wall and liver
E.g. propranolol, verapamil, morphine, nitrates
Define phase 1 metabolism? system used?
Creation of reactive, polar functional groups
Oxidation: usually by CyP450 system
Reduction and hydrolysis
Cytochrome P450 most important system in Phase 1 metabolism
CyP3A4 most important subtype
Define phase 2 metabolism?
Production of polar compounds for renal elimination
Either the drug or its phase 1 metabolite
Conjugation reactions
Glucuronidation, sulfonation, acetylation, methyl
List the pro-drugs
L-Dopa → dopamine Enalapril → enalaprilat Ezetimibe → ez-glucuronide Methyldopa → α-methylnorepinephrine Azathioprine → 6-mercaptopurine (by XO) Carbimazole → methimazole Cyclophosphamide
Define pharmacogenetics? examples?
Genetically determined variation in drug response
Acetylation
Fast vs. slow acetylators (↑↑ fast in Japan vs. Europe)
Affects: isoniazid, hydralazine and dapsone
Oxidation
There are genetic polymorphisms for all known CyP450 enzymes except for CyP3A4
G6PD Deficiency
Oxidative stress → haemolysis
Quinolones, primaquine, nitrofurantoin, dapsone
Acute Intermittent Porphyria
AD, ↑ in White South Africans
Large no. of drugs can → attacks: e.g. EtOH, NSAIDs…
