DONE Pharmacokinetics Part 2 Flashcards
What are the 2 methods of drug elimination?
Excretion (renal)
Metabolism (liver)
Generally, what occurs in phase 1 and 2 of drug metabolism in the liver?
Phase I = oxidation/reduction, hydrolysis, deacylation to inactivate drug
Phase II = conjugates with glucuronide/glutathione/sulphate/N-acyl = inactive
What do the phase 1 and 2 enzymes do in drug metabolism?
Increase ionic charge to enchance renal elimination
Describe phase 1 of drug metabolism
Cytochrome P450 enzymes on ER
Catalyse redox/de-acylation/hydroxylation reactions
Low specificity = use for wide range of molecules
Products have increased ionic charge, elimination via kidney or enter phase 2
Describe phase 2 of drug metabolism
Cytoplasm , hepatic enzymes
High specificity = more rapid than with CYP450s
Conjugation to increase hydrophilicity more, increasing charge = enhances renal elimination
What are 1st Order kinetics in drug elimination?
Rate of elimination is proportional to drug level
Constant fraction of drug eliminated in unit time (half life)
What is zero order kinetics in drug elimination?
Rate of elimination is constant
What is half life and what two factors provide an estimate of half life?
Period of time required for the concentration of drug in the body to be reduced by one half
Clearance (CL) and Vd
What is half life essential for informing?
Dosing schedules, minimising adverse drug reactions, repeat dosage
During repeated drug administration/repeated dosage/maintenance dosage, how long until a steady state is achieved?
5 half lives
E.g. digoxin half life of 36hrs, give maintenance dose = 36 x 5 = 180 hrs
What type of dose is given when the half life is long and a rapid effect is desired?
Loading dose
In renal excretion of drugs, what part of the drug is filtered?
Free fraction
What pH increases passive reabsorption in the distal tubule?
With weak acids = acid urine (therefore if aspirin poisoning, give bicarbonate treatment to force alkaline diuresis)
With weak bases = alkaline urine
