Pharmacodynamics/kinetics Flashcards
Define pharmacodynamics
Effects of a drug on the body
How and where a drug acts
Side effects
Define pharmacokinetics
Effects of the body on a drug:
Absorption
Distribution
Metabolism
Excretion
What is bioavailability?
The amount (%) of unchanged drug that reaches the systemic circulation after administration
What is first-pass metabolism?
When a substantial proportion of a drug is metabolised in the GIT or liver before reaching the systemic circulation
What are the 4 primary first-pass metabolism systems?
Enzymes of the gastrointestinal lumen
Gut wall enzymes
Bacterial enzymes
Hepatic enzymes
What is volume of distribution? How is it related to drug concentrations in the body?
Describes the extent of drug distribution in body tissues/dilution of plasma concentrations.
Vd = total amount of drug in body/plasma concentration
What clinically relevant value is volume of distribution used to calculate?
Loading dose
Loading dose = Vd x plasma concentration
Name the major tissues where drugs may be metabolised
Liver
Kidneys
GIT
Lungs
Phase 1 metabolism
Introduces or exposes a functional group on molecule (e.g. oxidation, hydrolysis)
Primes molecules for Phase 2
Some drugs are excreted straight after Phase 1
Phase 2 metabolism
Polar conjugate is added to exposed group (commonly glucuronide)
Makes drug polar, hydrophilic, allows for easy excretion in urine
Pro-drugs
Inactive compounds that are metabolised to become active drugs
Relatively uncommon
e.g. ACE inhibitors, prednisone
First-order elimination
Rate of metabolism increases with plasma concentration of drug
Increased dose = linear increase in drug concentration
Metabolising enzymes aren’t saturated (clinical scenario)
Rate of elimination = clearance x plasma []
[Elimination = excretion +-metabolism]
Zero-order elimination
Drugs are metabolised by rapidly-saturable enzyme system (occurs commonly in clinical practice)
Rate of metabolism is independent of drug concentration
Dose increase once enzymes saturated = exponential increase in drug concentrations
Rate of elimination = constant
e.g. Phenytoin, alcohol
Apparent clearance
Relates drug concentration to elimination from the body
Clearance = rate of elimination/plasma concentration
Enterohepatic circulation
Conjugated drug/metabolite excreted in bile
Bacteria in gut cleave conjugate
Metabolite/drug reabsorbed
Leads to prolonged drug effect
e.g. oral contraceptives, TCAs
[affected by Abx treatment]
Kinetics of CYP450 inhibition and induction
Inhibition occurs and wanes rapidly - minutes to hours
Induction occurs and wanes - up to 2-4 weeks
Potency vs efficacy vs effectiveness
Potency: Achieving same effect at lower dose/concentration
Efficacy: Ability to reach a certain therapeutic effect
Effectiveness: Efficacy in the practical setting i.e. actual patient, not theoretical therapeutic effect
Mechanism of action of aspirin at different doses
Low dose: Irreversibly inhibits COX in platelets –> no Thromboxane A2 –> no platelet aggregation
Higher dose: Inhibits prostacyclin in vascular endothelium –> inhibits vasodilation and inhibits inhibition of platelet aggregation
