Flashcards in Session 2 Deck (19):
What is the difference between an agonist and an antagonist?
Agonists = when it binds to receptor, it stabilises it in the active conformation.
Antagonist = when bound to receptor, it stabilises it in the inactive conformation.
What is the difference between affinity and efficacy?
Affinity = the tendency of the drug to bind to a specific receptor type.
Efficacy = the maximal effect of a drug when bound to a receptor. Expressed in percentage terms of the response, when no increase in drug concentration brings about any further increase. Antagonists have zero efficacy.
What is potency?
Agonist potency = the drug conc. at which 50% of the maximal response is obtained. EC50.
Antagonist potency = the conc. of the drug that reduces maximal activation of a receptor by 50%.
What is the drug therapeutic window?
The concentration range at which the drug exerts a clinically useful effect, but without exerting significant toxic effects.
Give examples of drugs that have narrow therapeutic windows.
Warfarin, aminophylline, digoxin and aminoglycosides.
How do you calculate the therapeutic window?
Lethal dose to 50% of people / effective dose to 50% of people.
What are the main mechanisms affecting drug excretion?
Changes in protein binding, inhibition of tubular secretion and changes in urine flow/pH.
What results following induction and inhibition of the CYP450 system?
Induction: faster elimination (shorter half-life and increased clearance). Dosing may then have to be increased.
Inhibition: Increased half life and reduced clearance, hence causes adverse drug reactions.
Why can a falling cardiac output affect drug clearance?
Reduces organ perfusion, resulting in both reduced hepatic blood flow and renal blood flow, hence reducing clearance of the drug.
What are the two types of adverse drug reactions?
On target ADRs: exaggerated therapeutic effect of the drug. Often consist of effect on the same receptor, but in different tissues. E.g. drugs for hypertension resulting in hypotension.
Off target ADRs: interactions with other receptor types secondarily to the one intended for therapeutic effect.
When are drug interactions most likely to occur?
Hospital patients on a cocktail of six or more drugs, taking the overall chance of an ADR to 80%.
Name factors that affect bioavailability.
Drug formulation, age, food, vomiting, malabsorption, first pass metabolism.
Give three sites that first-pass metabolism can take place.
The gut lumen - gastric acid, proteolytic enzymes etc.
The gut wall - p-glycoprotein efflux pumps drugs out back into the lumen.
The liver - enzyme metabolism.
What is pharmacogenetics?
The effect of genetic variations on pharmacokinetics/dynamics.
Why three criteria are important when assessing changes in drug distribution due to protein binding?
1) High protein binding
2) Low volume of distribution
3) Drug has a narrow therapeutic ratio
Give four factors that affect protein binding.
3) Renal failure
4) Displacement by other drugs
Describe the two ways that a non-competitive antagonist can bind.
1) At the same site for the agonist binding irreversible or unbinding very slowly
2) At a separate site to the agonist either reversibly or irreversibly.
Give five classes of drugs in which drug-drug interactions commonly arise