4. Pharmacodynamics Flashcards
What is affinity?
The tendency of a drug to bind to a receptor. Denoted Kd. The lower the Kd the higher the affinity.
What is efficacy?
The tendency of a drug when bound to activate the receptor and cause an effect.
Governed by intrinsic efficacy (activation of receptor) and cell/tissue factors e.g. if a cell has more or less muscle fibres.
What is potency?
The dose required to produce the desired biological response. Designated as EC50 - i.e the concentration of the drug that produces an effect that is 50% of the maximum is used to determine potency.
What is the therapeutic index?
It is the relationship between concentrations causing adverse effects and the concentrations producing desired effects.
TI = EC50 (adverse effect)/EC50 (desired effect)
Or
TI = Toxic dose (TD50)/Effective dose (ED50)
Give 2 examples of drugs with a narrow therapeutic window
Warfarin - monitor the INR
Digoxin - measure the drug concentration directly
What is the effect of fatty food on absorption of drugs?
- Fatty food slow down gastric transit time (the speed that the contents of the stomach move into the small intestine, the next part of the gut, so drugs taken with fatty food will stay in the stomach longer than drugs taken with non-fatty food.)
- As drugs are mostly absorbed in the small intestine, if the stomach empties more slowly, the drugs will be absorbed more slowly.
- so if alcohol is taken with a fatty meal will be sober for longer and you don’t get such peak alcohol concentrations (as it is absorbed in the duodenum so if delay it getting there more sober)
Does a large amount of free drug lead to an increased or decreased rate of excretion? Why is this important?
-an increased rate of excretion Important for: -IV drugs -short half life (rapidly cleared) -narrow therapeutic index: even small changes in protein binding can have a significant effect e.g. phenytoin
What is CYP450 inhibition and give some examples?
ODE VICES
- enzyme inhibition keeps the drug in the body for longer (prolonged effects)
- half life will be increased, and clearance will be reduced
O-omerprazole D-disulfiram E- erythromycin V- valproate I- isoniazid C- ciprofloxacin and cimetidine E- ethanol S-sulphonamides
What is enzyme induction and give some examples?
PC BRAS
- increases the amount of enzyme present
P- phenytoin C- carbamezapine B- barbiturates R- rifampicin A- alcohol (chronic us) S- sulphonylureas and St. John’s wart
What are the ‘usual suspects’ for drug interactions?
5 A’s/antis
1) Anticonvulsants
2) anti coagulants
3) anti depressants
4) anti arrhythmics
5) antibiotics
Drugs that prolong the QT interval can lead to what condition?
Torsade de pointes
Many anti arrhythmic’s can lead to a lengthened QT interval particularly when taken with CYP450 inhibitors.
Torsade de pointes is an uncommon and distinctive form of polymorphic ventricular tachycardia (VT) characterized by a gradual change in the amplitude and twisting of the QRS complexes around the isoelectric line. Torsade usually terminates spontaneously but frequently recurs and may degenerate into ventricular fibrillation.
Which 3 broad diseases can lead to serious drug disease interactions?
1) renal disease: fall in GFR will lead to reduced clearance of renally excreted drugs e.g. digoxin.
2) hepatic disease: reduced clearance of hepatically metabolised drugs, reduced CYP 450 activity hence longer half lives, toxicity e.g. opiates in cirrhosis even in small doses can accumulate and can lead to coma.
3) cardiac disease: fall in CO (HR x SV) will have an excessive responsive to hypotensive agents. Reduced organ perfusion therefore reduced hepatic and renal blood flow and so reduced clearance.
Explain the effect of grapefruit juice on the CYP45- isoenzymes.
Grapefruit juice inhibits several CYP450 enzymes so will decrease their clearance and increase their half life. E.g simvastatin or amiodarone.
In some cases can lead to prolonged QT interval.
Explain the effect of cranberry juice on CYP2C9
Inhibit the CYP2C9 and therefore decreases clearance of warfarin and therefore increases the half life. So you get an enhanced anticoagulant effect and therefore have an increased risk of haemorrhage.
Patients should be advised not to drink cranberry juice if on warfarin.
What is an adverse drug reaction?
An unwanted or harmful reaction after administration of a drug/drugs which is suspected/known to be due to the drug.
It can be mild, moderate or major. Major is permanent or life threatening, moderate requires additional treatment and mild is trivial or unnoticeable.
