Pharmacodynamics Flashcards
Define agonist
Activate endogenous proteins
Full = 100% efficacy
Partial = <100%
Define antagonist
Antagonise, block or inhibit endogenous proteins
Competitive = blocks site
Non-competitive = works at site distant to receptor
Where do drugs typically work?
Cell surface receptors
Nuclear receptors
Enzyme inhibitors
Ion channel blockers
Transport inhibitors
Inhibitor of signal transduction proteins
Define drug selectivity
The more the selective a drug is for its target, the less chance that it will interact with diff targets and have less undesirable side effects
Define drug specificity
Targeting drugs against specific receptor subtypes often allows drugs to be targeted against specific organ
Define Affinity
The tendency of a drug to bind to a specific receptor type
Define Efficacy
Ability of a drug to produce a response as a result of the receptor or receptors being occupied
Describes the max effect of a drug
Define Potency
Dose required to produce the desired biologic response
Define the Therapeutic Window
Range of [plasma] that the drug has a desired effect
= EC50 (adverse effect) / EC50 (desired effect)
Like to devel drugs that have a large therapeutic index
Describe with examples pharmacokinetic and pharmacodynamic drug interactions
Alcohol + food = lowers [alcohol]
Tetracycline + Fe = bind forming chelate = lowers [plasma tetracycline]
Cimetidine + warfarin = raises [plasma warfarin] = increased prothrombin time
Describe the induction and inhibition of the Cytochrome P450 system
Induction = increases amount of enzyme, takes time
Inhibition = block enzyme, half-life increased, plasma conc higher for a longer period of time
What drugs induce CYP450s?
P CBRAS
P – phenytoin
C – carbamazepine
B – barbituates
R – rifampicin
A – alcohol
S – sulphonylureas
What drugs inhibit CYP450s?
O DECICES
O – omperazole
D – disulfiram
E – erythromycin
V – valproate
I – isoniazid
C – cimetidine
E – ethanol
S – sulphonamides
Outline how hepatic disease affects drugs
Reduced clearance of hepatic metabolised drugs
Reduced CYP 450
Longer half-lives
Toxicity
Opiates in cirrhosis = small doses accumulating leading to coma
Discuss how renal disease effects drugs
Reduced clearance
Disturbances of electrolytes may predispose to toxicity
Outline how cardiac disease affects drugs
Reduced organ perfusion = reduced hepatic blood flow and clearance, reduced renal blood flow and clearance
Give an example in a drug interaction has altered a normal ECG
Erythromycin + fluconzole = prolonged QT = torsade de pointes
Discuss some drug-food interactions
Grape fruit juice = inhibits CYP450 isoenzymes
Cranberry juice = inhibits bacterial adherence to urothelium, inhibits CYP2C9 which decreases clearance of warfarin
Recognise the main ADR types and give examples of these
A – augmented pharmacologic effects = hypoglycaemia due to insulin
B – bizarre effects = anaphylaxis due to penicillin
C – chronic effects = colonic dysfunction due to laxatives
D – delayed effects = 2nd cancers in those treated with alkylating agents for hodgkins disease
E – end of treatment effects = withdrawal seizures when anticonvulsants are stopped
Recognise circumstances in which drug interactions are most likely to occur
Polypharmacy
Extremes of age
Multiple medical problems
Use of drugs with narrow therapeutic indexes
Drugs are being used near their minimum effective conc
