Pharmacology: Pharmacodynamics Flashcards
What is the affinity of a drug?
The tendency of the drug to bind to a specific receptor type. It is denoted by Kd (agonists) or Ki (antagonists), these are the concentration of drug at which half the available receptors are bound.
What is the efficacy of a drug?
The maximal effect of a drug when bound to its receptor. It is expressed as a percentage of the response, when no increase in drug conc will produce any further increase.
NB. Antagonists are said to have 0% efficacy because they bind to inactive receptors and act to block agonist binding.
What is the potency of a drug?
Agonists: The drug conc which produces 50% of the maximal activity. (EC50)
Antagonists: The drug conc that reduces maximal activation of a receptor by 50%
What is the therapeutic window of a drug?
The concentration range which the drug exerts a clinically useful effect without significant toxic effects.
A wide therapeutic window reduces likelihood of serious toxicity
What are the 2 generalised categories of drug-drug interactions?
- pharmacokinetic interactions
- pharmacodynamic interactions
Give examples of pharmacokinetic drug-drug interactions?
Absorption - drugs given orally can affect other agents by affecting gut motility of absorption of the drug.
Distribution - drugs can compete for protein/lipid binding sites
Metabolism - drugs that either induce or inhibit CYPs will affect metabolism of other drugs
Excretion - drugs can alter protein binding, tubular secretion and urine pH
What is the effect of induction of CYPs?
Give examples of inducers
There is more rapid elimination of the therapeutic substate and therefore drug dosing needs to be increased.
St johns wort is a CYPs inducer
What is the effect of inhibition of CYPs?
Give examples of inhibitors
Inhibition slows elimination and therefore drug dosing needs to be decreased.
Grapefruit juice is a CYPs inhibitor
Give examples of pharmacodynamic drug-drug interactions?
Pharmacodynamic drug interactions can be deliberate to enhance therapeutic outcome (eg Ca2+ channel blockers which act on arterial smooth muscle used with ACEI targetting pulmonary and coronary arteries)
or not deliberate and cause reduced therapy or an ADR. (eg a B-adrenergic antagonist such as propanolol will reduce the effect of salbutamol a B agonist)
What are the 5 major classes of drugs that commonly produce drug-drug interactions?
- Anticonvulsants
- Anticoagulants esp warfarin
- Antidepressants
- Antibiotics esp quinolones, macrolides and rifampicin
- Antiarrhythmics
Give some examples of drug-disease interactions
More common in young and elderly
H- hepatic disease causes reduced clearance due to reduced CYP activity. Much longer t1/2
R- renal disease causes falling GFR so reduced clearance of renally excreted drugs eg digoxin, aminoglycoside antibiotics, can get disturbances of elecrolytes
H- heart disease causing falling CO causing reduces hepatic and renal blood flow so reduces clearance, excessive response to hypotensives
Give some examples of drug-food interactions
- Grapefruit juice inhibits several CYPs leading to reduces clearance
- Cranberry juice used in UTI treatment inhibits CYPs esp affecting warfarin so theres increased risk of haemorrhage
What are ‘on target’ and ‘off target’ ADRs?
An on target ADR is due to exaggerated therapeutic effect eg using agents for hypertension could lead to hypotension.
An off target ADR is where the drug (or metabolite) reacts with other receptor types not targeted eg liver failure in paracetamol overdose
