3. Pharmacodynamics, Drug Interactions, and Toxicology Flashcards
What is an agonist?
Binds to the receptor and stabilises it into its active state.
What is an antagonist?
Binds to the receptor and stabilises it into its inactive state.
What is a partial agonist?
Binds to receptor but not perfectly so doesn’t bring about maximal response.
What is a competitive antagonist?
Binds to the site where the natural ligand binds and completely removes all response from receptor.
What is a non-competitive antagonist?
Binds to another site on the receptor to where ligand binds and partially reduces overall response of receptor.
What is specificity?
Relates to complementary drug and receptors. If good then a drug only works on one receptor.
What is selectivity?
Clinical effect of the drug, measure with therapeutic indices linked with side effects.
What is affinity?
Ability of a drug to bind to a specific receptor type.
What is Kd/Ki?
Kd - agonists, Ki - antagonists, refers to concentration at which half the receptors are occupied.
What is efficacy?
Maximal effect of a drug when bound to the receptor.
How does efficacy differ in agonists and antagonists?
Agonists have 100% efficacy, partial agonists have reduced affinity/efficacy or both, and antagonists have affinity but no efficacy.
What is potency?
The overall response seen by the receptor once the ligand has bound.
How is potency measured?
By EC50 - concentration where 50% of maximal response is obtained.
What is the therapeutic index?
Relationship between concentrations causing adverse effects and concentrations causing desirable effects.
How is the therapeutic index calculated?
LD50/ED50
What is the therapeutic window?
Range of drug concentrations where they exert a clinically useful effect without exerting toxic effects.
Name four examples of drugs with narrow therapeutic windows.
Warfarin, aminophylline, digoxin, aminoglycosides.
Why are drug-drug interactions important?
Increasing polypharmacy.
How can absorption be impacted by drug-drug interactions?
Changes in gut motility affecting absorption - slowing it down or increasing it.
How do opiates, atrophine, and metoclopramide impact absorption in drug-drug interactions?
Opiates and atrophine slow gut down so Cmax is decreased and Tmax is increased. Metoclopramide speed up gut to increase Cmax and decrease Tmax.
How do calcium salts impact absorption of tetracycline?
Reduce absorption by binding.
How does cholestyramide impact absorption of warfarin and digoxin?
Binds to them to reduce absorption.
What is a class I object drug?
Dose where number of molecules of that drug is lower than binding sites available for that drug.
What is a class II precipitant drug?
Drug used at higher numbers than number of binding sites available so displace.
How can administration of a precipitant drug impact distribution of an object drug?
Causes free object drug concentration to rise outside therapeutic window.
How can metabolism of drugs be impacted?
By induction or inhibition.
How can excretion be impacted by drug-drug interactions?
Changes in protein binding (if decreased, increases amount of unbound drug for removal), inhibiting tubular secretion (increased plasma levels) and changes to urine flow/pH.
What are the five major drug groups that contribute to drug-drug interactions?
Anticonvulsants, anticoagulants, antidepressants, antibiotics, antiarrhythmics.
How does renal disease impact clearance of drugs?
Falling GFR causes reduced clearance of renally excreted drugs.
What drugs should be avoided with renal disease?
NSAIDs, ACEis that reduce GFR and can cause AKI - nephrotoxic.
How does hepatic disease impact clearance of drugs?
Reduced clearance of hepatically metabollised drugs due to reduced CYP450 activity. So longer half-lives.
How does cardiac disease impact drug pharmacokinetics?
Reduced organ perfusion leads to reduced hepatic and renal blood flow so reduced clearance.
Why does hypoalbuminaemia impact drugs?
Many drugs bind to albumin so PD and PK are impacted by this.
Explain two drug-food interactions.
Cranberry juice inhibits CYP2C9 so reduces clearance of warfarin leading to raised INR and risk of haemorrhage. Grapefruit juice inhibits CYP450 so reduces clearance of many drugs.
What are on target ADRs?
Due to exaggerated therapeutics effect of the drug, due to increased dosing or factors affecting PK and PD.
What are off target ADRs?
Interaction of other receptor subtypes secondarily to the one intended for therpeutic effect.
What are the protein targets for drug action?
Receptors, ion channels, enzymes, and transporters.
How can drugs act on receptors?
As agonists, partial agonists, or antagonists for known endogenous mediators.
How can drugs act on ion channels?
Incorporate a receptor only open when receptor occupied by agonist so drugs act on that directly or indirectly (GPCRs) to alter function.
How can drugs act on enzymes?
Act as competitive or non-competitive inhibitors of the enzyme - can be reversible or irreversible. Can also act as false substrates - drug molecules undergo chemical transformation to form abnormal products that subvert normal metabolism.
How can drugs act on transporters?
Transport of ions and molecules sometimes require carrier proteins for facilitated diffusion. Drugs can block these
