3. Pharmacodynamics, Drug Interactions, and Toxicology

Question 1

What is an agonist?

Answer 1

Binds to the receptor and stabilises it into its active state.

Question 2

What is an antagonist?

Answer 2

Binds to the receptor and stabilises it into its inactive state.

Question 3

What is a partial agonist?

Answer 3

Binds to receptor but not perfectly so doesn’t bring about maximal response.

Question 4

What is a competitive antagonist?

Answer 4

Binds to the site where the natural ligand binds and completely removes all response from receptor.

Question 5

What is a non-competitive antagonist?

Answer 5

Binds to another site on the receptor to where ligand binds and partially reduces overall response of receptor.

Question 6

What is specificity?

Answer 6

Relates to complementary drug and receptors. If good then a drug only works on one receptor.

Question 7

What is selectivity?

Answer 7

Clinical effect of the drug, measure with therapeutic indices linked with side effects.

Question 8

What is affinity?

Answer 8

Ability of a drug to bind to a specific receptor type.

Question 9

What is Kd/Ki?

Answer 9

Kd - agonists, Ki - antagonists, refers to concentration at which half the receptors are occupied.

Question 10

What is efficacy?

Answer 10

Maximal effect of a drug when bound to the receptor.

Question 11

How does efficacy differ in agonists and antagonists?

Answer 11

Agonists have 100% efficacy, partial agonists have reduced affinity/efficacy or both, and antagonists have affinity but no efficacy.

Question 12

What is potency?

Answer 12

The overall response seen by the receptor once the ligand has bound.

Question 13

How is potency measured?

Answer 13

By EC50 - concentration where 50% of maximal response is obtained.

Question 14

What is the therapeutic index?

Answer 14

Relationship between concentrations causing adverse effects and concentrations causing desirable effects.

Question 15

How is the therapeutic index calculated?

Answer 15

LD50/ED50

Question 16

What is the therapeutic window?

Answer 16

Range of drug concentrations where they exert a clinically useful effect without exerting toxic effects.

Question 17

Name four examples of drugs with narrow therapeutic windows.

Answer 17

Warfarin, aminophylline, digoxin, aminoglycosides.

Question 18

Why are drug-drug interactions important?

Answer 18

Increasing polypharmacy.

Question 19

How can absorption be impacted by drug-drug interactions?

Answer 19

Changes in gut motility affecting absorption - slowing it down or increasing it.

Question 20

How do opiates, atrophine, and metoclopramide impact absorption in drug-drug interactions?

Answer 20

Opiates and atrophine slow gut down so Cmax is decreased and Tmax is increased. Metoclopramide speed up gut to increase Cmax and decrease Tmax.

Question 21

How do calcium salts impact absorption of tetracycline?

Answer 21

Reduce absorption by binding.

Question 22

How does cholestyramide impact absorption of warfarin and digoxin?

Answer 22

Binds to them to reduce absorption.

Question 23

What is a class I object drug?

Answer 23

Dose where number of molecules of that drug is lower than binding sites available for that drug.

Question 24

What is a class II precipitant drug?

Answer 24

Drug used at higher numbers than number of binding sites available so displace.

Question 25

How can administration of a precipitant drug impact distribution of an object drug?

Answer 25

Causes free object drug concentration to rise outside therapeutic window.

Question 26

How can metabolism of drugs be impacted?

Answer 26

By induction or inhibition.

Question 27

How can excretion be impacted by drug-drug interactions?

Answer 27

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.

Question 28

What are the five major drug groups that contribute to drug-drug interactions?

Answer 28

Anticonvulsants, anticoagulants, antidepressants, antibiotics, antiarrhythmics.

Question 29

How does renal disease impact clearance of drugs?

Answer 29

Falling GFR causes reduced clearance of renally excreted drugs.

Question 30

What drugs should be avoided with renal disease?

Answer 30

NSAIDs, ACEis that reduce GFR and can cause AKI - nephrotoxic.

Question 31

How does hepatic disease impact clearance of drugs?

Answer 31

Reduced clearance of hepatically metabollised drugs due to reduced CYP450 activity. So longer half-lives.

Question 32

How does cardiac disease impact drug pharmacokinetics?

Answer 32

Reduced organ perfusion leads to reduced hepatic and renal blood flow so reduced clearance.

Question 33

Why does hypoalbuminaemia impact drugs?

Answer 33

Many drugs bind to albumin so PD and PK are impacted by this.

Question 34

Explain two drug-food interactions.

Answer 34

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.

Question 35

What are on target ADRs?

Answer 35

Due to exaggerated therapeutics effect of the drug, due to increased dosing or factors affecting PK and PD.

Question 36

What are off target ADRs?

Answer 36

Interaction of other receptor subtypes secondarily to the one intended for therpeutic effect.

Question 37

What are the protein targets for drug action?

Answer 37

Receptors, ion channels, enzymes, and transporters.

Question 38

How can drugs act on receptors?

Answer 38

As agonists, partial agonists, or antagonists for known endogenous mediators.

Question 39

How can drugs act on ion channels?

Answer 39

Incorporate a receptor only open when receptor occupied by agonist so drugs act on that directly or indirectly (GPCRs) to alter function.

Question 40

How can drugs act on enzymes?

Answer 40

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.

Question 41

How can drugs act on transporters?

Answer 41

Transport of ions and molecules sometimes require carrier proteins for facilitated diffusion. Drugs can block these