2.2 Pharmacodynamics, DDIs and Toxicology

Question 1

What are the 4 principal classes of receptor site?

Answer 1

Receptors
Ion channels
Carriers/transporters
Enzymes

Question 2

What is the active state?

Answer 2

Receptor which carries out a specific task

Question 3

What is the inactive state?

Answer 3

Not active- no receptor activation

Question 4

What is an agonist?

Answer 4

Ligand which binds to a receptor to move it into the active state

Question 5

What is an antagonist?

Answer 5

Ligand which binds to a receptor but keeps it in the inactive state

Question 6

What is a partial agonist?

Answer 6

Ligand bound to a receptor but the receptor action is not at 100%

Question 7

What is a partial antagonist?

Answer 7

Ligand bound to a receptor and the receptor action is low but not at 0%

Question 8

What is the affinity of a drug?

Answer 8

The tendency of a drug to bind to a specific receptor type

Question 9

What is the efficacy of a drug?

Answer 9

The maximal effect of a drug when bound to a receptor

Question 10

What is the agonist potency?

Answer 10

The drug concentration at which 50% of the maximal response is obtained

Question 11

What is the antagonist potency?

Answer 11

Concentration of the drug which reduces maximal response by 50%

Question 12

What is the therapeutic window?

Answer 12

The concentration range at which drugs produce a clinically useful effect without exerting toxic effects.

Question 13

How can DDIs affect the absorption of a drug?

Answer 13

Oral drugs can be affected by drugs which alter gut motility and passive absorption

Question 14

How can DDIs affect the distribution of a drug?

Answer 14

Can be affected by competition of drugs at protein/lipid binding sites.

Question 15

How can DDIs affect the metabolism of a drug?

Answer 15

Affected by induction or inhibition of enzymes in the liver

Question 16

How can DDIs affect the elimination of a drug?

Answer 16

Affected by changes in protein binding, inhibition of tubular secretion and changes in urine/pH

Question 17

What does inhibition of CYP450 enzymes do to a drug’s half life?

Answer 17

Increases

Question 18

What does induction of CYP450 enzymes do to a drug’s half life?

Answer 18

Decreases

Question 19

What does inhibition of CYP450 enzymes do to a drug’s clearance?

Answer 19

Decrease

Question 20

What does induction of CYP450 enzymes do to a drug’s clearance?

Answer 20

Increase

Question 21

How can DDIs be useful?

Answer 21

Some DDIs can enhance the clinical effects of a specific drug

Question 22

Give 5 classes of drugs that have common DDIs

Answer 22

Anticonvulsants
Anticoagulants
Antidepressants
Antibiotics
Antiarrhythmics

Question 23

How does renal disease affect drug pharmacology?

Answer 23

Reduction in clearance of renally excreted drugs

Some drugs are nephrotoxic or can create electrolyte imbalances

Question 24

How does hepatic disease affect drug pharmacology?

Answer 24

Reduced metabolism of drugs in the liver causing the half lives of the drugs to increase

Question 25

How does cardiac disease affect drug pharmacology?

Answer 25

Falling cardiac output leads to lower organ perfusion so metabolism in the liver and clearance in the kidneys is reduced.

Question 26

How does hypoalbuminaemia affect drug pharmacology?

Answer 26

Less albumin means there are less drug binding sites so the free drug concentration is in a higher concentration

Question 27

What is an 'on-target' ADR?

Answer 27

An exaggerated therapeutic effect, usually caused by a drug working on the same receptor in a different area of the body

Question 28

What is an 'off-target' ADR?

Answer 28

Drugs reacting with other receptor types to the one intended When a build up of metabolites become toxic

Question 29

Give 6 examples of CYP450 inducers

Answer 29

``` Phenytoin Carbamazepine Rifampicin Alcohol (Chronic) Barbiturates Sulphonylureas ```

Question 30

Give 8 examples of CYP450 inhibitors

Answer 30

``` Omperazole Disulfiram Erythromycin Valproate Isoniazid Ciprofloxacin Ethanol Sulphonamides ```