DRUG TARGETS 4

Question 1

What leads to receptor state changes?

Answer 1

• Rapid, desensitization of metabotropic receptors

- Homologous and heterologous desensitisation

Question 2

Where does rapid, pronounced desensitisation of metabotropic receptors take place?

Answer 2

• B1 adrenoceptor-agonist binding not affected but unable to activtate adenylate cyclase.
• Found to be due to phosphorylation of a serine residue by BARK

Question 3

What does homologous and heterologous desensitisation symbolize?

Answer 3

Homologous-The binding of a single agonist can desensitize

Heterologous-The enzyme gets desensitized by another agonist

Question 4

What leads to down-regulation of receptors? Give an example?

Answer 4

Chronic agonist can lead to downregulation.

E.g chronic salbutamol-decreased bronchodilation

Question 5

What leads to up-regulation of receptors? Give an example?

Answer 5

Chronic antagonist can lead to upregulation of receptors

E.g chronic propranolol- increased heart rate and blood pressure.

Question 6

What is the clinical significance for changes in receptor populations?

Answer 6

1. Tolerance
2. Adverse effects
3. Therapeutic effects

Question 7

How does tolerance occur? Give example?

Answer 7

Down reulation means that an increase in drug dose is required to produce the same effect.

Question 8

How do the adverse effects occur? Give example?

Answer 8

Increase in striatal D2 receptors-tardive dyskinesia(eye twitches, poking tongue)

Question 9

How do therapeutic effects occur?

Answer 9

Consistent with downregulation of B and a2 adrenoreceptors and 5HT2 receptors.
E.g tricyclic antidepressants-fluoxetine

Question 10

What are the non-receptor targets for drugs?

Answer 10

1. Enzymes
2. Ion channels
3. Carrier proteins

Question 11

What drugs target enzymes and what do they achieve?

Answer 11

NSAIDS(diclofenac, ibuprofen)- used to treat pain and inflammation
- Angiotensin converting enzymes and ACE inhibitors(captopril)- used to treat hypertension.

Question 12

What inhibits cyclooxegenases COX1 and COX2?

Answer 12

NSAIDS

Question 13

What does the inhibition of COX1 and COX2 lead to?

Answer 13

-Reduced inflammation
-Reduced pain
-Reduced fever
BUT side effects-Reduction of homeostatic pathways of kidney function and maintenance of gastric mucosa

Question 14

What are the COX 2 selective inhibitors that work better than NSAIDs for COX2?

Answer 14

-Rofecoxib, celecoxib

Question 15

Give examples of drugs that interact with carrier proteins?

Answer 15

Fluoxetine(prozac), Sibutramine(Reductil)

Question 16

How does Fluoxetine have an anti-depressant effect?

Answer 16

• Reuptake is the predominant removal mechanism for 5-HT(Serotonin)
• Blocking the 5HT uptake protein, levels of 5HT increase in the synapse
• Since depression is thought to result from decreased 5HT, increasing synaptic 5HT levels have an antidepressant effect.

Question 17

Give examples of drugs that act on ion channels?

Answer 17

• Local anaesthetics(NA+ blockers)

- Ca2+ channel blockers(verapamil, nifedipine)