DRUG TARGETS 4 Flashcards Preview

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Flashcards in DRUG TARGETS 4 Deck (17):
1

What leads to receptor state changes?

-Rapid, desensitization of metabotropic receptors
-Homologous and heterologous desensitisation

2

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

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

3

What does homologous and heterologous desensitisation symbolize?

Homologous-The binding of a single agonist can desensitize
Heterologous-The enzyme gets desensitized by another agonist

4

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

Chronic agonist can lead to downregulation.
E.g chronic salbutamol-decreased bronchodilation

5

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

Chronic antagonist can lead to upregulation of receptors
E.g chronic propranolol- increased heart rate and blood pressure.

6

What is the clinical significance for changes in receptor populations?

1.Tolerance
2.Adverse effects
3.Therapeutic effects

7

How does tolerance occur? Give example?

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

8

How do the adverse effects occur? Give example?

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

9

How do therapeutic effects occur?

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

10

What are the non-receptor targets for drugs?

1. Enzymes
2. Ion channels
3. Carrier proteins

11

What drugs target enzymes and what do they achieve?

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

12

What inhibits cyclooxegenases COX1 and COX2?

NSAIDS

13

What does the inhibition of COX1 and COX2 lead to?

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

14

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

-Rofecoxib, celecoxib

15

Give examples of drugs that interact with carrier proteins?

Fluoxetine(prozac), Sibutramine(Reductil)

16

How does Fluoxetine have an anti-depressant effect?

-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.

17

Give examples of drugs that act on ion channels?

-Local anaesthetics(NA+ blockers)
-Ca2+ channel blockers(verapamil, nifedipine)