Flashcards in DRUG TARGETS 4 Deck (17):
What leads to receptor state changes?
-Rapid, desensitization of metabotropic receptors
-Homologous and heterologous desensitisation
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
What does homologous and heterologous desensitisation symbolize?
Homologous-The binding of a single agonist can desensitize
Heterologous-The enzyme gets desensitized by another agonist
What leads to down-regulation of receptors? Give an example?
Chronic agonist can lead to downregulation.
E.g chronic salbutamol-decreased bronchodilation
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.
What is the clinical significance for changes in receptor populations?
How does tolerance occur? Give example?
Down reulation means that an increase in drug dose is required to produce the same effect.
How do the adverse effects occur? Give example?
Increase in striatal D2 receptors-tardive dyskinesia(eye twitches, poking tongue)
How do therapeutic effects occur?
Consistent with downregulation of B and a2 adrenoreceptors and 5HT2 receptors.
E.g tricyclic antidepressants-fluoxetine
What are the non-receptor targets for drugs?
2. Ion channels
3. Carrier proteins
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.
What inhibits cyclooxegenases COX1 and COX2?
What does the inhibition of COX1 and COX2 lead to?
BUT side effects-Reduction of homeostatic pathways of kidney function and maintenance of gastric mucosa
What are the COX 2 selective inhibitors that work better than NSAIDs for COX2?
Give examples of drugs that interact with carrier proteins?
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.