Please enable JavaScript.
Coggle requires JavaScript to display documents.
Drugs affecting serotonin, Prophylaxis of migraine, Ergot alkaloids:, The…
-
Prophylaxis of migraine
Prophylaxis of migraine is required if attacks are frequent > 2-3 per month.
The drugs useful for prophylaxis are
propranolol is the most commonly used drug for prophylaxis of migraine attacks.
Timolol, atenolol , metoprolol and nadolol can be used
but the drug with intrinsic sympathomimetic activity like pindolol are ineffective.
Calcium channel blockers like flunarizine which also blocks Na+ channels is also effective.
Diltiazem, verapamil and nimodipine can be used.
Methysergide, cyproheptadine
and TCAs like amitryptiline, imipramine and nor-triptyline can also be used.
-
Topiramate(anticonvulsant drug) has been approved for prophylaxis of migraine.
Valproate and gabapentin also possess some prophylactic activity.
Ergot alkaloids:
these are derived from a fungus claviceps purpurea.
Important compounds are
ergotamine, ergometrine(ergonovine), ergotoxine, bromocriptine, dihydroergotamine and methysergide.
These drugs possess partial agonistic and antagonistic effect
at 5HT, alpha and dopaminergic effects.
These drugs are only alpha blockers that can cause vasoconstriction
due to their partial agonistic activity on alpha and 5HT-2 receptors maximum with ergotamine.
Hydrogenation of the compound decreases alpha agonistic activity but increases the alpha blocking potential.
Therefore dihydroergotamine has very little vasoconstricting activity.
-
5HT2A/2C
5HT2A/2C is responsible for most of the direct actions of serotonin.
Ketanserin and ritanserin(antagonists) are useful as antihypertensive agents.
Clozapine and risperidone are atypical antipsychotics agents
that act through antagonistic activity at this receptor.
-
Treatment of migraine
Migraine is unilateral pulsatile headache due to
dilatation and inflammation of the affected cerebral vessels.
Mild and moderate attacks are usually controlled by NSAIDS
whereas severe attacks require ergot alkaloids or triptans for termination.
Sumatriptan
Sumatriptan is the drug of choice for aborting acute attack of migraine.
It acts as a selective agonist at 5HT1B/1D receptors.
Sumatriptan also suppresses the vomiting of migraine.
It is a short acting drug and has low oral bioavailability.
Serotonin
5-hydroxytryptamine(serotonin) is synthesized from tryptophan.
It is produced by hydroxylation followed by decarboxylation of tryptophan.
Steps similar to catecholamine synthesis.
-
triphasic response
Actions on IV injection, it produces triphasic response on blood pressure.
Early sharp fall due to Bezold jarisch reflex,
then brief rise due to vasoconstriction
followed by prolonged fall due to arteriolar dilation.
-
-
Serotonin functions
5HT is involved in regulation of sleep, cognition, behaviour and mood.
-
5HT1 receptor:
5HT1A is presynaptic autoreceptor.
Modulates the release of serotonin.
Partial agonist of this receptor(buspirone, ipsapirone and gepirone)
are useful as antianxiety agents.
5HT1B/1D
5HT1B/1D causes constriction of cranial vessels.
Agonists at this receptor sumatriptan and naratriptan
are useful for the treatment of acute migraine attacks.
5HT3
5HT3 is ionotropic receptor(all other receptors are G protein coupled receptors).
Mediates most of the reflex and indirect actions of serotonin.
Antagonists like ondansetron, granisetron and tropisetron
are the agents of choice for chemotherapy induced vomiting.
5HT4
5HT4 receptor present in GIT responsible for increase in peristalsis.
Agonists cisapride, mosapride, renzapride and tegaserod are useful in the treatment of GERD.
prucalopride approved for chronic idiopathic constipation.
Cyproheptadine:
it blocks 5HT2A, H1 and muscarinic receptors.
It increases appetite
and can be used in children to promote weight gain.
Methysergide:
it is a 5HT2A/2C antagonist and a 5HT1 agonist.
It is indicated for prophylaxis of migraine attacks
but prolonged use can result in pulmonary, endocardial and retroperitoneal fibrosis.
Flibanserin
is a new drug approved for hypoactive sexual desire disorder in premenopausal women.
It is 5HT2A receptor antagonist and 5HT1A receptor agonist.
LSD:
it is an ergot derivative and a powerful hallucinogen.
It acts as agonistic at several serotonin receptors including 5HT1A, 5HT2A/2C and 5HT5-7 receptors.
-
-
-
Bromocriptine
Bromocriptine is useful in
parkinsonism, hyperprolactinemia, acromegaly, and type 2 diabetes mellitus.
-
-
Caffeine in migraine
Caffeine enhances the absorption of ergotamine and is a powerful vasoconstrictor.
It is usually combined with ergotamine.
These drugs however increase the nausea and vomiting during attack.
Other triptans
Frovatriptan is the longest acting
and rizatriptan is the fastest acting congener.
Other drugs useful are zolmitriptan, eletriptan, naratriptan and almotriptan.
-
-
-
-
Onabotulinum toxin A
Onabotulinum toxin A has recently been approved for prophylaxis when headaches occur for more than 14 days per month.
It is given every 12 weeks as multiple injections around the head and neck to try to dull future headache symptoms.
-
-
-