(From Pharm book and lecture, 28 Jan 2001, by Brian Buschman)
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Many prostaglandins work in many different, often opposing, ways to regulate bodily functions. Clinically a half dozen Pg derivative drugs are available for clinical use. They are agonists. TxA2 and LtD4 are both able to cause asthma and PgI2 is an agonist of clotting.
Ob/Gyn use of dinoprostone and misprostol can be used to induce abortion. Dinoprostone can also be used to induce labor and dilate the cervix.
Alprostadil can be used to treat erective dysfunction. Unfortunately it must be injected intra-penally which I don’t think anybody wants. Alprostadil also works to maintain patency of the ductus arteriosus.
Misprostol is used to prevent excess HCl secretion in patients on long term NSAIDS.
Latanoprost is used to lower intraocular pressure through by increasing uveoscleral outflow.
Adverse affects of prostaglandins include problems at any site of action. They cause nausea and vomiting, abdominal pain, headache, agitation, vaginal pain, priapism, blurred vision, conjunctivitis, chills and so forth.
Histamine is found in all tissues but epically the ones that come into contact with outside material like the lungs and stomach.
Anti-H1 drugs can be divided into 1st and 2nd generation drugs. The first are cheaper and more often used but the second do not enter the CNS. Drugs of the first generation include:
1) Diphenhydramine (benadryl)
2) Dimenhydrinate
3) Promethazine
Second generation drugs include:
1) Astemizole
2) Loratadine (no arrhythmias)
Treatment of allergic reactions is the main use of anti-histamines. Epi is still the treatment of choice for anaphylaxis as H1-blockers do not work fast enough.
Like the anti-muscarinic scopolamine, anti-histamines like diphenhydramine and dimenhydrinate function in the prevention of motion sickness by calming the GI.
H1-blockers (that enter the CNS) are the 2nd line of treatment for Parkinson’s disease.
They are well absorbed orally with a short (4-6 hour) half like. They are able to cause arrhythmias except for the second generation loratadine. The arrhythmic effects are worsened if the patient is also taking MAO inhibitors as it causes too high of a lever of antihistamine in the body. Other adverse affects include sedation from CNS involvement and dry mouth from minor anticholinergic effects.
Anti-H2 agents like cimetidine and ranitidine are useful in reducing gastric HCl in the case of gastric ulcer. One must watch out for drug interactions as cimetadine (not ranitidine) inhibits Cyt-P450.
There are three major classes of seretonin receptors:
5-HT1 receptors have all CNS effects and mediate synaptic inhibition.
5-HT2 receptors function in the CNS and mediate smooth muscle contraction.
5-HT3 receptors function in the CNS, specifically in the vomiting center.
sumatriptan is the only clinically approved 5-HT agonist that is used in treatment of migraine and cluster headache.
Methysergide with 5-HT2 and the a-blocking phenoxybenzamine and 5-HT2A blocker cyproheptadine are al used for migraine prophylaxis. Ondansetron is a 5-HT3 blocker used to reduce chemo-induced emesis.
These are fungus products like LSD that are partial agonists at a and 5-HT receptors. Some have dopamine effects.
Uses include treatment of:
1) Migraine with ergotamine
2) Migraine prophylaxis using methysergide
3) Hyperprolactinemia and Parkinson’s using bromocriptine.
4) Postpartum hemorrhage with ergonovine
You do not want to use them in people with collagen disease or the pregnant. Some have a very low bioavailability and some, like ergonovine, very high.
There are three main types of headache:
1) Migraine headaches usually have a family history and are unilateral. They tend to last 2-72 hours and have a preceding/accompanying visual aura, sensitivity to light or sound and/or nausea/vomiting.
2) Cluster headaches (sinus headache) begin during sleep and have a big pressure often unilaterally behind the eye. They last 15-90 min. They are associated with congestion/sinus pressure.
3) Tension headaches are bilateral, dull and are stress induced. They last for 30 min up to a week.
It is believed that migrans are brought on by vascular distention that is mediated by 5-HT releasing neurons. This means that it can be stopped at ether the vascular or neuronal levels. This can be treated (prophylaxis) by methysergide (5-HT2A). The 5-HT agonist sumatriptan can also help (because of it’s vasoconstrictive effects).
They can be treated by NSAIDs because of the vasodilatory inflammation response that is causing the pain.
The DOC for severe migraine would be the ergot ergotamine.
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