What are autacoids?

Autacoids are a group of compounds such as prostaglandins, histamine, and serotonin that are heterogeneous substances which have widely differing structures and pharmacologic activities.

They are called autacoids meaning they are formed by the tissues on which they act

Briefly describe the use of prostaglandins (PG) in the treatment of:

1. pulmonary hypertension

2. peptic ulcer disease

3. as an abortifacients.

1. Prostaglandins are unsaturated fatty acid derivatives that act on the tissues in which they are synthesized and are rapidly metabolized to inactive products at the site of action.

Pulmonary HTN and cause Beta-2 receptor stimulation, causing broncho and vasodilation by increasing cAMP.

PUD: Misoprostol can be used to treat peptic ulcer disease by inhibiting secretion of HCl and pepsin, and enhancing mucosal resistance. Useful for patients with gastric ulcers who chronically take NSAIDs
Abortifacients: Mifepristone (RU-486) is a synthetic steroid given orally with antiprogestational effects, followed within 24 hours by Misoprostol, a synthetic prostaglandin, administered vaginally.

Summarize the pharmacology of histamine. Include mechanism of action and role in allergy and anaphylaxis.

1. Histamine, an amine, is a chemical messenger located in all tissues, released in response to stimuli.

2. Histamine can bind to histamine receptors, H1-H4. Antihistamines are aimed at blocking the receptor sites.

      *H/H2 are widely expressed and are the targets of clinically useful drugs

      *H3/H4 receptors only a few cell types and use is unclear

3. Stimulation of H1 receptors promote vasodilation and increase capillary permeability, cause an increased production of nasal and bronchial mucus, constrict bronchioles decreasing lung capacity, constrict intestinal smooth muscle causing cramps and diarrhea, and can cause itching and pain at sensory nerve endings. H1 receptor stimulation causes vascular endothelium to release nitric oxide (NO) which in turn causes vasodilation.

4. Stimulation of H2 receptors increases gastric HCL secretion, and also has an effect on vasodilation and increased capillary permeability. In response to an allergic reaction, histamine is released and can either cause a local response, producing reactions on the skin or respiratory system, or a full-blown anaphylactic response systemically.

5. It is thought that the major determinant on type of reaction, local or anaphylactic, is dependent on the rate of release of histamine. If it is released slow enough --> inactivation before entering the bloodstream, only a local response will occur.

True or False: H-2 receptors are located in the stomach and skin?

True

If you want to block a systemic histamine reaction (eg, allergic reaction), you would administer an H1 blocker (eg, diphenhydramine) plus an H2 blocker (eg, famotidine, ranitidine or cimetidine). The H2 blocker works in the stomach and to prevent skin flushing, the H1 blocker works everywhere else. The other histamine receptors (H3 and H4) are clinically unimportant. If on the other hand you wanted to block histamine receptors in the stomach to reduce acid production, then you would just administer an H2 blocker. If you are treating cold symptoms or chronic sinusitis, you would use an H1 blocker.

Outline the pathophysiology and medical management of Migraine Headaches.

Make sure to include the role of the triptans

1. There are two types of migraines: with and w/o aura
2. In both types of migraines, pain caused by extracranial and intracranial arterial dilation in response to stretch --> release of neuroactive molecules. Migraines are caused by arterial dilation, serotonin is a vasoconstrictor, so if a drug acting on serotonin receptors is useful in treating migraines then it must be a 5HT agonist.
3. Some meds, such as Beta-blockers , TCA, Anticonvulsant. Calcium-channel blocker have been successful in reducing the frequency and severity of migraines prophylactically from episodes

4. During an attack, symptomatic treatment may be used to reduce severity of symptoms. The triptans (sumatriptan or imitrex) have been shown to rapidly and effectively abort or reduce severity of migraine headaches.

5. Serotonin agonists and act at 5-HT1D receptors.
6. It is easy to confuse whether drugs like ondansetron, sumatriptan and many other drugs acting on 5HT are agonists or antagonists. Here is how I remember the triptans: 5HT = 5-hydroxytryptamine which was named "serotonin" because it was found in serum = "sero" + "tonin" = it increases vascular tone (in other words, serotonin is a vasoconstrictor).