B2 agonists (B2 receptors are found on mast cell surfaces! this one reason epinephrine is good in anaphylaxis)

Theophylline

Cromolyn Sodium

Glucocorticoids if IgE dependent (histamine has an IgE-dependent release mechanism. because glucocorticoids reduce IgE production, they reduce histamine release)

1st generation:

Diphenhydramine

Meclizine

Promethazine

2nd generation:

Loratadine

Fexofenadine

Cimetidine

Ranitidine

Famotidine

heart= increased HR and contractility

Vessels= increased dilation and permeability (H1, H2)

GI= increased HCl and Pepsin (H2)

Lung= contraction

Nerves= pain and itching

Known on da streets as 'benadryl', Diphenhydramine is a first generation H1 antagonist.  As a first generation H1 antihistamine, it can cross the blood brain barrier, and therefore also exhibits sedative and antiemetic properties.

4-6hr duration

Promethazine is a first generation H1 antagonist

 with a STRONG sedative and antiemetic effect. Because it has such a strong sedetive effect, it is sometimes prescribed for insomnia

4-6hr duration

Meclizine is a first generation H1 antagonist

antiemetic effect

12-24hr duration

Loratadine is a second generation H1 antagonist (Claritin)

It has no sedative effect! and is not an antiemetic

24hr duration

Fexofenadine is a second generation H1 antagonist

Like loratadine, it has no sedative effect! and is not an antiemetic

10-15hr duration

What conditions would you treat with Cimetidine?

Why should you be concerned about cimetidine administration in concert with other drugs.

Cimetidine is an H2 antagonist and therefore reduces gastric acid secretion.  Recall that histamine is a very stong stimulator of acid secretion in the stomach!

Cimetidine treatment is therefore indicated in ulcers, Zollinger-Ellison Syndrome, and GERD.

Systemic mastocytosis (a disease with tremendously increased numbers of mast cells and therefore excessive systemic histamine levels), is also treated with H2 antagonists along with H1-blockers

Cimetidine Inhibits CYP450 system and is one of the most powerful inhibitors.  Can increase the toxicity of other drugs metabolized by the CYP450 system (beta-blockers, phenytoin, carbamazepine, benzodiazepines, tricyclic antidepressants, lidocaine, quinidine, theophylline, warfarin)

Cimetidine can also can block androgen receptors at high doses

2hr half life

Ergotamine is a 5HT-1 serotonin agonist used in migraine therapy.  Specifically, it acts on the 5HT-1b and 5HT-1d receptors of the trigeminovascular system, causing vasoconstriction and relieving the painful headache.

ergotamine has a low oral bioavailability

Why would you prescribe Sumatriptan?

How does it work and when would it be contraindicated?

Sumatriptan is a member of the triptan drug family and is prescribed in migraine therapy.  It is a 5HT-1b and 1d agonist, which causes constriction of the trigeminovascular system. Recall that the dilation of the trigeminovascular system is implicated in the neurovascular hypothesis of migraines. 

 Similar to ergot alkaloids, triptans are contraindicated in patients with heart issues and pregnant women.

Why would ergonovine be administered in the birthing process?

What else is a use of ergonavine?

Ergonavine is a 5HT-1 and 5HT-2 agonist with good bioavailability (unlike ergotamine).  Additionally, ergonovine stimulates serotonin, dopamine, and alpha receptors!

Ergonovine may be used to stop postpartum bleeding because it causes very intense uterine contraction. 

Ergonovine and other ergot alkaloids are used in the treatment of migraines because of their stimulation of serotonin receptors.  They are contraindicated in pregnancy because the strong uterine contractions can cause abortion.  Propranolol is an acceptable drug to treat migraines with during times of pregnancy.

(induce vasoconstriction and such strong uterine contraction that they help prevent hemorrhage and decrease blood loss.  Because of increased uterine contraction, can also cause abortion)

Intestinal hypermotility!  Cyproheptadine is an H1 and 5HT-2A antagonist.  By inhibiting the 5HT2 receptors, it reduces mobilizing effect of serotonin in the GI

Cyproheptadine is also a useful addition to the treatment of serotonin syndrome. 

Triptans are widely used drugs with a selective activation of 5HT-1b and 5HT-1d receptors. These receptors are found in the trigeminovascular system, the vasodilation of which is implicated in the neurovascular hypothesis of migraines.

Vasoconstriction of these vessels due to activation of the above receptors makes triptans the DRUGS OF CHOICE for migraines

Triptans are Contraindicated in cerebrovascular disease and patients at risk of coronary ischemia... triptans will constrict the already partially occluded vessels, causing increased likelihood of MI and stroke.  Additionally, they must not be administered to pregnant women for risk of abortion.

Serotonin syndrome is a potentially fatal state in which there are excessive levels of synaptic serotonin.  High serotonin levels will lead to hyperactive bowels, high blood pressure (vasoconstrictive), tachycardia, agitation and delerium, eventual coma, and muscle rigidity.  This condition may be caused by concomitant administration of a 5HT agonist (ex: ergotamine) while the patient is taking an MAO inhibitor or SSRI!

Additionally, increased tyrosine levels, found in wine and cheese, can lead to serotonin syndrome while the patient is on an MAO inhibitor.

What activates phospholipase A2?

what inhibits it?

Activates: Angiotensin II, bradykinin, epinephrine

Inhibits: Glucocorticoids

Phospholipase A2 releases arachidonic acid from phospholipids. It is the first enzyme in the production of prostaglandins and leukotrienes

PGE1

IV administration

*maintain patency of ductus arteriosus

*impotence

PGE2

intravaginal administration

to induce labor, cervical ripening, abortion

PGI2

IV administration

for pulmonary hypertension

PGE1 analog

large oral bioavailability

intravaginal or pulmonary administration

To treat NSAID-induced ulcer

induce abortion

PGF2a analog

eye drop edministration

Glaucoma

(increases outflow through uvealscleral tract)

Selective COX-2 inhibitor ('celebrex')

anti-inflammatory drugs- rheumatoid arthritis, osteoarthritis

benefits: no effect on platelet aggregation, low incidence of gastric ulcers

A second generation h1-antagonist (loratadine or fexofenadine).  A 1st generation antihistamine would also antagonize the M3 receptors of the detrusor muscle, furthering the patients inability to urinate.

in the same line of reasoning, you wouldn't want to give him any antimuscarinics either

because they block muscarinic, alpha-adrenergic, and serotonergic receptors they are contraindicated in:
 -Glaucoma -recall, we want M receptors stimulated to cause constriction of the ciliary muscle and promote outflow through Canal of Schlemm. 

-prostatic hypertrophy -inhibiting the M3 receptor of the detrusor muscle would only further decrease the ability of the patient to urinate 

-COPD -recall that antimuscarinics decrease bronchial secretions and mucociliary clearance (except ipratropium) 

the list goes on with GI obstructions, pregnacy..etc. --Second generation drugs like Loratadine have none of these contraindications.

Administration of the ergot alkaloids like ergotamine or ergonovine result in strong uterine contraction, which could result in abortion.  These are therefore not given to pregnant women.

Alternatively, you could prescribe propranolol or other beta-blockers, which do not contract the uterus and are also listed as having negligible teratogenic effects.

ergot alkaloids (and triptans) are also contraindicated in patients with previous heart conditions because of their potent vasoconstrictive effects.