Prostaglandins-Pharmacology-Exam 6

Refers to prostaglandins, leukotrienes, prostacyclin (PGI2) thromboxane A2 refers to what

Eicosanoids

What are lipids derived from membrane arachidonic acid (AA) following the action of phospholipase A2 on membrane phospholipids

Prostaglandin

-AA serves as a substrate for cyclooxygenases

Eicosanoid biosynthesis is blocked by

NSAIDs

What is the rate-limiting step in biosynthesis of prostaglandins and Thromboxanes

Phospholipase A2

COX-1 is found in what tissues

Platelets

Endothelium

Lungs

GI Tract

Uterus

Kidney

COX-2 is found in what tissues

Constitutive in brain/kidney/endothelium

Macrophages, myocytes, synoviocytes, fibroblasts, cancer cells

COX-2 Inducers

Induced at sites of inflammation by TNFa, IL-1B, Growth Factors, Tumor Promoters, Inflammation, Parturition

Glucocorticoids/Corticosteroids block what step in COX production

Phospholipase A2

Prostaglandin Functions

Ang II as a vasoconstrictor

Causes renal vasoconstriction- regulates Renal Blood Flow- induces PGE2/PGI2

$ TXA2 does what to platelets

Increases platelet aggregation

-resulting in TIA, stroke, AMI, PTCA- prevent by blocking TXA2R

Pharmacologic effects of Thromboxane A2

Vasoconstriction

Proaggregatory

Bronchoconstriction

TXA2 & COX-1 are only in

Platelets

Aspirin MOA

Irreversible COX-1

Inhibits Platelet aggregation

-Inhibits platelet prostaglandin & thromboxane A2

What is the typical aspirin dose of Cardiovascular Disease

Low dose aspirin- 81mg

COX-1 acetylation- platelet aggregation inhibited 48h- lower is better- GI toxicity

What endogenous chemical is a potent vasodilator, anti-aggregatory by inhibiting platelet activation and is principally synthesized by COX-2

Prostacyclin

TXA2 and PGI2 have what kind of effects compared to one another

TXA2- Pro-Thrombotic

PGI2- Anti-thrombotic

Prostaglandin F2a has what unique effect

Contracts Uterus

What 2 Prostaglandins have effect has labor inducing agents

PGF2 & PGE2

Arachidonic acid delivered intra-amniotically can induce parturition

Celebrex has been shown to suppress what

Labor Supressant

Not on drug list

15-methyl-PGF2a (Hemabate- Carboprost)

Induce abortion

-contracts uterus, decreases blood flow and bleeding

History of what is a contraindications of PGF2a analogs like Carboprost (15-methyl prostaglandin PGF2a)

Asthma

What 2 drugs are ophthalmic solutions that are stable analogs of PGF2a to reduce intraocular pressure by increasing fluid outflow

Latanoprost

What 2 drugs are used for treating open angle glaucoma

Latanoprost

What drug has adverse effects that cause irreversible brown pigmentation of the iris and eyelashes, drying of the eyes, and conjunctivitis

Latanoprost

What Prostaglandin is responsible for induced fever response

Prostaglandin E2

Physiologic effects of Prostaglandin E2

Contracts gravid uterus

-Dinoprostone (labor inducer)

What is a synthetic PGE1, analog and prodrug that decreases gastric acid secretion and stimulates mucus secretion in the gut (protects against NSAIDs)

Misoprostol

What drug is given as prevention of NSAID-induced ulcers- cytoprotective

Misoprostol

Misoprostol Adverse Effects

Uterine Contraction

-no pregnant women

Used to terminate when combined with RU486 or methotrexate

What synthetic PGE1 is used for for the treatment of all 3 types of erectile dysfunction ( vascular, neurogenic, psychological)

Alprostadil

What prostaglandin E1 does not act through EP receptors and is used to treat Constipastion

Lubiprostone

Lubiprostone MOA

Activates intestinal Cl channels- Type III channels on apical surfaces

-Na & H2O follows (bulk laxative

-softens stool and increases intestinal mobility promoting spontaneous bowel movements

Aloprostadil has been shown to save lives.

Maintains patency of the ductus

Indomethacin- closes to prevent surgery

What synthetic PGI2 is used to treat pulmonary hypertension and has a half life of 3-5min

Epoprostenol

What Synthetic PGI2 is used as an inhalant for the treatment of pulmonary hypertension and has a half life for 30 min

Iloprost

What synthetic PGI2 is used for pulmonary hypertension orally and has a half life of 4hr

Treprostinil

Not on drug table

What is the MOA of synthetic PGI2 like Epoprostenol, Iloprost, Treprostinil

Vasodilation- decreases pulmonary arterial pressure

For Pulmonary Hypertension

Biosynthesis of Leukotrienes

1. LOX incorporates an oxygen on one of the carbons that is in a double bond (5-Lipoxygenase)

2. Glutathione mediates the formation of the more stable hydroxy group

Leukotrienes Physiological Effects

Bronchoconstrictor- Plays a role in asthma and anaphylaxis

Potent Vasoconstrictor

Increased Capillary Permeability

Zafirlukast and Montelukast MOA

CysLT1 receptor Antagonists

Stimulates Bronchodilation

What drugs stimulate bronchodilation by relaxing smooth muscle in asthma patients and block exercise-induced asthma acting as a CystLT1 Antagonists

Zafirlukast and Montelukast

Zafirulast Drug Interactions

Warfarin- metabolism decreased (Bleeding risk)

Inhibits CP450

Montelukast does not have this effect

Adverse Effects of Montelukast

Neuropsychiatric

-depression, aggression, nightmares, headaches

What drug is a 5-Lipoxygenase inhibitor that blocks production of leukotrienes that induce bronchoconstriction

Zileuton

Side effects of Zileuton

Hepatotoxicity

Drug interactions

Inflammation is a function of what 2 biological molecules

Leukotrienes and Prostaglandins