Pharmacology E2 - Autocoids Flashcards
Mastocytosis
rare disease, increased number of mast cells in skin, bone marrow, other tissues.
- mast cells in these pt respond to non-allergic triggers 15x more likely anaphylactic attacks (bronchoconstriction, hypotension)
Major source of autocoids
Mast cells
Mast cell activation also induces de novo synthesis and secretion (12-24 hours later) of various cytokines, chemokines17, and growth factors
Autocoids
- histamine
- kinins (bradykinin)
- leukotrienes
- platelet activating factor
- prostaglandins
Which autocoids are responsible for Triple Response of Lewis?
histamine & kinins
COX-1
forms thromboxanes, prostaglandins in GI tract, prostaglandins in kidney
Thromboxane
promotes platelet aggregation, vasoconstrictor
COX-2
generates pro-inflammatory prostaglandins:
- prostacyclin (PgI2)
- prostaglandins in kidney,
- prostaglandins involved in pain, fever, inflammation
Prostacyclin
inhibits platelet aggregation, vasodilator. Natural anti-clotting agent.
selective inhibition of COX-2
(inhibition of prostacyclin) –> clot formation and possibly MI
Aspirin-induced asthma
Cyclooxygenase inhibitors
can shift precursors to the
lipoxygenase pathway and
exacerbate asthma
(lipooxygenases–> leukotrienes –> involved in inflammatory conditions of the lung)
PGE1
Intracavernosal administration for erectile dysfunction
Adverse effect: burning, Priapism
Reduces incidence of gastric ulcerations in patients on chronic nonsteroidal anti-inflammatory drugs
PGE2
Cervical/vaginal suppository to induce full-term labor
Adverse effects: Nausea, vomiting (75%), fever
PGF2a
Increase outflow of vitrous humor reducing intraocular pressure in glaucoma
Adverse effects: Darken eye color, lengthens eye lashes (20% of cases)-SOLD AS COSMETIC
PGI2
PROSTACYCLIN
Pulmonary hypertension
Adverse effect: burning
Leukotrienes
- key mediators of asthma
- 10k more potent than histamine in causing bronchoconstriction
- leukotriene receptor antagonists –> tx asthma
- lipoxygenase enzyme itself may be a target
Bradykinin
activates NO synthase (NOS) –> NO –> inc GMP –> smc relaxation
Kininase I/II (ACE) and HTN tx
degrades bradykinins
also facilitates conversion of angiotensin I –> angiotensin II (vasoconstrictor)
So ACE inhibitors (catopril) inc levels of kinins and vasodilation (tx HTN)
Direct vasodilators that generate NO
Isosorbide (oral and sublingual)
Nitroglycerin (sublingual)
Nitropaste (transdermal)
Nitroprusside (IV)
use: Tx angina
adverse effects: throbbing HA
Rich sources of histamine
Tissues: basophils, mast cells
Foods: cheeses, spinach, tuna
Dx of systemic mastocytosis
N-Methylhistamine is measured in 24-hour urine (cold)
N-Methylhistamine=prod of histamine breakdown
DOA (diamine oxidase) deficiency
check for this in pts sensitive to histamine containing foods
H1 receptor
blood vessels (veins)
- involved in allergic rxns
target of anti-histamines
- drugs that block H1: anti-muscarinic effects
- IV injection of histamine: burning, itching, etc
Histamine shock
severe hypotension, diminished blood volume, reduced venous return, low cardiac output during anaphylaxis
(via H1)
H2
exocrine glands, mostly gastric & parietal glands
- stimulation of gastric acid and other secretions
- drugs that BLOCK H2 –> tx gastritis, peptic ulcers, reflux esophagitis
H3
autoinhibitory: brain (neurons and vessels)
- decrease synthesis/secretion of histamine
- Pitolisant: histamine H3-receptor antagonist/inverse agonist –> used to Tx narcolepsy and possibly ADHD
H4
pro inflammatory: immune cells
Helicobacter Pylori associated with chronic gastritis, tx?
Tx: 2-week course of antacid (Ranitidine (H2 antagonist) or Omeprazole) + multiple abx (eg, Amoxicillin and Clarithromycin)
