Pharmacology E2 - Autocoids

Question 1

Mastocytosis

Answer 1

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)

Question 2

Major source of autocoids

Answer 2

Mast cells

Mast cell activation also induces de novo synthesis and secretion (12-24 hours later) of various cytokines, chemokines17, and growth factors

Question 3

Autocoids

Answer 3

• histamine
• kinins (bradykinin)
• leukotrienes
• platelet activating factor
• prostaglandins

Question 4

Which autocoids are responsible for Triple Response of Lewis?

Answer 4

histamine & kinins

Question 5

COX-1

Answer 5

forms thromboxanes, prostaglandins in GI tract, prostaglandins in kidney

Question 6

Thromboxane

Answer 6

promotes platelet aggregation, vasoconstrictor

Question 7

COX-2

Answer 7

generates pro-inflammatory prostaglandins:

• prostacyclin (PgI2)
• prostaglandins in kidney,
• prostaglandins involved in pain, fever, inflammation

Question 8

Prostacyclin

Answer 8

inhibits platelet aggregation, vasodilator. Natural anti-clotting agent.

Question 9

selective inhibition of COX-2

Answer 9

(inhibition of prostacyclin) –> clot formation and possibly MI

Question 10

Aspirin-induced asthma

Answer 10

Cyclooxygenase inhibitors
can shift precursors to the
lipoxygenase pathway and
exacerbate asthma

(lipooxygenases–> leukotrienes –> involved in inflammatory conditions of the lung)

Question 11

PGE1

Answer 11

Intracavernosal administration for erectile dysfunction
Adverse effect: burning, Priapism

Reduces incidence of gastric ulcerations in patients on chronic nonsteroidal anti-inflammatory drugs

Question 12

PGE2

Answer 12

Cervical/vaginal suppository to induce full-term labor

Adverse effects: Nausea, vomiting (75%), fever

Question 13

PGF2a

Answer 13

Increase outflow of vitrous humor reducing intraocular pressure in glaucoma

Adverse effects: Darken eye color, lengthens eye lashes (20% of cases)-SOLD AS COSMETIC

Question 14

PGI2

Answer 14

PROSTACYCLIN
Pulmonary hypertension
Adverse effect: burning

Question 15

Leukotrienes

Answer 15

• key mediators of asthma
• 10k more potent than histamine in causing bronchoconstriction
• leukotriene receptor antagonists –> tx asthma
• lipoxygenase enzyme itself may be a target

Question 16

Bradykinin

Answer 16

activates NO synthase (NOS) –> NO –> inc GMP –> smc relaxation

Question 17

Kininase I/II (ACE) and HTN tx

Answer 17

degrades bradykinins

also facilitates conversion of angiotensin I –> angiotensin II (vasoconstrictor)

So ACE inhibitors (catopril) inc levels of kinins and vasodilation (tx HTN)

Question 18

Direct vasodilators that generate NO

Answer 18

Isosorbide (oral and sublingual)
Nitroglycerin (sublingual)
Nitropaste (transdermal)
Nitroprusside (IV)

use: Tx angina
adverse effects: throbbing HA

Question 19

Rich sources of histamine

Answer 19

Tissues: basophils, mast cells
Foods: cheeses, spinach, tuna

Question 20

Dx of systemic mastocytosis

Answer 20

N-Methylhistamine is measured in 24-hour urine (cold)

N-Methylhistamine=prod of histamine breakdown

Question 21

DOA (diamine oxidase) deficiency

Answer 21

check for this in pts sensitive to histamine containing foods

Question 22

H1 receptor

Answer 22

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

Question 23

Histamine shock

Answer 23

severe hypotension, diminished blood volume, reduced venous return, low cardiac output during anaphylaxis

(via H1)

Question 24

H2

Answer 24

exocrine glands, mostly gastric & parietal glands

• stimulation of gastric acid and other secretions
• drugs that BLOCK H2 –> tx gastritis, peptic ulcers, reflux esophagitis

Question 25

H3

Answer 25

autoinhibitory: brain (neurons and vessels)

• decrease synthesis/secretion of histamine
• Pitolisant: histamine H3-receptor antagonist/inverse agonist –> used to Tx narcolepsy and possibly ADHD

Question 26

H4

Answer 26

pro inflammatory: immune cells

Question 27

Helicobacter Pylori associated with chronic gastritis, tx?

Answer 27

Tx: 2-week course of antacid (Ranitidine (H2 antagonist) or Omeprazole) + multiple abx (eg, Amoxicillin and Clarithromycin)