Autonomic pharmacology pt. 3: Autacoids

Question 1

Leukotrienes are generated from _______ using the enzyme ________.

Answer 1

arachidonic acid, lipooxygenase

Question 2

In which major organ do leukotrienes bind receptors primarily? What does this cause?

Answer 2

Lungs. Causes bronchoconstriction

Question 3

How is asthma commonly treated?

Answer 3

With leukotriene receptor antagonists.

Question 4

In which organ(s) is/are COX-1 found?

Answer 4

GI tract and kidneys

Question 5

In which organ(s) is/are COX-2 found?

Answer 5

Kidneys

Question 6

What is one AE that inhibition of prostacyclin (PGI2) can cause?

Answer 6

MI or thrombotic stroke

Question 7

Why do NSAIDs cause AEs like GI ulceration and bleeding?

Answer 7

They non-selectively inhibit cyclooxygenases 1 and 2. COX-1 produces PGE2 which makes the protective mucosal barrier in the GI tract. COX-1 also produces thromboxane TXA2 which promotes platelet aggregation.

Question 8

What do prostacyclins like PGI2 do? Which enzyme makes it? Does aspirin affect COX-2?

Answer 8

Inhibit platelet aggregation and vasodilate. COX-2 makes it. Aspirin does not affect COX-2 in small doses, and that is the basis for its blood-thinning effects. It inhibits COX-1, preventing TXA2 formation.

Question 9

Do prostaglandins produced in the kidney help promote healthy renal blood flow?

Answer 9

Yeah

Question 10

What are the two types of histamine receptors? Which one is involved in allergic reactions and therefore is a target of anti-histamines?

Answer 10

H-1 and H-2. H-1 is involved in allergic reactions and is a target of diphenhydramine and loratidine.

Question 11

Can diphenhydramine cross the blood-brain barrier? What is the clinical significance of this?

Answer 11

It can because it is lipophilic. It is therefore a sedative because it can bind H-1 receptors in the CNS.

Question 12

Where are H-2 receptors primarily found? What does stimulation of these receptors do? What drugs target these receptors?

Answer 12

Found in the stomach. Stimulation results in parietal cell acid secretion. Drugs target these receptors to treat acid reflux: ranitidine, nizatidine, famotidine.

Question 13

What do bradykinins do?

Answer 13

Vasodilation and pain

Question 14

What is the relationship between ACE and bradykinins? What do ACE inhibitors do?

Answer 14

ACE degrades bradykinins. ACE inhibitors increase endogenous bradykinins and also reduce angiotensin II, resulting in vasodilation.

Question 15

Does increased serotonin levels in the brain improve mood and sleep?

Answer 15

Yeah

Question 16

In which organ is the majority of serotonin found?

Answer 16

GI (~80%)

Question 17

What does serotonin do to smooth muscle?

Answer 17

Constriction (remember serotonin agonist treat migraines in phase 2 - vasodilation)

Question 18

What two molecules are responsible for symptoms of allergy? What is the Triple response of Lewis?

Answer 18

Histamine and kinins causes Triple response of Lewis: heat, itching, swelling, pain (HISP).

Question 19

Where are mast cells located?

Answer 19

Perivascularly and close to nerve endings

Question 20

Can mast cells release cytokines without degranulating?

Answer 20

Yeah

Question 21

Does mast cell degranulation affect all body organs?

Answer 21

Yeah

Question 22

What does nitric oxide do?

Answer 22

Vasodilator

Question 23

Which two cell types have lots of histamine?

Answer 23

Basophils, mast cells

Question 24

What is measured in a 24-hour urine collection to diagnose systemic mastocytosis?

Answer 24

N-methylhistamine/1,4-methylimidazole acetic acid

Question 25

Why are opioids often given in conjunction with antihistamines?

Answer 25

Opiates degranulate mast cells causing histamine release and hypotension, so antihistamines are given.

Question 26

What is Cemetidine?

Answer 26

A H-2 receptor antagonist that treats acid reflux and also inhibits microsomal liver CYP450 resulting in increased estrogen levels –> gynecomastia and psychological problems

Question 27

What’s up with H. pylori?

Answer 27

It causes gastritis and likes low pH in GI tract.

Question 28

What do gastrin and acetylcholine do to the stomach?

Answer 28

Increase gastric acid secretion

Question 29

Selective serotonin reuptake inhibitors (SSRIs) can be used to treat _______. They also antagonize ________ receptors.

Answer 29

depression. They antagonize Ach muscarinic receptors

Question 30

What drug treats carcinoid tumors?

Answer 30

Cyproheptadine

Question 31

H-1 receptor antagonists are also ______ receptor angatonists.

Answer 31

Ach-muscarinic

Question 32

Prophylactic treatment of asthma involves blocking ______ receptors whereas treatment of an acute attack involves stimulating _______ receptors.

Answer 32

leukotriene receptors for phophylactic, beta 2 stimulation for acute attacks