(4) Smooth Muscle: Vasoactive (1.1-1.3)

Question 1

What enzyme do nitrates activate?

Answer 1

Guanylyl cyclase ⇒ ↑ cGMP

Question 2

Describe the effect nitrates have on the vasculature

Answer 2

(1) Significant venous dilation
(2) Moderate dilation of large arteries

Question 3

Which hemodynamic factor do nitrates predominantly affect?

Answer 3

Preload

Question 4

Indications (3) : Nitrates

Answer 4

(1) Stable angina
(2) Prinzmetal angina
(3) Acute coronary syndrome

Question 5

ROA: Nitroglycerin

Answer 5

Sublingual

Question 6

ROA: Isosorbide Nitrate

Answer 6

Oral

Question 7

When are nitrates contraindicated in the treatment of MI?

Answer 7

Right-sided MI

(Due to ↑ sensitivity to preload)

Question 8

Why would β-blockers be given with nitrates?

Answer 8

Prevent reflex tachycardia

(Venous vasodilation ⇒ ↓ Preload ⇒ ↓ MAP ∴ Body compensates by ↑ HR)

Question 9

How can nitrates cause hypoxia?

Answer 9

Oxidize heme Fe²⁺ → Fe³⁺

(Nitrates have many oxygens ∴ oxidizing agents ∴ oxidize iron)

Question 10

How is nitrate tolerance avoided?

Answer 10

Nitrate free interval every day

(to avoid tolerance)

Question 11

What drug class is an absolute contraindication to nitrates?

Answer 11

PDE-5 inhibitors

Question 12

What type of heart disease are nitrates contraindicated in?

Answer 12

Hypertrophic cardiomyopathy

(↓ Chamber volume exacerbates outflow obstruction and mitral regurgitation)

Question 13

What nerve is irritated during a migraine?

Answer 13

Trigeminal n.

Question 14

What drug is first-line therapy for migraines?

Answer 14

Triptans

(i.e., Sumatriptan)

Question 15

MOA: Triptans

Answer 15

(1) 5-HT_1b agonist
(2) 5-HT_1d agonist
* (Specifically on the meningeal vessels)*

Question 16

What is the effect of stimulating vascular 5-HT_1b and 5-HT_1d receptors?

Answer 16

Vasoconstriction

Question 17

What is the effect of stimulating 5-HT_1b and 5-HT_1d receptors on the trigeminal nerve?

Answer 17

prevents the release of vasoactive peptides

Question 18

What is the effect of stimulating 5-HT_1b and 5-HT_1d receptors in the brain stem?

Answer 18

Inhibits pain pathway

Question 19

Adverse Effect: Triptans

Answer 19

Coronary vasospasm

Question 20

Contraindication: Triptans

Answer 20

Patients with angina

(Also are known to trigger Prinzmetal angina)

Question 21

Treatment: Acute cluster headache

Answer 21

Triptans + O₂

Question 22

Name 5 options available for migraine prophylaxis

Answer 22

(1) Calcium channel blockers
(2) β-blockers
(3) Valproic acid
(4) Topiramate
(5) Tricyclic antidepressants

Question 23

Alprostadil is an analog of?

Answer 23

PGE₁

Question 24

Indications (2) : Alprostadil

Answer 24

(1) Erectile dysfunction
(2) Maintain patent ductus arteriosus
* (Second-line therapy for ED)*

Question 25

Name 3 physiologic effects of PGE₁

Answer 25

(1) Arteriolar vasodilation
(2) ↑ Gastric mucus secretion
(3) ↑ Uterine contraction
* (Also prevents platelet aggregation)*

Question 26

Which prostanoid keeps the ductus arteriosus open?

Answer 26

PGE₁

Question 27

Misoprostol is an analog of?

Answer 27

PGE₁

(Don’t confuse with Mifepristone which is a progesterone antagonist)

Question 28

Indications (2) : Misoprostol

Answer 28

(1) Prevent NSAID-induced peptic ulcer
(2) Induce contractions

Question 29

What is the main side effect of Misoprostol?

Answer 29

Diarrhea

(Given its used as abortifacient, it likely causes uterine cramps too)

Question 30

Dinoprostone is an analog of?

Answer 30

PGE₂

(Dino is right of Dill pickle ∴ PGE2 instead of PGE1)

Question 31

Indications (2) : Dinoprostone

Answer 31

(1) Facilitate labor
(2) Terminate pregnancy

Question 32

Name 3 analogs of PGF_2α

Answer 32

(1) Carboprost
(2) Latanoprost
(3) Travoprost

Question 33

What is Carboprost used for?

Answer 33

Promotes uterine contraction

(↑ Uterine contraction ∴ controls postpartum hemorrhage and terminates pregnancy)

Question 34

What is Latanoprost used for?

Answer 34

↑ Aqueous humor outflow

(∴ Useful for OPEN-angle glaucoma)

Question 35

What is the distinctive side effect of Travoprost?

Answer 35

Brown pigmentation of the iris

(Also occurs with Latanoprost)

Question 36

Who does idiopathic pulmonary hypertension most commonly manifest in?

Answer 36

Women 20-40 y/o

(As shown by the woman holding tennis rackets)

Question 37

Describe the side effects of PGI₂ analogs

Answer 37

Consequences of vasodilation

(Hypotension, cutaneous vasodilation, flushing)

Question 38

Name 2 PGI₂ analogs used to treat pulmonary hypertension

Answer 38

(1) Iloprost
(2) Epoprostenol

Question 39

Suffix: PDE-5 inhibitors

Answer 39

“-fil”

Question 40

PDE-5 inhibitors increase the intracellular concentration of?

Answer 40

cGMP

Question 41

Indications (2) : PDE-5 inhibitors

Answer 41

(1) Erectile dysfunction
(2) Pulmonary hypertension

Question 42

What is the major toxicity associated with Bosentan?

Answer 42

Fatal hepatotoxicity

Question 43

MOA: Bosentan

Answer 43

Inhibits endothelin

(Boss stan ∝ Bosentan)