(4) Smooth Muscle: Vasoactive (1.1-1.3) Flashcards
What enzyme do nitrates activate?
Guanylyl cyclase ⇒ ↑ cGMP
Describe the effect nitrates have on the vasculature
(1) Significant venous dilation
(2) Moderate dilation of large arteries
Which hemodynamic factor do nitrates predominantly affect?
Preload
Indications (3) : Nitrates
(1) Stable angina
(2) Prinzmetal angina
(3) Acute coronary syndrome
ROA: Nitroglycerin
Sublingual
ROA: Isosorbide Nitrate
Oral
When are nitrates contraindicated in the treatment of MI?
Right-sided MI
(Due to ↑ sensitivity to preload)
Why would β-blockers be given with nitrates?
Prevent reflex tachycardia
(Venous vasodilation ⇒ ↓ Preload ⇒ ↓ MAP ∴ Body compensates by ↑ HR)
How can nitrates cause hypoxia?
Oxidize heme Fe2+ → Fe3+
(Nitrates have many oxygens ∴ oxidizing agents ∴ oxidize iron)
How is nitrate tolerance avoided?
Nitrate free interval every day
(to avoid tolerance)
What drug class is an absolute contraindication to nitrates?
PDE-5 inhibitors
What type of heart disease are nitrates contraindicated in?
Hypertrophic cardiomyopathy
(↓ Chamber volume exacerbates outflow obstruction and mitral regurgitation)
What nerve is irritated during a migraine?
Trigeminal n.
What drug is first-line therapy for migraines?
Triptans
(i.e., Sumatriptan)
MOA: Triptans
(1) 5-HT1b agonist
(2) 5-HT1d agonist
* (Specifically on the meningeal vessels)*
What is the effect of stimulating vascular 5-HT1b and 5-HT1d receptors?
Vasoconstriction
What is the effect of stimulating 5-HT1b and 5-HT1d receptors on the trigeminal nerve?
prevents the release of vasoactive peptides
What is the effect of stimulating 5-HT1b and 5-HT1d receptors in the brain stem?
Inhibits pain pathway
Adverse Effect: Triptans
Coronary vasospasm
Contraindication: Triptans
Patients with angina
(Also are known to trigger Prinzmetal angina)
Treatment: Acute cluster headache
Triptans + O2
Name 5 options available for migraine prophylaxis
(1) Calcium channel blockers
(2) β-blockers
(3) Valproic acid
(4) Topiramate
(5) Tricyclic antidepressants
Alprostadil is an analog of?
PGE1
Indications (2) : Alprostadil
(1) Erectile dysfunction
(2) Maintain patent ductus arteriosus
* (Second-line therapy for ED)*
Name 3 physiologic effects of PGE1
(1) Arteriolar vasodilation
(2) ↑ Gastric mucus secretion
(3) ↑ Uterine contraction
* (Also prevents platelet aggregation)*
Which prostanoid keeps the ductus arteriosus open?
PGE1
Misoprostol is an analog of?
PGE1
(Don’t confuse with Mifepristone which is a progesterone antagonist)
Indications (2) : Misoprostol
(1) Prevent NSAID-induced peptic ulcer
(2) Induce contractions
What is the main side effect of Misoprostol?
Diarrhea
(Given its used as abortifacient, it likely causes uterine cramps too)
Dinoprostone is an analog of?
PGE2
(Dino is right of Dill pickle ∴ PGE2 instead of PGE1)
Indications (2) : Dinoprostone
(1) Facilitate labor
(2) Terminate pregnancy
Name 3 analogs of PGF2α
(1) Carboprost
(2) Latanoprost
(3) Travoprost
What is Carboprost used for?
Promotes uterine contraction
(↑ Uterine contraction ∴ controls postpartum hemorrhage and terminates pregnancy)
What is Latanoprost used for?
↑ Aqueous humor outflow
(∴ Useful for OPEN-angle glaucoma)
What is the distinctive side effect of Travoprost?
Brown pigmentation of the iris
(Also occurs with Latanoprost)
Who does idiopathic pulmonary hypertension most commonly manifest in?
Women 20-40 y/o
(As shown by the woman holding tennis rackets)
Describe the side effects of PGI2 analogs
Consequences of vasodilation
(Hypotension, cutaneous vasodilation, flushing)
Name 2 PGI2 analogs used to treat pulmonary hypertension
(1) Iloprost
(2) Epoprostenol
Suffix: PDE-5 inhibitors
“-fil”
PDE-5 inhibitors increase the intracellular concentration of?
cGMP
Indications (2) : PDE-5 inhibitors
(1) Erectile dysfunction
(2) Pulmonary hypertension
What is the major toxicity associated with Bosentan?
Fatal hepatotoxicity
MOA: Bosentan
Inhibits endothelin
(Boss stan ∝ Bosentan)
