Lecture 8: Smooth Muscle

Question 1

Nitroglycerin/Isosorbide Dinitrate/Isosorbide-5-mononitrate

Answer 1

Mechanism: Generation of nitric oxide, activating guanylate cyclase, increasing cGMP, resulting in relaxation. Venous dominant,

Uses: Heart failure

SE: hypotension

Question 2

Nitroprusside

Answer 2

Mechanism: NO releasing, guanylate cyclase action, increase cGMP, relaxation. Arterial/venous both affected

Use: hypertensive emergencies

SE: hypotension

Question 3

Hydralazine

Answer 3

Mechanism: Unknown. Direct vasodilator working on arterial circulation.

Uses:
Severe/emergencies hypertension.

Heart failure, pill with Isosorbide dinitrate (works on venous circulation),

Question 4

Minoxidil

Answer 4

Mechanism: K+ATP channel opening. Works on arterial circulation. Direct vasodilator

Uses: Severe hypertension and hair growth for males.

SE: Fluid retention (so use with diuretics)

Question 5

Diazoxide

Answer 5

Mechanism: K+ channel opener, efflux of K+ leads to hyperpolarization, closing Ca2+ channel, preventing contraction

Uses: in hypertensive emergencies and hypoglycemia

Question 6

Ca2+ Channel blockers

Answer 6

Examples: Nifedipine, Verapamil, Diltazem

Mechanism: Block the L-type Ca2+ channels. Non selective, and affect arterial circulation, block Ca2+ influx.

Heart vs. Vascular Smooth Muscle: PKA phosphorylates Ca2+ channel causing influx and contraction. Versus. PKA phosphorylates and inactivates MLCK, normally activating by phosphorylation Myosin light chain.

Question 7

Phosphodiesterase inhibitors PDE3/PDE5

Answer 7

Inhibiting PDE3 in heart muscle increases cAMP levels, increasing contraction in heart. (This increases relaxation in vascular smooth muscle)

Inhibiting PDE5 in smooth muscle increases cGMP levels, increasing relaxation (also PDE3 in smooth muscle)

Question 8

PDE3 inhibitors

Answer 8

Milrinone, inamrinone, cilostazol

Intracellular signaling

Used for heart failure (and dilate vacular smooth muscle)

Question 9

PDE5 inhibitors

Answer 9

Sildenafil, tadalafil
Intracellular signaling
Erectile dysfunction

Question 10

Renin angiotensin inhibitors mechanism

Answer 10

Enzymatic pathway
Angiotensin receptor/intracellular signaling
Arterial (Dominant) and venous circulation

Question 11

Bradykinin

Answer 11

Mechanism: Vasodilator on endothelial through action on B2 receptor through release
prostaglandins, nitric oxide, and epoxygenase metabolites.

Increased by ACE inhibitor. (because ACE breaks down bradykinin). SO A LITTLE DIFF THAN AT1 RECEPTOR BLOCKER.

Works on both arterial and venous circulation

Question 12

Fenoldopam

Answer 12

Mechanism: Dopamine 1 receptor agonist. Arterial and venous circulation

Use: Good for hypertensive crisis. Renal blood flow and Na excretion increased

Question 13

Prazosin

Answer 13

Mechanism: Vasodilator that blocks NE acting on Alpha-adrenergic receptors. Arterial and venous circulation

Question 14

Methylxanthine class of drugs

Answer 14

Examples: Theophylline, aminophylline

Use: Bronchodilator

Mechanism: Adenosine receptor antagonism and phosphodiesterase inhibition. Increasing cAMP leading to bronchodilation. Also inhibits Adenosine from causing bronchoconstriction.

Use: Good for mucous clearance, anti inflammatory actions, prevent edema by decreasing permeability.

Question 15

Anti cholinergic bronchodilator

Answer 15

Bronchodilators
Examples: Ipratropium, tiotropium

Mechanism: Block muscarinic receptors, blocking a contraction pathway. (Acetylcholine acting on M3 receptor typically causes contraction)

Use: Can also be used for inhibiting mucous secretion

Question 16

Vasodilator drugs

Answer 16

Nitroglycerin, Nitroprusside,

Hydralazine,
Minoxidil, Diazoxide,

Ca2+ channel blockers, Verapamil, Diltiazem,

Milrinone, Inamrinone, Cilostazol,
Sildenafil, Tadalafil,

Fenoldopam, Prazosin

Question 17

Bronchodilator drugs:

Answer 17

Albuterol, Pirbuterol, Terbutaline, Salmeterol, Formoterol, Ipratropium, Tiotropium, Theophylline, Aminophylline

Question 18

B2 adrenergic agonists

Answer 18

Bronchodilators
Examples: Albuterol (most widely used), Pirbuterol, terbutaline, Salmeterol, Formoterol

Mechanism: Beta 2 agonist causes rise in cAMP/PKA resulting in relaxation. Also acts on Calcium activated potassium channels to cause Potassium efflux and hyperpolarization and relaxation.

SE: Cardiotoxicity-tachycardia (Beta 2 on the cardiac smooth muscle)