Smooth muscle pharmacology

Question 1

Conditions managed by pharmacological manipulation of smooth muscle contraction

Answer 1

Angina
Inadequate myocardial oxygen supply
→ Fixed vessel narrowing
→ Endothelial dysfunction
Stable angina
* Episodic, brought on by exertion, relieved by rest

Unstable angina
* Symptomatic even at rest

Question 2

Pharmacological Management of angina

Answer 2

Organic nitrates act directly on the smooth muscle cell to increase nitric oxide (NO)production

The same signaling cascade as endogenous NOrelease leads to smooth muscle relaxation and therefore vasodilation

Acts primarily on veins to reduce preload and oxygen demand in the myocardium

Secondary action on the coronary collaterals improve oxygen delivery to the ischaemic myocardium

Question 3

effects of organic nitrates on venodilation

Answer 3

→ The primary action of organic nitrates is to induce venodilation
→ Venodilation reduces venous pressure and thevenous return to the heart
→ This reduces work of the heart (by Starling’sLaw)
→ Reduces oxygen demand

Question 4

Pharmacology of the organic nitrates
Glyceryl trinitrate (GTN)

Answer 4

→ Do not directly release NO
→ GTN-NO2-NO-Guanylate cyclase
→ Biologically inactive
→ Half life ~40 mins
→ Low bioavailability if given orally

Question 5

Pharmacology of the organic nitrates
Isosorbide dinitrate or isosorbide mononitrate

Answer 5

→ Do not directly release NO
→ Isosorbide dinitrate/mononitrate-NO2-NO-Guanylate cyclase
→ Biologically inactive
→ Half life ~2-4 hour
s→ Bioavailability varies

Question 6

nitric oxide produced in the mouth can affect what

Answer 6

blood pressure

Question 7

Hypertension

Answer 7

→ Diastolic blood pressure 90 mmHg
→ Systolic blood pressure 140 mmHg

Question 8

Consequences of hypertension include

Answer 8

→ Left ventricular hypertrophy
→ Renal failure
→ Stroke

Question 9

what do calcium channels act as on management of hypertension

Answer 9

Calcium channel blockers act at l-type calcium channels on vascular smooth muscle but ALSO at l-typecalcium channels in cardiac myocytes

Question 10

what do calcium channels act as on management of hypertension

Answer 10

Calcium channel blockers act at l-type calcium channels on vascular smooth muscle but ALSO at l-typecalcium channels in cardiac myocytes

Question 11

what are the three main calcium channel blockers

Answer 11

→ Dihydropyridines
→ Nifedipine and amlodipine
→ Benzothiazepines
→ Diltiazem
→ Phenylalkylamines
→ Verapamil

Question 12

KATP channel opener

Answer 12

→ In severe hypertension can be used with beta blocker and diuretics
→ Open KATP channels in the smooth muscle cell membrane and hyperpolarise the smooth muscle cell
→ Examples include minoxidil and nicorandil

Question 13

α blockers

Answer 13

-a1 adrendoreceptors are the first part of the signalling cascade that ultimately leads to smooth muscle contraction following activation of the sympathetic nervous system
-a1 antagonists aka. a blockers prevent signalling cascade and therefore lead to vasodilation
-example - prazonin

Question 14

summary

Answer 14

Pharmacological modulation of smooth muscle tone can be used in the management of conditions likehypertension and angina
→ Angina can be managed by exploiting smooth muscle tone through NO-mediated vasodilation
→ Hypertension can be managed by preventing the rise in intracellular calcium needed to initiate cross-bridgeformation by:
→ Blocking calcium channels
→ Opening potassium channels
→ Blocking α adrenoreceptor