smooth muscle pharmacology

Question 1

endothelium-dependent vasodilation

Answer 1

Regulation of Guanylate cyclase by Nitric oxide formed by adjacent endothelium cells. leading to the relaxation of smooth muscle in the vasculature

Question 2

Akt

Answer 2

protein kinase that phosphorylates NOS making it more sensitive to calcium-calmodulin

Question 3

what is the role of protein kinase G in muscle relaxation

Answer 3

• stimulates MLCP
• stimulates plasma membrane Ca2+ - ATPase
  -Stimulates SERCA
  -activates K+ channels that cause hyperpolarization and inactivate Ca2+ Channels

Question 4

Angina

Answer 4

-inadequate myocardial supply
-fixed vessel narrowing
-endothelial dysfunction

Question 5

stable angina

Answer 5

-episodic
-brought on by exertion
-relieved by rest

Question 6

unstable angina

Answer 6

symptomatic even at rest

Question 7

how is angina managed pharmacologically ?

Answer 7

Via Organic Nitrates

Question 8

what is the primary action of Organic nitrates ?

Answer 8

induce venodilation to reduce preload and oxygen demand in the myocardium

Question 9

how do organic nitrates induce venodilation ?

Answer 9

• act directly on the smooth muscle cell to increase NO production

Question 10

Why does inducing venodilation help manage angina

Answer 10

• reduces venous pressure and the venous return to the heart
  -this reduces the work of the heart and reduces oxygen demand

Question 11

what is the secondary action of Organic Nitrates

Answer 11

dilates coronary collaterals to improve oxygen delivery to the ischemic myocardium

Question 12

what is the half life of glyceryl trinitrates

Answer 12

40 mins

Question 13

what is the half life of Isosorbide dinitrate or isosorbide mononitrate

Answer 13

2 to 4 hours

Question 14

bioavailability

Answer 14

extent and rate at which an active substance enters systemic circulation

Question 15

what is the bioavailability of Isosorbide dinitrate or isosorbide mononitrate

Answer 15

varies

Question 16

what reduces the bioavailability of Glyceryl trinitrate ?

Answer 16

oral administration

Question 17

above what bp is considered hypertension ?

Answer 17

diastolic- 90mmHg
systolic - 140mmHg

Question 18

what are the consequences of Hypertension ?

Answer 18

-left ventricular hypertrophy
-renal failure
-stroke

Question 19

how is hypertension managed

Answer 19

• blocking calcium channels
  -opening K+ channels
  -blocking alpha adrenoreceptors

Question 20

what are the three main classes of calcium channel blockers ?

Answer 20

dihydropyridines
Benzothiazepines
Phenylalkylamines

Question 21

examples of Dihydropyridines

Answer 21

Nifedipine and amlodipine

Question 22

examples of Benzothiazepines

Answer 22

Diltiazem

Question 23

example of Phenylalkylamines

Answer 23

Verapamil

Question 24

how are calcium channel blockers usually administered ?

Answer 24

orally

Question 25

what is the bioavailability of Calcium Channel blockers ?

Answer 25

10-30%

Question 26

what is the half life of calcium channel blockers ?

Answer 26

2-4 hours

Question 27

what are KATP channel openers used in conjunction with when treating severe hypertension ?

Answer 27

- beta blockers and diuretics

Question 28

what is the mechanism of K+ channel openers ?

Answer 28

Open KATP channels in the smooth muscle cell membrane and hyper polarise the smooth muscle cell

Question 29

what are examples of K+ channel openers

Answer 29

minoxidil and nicorandil

Question 30

what is the mechanism of action of alpha blockers

Answer 30

α1 adrenoreceptors are the first part of the signalling cascade that ultimately leads to smooth muscle contraction following activation of the sympathetic nervous system α1 antagonists aka. α blockers prevent this signaling cascade and therefore lead to vasodilation

Question 31

example of an alpha blocker

Answer 31

prazosin