Drugs affecting Vasculature

Question 1

What causes contraction of vascular smooth muscle?

Answer 1

GPCR coupled to Gq/11 stimulates the SR to release Ca, Ca induced Ca release and formation of Ca-CaM which activates MLCK which phosphorylates MLC and causes contraction

Question 2

What causes relaxation of vascular smooth muscle?

Answer 2

cGMP activates PKG which activates MLC phosphatase, dephosphorylating MLC and causing relacation

Question 3

How do organic nitrates cause relaxation?

Answer 3

Stimulate guanylate cyclase which phosphorylates GTO to cGMP activating protein kinase G and causing relocation

Question 4

How to vasodilating substances such as bradykinin and NO work?

Answer 4

Increase cellular calcium, increasing the level of Ca-CaM which stimulates eNOS and the formation of NO, activating guanylate cyclase and hyper polarising the cell causing relaxation

Question 5

Describe the effects of organic nitrates

Answer 5

• venorelaxation at small doses
• arteriolar dilatation higher doses
• increased coronary blood flow

Question 6

Describe the effects of GTN

Answer 6

Extensive first pass metabolism and short acting

Question 7

Describe the effects of isosorbide mononitrate

Answer 7

Longer acting

resistant to first pass metabolism

Question 8

How does endothelin work?

Answer 8

Through ETa receptor to cause contraction

Question 9

What does the RAAS system regulate?

Answer 9

Sodium excretion

Vascular tone

Question 10

What causes Renin release?

Answer 10

Increased renal sympathetic nerve activity

Decreased renal perfusion pressure

Decreased glomerular filtration rate

Question 11

Describe the effects of ACE inhibitors?

Answer 11

1. block the conversion of angiotensin I to angiotensin II meanwhile activating bradykinin (vasodilator)
2. no effect on cardiac contractility- CO increase as a result of decreased TPR
3. reduce release of aldosterone by the kidneys
4. greatest effect in brain, heart, kidneys
5. hypotension and dry cough

Question 12

How do AT1 receptor antagonists work?

Answer 12

Block the agonist action of angiotensin II receptors in a competitive manner

Dont inhibit the metabolism of bradykinin

Question 13

What are the clinical uses of AT1 receptor antagonists and ACE inhibitors

Answer 13

hypertension= benefit from

1) reduced TPR and MABP and
2) possible suppression of proliferation of smooth muscle cels in the media of resistance vessels

cardiac failure

1) decrease vascular resistance improving perfusion
2) increase excretion of Na and H20
3) regression of LVH

Post MI

Question 14

What is the clinical use of B clockers?

Answer 14

Treatment of angina pectoris (particularly B1 blockers)

Treatmment of hypertension

Treatment of heart failure

Question 15

How do B blockers work in angina?

Answer 15

decreased myocardial O2 requirement

counter elevated sympathetic activity associated with ischaemic pain

increase the time for diastole

Question 16

What is the function of B blockers in heart failure?

Answer 16

in combo with other drugs to suppress adverse effects associated with elevated activity of the sympathetic nervous system and RAAS

cause reflex activity

Question 17

How do Ca antagonists work?

Answer 17

Calcium antagonists block, or prevent the opening of L-type channels in excitable tissues
clinically useful Ca blockers act preferentially or solely with L type Ca channels in the hears and smooth muscle

Question 18

What do L-type calcium antagonist mediate?

Answer 18

upstroke of the AP in the SA and AV node

reduce the rate of conduction through the AV node
reduce the ventricular force of contraction in phase 2

Question 19

Describe verapamil

Answer 19

Relatively selective for cardiac L-type channels

Avoid in heart failure

Question 20

Describe Amlodipine

Answer 20

Dihydropiridine compound- relatively selective for smooth muscle type L-channels

Preferred for minimisation of unwanted effects upon cardiac muscle

Angia
Hypertension
Systolic hypertension

Question 21

Describe diltiazem

Answer 21

Intermediate selectivity

Question 22

How do potassium channel openers work?

Answer 22

Open ATP-modulated K+ channels in vascular smooth muscle by antagonising intracellular ATP
Cause hyperpolarisating which switches of L-type channels
act potentially and primarily on arterial smooth muscle

Question 23

Describe minoxidil

Answer 23

Last resort in severe hypertension
Counteract reflex tach with B-blocker
Counteract salt and water retention with diuretic

Question 24

Describe nicorandil

Answer 24

Angina

Question 25

How do a1-adrenoreceptors work?

Answer 25

Cause vasodilatation, reducing MABP
Prazosin and doxasosin- competitive antagonists
symptomatic relief in prostatic hyperplasia
may get dizzy