Flashcards in Drugs affecting Vasculature Deck (25):
What causes contraction of vascular smooth muscle?
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
What causes relaxation of vascular smooth muscle?
cGMP activates PKG which activates MLC phosphatase, dephosphorylating MLC and causing relacation
How do organic nitrates cause relaxation?
Stimulate guanylate cyclase which phosphorylates GTO to cGMP activating protein kinase G and causing relocation
How to vasodilating substances such as bradykinin and NO work?
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
Describe the effects of organic nitrates
-venorelaxation at small doses
-arteriolar dilatation higher doses
-increased coronary blood flow
Describe the effects of GTN
Extensive first pass metabolism and short acting
Describe the effects of isosorbide mononitrate
resistant to first pass metabolism
How does endothelin work?
Through ETa receptor to cause contraction
What does the RAAS system regulate?
What causes Renin release?
Increased renal sympathetic nerve activity
Decreased renal perfusion pressure
Decreased glomerular filtration rate
Describe the effects of ACE inhibitors?
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
How do AT1 receptor antagonists work?
Block the agonist action of angiotensin II receptors in a competitive manner
Dont inhibit the metabolism of bradykinin
What are the clinical uses of AT1 receptor antagonists and ACE inhibitors
hypertension= benefit from
1) reduced TPR and MABP and
2) possible suppression of proliferation of smooth muscle cels in the media of resistance vessels
1) decrease vascular resistance improving perfusion
2) increase excretion of Na and H20
3) regression of LVH
What is the clinical use of B clockers?
Treatment of angina pectoris (particularly B1 blockers)
Treatmment of hypertension
Treatment of heart failure
How do B blockers work in angina?
decreased myocardial O2 requirement
counter elevated sympathetic activity associated with ischaemic pain
increase the time for diastole
What is the function of B blockers in heart failure?
in combo with other drugs to suppress adverse effects associated with elevated activity of the sympathetic nervous system and RAAS
cause reflex activity
How do Ca antagonists work?
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
What do L-type calcium antagonist mediate?
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
Relatively selective for cardiac L-type channels
Avoid in heart failure
Dihydropiridine compound- relatively selective for smooth muscle type L-channels
Preferred for minimisation of unwanted effects upon cardiac muscle
How do potassium channel openers work?
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
Last resort in severe hypertension
Counteract reflex tach with B-blocker
Counteract salt and water retention with diuretic