Drugs and the cardiovascular system: The vasculature Flashcards
identify the mechanisms regulating vascular tone and peripheral vascular resistance
vasoconstriction - decreased radius and flow, increased resistance
Vasodilation - increased radius and flow, decreased resistance
What is vascular tone
Arteriolar smooth muscle normally displays a state of partial constriction
How is blood pressure calculated
Cardiac output x Total peripheral resistance
What is the clinical definition of hypertension and what is an important risk factor for
BP consistently above 140/90 mmHg
Single most important risk factor for stroke, causing about 50% of ischaemic strokes
Major risk factor for myocardial infarction (MI) + chronic kidney disease (KD)
What is the first step in hypertension treatment
<55 - ACE inhibitor OR angiotensin receptor blocker (ARB)
> 55 / afro caribbean - Calcium channel blocker (CCB) or thiazide-like diuretic
What is the second step in hypertension treatment
CCB + ACEi or ACEi + thiazide type diuretic
Afro caribbean - ARBs preferred to ACEi
What is the third step in hypertension treatment
Combination of ACEi/ ARB with CCB and thiazide-like diuretic is recommended
What is the fourth step in hypertension treatment/ treatment for resistant hypertension
Consider low-dose spironolactone
Consider beta-blocker or alpha blocker
What is the mechanism of action for ACEi
Inhibit the somatic form of angiotensin converting enzyme (ACE)
Prevent the conversion of angiotensin I to angiotensin II by ACE
What are the uses of ACEi
Hypertension Heart failure Post-myocardial infarction Diabetic nephropathy Progressive renal insufficiency Patients at high risk of cardiovascular disease
Give an example of an ACEi
Enalapril
suffix -pril is indicative
How does hypertension lead to an increased CO
Increased TPR directly contributes to increased BP and increased venous return leads to increased cardiac contractility (via Starling’s Law) and thus CO.
How does heart failure lead to oedema
Increased vasoconstriction increases the afterload and increases cardiac work. Increased venous return leads to long term fluid retention and congestion, leading to oedema.
Give an example of a angiotensin receptor blocker (ARB)
Losartan
Give the mechanism of action for ARBs
Antagonists of type 1 (AT1) receptors for Ang II, preventing the renal and vascular actions of Ang II
AT1 found on vessels, kidney and adrenaline glands
Reduction in vasoconstriction, salt and water retention and aldosterone secretion (and thirst via SNS/CNS)
What are the uses of ARBs
Hypertension
Heart failure
What are the side effects of ACE inhibitors and ARBs
COUGH (ACEi - due to bradykinin accumulation as ACE usually converts it to inactive metabolites)
Hypotension
Hyperkalaemia (care with K supplements or K-sparing diuretics)
Renal failure in patients with renal artery stenosis
Describe the excitation-contraction process of smooth muscle contraction
- Membrane depolarisation opens voltage-gated calcium (Ca2+) channels (VGCCs)
- Ca2+ enters & binds to calmodulin (CaM)
- Ca2+-CaM complex binds to & activates myosin light chain kinase (MLCK)
- MLCK mediated phosphorylation
- smooth muscle contraction
What are the two types of calcium channels blockers and describe them
dihydropyridines (DHPs)
More selective for blood vessels
Also licensed for prophylaxis of angina
Non-DHPs
Rate-limiting
Give an example of the two types of calcium channels blockers and their inotropic effects
Dihydropyridines (DHPs)
Amlodipine (no negative inotropy)
Non-DHPs
Verapamil (large negative inotropic effect)
Which of the calcium channel blockers would you use to treat hypertension?
Dihydropyridines
inhibits Ca2+ entry into vascular smooth muscle cells
Decreased TPR and BP
Why are alpha blockers used as anti-hypertensives
Blockade alpha1 receptors
Block vasoconstriction, reduce blood pressure
What are the targets of prazosin and phentolamine
Alpha blockers
Prazosin targets a1 receptors
Phentolamine targets a1 and a2 receptors
Why are ACEi and ARBs contraindicated for renal failure patients with renal artery stenosis
Glomerular pressure must be sufficient enough to drive GFR
ANG II controls this pressure usually. When pressure drops, ANG II is released and constricts the efferent arteriole so blood cannot leave the glomerulus effectively and GFR is restored
Patients with renal failure cannot regulate their glomerular pressure
Why are elderly and afro Caribbean given CCBs as first line
Low plasma renin activity
elderly - Hypertension is usually due to atherosclerosis, RAAS desensitises
Compare RASi to CCBs
CCBs reduce SBP more than RAS inhibitors
RAS inhibitors decrease heart failure
RAS inhibitors increase stroke
No difference for all-cause death
Compare RASi to thiazides
Thiazides reduce SBP more than RAS inhibitors
RAS inhibitors increase heart failure and stroke
No difference for all-cause death
Compare RASi to beta blockers
No difference in SBP reduction
RAS inhibitors reduce CV events and stroke
No difference for all-cause death
