Drugs and the cardiovascular system: The vasculature

Question 1

what happens to the radius, resistance and flow in vasoconstriction?

Answer 1

radius = decreases 
resistance = increases
flow = decreases

Question 2

what happens to the radius, resistance and flow in vasodilation?

Answer 2

radius = increases
resistance = decreases 
flow = increases

Question 3

what is the physiology behind hypertension?

Answer 3

Blood pressure (BP) = cardiac output (CO) x total peripheral resistance (TPR)

Question 4

what is hypertension defined as?

Answer 4

Hypertension is defined as being consistently above 140/90 mmHg

Question 5

what are the 4 steps of hypertension?

Answer 5

step 1:
Angiotensin converting enzyme (ACE) inhibitor OR angiotensin receptor blocker (ARB) for under 55s
Calcium channel blocker (CCB) or thiazide-like diuretic for over 55s or afro-Caribbean’s

step 2:
CCB or thiazide-like diuretic & ACEi or ARB
ARBs preferred to ACEi for AfroCaribbean’s

step 3:
Combination of ACEi/ ARB with CCB and thiazide-like diuretic is recommended

step 4:
Consider low-dose spironolactone
Consider beta-blocker or alpha blocker

Question 6

what increases renin secretion?

Answer 6

decrease in sodium absorption
decrease in renal perfusion pressure
increase in sympathetic NS

Question 7

what do angiotensin converting enzyme inhibitors do?

Answer 7

Inhibit the somatic form of angiotensin converting enzyme (ACE)
Prevent the conversion of angiotensin I to angiotensin II by ACE
Uses:• hypertension• heart failure• post-myocardial infarction• diabetic nephropathy• progressive renal insufficiency• patients at high risk of cardiovascular disease

Example: Enalapril

Question 8

what effect does BP = CO x TPR have on hypertension and heart failure

Answer 8

Increased TPR and increased venous return will worsen hypertension and heart failure.
Hypertension – Increased TPR directly contributes to increased BP and increased venous return leads to increased cardiac contractility (via Starling’s Law) and thus CO.
Heart failure: Increased vasoconstriction increases the afterload and increases cardiac work. Increased venous return leads to long term fluid retention and congestion, leading to oedema.

Question 9

example of angiotensin receptor blocker

what does it do?

Answer 9

Example: losartan
Antagonists of type 1 (AT1) receptors for Ang II, preventing the renal and vascular actions of Ang II.
Uses: hypertension, heart failure

Question 10

side effects of ACEi and ARB

Answer 10

Generally well tolerated – particularly ARB
Cough (ACEI) - Bradykinin
Hypotension (both)
Generally well tolerated – particularly ARB
Hyperkalaemia (care with K supplements or K sparing diuretics)
Renal failure in patients with renal artery stenosis (both)

Question 11

how does smooth muscle contraction occur?

Answer 11

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

Question 12

examples of calcium channel blockers

Answer 12

Calcium Channel Blockers (CCBs)
Dihydropyridines (DHPs)
More selective for blood vessels
Amlodipine -does not cause any negative inotropy
Also licensed for prophylaxis of angina
Non-DHPs (aka rate-limiting)
Verapamil - large negative inotropic effect

Question 13

calcium channel blocker for hypertension

Answer 13

Hypertension:

Dihydropyridines inhibit Ca2+ entry into vascular smooth muscle cells

↓ T.P.R. = ↓ B.P.

N.B. Powerful vasodilation can lead to reflex tachycardia and
increased inotropy thus increased myocardial oxygen demand

Question 14

RAS vs CCB

Answer 14

RAS vs CCBs
CCBs  SBP more than RAS inhibitors
RAS inhibitors  heart failure
RAS inhibitors  stroke
No difference for all-cause death

Question 15

RAS vs thiazide

Answer 15

RAS vs thiazides
Thiazides  SBP more than RAS inhibitors
RAS inhibitors  heart failure
RAS inhibitors  stroke
No difference for all-cause death

Question 16

RAS vs beta-blockers

Answer 16

RAS vs beta-blockers
No difference in SBP reduction
RAS inhibitors  CV events
RAS inhibitors  stroke
No difference for all-cause death

Question 17

why are alpha blockers used as anti-hypertensives?

Answer 17

examples: prazosin and phentolamine
a1 = less calcium
a2 = less cAMP and PKA

Alpha blockers lower blood pressure by keeping the hormone norepinephrine from tightening the muscles in the walls of smaller arteries and veins. As a result, the vessels remain open and relaxed. This improves blood flow and lowers blood pressure