Drugs affecting cardiovascular system (blood pressure)

Question 1

High blood pressure is

Answer 1

140/90mmHg

130/80mmHg in diabetics, kidney disease

Question 2

Chronic BP >140/90mmHg is a risk factor for

Answer 2

• Stroke
• TIA
• MI
• Ischaemic heart disease
• CHF
• Aortic aneurism
• Retinal Haemorrhage
• Renal failure
• Death

Question 3

BP =

Answer 3

CO x TPR

Question 4

CO =

Answer 4

HR x SV

Question 5

What is the major neuronal influence on BP?

Answer 5

Sympathetic tone: releases NA

-P = +SNS tone

Question 6

How does NA influence BP at the blood vessels?

Answer 6

• activate A1-aR –> vasoconstriction

Question 7

How does NA affect BP at the heart?

Answer 7

• activates B1-aR, +HR through SA and +contractility through ventricular muscle

Question 8

How does NA affect BP at the kidneys?

Answer 8

• B1-aR: +Renin release
• Angiotensinogin –> Ang1 –>
• Angiotensin converting enzyme –> AngII
• AngII acts on kidney, heart, and blood vessels
• AngII +fbk to SNS to +BP
• AngII important in remodelling in heart failure

Question 9

What are the antihypertensive drug classes?

(ABCD)

Answer 9

• Angiotensin system inhibitors (BV, heart, kidney)
• B-aR antagonists (kidney, heart)
• Ca2+ channel blockers (BV, heart)
• Diuretics (kidney)
• (other)

Question 10

Aldosterone

Answer 10

• Steroid hormone, adrenal cortex
• Rl by angiotensin 1 receptors in kidney
• Causes salt and water retention
• tf +blood volume, +CO, +SV

Question 11

What are the targets for angiotensin system inhibitors?

Answer 11

Angtiotensin converting enzyme (ACE)

AT1 receptrors (vasoconstriction, aldosterone stimulation)

Question 12

What are -pril drugs?

Answer 12

Angiotensin converting enzyme inhibitors

e.g. captopril, enalapril, perindopril, ramipril

Question 13

What is the mechanism of angiotensin converting enzyme inhibitors?

Answer 13

‘-prils’

• block Ang I –> Ang II tf -vascular tone, -aldosterone, -cardiac hypertrophy
• preven bradykinin (vasodilator) breakdown

Question 14

What are the adverse effects of angiotensin converting enzyme inhibitors?

Answer 14

• First-dose hypotension (must taper dose)
• Dry cough
• Loss of taste (bradykinin?)
• Hyperkalaemia (+K+ in plasma)
• Acute renal failure
• Itching
• Rash
• Angio-oedema
• Foetal malformations

Question 15

What must usually be prescribed with a ‘-pril’ and/or a ‘-sartan’?

Answer 15

A thiazide diuretic to combat hyperkalaemia (+K+ in plasma)

Question 16

What are the contraindications for ‘-pril’ drugs?

Answer 16

• Pregnancy
• Bilateral renal stenosis
• Angioneurotic oedema

Question 17

What type of drugs are ‘-sartan’?

Answer 17

Angiotensin receptor antagonists

e.g. losartan, candesartan

Question 18

What are the contraindications for angiotensin receptor antagonists?

Answer 18

Same as for angiotensin converting enzyme inhibitors:

• Pregnancy
• Bilateral renal stenosis
• Angioneurotic oedema

Question 19

What is the mechanism of angiotensin receptor antagonists?

Answer 19

‘-sartan’

• Block AT1 receptor subtype (not known what AT2 does) to:
• Reduce vasoconstriction
• Reduce aldosterone
• Reduce cardiac hypertrophy
• *Reduce SNS activity

Question 20

What are the adverse effects of ‘-sartan’ drugs?

Answer 20

Angiotensin receptor antagonists

• Hyperkalaemia (Tx thiazide diuretic)
• Headache
• Dizziness

Question 21

What type of drug are the ‘-olol’s?

Answer 21

B-aR antagonists

e.g. propranalol, atenolol, pindolol, timolol, metoprolol

Question 22

What is the mechanism of B-aR antagonists?

Answer 22

‘-olol’

• reduce CO (initially), BP stays down
• decreased rate, contractility
• reduce renin release
• LT effects on TPR, blood volume

Question 23

What is the selectivity of B-aR antagonists?

Answer 23

Beta-1: heart and kidney

Beta-2: vascular smooth muscle, airway smooth muscle

Question 24

What is sympathomimetic activity?

Answer 24

Mimics transmitters of the SNS e.g. catecholamines, adrenaline, noradrenaline, dopamine

These drugs are used to treat cardiac arrest and hypotension

Question 25

What are the adverse effects of B-aR antagonists?

Answer 25

• Cold extremities (a1 constrictiors, block of b2 dilators)
• Fatigue (b1 block reduced CO/HR, b2 block constricts skeletal muscle vessels, -O2)
• hypoglycaemia
• Dreams, insomnia (CNS effects, related to lipid solubility)
• Bronchoconstriction (b2 blockade in airway smooth muscle)

Question 26

Why are B-aR antagonists contraindicated in diabetics?

Answer 26

B1 blockade reduces cardiac response tf it cannot +HR to +flow. Leads to drop in blood sugar

HR is an indicator of sugar levels

Question 27

Why are B-aR antagonists contraindicated in asthma?

Answer 27

Bronchoconstriction by the B2 blockade stopping the relaxation of airway smooth muscle

Question 28

How are beta blockers used in heart failure?

Answer 28

Reduce high sympathetic drive

Question 29

What are the contraindications of beta blockers?

Answer 29

• Asthma
• Diabetes
• AV block

Care with:

• Heart failure (can be good or bad)
• Metabolic syndrome (men may develop diabetes)

Question 30

What is the mechanism of Ca2+ channel blockers?

Answer 30

• Inhibit voltage-gated L-type Ca2+ channels in myocardium and vasculature
• reduce cardiac/vascular contractility
• reduce vascular resistance

Question 31

Dihydropyridines

Answer 31

• Ca2+ channel blockers
• selective to vasculature
• increase HR
• use in hypertension tx
• contra if tachyarrhythmias present
• adverse affects include oedema, flushing, headache, and reflex tachycardia
• e.g. felodipine, nifedipine

Question 32

Verapamil

Diltiazem

Answer 32

• Ca2+ channel blockers
• non-selective
• cause brady cardia
• adverse: oedema, flushing headache
• contra in heart failure
• tx in tachy

Question 33

Thiazide diuretics

Answer 33

• Prescribed with ACEI and AT receptor antagonists
• combat hyperkalaemia (K+ retention)