Drugs affecting cardiovascular system (blood pressure) Flashcards
High blood pressure is
140/90mmHg
130/80mmHg in diabetics, kidney disease
Chronic BP >140/90mmHg is a risk factor for
- Stroke
- TIA
- MI
- Ischaemic heart disease
- CHF
- Aortic aneurism
- Retinal Haemorrhage
- Renal failure
- Death
BP =
CO x TPR
CO =
HR x SV
What is the major neuronal influence on BP?
Sympathetic tone: releases NA
-P = +SNS tone
How does NA influence BP at the blood vessels?
- activate A1-aR –> vasoconstriction
How does NA affect BP at the heart?
- activates B1-aR, +HR through SA and +contractility through ventricular muscle
How does NA affect BP at the kidneys?
- 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
What are the antihypertensive drug classes?
(ABCD)
- Angiotensin system inhibitors (BV, heart, kidney)
- B-aR antagonists (kidney, heart)
- Ca2+ channel blockers (BV, heart)
- Diuretics (kidney)
- (other)
Aldosterone
- Steroid hormone, adrenal cortex
- Rl by angiotensin 1 receptors in kidney
- Causes salt and water retention
- tf +blood volume, +CO, +SV
What are the targets for angiotensin system inhibitors?
Angtiotensin converting enzyme (ACE)
AT1 receptrors (vasoconstriction, aldosterone stimulation)
What are -pril drugs?
Angiotensin converting enzyme inhibitors
e.g. captopril, enalapril, perindopril, ramipril
What is the mechanism of angiotensin converting enzyme inhibitors?
‘-prils’
- block Ang I –> Ang II tf -vascular tone, -aldosterone, -cardiac hypertrophy
- preven bradykinin (vasodilator) breakdown
What are the adverse effects of angiotensin converting enzyme inhibitors?
- 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
What must usually be prescribed with a ‘-pril’ and/or a ‘-sartan’?
A thiazide diuretic to combat hyperkalaemia (+K+ in plasma)
What are the contraindications for ‘-pril’ drugs?
- Pregnancy
- Bilateral renal stenosis
- Angioneurotic oedema
What type of drugs are ‘-sartan’?
Angiotensin receptor antagonists
e.g. losartan, candesartan
What are the contraindications for angiotensin receptor antagonists?
Same as for angiotensin converting enzyme inhibitors:
- Pregnancy
- Bilateral renal stenosis
- Angioneurotic oedema
What is the mechanism of angiotensin receptor antagonists?
‘-sartan’
- Block AT1 receptor subtype (not known what AT2 does) to:
- Reduce vasoconstriction
- Reduce aldosterone
- Reduce cardiac hypertrophy
- *Reduce SNS activity
What are the adverse effects of ‘-sartan’ drugs?
Angiotensin receptor antagonists
- Hyperkalaemia (Tx thiazide diuretic)
- Headache
- Dizziness
What type of drug are the ‘-olol’s?
B-aR antagonists
e.g. propranalol, atenolol, pindolol, timolol, metoprolol
What is the mechanism of B-aR antagonists?
‘-olol’
- reduce CO (initially), BP stays down
- decreased rate, contractility
- reduce renin release
- LT effects on TPR, blood volume
What is the selectivity of B-aR antagonists?
Beta-1: heart and kidney
Beta-2: vascular smooth muscle, airway smooth muscle
What is sympathomimetic activity?
Mimics transmitters of the SNS e.g. catecholamines, adrenaline, noradrenaline, dopamine
These drugs are used to treat cardiac arrest and hypotension
What are the adverse effects of B-aR antagonists?
- 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)
Why are B-aR antagonists contraindicated in diabetics?
B1 blockade reduces cardiac response tf it cannot +HR to +flow. Leads to drop in blood sugar
HR is an indicator of sugar levels
Why are B-aR antagonists contraindicated in asthma?
Bronchoconstriction by the B2 blockade stopping the relaxation of airway smooth muscle
How are beta blockers used in heart failure?
Reduce high sympathetic drive
What are the contraindications of beta blockers?
- Asthma
- Diabetes
- AV block
Care with:
- Heart failure (can be good or bad)
- Metabolic syndrome (men may develop diabetes)
What is the mechanism of Ca2+ channel blockers?
- Inhibit voltage-gated L-type Ca2+ channels in myocardium and vasculature
- reduce cardiac/vascular contractility
- reduce vascular resistance
Dihydropyridines
- 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
Verapamil
Diltiazem
- Ca2+ channel blockers
- non-selective
- cause brady cardia
- adverse: oedema, flushing headache
- contra in heart failure
- tx in tachy
Thiazide diuretics
- Prescribed with ACEI and AT receptor antagonists
- combat hyperkalaemia (K+ retention)
