Drugs Affecting the Cardiovascular System Flashcards
What are the requirements for hypertension diagnosis?
- Chronic is when BP> 140/90mmHg and is a risk factor for stroke, TIA, MI, ischemic heart disease, CHF, aortic aneurism, retinal hemorrhage, renal failure and death
- It is a multifactorial disease often with no known cause.
- It has many risk factors including smoking, diet, weight and stress and treatment benefits are unequivocal leading to less morbidity and fewer deaths.
What are the principles for the treatment of hypertension?
Reduce BP <140/85 (130/80 if diabetes/kidney disease is present) through lifestyle modifications.
This requires the reduction of known risk factors for hypertension:
Smoking: quit
Diet: reduce alcohol, salt, fats
Weight: reduce BMI
Stress: exercise, relaxation
Explain the homeostatic control of BP.
Regulated Variable: Blood pressure
Sensors: Baroreceptors; osmoreceptors
Controlled Variables: Heart rate & Stroke volume (Cardiac output); total peripheral resistance
Effectors: Blood vessels, heart, kidney
Effector Signals: neuronal & hormonal
Explain: Angiotensin Converting Enzyme (ACE) Inhibitors
Drug: Angiotensin Converting Enzyme (ACE) Inhibitors
Examples: captopril, enalapril, perindopril, ramipril
These drugs block conversion of AngI to AngII:
- reducing vascular tone
- reducing aldosterone production
- reducing cardiac hypertrophy
They prevent bradykinin breakdown (ACE- kininaseII)
Adverse Effects: first-dose hypotension, dry cough, loss of taste, hyperkalaemia (+thiazide diuretic), acute renal failure, itching, rash, angio-oedema and foetal malformations
Contraindications: pregnancy, bilateral renal stenosis, angioneurotic oedema.
Explain: Angiotensin Receptor Antagonists
Drug: Angiotensin Receptor Antagonists
Examples: losartan, candesartan
Two receptor subtypes AT1 and AT2; clinically it is most useful to block AT1 receptors to:
- reduce casoconstriction
- recude aldosterone
- reduce cardiac hypertrophy
- reduce sympathetic activity
Adverse Effects: hyperkalaemia (+thiazide diuretic), headache, dizziness
Contraindications: pregnancy, bilateral renal stenosis, angioneurotic oedema.
Explain: β-adrenoceptor Antagonists
Drug: β-adrenoceptor Antagonists
Examples: propanolol, timolol, (non-selective 1&2) atenolol, metoprolol, (selective 1) pindolol (partial Agonist 1&2)
The mechanism of beta blockers is to reduce cardiac output (rate, contractility) and renin release (blood volume, TPR).
Beta blockers vary with respect to their selectivity (beta1 vs. beta2), their intrinsic sympathomimetic activity (partial agonist activity) and lipid solubility.
Adverse Effects:
Cold extremities: reflex alpha1-adrenoceptor constriction and blockade of dilatory beta2- adrenoceptors
Fatigue: beta1 blockade reduces cardiac response (Therefore contraindicated in diabetes) and beta2 blockafe constriction of skeletal muscle blood vessels
Dreams, Insomnia: CNS effects related to lipid solubility
Bronchoconstriction: beta2 blockade in airways smooth muscle (therefore contraindicated in asthma)
Contraindications: asthma, diabetes, AV block, care should be taken with heart failure and metabolic syndrome.
The drug choice should be made for the effect on the heart and kidney. Beta1 selective may be preferred.
Explain: Calcium Channel Blockers
Drug: Calcium Channel Blockers
Examples: verapamil, diltiazem, felodipine, nifedopine
Inhibit voltage-gated L-type Ca2+ channels in myocardium and vasculature by reducing cardiac/vascular contractility as well as reducing vascular resistance.
- Varapamil: significant effects on cardiac and vascular muscle
- Diltiazem: less pronounced effect on cardiac cells.
- Dihydropyridines (felodipine, nifedipine): considered vascular selective
Adverse Effects:
Varapamil, Diltiazem: oedema, flushing, headache, bradycardia
Dihydropyridines: oedema, flushing, headache, reflex tachycardia
Contraindications: Heart failure, tachyarrhythmias
Explain: Diuretics
Examples: losartan, candesartan
