Drugs used in treating cardiovascular diseases Flashcards
Common CV conditions requiring drug therapy
Hypertension
Ischaemic heart disease and other atheromatous diseases
Heart failure
Arrhythmia
Hypertension
Most cases asymptomatic and 95% cases are ‘essential’ hypertension e.g. no secondary cause
CV morbidity and mortality can be < significantly by BP reduction
How can CV morbidity and mortality be reduced?
by BP reduction
Early detection of hypertension allows
Most effective risk management and treatment of hypertension
End organ damage in hypertension
Brain
Heart
Kidney: renal failure
Eyes: hypertensive retinopathy
End organ damage in hypertension: brain
Thrombotic, thromboembolic and haemorrhagic stroke, multi-infarct dementia, hypertensive encephalopathy
End organ damage in hypertension: heart
LVH, LV failure, coronary artery disease
Major risk factors for cerebrovascular atherosclerosis
Hypertension increases risk by x5-10 Smoking x2 Diabetes x2 Hyperlipidemia x1.5 Obesity x1.5
Prognosis of hypertension
Related to level of systolic and diastolic BPs
Related to age, sex and other risk factors such as hyperlipidaemia and diabetes
Worse if there is evidence of end-organ damage
Improved with antihypertensive therapy
Non-pharmalogical treatment of hypertension
Weight reduction < salt intake < fat intake < alcohol intake Exercise Smoking cessation
Common antihypertensive drugs
Thiazide diuretics ACE inhibitors Angiotensin II receptor antagonists Beta blockers Calcium channel blockers Alpha blockers
Thiazide diuretics
Inhibit reabsorption of NaCl in proximal and early distal tubules of nephron Cheap and recommended for first line use Bendroflumethiazide Metolazone Thiazide-related compounds
Renin-angiotensin system
Learn diagram
Regulates salts and fluid?
ACE inhibitors mechanism
-example
Inhibit conversion of angiotensin I to angiotensin II
e.g. ramipril < MI, stroke, CV death
Angiotensin receptor blocker
Acts on AT-1 receptor
Sprionolactone
Acts on aldosterone
Angiotensin II receptor antagonists (ARBs)
Similar effects to ACE inhibitors but do not influence bradykinin degradation so do not cause dry cough
Examples of ARBs
Losartan, valsartan, candesartan, irbesartan
Beta blockers (beta-adrenoreceptor antagonists)
< heart rate, BP and cardiac output
Variable selectivity for cardiac beta 1 receptors (which mediate sympathetic action)
Side effects of beta blockers
Fatigue Hypotension Cold peripheries Bronchospasm Impotence
Sympathetic and Parasympathetic action on heart and vessels
Symp > force and rate of heart contractions
-beta-1 receptors of heart mediate sympathetic action
-B-blockers can have adverse effects on vascular supply to the legs as sympathetic system increasing vasoconstriction in arterioles
Parasymp opposite
Calcium channel antagonists
Vasodilators - < systemic vascular tone
Main types of calcium channel antagonists
Two main types: Verapamil and diltiazem -cause bradycardia, inhibit AV node conduction, negative inotropes Amlopidine, larcanipidine ... dipine -may cause a reflex tachycardia
Side effects of calcium channel antagonists
Oedema Flushing Headache Dizziness Hypotension
Alpha blockers and others
A variety of other vasodilators are used to treat hypertension:
- alpha blockers: doxazosin, indoramin
- hydralazine
- methyldopa (can be used in pregnancy)
Alpha blockers and others: side effects
Hypotension
Headache
Tachycardia
Oedema
Thiazide diuretics side effects
Side effects include electrolyte disturbance, rash and postural hypotension
Most commonly used thiazide diuretic
Bendroflumethiazide most commonly used thiazide
Thiazide diuretic used for severe congestive heart failure
Metolazone used in combination with loop diuretics
Thiazide related compounds
chlorthalidone, indapamide
Side effects of ACE inhibitors
Relatively infrequent side effects except for dry cough
- hypotension
- rash
- hyperkalaemia
- renal failure (especially in presence of renal artery stenosis)
- angioedema
- ageusia
Ischaemic heart disease
Atherosclerosis of coronary arteries may lead to stenosis and arterial thrombosis
Spectrum of presentations from stable angina to acute coronary syndromes – unstable angina and myocardial infarction – to heart failure and sudden death
Progression of atherosclerosis to arterial thrombosis
Normal –> fatty streak –> (clinically silent) fibrous plaque –> athero-sclerotic plaque (can happen with age and can cause angina, transient ischemic attack and claudication/ PAD) –> plaque rupture/ fissure and thrombosis
This can lead to MI/ ischemic stroke / critical leg ischemia/ CV death
Anti-anginal drugs
Beta blockers
Nitrates
Calcium channel blockers
Potassium channel activators
Relative contraindications of beta-blockers
asthma, uncontrolled heart failure, bradycardia
Anti-anginal drugs: beta blockers
Lower myocardial oxygen demand by < HR, BP and myocardial contractility
May exacerbate cardiac failure (need to be introduced slowly) and peripheral vascular disease (claudication), and cause bronchospasm
Abrupt withdrawal from beta blockers as anti-anginal drugs
may lead to arrhythmia, worsening angina or myocardial infarction
Anti-anginal drugs: nitrates
-how do you take them
Oral, sublingual (GTN tabs/spray), buccal, transdermal and intravenous forms used commonly
Anti-anginal drugs: nitrates
-action
Symptomatic relief of angina
Produce nitric oxide at endothelial surface leading to vascular smooth muscle relaxation and arteriolar and venous dilatation
< myocardial oxygen demand (lower preload and afterload) and increase myocardial oxygen supply (coronary vasodilatation)
Side effects of anti-anginal drugs: nitrates
Headache
Flushing
Postural hypotension
Anti-anginal drugs: calcium antagonists
Lower myocardial oxygen demand by < BP and myocardial contractility and < myocardial oxygen supply by dilating coronary arteries
Anti-anginal drugs: calcium antagonists
-when to avoid
Verapamil and diltiazem should be avoided in heart failure
Anti-anginal drugs: Potassium channel activators
Nicorandil
Arterial and venous dilating properties
No problems with tolerance as seen with nitrates
Anti-anginal drugs: Potassium channel activators
-side effects
Can cause mucocutaneous ulceration
-relegated to second-line therapy
Anti-platelet drugs: action
Inhibit platelet aggregation and arterial thrombus formation, thus preventing heart attack, stroke and CV death
Anti-platelet drugs: aspirin
blocks platelet cyclo-oxygenase (COX1) and the production of thromboxane A2, a platelet activating substance
Anti-platelet drugs: clopidogrel, prasugrel and ticagrelor
platelet ADP (P2Y12) receptor inhibitors; used alone or, more often, in combination with aspirin
Anti-platelet drugs: dipyridamole
Mainly used in combination with aspirin to prevent stroke
Bleeding time in healthy volunteers treated with ticagrelor +/- aspirin
-in Lancet bleeding time (s)
Non antiplalet treatment: 150 +/- 54
Ticagrelor 250 +/- 77
Ticagrelor + aspirin: 541 +/- aspirin
Statins
Hydroxymethyl-glutaryl (HMG) CoA reductase inhibitors
Lower LDL cholesterol and may increase HDL cholesterol
< risks of MI stroke and CV death
Examples of statins
Simvastatin, pravastatin, atorvastatin, rosuvastatin, …statin
Heart failure
imprecise term describing state that develops when heart cannot maintain adequate cardiac output or can do so only at the expense of an elevated filling pressure
Associated with activation of RAS axis and sympathetic nervous system
How do pulmonary and/ or peripheral oedema develop?
due to high atrial pressures and salt/water retention caused by impaired renal perfusion and secondary aldosteronism
Drug treatment for chronic heart failure
Diuretics
ACE inhibitors
Beta Blockers
Aldosterone antagonists
Diuretics for treatment of heart failure
Thiazides
K-sparing
Loop diuretics
-strongest
more powerful than those used for hypertension
synergistic effects of combining all diuretics
Thiazides for treatment of heart failure
Inhibit active exchange of Cl-Na in the cortical diluting segment of the ascending loop of Henle
Acts on cortex
K-sparing diuretics for treatment of heart failure
Acts on cortex
Inhibit reabsorption of Na in the
distal convoluted and collecting tubule
Loop diuretics for treatment of heart failure
Inhibit exchange of Cl-Na-K in
the thick segment of the ascending
loop of Henle
Acts on medulla
Aldosterone inhibitors
Spironolactone
Eplerenone
-competitive antagonist of the aldosterone receptor
-acts on myocardium, arterial walls, kidney
-tackle salt and water retention
-prevent potassium level from going too low
-may reduce fibrosis in the myocardium
Tacharryhthmias
Abnormal rapid heart rhythms
Different types depending on origin in heart of abnormal electrical activity including:
-atrial fibrillation (AF) or atrial flutter with rapid ventricular rate response
-supraventricular tachycardia (SVT)
-ventricular tachycardia (VT)
Digoxin (digitalis)
Most often used to treat AF and heart failure
Glycoside drug
Blocks Na+/ K+ ATPase –> Ca++
> vagal tone - slows conduction in atrial fibrillation
Oral antiarrhythmics
Drugs for controlling tachyarrhythmia
Class Ia,b,c – disopyramide, flecainide, procainamide
Class II – beta blockers
Class III – amiodarone, dronedarone, sotalol
Class IV – calcium antagonists (verapamil, diltiazem)
What can low potassium lead to?
Heart rhythm disturbance (arrhythmia)
Interaction between anticoagulants and antiplatelets
Both interact (antithrombotics)
Both coagulation and platelet formation are driven by thrombin
-if you block thrombin by one drug, will affect other pathway
Higher bleeding risk if on both
