cardiovascular pharmacology Flashcards
what are the targets for therapy to manage BP control?
- Cardiac output and Peripheral Resistance
- Interplay between:
a. Renin-Angiotensin-Aldosterone system
b. Sympathetic nervous system (noradrenaline) - Local vascular vasoconstrictor and vasodilator mediators
what are 4 Angiotensin Converting Enzyme (ACE) inhibitors?
- ramipril
- enalapril
- perindopril
- trandolapril
what are the main clinical indications that would result in a patient having ACE inhibitors?
Hypertension
Heart failure
Diabetic nephropathy
what are the main adverse effects of ACE inhibitors related to reduced angiotensin II formation?
a. Hypotension- can reduce BP too much
b. Acute renal failure- angiotensin 2 restrict efferent arteriole
c. Hyperkalaemia
d. Teratogenic effects in pregnancy
what are the main adverse effects of ACE inhibitors related to increased kinins?
a. Cough
b. Rash
c. Anaphylactoid reactions
( ace inhibitors prevent the conversion from angiotensin I to II but increases the conversion of bradykinin to inactive peptides)
what are the main clinical indications that would result in a patient taking Angiotensin II receptor blockers ( ARB)?
Hypertension
Diabetic nephropathy
Heart failure (when ACE-I contraindicated)
what are 5 examples of Angiotensin II receptor blockers ( ARB)?
- Candesartan
- Losartan
- valsartan
- irbesartan
- telmisartan
what are the main adverse effects of Angiotensin II receptor blockers ( ARB)?
Symptomatic hypotension (especially volume deplete patients)
Hyperkalaemia
Potential for renal dysfunction
Rash
Angio-oedema
Contraindicated in pregnancy
Generally very well tolerated
what are the main clinical indications that would result in a patient taking Calcium Channel Blockers ( CCB)?
Hypertension
Ischaemic heart disease (IHD) – angina
Arrhythmia (tachycardia)
What are 6 calcium channel blockers?
- Amlodipine
- Nifedipine
- Diltiazem
- Felodipine
- Lacidipine
- verapamil
what are 3 L-type calcium channel blockers?
- Dihydropyridines
- Phenylalkylamines
- Benzothiazepines
name 4 examples of Dihydropyridines
nifedipine, amlodipine, felodipine, lacidipine
what do Dihydropyridines do?
Preferentially affect vascular smooth muscle
Peripheral arterial vasodilators
name an example of a Phenylalkylamines
verapamil
what do Phenylalkylamines do?
Main effects on the heart
Negatively chronotropic, negatively inotropic
name an example of a Benzothiazepines
diltiazem
what do Benzothiazepines do?
Intermediate heart/peripheral vascular effects
what are the main adverse effects of CCB blockers due to peripheral vasodilatation (mainly dihydropyridines)
?
Flushing
Headache
Oedema
Palpitations
what are the main adverse effects of CCB blockers due to negatively chronotropic effects (mainly verapamil/diltiazem)?
Bradycardia
Atrioventricular block
what are the main adverse effects of CCB blockers due to negatively inotropic effects (mainly verapamil)?
Worsening of cardiac failure
what is an adverse effect of verapamil?
causes constipation
what are the main clinical indications that would result in a patient taking Beta- adrenoreceptor Blockers ( BB)?
Ischaemic heart disease (IHD) – angina
Heart failure
Arrhythmia
Hypertension
Name 6 beta- adrenoreceptor blockers
- Bisoprolol
- carvedilol
- propranolol
- metoprolol
- atenolol
- nadolol
describe the term cardioselective
often used to imply β-1 selectivity
This is a misnomer since up to 40% of cardiac β-adrenoceptors are β-2
what are the main adverse effects of Beta- adrenoreceptor blockers ( BB)?
Fatigue
Headache
Sleep disturbance/nightmares
Bradycardia
Hypotension
Cold peripheries
Erectile dysfunction
what three conditions do beta blockers worsen?
- Asthma (may be severe) or COPD
- PVD – Claudication or Raynaud’s
- Heart failure – if given in standard dose or acutely
what are the major clinical indications that would result in diuretics?
Hypertension
Heart failure
what are the 4 classes of diuretics?
- Thiazides and related drugs (distal tubule)
- Loop diuretics (loop of Henle)
- Potassium-sparing diuretics
- Aldosterone antagonists
name 3 thiazide related diuretics
1.BENDROFLUMETHIAZIDE
2. HYDROCHLOROTHIAZIDE
3. CHLORTHALIDONE
name 3 loop diuretics
- FUROSEMIDE
- BUMETANIDE
name 4 potassium sparing diuretics
- SPIRONOLACTONE
- EPLERENONE
- AMILORIDE
- TRIAMTERINE
what are main adverse effects of diuretics?
Hypovolaemia (mainly loop diuretics)
Hypotension ( “ )
Low serum potassium (hypokalaemia)
Low serum sodium (hyponatraemia)
Low serum magnesium (hypomagnesaemia)
Low serum calcium (hypocalcaemia)
Raised uric acid (hyperuricaemia – gout)
Impaired glucose tolerance (mainly thiazides)
Erectile dysfunction (mainly thiazides)
name 1 α-1 adrenoceptor blockers
doxazosin
name 2 centrally acting anti hypertensitives
MOXONIDINE
METHYLDOPA
name 1 direct renin inhibitor
ALISKIREN
what are 3 other antihypertensives?
α-1 adrenoceptor blockers
Centrally acting anti-hypertensives
Direct renin inhibitor
what is LVSD?
Heart failure due to left ventricular systolic dysfunction
What is HFPEF
Heart failure with preserved ejection fraction (diastolic failure)
what does heart failure suggest?
the efficiency of the heart as a pump is impaired.
what is heart failure caused by?
by structural or functional abnormalities of the heart.
what is the most common cause of heart failure?
is coronary artery disease
what does heart failure cause?
morbidity, mortality, hospital admissions and substantial cost
what is the treatment with the most benefits for heart failure?
is with vasodilator therapy via neurohumoral blockade (RAAS - SNS) and not from LV stimulants
what is a symptomatic treatment of congestion?
diuretics- usually loop
what is disease influencing therapy and what does it do/ target?
neurohumoral blockade
Inhibition of renin-angiotensin-aldosterone system
Inhibition of the sympathetic nervous system
what is the first line of treatment for heart failure ?
ACE inhibitors and beta blocker therapy
Low dose and slow uptitration
what are
a. First line: ACE inhibitors and beta blocker therapy
Low dose and slow uptitration
b. Aldosterone antagonists
c. Consider ARNI – Aldosterone Receptor antagonist and Neprilysin Inhibitor
d. Consider SGLT2 inhibitor
e. ACE-I intolerant: Angiotensin receptor blocker
f. ACE-I and ARB intolerant: Hydralazine/nitrate combination
g. Consider digoxin or ivabradine
what do nitrates do?
Arterial and venous dilators
Reduction of preload and afterload
Lower BP
what is the main use of nitrates?
Ischaemic heart disease (angina)
Heart failure
name three nitrate medications
ISOSORBIDE MONONITRATE
GTN SPRAY
GTN INFUSION
describe chronic stable angina
Anginal chest pain
Predictable
Exertional
Infrequent
Stable
describe Unstable angina / acute coronary syndrome (NSTEMI)
Unpredictable
May be at rest
Frequent
Unstable
describe ST elevation myocardial infarction/ ( STEMI)
Unpredictable
Rest pain
Persistent
Unstable
Whattwo types therapy are used to treat chronic stable angina ?
- Antiplatelet therapy
Aspirin
Clopidogrel if aspirin intolerant - Lipid-lowering therapy
Statins (simvastatin, atorvastatin, rosuvastatin, pravastatin)
(Comorbidities may determine which therapy)
what short acting nitrate is used for chronic stable angina?
GTN spray for acute attack
what is the first line of treatment for chronic stable agina?
Beta blocker or Calcium channel blocker
if intolerant switch
if not controlled combine
with chronic stable angina - if intolerant or uncontrolled than combine BB or CCB with..?
Long acting nitrate
Ivabradine
Nicorandil
Ranolazine
what pain relief is used in Acute coronary syndromes (NSTEMI and STEMI)?
GTN spray
Opiates – diamorphine
what therapies are used In Acute coronary syndromes (NSTEMI and STEMI)?
Dual antiplatelet therapy: Aspirin plus ticagrelor or prasugrel or clopidogrel
Antithrombin therapy: Fondaparinux
.
Background angina therapy: beta blocker, long acting nitrate, calcium channel blocker
- Lipid lowering therapy: Statins
- Therapy for LVSD/heart failure as required: ACE-I, beta blocker, aldosterone antagonist
in Acute coronary syndromes (NSTEMI and STEMI when would you Consider Glycoprotein IIb IIIa inhibitor/ which ones?
(high risk cases):
): tirofiban, eptifibatide, abciximab
describe class I of Vaughan Williams Classification?
Sodium channel blockers
describe class Ia of Vaughan Williams Classification
Ia - disopyramide, quinidine, procainamide
describe class Ib of Vaughan Williams Classification
Ib - lidocaine, mexilitene
describe class Ic of Vaughan Williams Classification
Ic - flecainide, propafenone
describe class II of Vaughan Williams Classification
Beta adrenceptor antagonists - propranolol, nadolol, carvedilol (non-selective)
- bisoprolol, metoprolol (β1-selective)
describe class III of Vaughan Williams Classification
Prolong the action potential - amiodarone, sotalol
describe class IV of Vaughan Williams Classification
Calcium channel blockers - verapamil, diltiazem
what is digoxin?
Cardiac glycoside
what does digoxin do?
Inhibit Na/K pump
what are the main effects of digoxin on the heart?
Bradycardia (increased vagal tone)
Slowing of atrioventricular conduction (increased vagal tone)
Increased ectopic activity
Increased force of contraction (by increased intracellular Ca)
side effects of digoxin
Narrow therapeutic range
Nausea, vomiting, diarrhoea, confusion
when is digoxin usually used?
Used in atrial fibrillation (AF) to reduce ventricular rate response
Use in severe heart failure as positively inotropic
what are the adverse side effects of amiodarone ?
QT prolongation
Polymorphic ventricular tachycardia
Interstitial pneumonitis
Abnormal liver function
Hyperthyroidism / Hypothyroidism
Sun sensitivity
Slate grey skin discolouration
Corneal microdeposits
Optic neuropathy
Multiple drug interactions
Very large volume of distribution
