Pharmacology Flashcards
Symptomatic treatment of congestion in heart failure
Diuretics (usually loop)
1st line pharmacological treatment of heart failure
ACE inhibitors and Beta Blocker therapy
Low dose and slow uptitration
Pharmacological management of heart failure
a. First line: ACE inhibitors and beta blocker therapy
Low dose and slow uptitration
b. Aldosterone antagonists
c. ACE-I intolerant: Angiotensin receptor blocker
d. ACE-I and ARB intolerant: Hydralazine/nitrate combination
e. Consider digoxin or ivabradine
What is ANP and BNP
Atrial natriuretic peptide - atria
B-(brain) natriuretic peptide - ventricles
What causes release of natriuretic peptide hormones
Stretching of atrial and ventricular muscle cells
Raised atrial or ventricular pressures
Volume overload
Main effects of natriuretic peptide hormones
Increase renal excretion of sodium (natriuresis) and water (diuresis)
Relax vascular smooth muscle (except efferent arterioles of renal glomeruli)
Increased vascular permeability
Inhibit the release or actions of:
Aldosterone, angiotensin II, endothelin, anti-diuretic hormone (ADH)
Counters RAAS
What metabolises cardiac natriuretic peptides
Neutral Endopeptidase (NEP, Neprilysin) NEP inhibition increases levels of natriuretic peptides
Example of Neprilysin inhibitor - how does it work
Sacubitril
Inhibits neutral endopeptidase, increasing levels if natriuretic peptides. NPs reduce pressure on heart
Example of angiotensin II blocker
Valsartan
Examples of beta-blockers in heart failure
Carvedilol
Bisoprolol
Metoprolol
Effects of nitrates
Arterial and venous dilators
Reduction of preload and afterload
Lower BP
Main uses of nitrates
Ischaemic heart disease (angina)
Heart failure
Examples of nitrates
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
Unpredictable
Rest pain
Persistent
Unstable
Management of chronic stable angina
- Antiplatelet therapy
- Lipid-lowering therapy = Statins
- Short acting nitrate = GTN spray for acute atack
- FIRST LINE TREATMENT = Beta blocker or Calcium channel blocker
- If intolerant then switch
- If intolerant then combine
- If intolerant or uncontrolled, consider monotherapy or combinations:
Long acting nitrate
Ivabradine (inhibits If current)
Nicorandil (K channel activator)
Ranolazine (inhibits late inward sodium current)
Management of chronic stable angina. Examples of drugs for:
- Antiplatelet therapy
- Lipid-lowering therapy
- Short acting nitrate
- Antiplatelet therapy - Aspirin or Clopidogrel (if aspirin intolerant)
- Lipid-lowering therapy - Statins (simvastatin, atorvastatin)
- Short acting nitrate - GTN spray
Management of chronic stable angina: if intolerant to Beta blocker and Calcium channel blocker combined
Consider monotherapy or combinations with:
Long acting nitrate
Ivabradine (inhibits If current)
Nicorandil (K channel activator)
Ranolazine (inhibits late inward sodium current)
(Co-morbidities may determine which therapy)
*Management of acute coronary syndromes (NSTEMI and STEMI)
- Pain relief
- Dual antiplatelet therapy
- Antithrombin therapy
- Consider Glycoprotein IIb-IIIa inhibitor (high risk cases)
- Background angina therapy
- Lipid lowering therapy
- Therapy for LVSD/heart failure as required
Most patients will undergo invasive management with coronary angiography and revascularisation (angioplasty or CABG)
Management of acute coronary syndromes (NSTEMI and STEMI): Pain relief
GTN spray
Opiates - diamorphine
Management of acute coronary syndromes (NSTEMI and STEMI): Dual antiplatelet therapy
Aspirin
PLUS:
Ticagrelor or Prasugrel or Clopidogrel
Management of acute coronary syndromes (NSTEMI and STEMI): Antithrombin therapy
Fondaparinux
Management of acute coronary syndromes (NSTEMI and STEMI): Consider Glycoprotein IIb-IIIa inhibitor (high risk cases)
Tirofiban
Eptifibatide,
Abciximab
Management of acute coronary syndromes (NSTEMI and STEMI): Background angina therapy
Beta blocker
Long acting nitrate
Calcium channel blocker
Management of acute coronary syndromes (NSTEMI and STEMI): Lipid lowering therapy
Statins
Management of acute coronary syndromes (NSTEMI and STEMI): Therapy for LVSD/heart failure as required
ACE-inhibitor
Beta-blocker
Aldosterone antagonist
How can you classify antiarrhythmic drugs
Vaughan Williams classification
Describe the Vaughan Williams classification for anti-arrhythmic
Class I - sodium channel blockers
Class II - beta adrenoreceptor antagonists
Class III - Prolong the action potential
Class IV - Calcium channel blockers
Vaughan Williams classification: Subtypes/Examples of Class I anti-arrhythmics (sodium channel blockers)
Ia - disopyramide, quinidine, procainamide
Ib - lidocaine, mexilitene
Ic - flecainide, propafenone
Vaughan Williams classification: Examples of Class II anti-arrhythmics (beta-adrenoreceptor antagonists)
Propranolol, nadolol, carvedilol (non-selective)
Bisoprolol, metoprolol (β1-selective)
Examples of non-selective beta-adrenoreceptor antagonists
Propranolol, nadolol, carvedilol
Examples of β1-selective beta-adrenoreceptor antagonists
Bisoprolol
Metoprolol
Vaughan Williams classification: Examples of Class III anti-arrhythmics (prolong the action potential)
Amiodarone
Sotalol
Vaughan Williams classification: Examples of Class IV anti-arrhythmics (calcium channel blockers)
Verapamil
Diltiazem
What is Digoxin
Cardiac glycoside
Inhibit Na/K pump
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)
True or False:
Digoxin has a narrow therapeutic range
True
Excess can cause: Nausea, Vomiting, Diarrhoea, Confusion
Is digoxin positively or negatively inotropic
Positively inotropic
Where is digoxin used
Used in atrial fibrillation (AF) to reduce ventricular rate response
Use in severe heart failure as positively inotropic
What is function of Amiodarone
Prolong the action potential
Class III Anti-arrhythmic
Adverse effects of amiodarone on heart
QT prolongation
Polymorphic ventricular tachycardia
Adverse effects of amiodarone
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
What is hypertension a risk factor for?
Stroke – ischaemic and haemorrhagic Myocardial infarction Heart failure Chronic renal disease Cognitive decline Premature death
Increases risk of atrial fibrillation
Each 2mmHg rise in systolic BP is associated with…
7% increased mortality from ischaemic heart disease
10% increased mortality from stroke
What is clinical hypertension
140/90mmHg or higher
True or False:
People with suspected hypertension are offered ambulatory blood pressure monitoring (ABPM) to confirm a diagnosis of hypertension
True
Mechanisms of BP control - targets for therapy
Cardiac output and peripheral resistance
Interplay between RAAS and Sympathetic nervous system (noradrenaline)
Local vascular vasoconstrictor and vasodilator mediators
Main clinical indications of Angiotensin Converting Enzyme (ACE) inhibitors
Hypertension
Heart failure
Diabetic nephropathy
Examples of ACE inhibitors
Ramipril
Enalapril
Perindopril
Trandolapril
Main adverse effects of ACE inhibitors
Related to reduced angiotensin II formation:
- Hypotension
- Acute renal failure
- Hyperkalaemia
- Teratogenic effects in pregnancy
Related to increased kinin production
- Cough
- Rash
- Anaphylactoid reactions
Main clinical indications of Angiotensin II receptor blockers (ARBs)
Hypertension
Diabetic nephropathy
Heart failure (when ACE-I contraindicated)
Examples of ARBs
Candesartan Valsartan Losartan Irbesartan Telmisartan
Main adverse effects of ARBs
Symptomatic hypotension (especially volume deplete patients) Hyperkalaemia Potential for renal dysfunction Rash Angio-oedema
Contraindicated in pregnancy
Generally well tolerated
Main clinical indications of Calcium channel blockers (CCB)
Hypertension
Ischaemic heart disease (IHD) - angina
Arrhythmia (tachycardia)
Examples of CCBs
Amlodipine Felodipine Nifedipine Lacidipine Diltiazem Verapamil
Types of L-type CCBs
Dihydropyridines
Phenylalkylamines
Benzothiazepines
Main effects of Dihydropyridines (CCB)
Preferentially affect vascular smooth muscle
Peripheral arterial vasodilators
Main effects of Phenylalkylamines (CCB)
Main effects on the heart
Negatively chronotropic, negatively inotropic
Main effects of benzothiazepines (CCB)
Intermediate heart/peripheral vascular effects
Examples of Dihydropyridines (CCB)
Nifedipine
Amlodipine
Felodipine
Lacidipine
Examples of Phenylalkylamines (CCB)
Verapamil
Examples of benzothiazepines (CCB)
Diltiazem
Adverse effects of calcium channel blockers
Due to peripheral vasodilatation (mainly dihydropyridines)
- Flushing
- Headache
- Oedema
- Palpitations
Due to negatively chronotropic effects (mainly verapamil/diltiazem)
- Bradycardia
- Atrioventricular block
Due to negatively inotropic effects (mainly verapamil)
- Worsening of cardiac failure
Adverse effects specific to or mainly in Verapamil (calcium channel blocker)
Constipation
(specific to verapamil)
Worsening cardiac failure due to negatively inotropic effects
Bradycardia and Atrioventricular block due to negatively chronotropic effects
Main clinical indications of Beta-adrenorecoptor blockers
Ischaemic heart disease (IHD) – angina
Heart failure
Arrhythmia
Hypertension
Examples of Beta-adrenorecoptor blockers
Bisoprolol Carvedilol Propanolol Metoprolol Atenolol Nadolol
Beta-1 selective Beta-adrenorecoptor blockers
Metoprolol
Bisoprolol
Non selective Beta-adrenorecoptor blockers
Propranolol
Nadolol
Carvedilol
Main adverse effects of Beta-adrenoceptor blocker
Fatigue
Headache
Sleep disturbance/nightmares
Bradycardia
Hypotension
Cold peripheries
Erectile dysfunction
Worsening of:
Asthma (may be severe) or COPD
PVD – Claudication or Raynaud’s
Heart failure – if given in standard dose or acutely
Main clinical indications of Diuretics
Hypertension
Heart failure
Classes of Diuretics
Thiazides and related drugs (distal tubule)
Loop diuretics (loop of Henle)
Potassium-sparing diuretics
Aldosterone antagonists
Examples of thiazide and related diuretics
Bendroflumethiazide
Hydrochlorothiazide
Chlorthalidone
Examples of loop diuretics
Furosemide
Bumetanide
Examples of potassium-sparing diuretics
Spironolactone
Eplerenone
Amiloride
Triamterine
Main adverse effects of diuretics
Hypovolaemia Hypotension Hypokalaemia Hyponetraemia Hypomagnesaemia Hypocalcaemia Erectile dysfunction Raised uric acid (gout) Impaired glucose tolerance
Adverse effects of diuretics - effects mainly in loop diuretics
Hypovolaemia
Hypotension
Adverse effects of diuretics - effects mainly in thiazides
Erectile dysfunction
Impaired glucose tolerance
Example of α-1 adrenoceptor blockers
DOXAZOSIN
Examples of Centrally acting anti-hypertensives
Moxonidine
Methyldopa
Example of direct renin inhibitor
Aliskiren
Treatment of hypertension <55 years
ACEi or ARB
ACEi or ARB + CCB
ACEi or ARB + CCB +Thiazide-like diuretic
(Resistance hypertension:) Consider addition of Spironolactone, high dose thiazide-like diuretic, Alpha blocker, beta blocker, (others)
Treatment of hypertension >55 years or Afro-Carribean any age
Calcium channel blocker
ACEi or ARB + CCB
ACEi or ARB + CCB +Thiazide-like diuretic
(Resistance hypertension:) Consider addition of Spironolactone, high dose thiazide-like diuretic, Alpha blocker, beta blocker, (others)