Pharmacology of HF and HTN Flashcards
What classes of drugs are used to target the RAAS system in HTN/HF?
- Acei
- Renin inhibitors
- Angiotensin receptor blockers (ARBs)
What classes of drugs are used to target the sympathetic nervous system in HF/HTN?
- Alpha blockers
- Beta blockers
- Calcium channel blockers
- Aldosterone antagonists
How do ACEi work?
What are the main clinical indications for using ACEi?
Name some ACEi.
What are the main adverse effects of ACEi?
Blocks angiotensin II formation and therefore, reduces peripheral resistance
Used in:
- Hypertension
- Heart failure
- Diabetic nephropathy
Drugs:
- Ramipril - most common
- Enalapril
- Perindopril
- Trandolapril
Side effects:
- Hypotension
- Acute renal failure - as kidneys are not being perfused as well as blocking ang II lowers filtration pressure in kidneys
- Hyperkalaemia
- Teratogenic effects in pregnancy
- cough as causes breakdown of bradykinin into inactive peptides which irritate the airways
- rash
- anaphylactoid reactions
How do ARBs work?
What are the main clinical indications?
Name some ARBs
What are the main adverse effects of ARBs?
These block angiotensin II at AT-1 receptor found in heart, blood vessels and kidneys.
Main clinical indications
- Hypertension
- Diabetic nephropathy
- Heart failure (only when ACEi not tolerated due to cough)
Examples:
- Candesartan
- Valsartan
- Losartan
- Irbesartan
- Telmisartan
Main adverse effects:
- Symptomatic hypotension
- Hyperkalaemia
- Potential for renal dysfunction
- Rash
- Angio-oedema
- Contraindicated in pregnancy
- Generally very well tolerated and effective medication - do not cause cough as they do not potentiate bradykinin
How do CCBs work?
What are the main clinical indications?
Name some CCBs
What are the main adverse effects of CCBs?
These drugs affect entry of calcium into cells by affecting the L-type calcium channels.
Main clinical indications
- Hypertension
- Ischaemic heart disease - angina
- Arrhythmia (tachycardia)
- They do not have indication in HF
Examples:
- Amlodipine*
- Nifedipine*
- Felodipine*
- Lacidipine*
- Diltiazem
- Verapamil - phenylalkylamines - used in angina
- = dihydropiridines - most commonly used in practice. Used in HTN and angina - peripheral vasodilators.
Adverse effects Effects due to peripheral vasodilation (mainly dihydropyridines) - Flushing - Headache - Oedema - Palpitations
Effects due to negatively chronotropic effects (mainly verapamil and diltiazem)
- Bradycardia
- Atrioventricular block
Effects due to negatively inotropic effects (mainly verapamil)
- Worsening of cardiac failure
Other effects
- Constipation
How do BBs work? What do we mean by cardioselective? What are the main clinical indications? Name some BBs What are the main adverse effects of BBs?
These slow the HR, reduce workload and oxygen demand by the heart
- There are more ‘selective’ BBs than others: some are B1 selective, others are non-selective
- Cardioselective is a term used to describe those which are B1 selective
- B1 has effect in the heart but not in the lungs, B2 is found in lungs but also heart.
- There are no B-2 selective drugs
Main clinical indications
- Ischaemic heart disease - angina
- Heart failure
- Arrhythmias
- Hypertension
Examples
- Bisoprolol - most common
- Metoprolol
- Carvedilol
- Atenolol
- Propanolol
- Nadolol
Main adverse effects
- Fatigue - as it affects adrenaline
- Headache - as it affects adrenaline
- Sleep disturbances & nightmares - as it crosses BBB
- Bradycardia - effects on heart
- Hypotension
- Cold peripheries
- Erectile dysfunction
- Worsening of:
- Asthma or COPD
- PVD
- Heart failure if given in standard dose - need to give in small doses and small increments
What are the 4 classes of duiretics?
- Thiazide and related drugs (affect distal tubule)
- Bendroflumethiazide, Hydrochloride, Chlorthalidone (weak diuretic but good for long term use)
- Loop diuretics (affect loop of Henle)
- Furosemide & bumetanide
- Potassium-sparing diuretics
- Spironolactone, eplerenone, amlioride, triamterine
- Aldosterone antagonists - also function as diuretics but they act on aldosterone in the RAAS
Main clinical indications for diuretics?
Hypertension
HF
Main adverse effects of diuretics?
- Hypovolaemia - mainly loop diuretics due to too much fluid loss
- Hypotension - mainly loop diuretics
- Low serum potassium - hypokalaemia
- Low serum sodium - hyponatraemia
- Low serum magnesium - hypomagneaemia
- Low serum calcium - hypocalcaemia
- Raised uric acid - hyperuricaemia - gout due to uric acid crystal deposits
- Erectile dysfunction - mainly thiazides
- Impaired glucose intolerance - mainly thiazides - diabetic issue & risk factor
Which antihypertensives can be used in pregnancy?
Methyldopa and labetalol
Nifedipine second line
Treatment pathway for chronic HF?
- ACEi and Beta blocker first line treatment - low dose and slow titration of bblocker
- Add aldosterone antagonist
- Spironolactone old but effective and used
- Specific neg effect is it can cause male breast enlargement
- ARB (candersartan) if ACEi intolerant due to cough
- Not first line as not as well proven as ACEi
- If ACEi and ARB both intolerable = running out of options!
- Hydralazine or nitrates combination are an option as they cause vasodilation which has a beneficial effect on afterload and reduces preload which reduces CO and workload on heart
- We don’t usually have to go to this step as ACEi or ARB is tolerated usually - Digoxin or Ivabradine
- Work by reducing HR through affecting SAN in the heart
Why are nitrates not used for long term HTN or HF control?
- These are arterial and venous dilators
- They reduce preload and afterload through the Frank-Starling mechanism (less venous pressure, less cardiac stretch, less output, less workload)
- Lower BP
- We don’t use for long term management as nitrates are not predictable and people can develop tolerance to nitrates if used over long time & constantly. People need to have time free of nitrates so this would not be an effective antihypertensive/HF therapy.
Treatment regime for chronic stable angina?
- Antiplatelet therapy (aspirin)
- Lipid lowering therapy (statin)
- Short acting nitrate for acute attack (GTN)
- First line treatment = B-blocker or CCB
- If not tolerant, switch
- If not controlled = combine both (not a CCB which is rate limiting)
- If intolerant or uncontrolled, consider Ivabradine (reduced HR for patients in sinus rhythm), Ranzolazine (caution in HF, elderly of <60kg), Nicorandil (CI in acute pulmonary oedema, severe HTN, hypovolemia, LV failure)
Treatment regime for ACS (STEMI and NSTEMI)
- Pain relief (GTN, opiates - diamorphine)
- Dual antiplatelet therapy (aspirin + ticagrelor or prasugrel or clopidogrel)
- Antithrombin therapy: Fondaparinux
- Consider Glycoprotein IIb IIIa inhib in high risk cases - STEMI patient undergoing PCI (tirofiban, eptifibatide)
- Background angina therapy (b-blocker, long acting nitrate, CCB)
- Secondary prevention: statin, ACEi, BB
- Therapy for LVSD or HF as needed - ACEi, BB, ARB, diuretics, aldosterone antagonist (spironolactone).
- Most patients undergo CABG or PCI.
What are the classifications of antiarrythmic drugs?
Class I: sodium channel blockers
- Ia - dispyramide, quinidine, prcainamide
- Ib - lidocaine, mexilitene
- Ic - flecainide, propafenone
Class II: Beta adrenceptor antagonists
- Propanolol, nadolol, carvedilol (non-selective)
- Bisoprolol, metoprolol (B1-selective)
Class III: Prolong the action potential
- Amiodarone, sotalol
Class IV: Calcium channel blockers
- Verapamil, diltiazem
