S3: hypertension, heart failure & diuretics Flashcards
What are the target BP measurements for different age groups?
<140/90 in patients younger than 80 including type II diabetes
<150/90 in patients older than 80
<135/85 in patients with type I diabetes (without metabolic syndrome)
What are the different stages in hypertension?
Stage 1: clinic BP ranging from 140/90-159/99; ABPM/HPBM > 135/85 mmHg
Stage 2: clinic BP ranging from 160/100-180/120; ABPM/HPBM > 150/95 mmHg
Stage 3: clinic systolic BP of 180mmHg or higher OR clinic diastolic BP of 120mmHg or higher
Describe the action of ACE
Found on luminal surface of capillary endothelial cells, predominantly in the lungs
ACE catalyses conversion of angiotensin-I to potent, active vasoconstrictor – angiotensin II
Describe the action of angiotensin-II
Affords action through AT1 (and AT2 receptors)
AT1 receptor subtype typical of classical angiotensin-II actions
-stimulation of aldosterone which acts at distal renal tubule
-cardiac and vascular muscle cell growth
-ADH release from posterior pituitary
Describe the action of ACEi
Limits the conversion of angiotensin-I to angiotensin-II by inhibiting circulating and tissue ACE
A reduction in angiotensin-II activity, resulting in:
-vasodilation (decrease peripheral resistance, decrease afterload)
-reduction in aldosterone release
-reduced ADH release
-reduced cell growth and proliferation
(NOTE: angiotensin-II also produced from angiotensin-I independently of ACE via chymases)
Describe the relationship between ACEi and bradykinin
Bradykinin is a substrate for ACE
Use of ACEi therefore increases the amount of bradykinin
-bradykinin causes vasodilation via NOS/NO and PGI2
List examples of ACEi
Lisinopril
Ramipril
What are the adverse effects, warnings, contraindications & important drug interactions of ACEi?
Adverse effects: hypotension, dry cough, hyperkalaemia, cause or worsen renal failure & angioedema
Warnings, contraindications: renal artery stenosis, AKD, pregnancy, CKD, idiopathic angioedema
Important drug interactions: increasing K+ drugs, NSAIDs & other antihypertensive agents
List examples of angiotensin II receptor antagonists
Candesartan
Losartan
Describe the action of angiotensin II receptor antagonists (ARB)
AT1 receptors
No effect on bradykinin – less effective in low-renin hypertensive patients
What are the adverse effects, warnings, contraindications & important drug interactions of angiotensin II receptor antagonists?
Adverse effects: hypotension, hyperkalaemia & cause or worsen renal failure
Warnings, contraindications: renal artery stenosis, AKD, pregnancy, (CKD-caution)
Important drug interactions: increasing potassium drugs & NSAIDs
Describe the action of L-type calcium channels and calcium channel blockers
LTCCs allow inward Ca2+ flux into cells – voltage operated calcium channel (VOCC)
Expressed throughout the body, including vascular smooth muscle cells and cardiac myocytes plus SA and AV nodes
CCBs target calcium initiated smooth muscle contraction
3 classes of CCB interact with different sites on (a1) subunit of VOCC – they have different selectivity for VSM/myocardium
What are the different classes of calcium channel blockers?
Dihydropyridines – selective for peripheral vasculature, little chronotropic (rate) or inotropic (force) effects
Phenylalkylamines – depresses SA node and slows AV conduction, negative inotropy
Benzothiazapines sit in the middle
CCBs – primary choice antihypertensive in low renin patients
List examples of the dihydropyridine class
Amlodipine – has a long half life, others tend to be shorter
Nimodipine – selectivity for cerebral vasculature (useful in subarachnoid haemorrhage)
Nifedipine
What are the adverse effects, warnings, contraindications & important drug interactions of dihydropyridine class?
Adverse effects: ankle swelling, flushing, headaches, palpitations
Warnings, contraindications: unstable angina, severe aortic stenosis
Important drug interactions: amlodipine & simvastatin causes increased effect of the statin
Describe the action of phenylalkylamines
Class IV anti-arrhythmic agent, prolongs the action potential (effective refractory period)
Less peripheral vasodilation, negative chronotropic and inotropic effects
Used for arrhythmias, angina, (hypertension)
What are the adverse effects, warnings, contraindications & important drug interactions of phenylalkylamines?
Adverse effects: constipation, bradycardia, heart block and cardiac failure
Warnings, contraindications: poor LV function, AV nodal conduction delay
Important drug interactions: B-blockers, caution with other antihypertensive and antiarrhythmic agents
List examples of phenylalkylamines
Verapamil
List examples of benzothiazapines
Diltiazem
Describe the action of thiazide and thiazide-like diuretics
Inhibit Na+/Cl- transporter in DCT
-decreased Na+ and H20 reabsorption
(Long term effects mediated by sensitivity of VSM to vasoconstrictors Ca2+/NAd)
Useful over CCB in oedema
What are the adverse effects, warnings, contraindications & important drug interactions of thiazide and thiazide-like diuretics?
Adverse effects: hypokalaemia, hyponatraemia, hyperuricemia (gout), arrhythmia, increased glucose (especially with beta-blockers), small increase in cholesterol & triglyceride
Warnings, contraindications: hypokalaemia, hyponatraemia, gout
Important drug interactions: NSAIDs, decreasing K+ drugs such as loop diuretics
List examples of thiazide and thiazide-like diuretics
Bendroflumethiazide
Indapamide
What is the two-pronged approach in treated hypertension with primary diabetes?
ACEi/ARB decreases diabetic nephropathy and CKD with proteinuria by dilation of efferent glomerular arteriole
Decreased peripheral vascular resistance -> decreased BP and dilation of efferent glomerular arteriole -> reduced intraglomerular pressure (good for type II diabetes)
What drugs can be given for resistant hypertension (if BP is not controlled after step 3)?
Spironolactone – aldosterone receptor antagonist (stops the transcription of ENaC channel)
Alpha and beta blockers would be considered instead of spironolactone if high K+
Centrally acting drugs – labetalol (pregnancy, hypertensive emergency) -> reduces sympathetic outflow
What are the adverse effects, warnings, contraindications & important drug interactions of spironolactone?
Adverse effects: hyperkalaemia, gynaecomastia (due to anti androgen actions)
Warnings, contraindications: hyperkalaemia, Addison’s
Important drug interactions: increasing K+ drugs, pregnancy
Describe the action of beta-adrenoreceptor blockers
Decrease sympathetic tone by blocking NAd and reducing myocardial contraction resulting in reduced cardiac output
Reduced renin secretion (B1)
What are the adverse effects, warnings, contraindications & important drug interactions of beta-adrenoreceptor blockers?
Adverse effects: bronchospasm, heart block, Raynaud’s (cold hands), lethargy, impotence, mask tachycardia (sign of insulin induced hypoglycaemia)
Warnings, contraindications: asthma, haemodynamic instability, hepatic failure
Important drug interactions: verapamil and diltiazem (asystole)
List examples of beta-adrenoreceptor blockers
Labetalol
Bisoprolol
Metoprolol
Describe the action of alpha-adrenoreceptor blockers
Selective antagonism of alpha-1 adrenoreceptors
Reduce peripheral vascular resistance
Urinary tract including bladder neck and prostate (BPH – tamsulosin)
Relatively safe in renal disease
What are the adverse effects, warnings, contraindications & important drug interactions of alpha-adrenoreceptor blockers?
Adverse effects: postural hypotension (dizziness, syncope, headache and fatigue)
Warnings, contraindications: postural hypotension
Important drug interactions: patients affected by dihydropyridine CCB (increased oedema)
List examples of alpha-adrenoreceptor blockers
Doxazosin
tamsulosin for BPH
Describe management of heart failure
Correct underlying cause if you can
Non pharmacological management – decrease salt intake and liquid reduction if high
Avoid K+ salt substitutes
Diuretics and other therapeutic agents
AIMS: reduction in symptoms, managed increase in exercise tolerance, increase quality of life and slow morbidity
Describe the action of loop diuretics
Inhibit Na+/K+/2Cl- co-transporter in ascending limb of LoH
Direct dilation of capacitance veins – reduces preload
Used for acute pulmonary oedema, fluid overload in HF, adjunct in nephrotic syndrome
What are the adverse effects, warnings, contraindications & important drug interactions of loop diuretics?
Adverse effects: dehydration, hypotension, hypokalaemia, hyponatraemia, hyperuricaemia, arrhythmia, tinnitus, increased cholesterol and triglyceride
Warnings, contraindications: hypokalaemia, gout, hepatic encephalopathy
Important drug interactions: aminoglycosides, digoxin, lithium
List examples of loop diuretics
Bumetanide
Furosemide
Describe the action of potassium sparing diuretics
Block ENaC – decreases Na+ reabsorption in DCT and reduces K+ excretion
Often used as adjunct to loop or thiazide like in HF to limit decrease in K+
What are the adverse effects, warnings, contraindications & important drug interactions of potassium sparing diuretics?
Adverse effects: hyperkalaemia, potential arrhythmia
Warnings, contraindications: Addison’s, potassium supplements
Important drug interactions: other K+ sparing drugs, ACEi & ARBs
List examples of potassium sparing diuretics
Amiloride
Why is spironolactone given in HF?
In some individuals, refractory hyperaldosteronism occurs in spite of ACEi/ARB
Spironolactone given as an adjunct to ACEi/ARB and diuretic
All-cause mortality decreases significantly
