S3: hypertension, heart failure & diuretics

Question 1

What are the target BP measurements for different age groups?

Answer 1

<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)

Question 2

What are the different stages in hypertension?

Answer 2

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

Question 3

Describe the action of ACE

Answer 3

Found on luminal surface of capillary endothelial cells, predominantly in the lungs
ACE catalyses conversion of angiotensin-I to potent, active vasoconstrictor – angiotensin II

Question 4

Describe the action of angiotensin-II

Answer 4

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

Question 5

Describe the action of ACEi

Answer 5

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)

Question 6

Describe the relationship between ACEi and bradykinin

Answer 6

Bradykinin is a substrate for ACE
Use of ACEi therefore increases the amount of bradykinin
-bradykinin causes vasodilation via NOS/NO and PGI2

Question 7

List examples of ACEi

Answer 7

Lisinopril

Ramipril

Question 8

What are the adverse effects, warnings, contraindications & important drug interactions of ACEi?

Answer 8

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

Question 9

List examples of angiotensin II receptor antagonists

Answer 9

Candesartan

Losartan

Question 10

Describe the action of angiotensin II receptor antagonists (ARB)

Answer 10

AT1 receptors

No effect on bradykinin – less effective in low-renin hypertensive patients

Question 11

What are the adverse effects, warnings, contraindications & important drug interactions of angiotensin II receptor antagonists?

Answer 11

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

Question 12

Describe the action of L-type calcium channels and calcium channel blockers

Answer 12

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

Question 13

What are the different classes of calcium channel blockers?

Answer 13

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

Question 14

List examples of the dihydropyridine class

Answer 14

Amlodipine – has a long half life, others tend to be shorter
Nimodipine – selectivity for cerebral vasculature (useful in subarachnoid haemorrhage)
Nifedipine

Question 15

What are the adverse effects, warnings, contraindications & important drug interactions of dihydropyridine class?

Answer 15

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

Question 16

Describe the action of phenylalkylamines

Answer 16

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)

Question 17

What are the adverse effects, warnings, contraindications & important drug interactions of phenylalkylamines?

Answer 17

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

Question 18

List examples of phenylalkylamines

Answer 18

Verapamil

Question 19

List examples of benzothiazapines

Answer 19

Diltiazem

Question 20

Describe the action of thiazide and thiazide-like diuretics

Answer 20

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

Question 21

What are the adverse effects, warnings, contraindications & important drug interactions of thiazide and thiazide-like diuretics?

Answer 21

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

Question 22

List examples of thiazide and thiazide-like diuretics

Answer 22

Bendroflumethiazide

Indapamide

Question 23

What is the two-pronged approach in treated hypertension with primary diabetes?

Answer 23

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)

Question 24

What drugs can be given for resistant hypertension (if BP is not controlled after step 3)?

Answer 24

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

Question 25

What are the adverse effects, warnings, contraindications & important drug interactions of spironolactone?

Answer 25

Adverse effects: hyperkalaemia, gynaecomastia (due to anti androgen actions) Warnings, contraindications: hyperkalaemia, Addison’s Important drug interactions: increasing K+ drugs, pregnancy

Question 26

Describe the action of beta-adrenoreceptor blockers

Answer 26

Decrease sympathetic tone by blocking NAd and reducing myocardial contraction resulting in reduced cardiac output Reduced renin secretion (B1)

Question 27

What are the adverse effects, warnings, contraindications & important drug interactions of beta-adrenoreceptor blockers?

Answer 27

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)

Question 28

List examples of beta-adrenoreceptor blockers

Answer 28

Labetalol Bisoprolol Metoprolol

Question 29

Describe the action of alpha-adrenoreceptor blockers

Answer 29

Selective antagonism of alpha-1 adrenoreceptors Reduce peripheral vascular resistance Urinary tract including bladder neck and prostate (BPH – tamsulosin) Relatively safe in renal disease

Question 30

What are the adverse effects, warnings, contraindications & important drug interactions of alpha-adrenoreceptor blockers?

Answer 30

Adverse effects: postural hypotension (dizziness, syncope, headache and fatigue) Warnings, contraindications: postural hypotension Important drug interactions: patients affected by dihydropyridine CCB (increased oedema)

Question 31

List examples of alpha-adrenoreceptor blockers

Answer 31

Doxazosin | tamsulosin for BPH

Question 32

Describe management of heart failure

Answer 32

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

Question 33

Describe the action of loop diuretics

Answer 33

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

Question 34

What are the adverse effects, warnings, contraindications & important drug interactions of loop diuretics?

Answer 34

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

Question 35

List examples of loop diuretics

Answer 35

Bumetanide | Furosemide

Question 36

Describe the action of potassium sparing diuretics

Answer 36

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+

Question 37

What are the adverse effects, warnings, contraindications & important drug interactions of potassium sparing diuretics?

Answer 37

Adverse effects: hyperkalaemia, potential arrhythmia Warnings, contraindications: Addison’s, potassium supplements Important drug interactions: other K+ sparing drugs, ACEi & ARBs

Question 38

List examples of potassium sparing diuretics

Answer 38

Amiloride

Question 39

Why is spironolactone given in HF?

Answer 39

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