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