Hypertension Flashcards
What are the two stages of hypertension?
Stage 1:
> 140/90mmHg
Ambulatory or Home blood pressure >135/85
Stage 2:
>160/100
Ambulatory or Home blood pressure >150/96
Causes of hypertension?
- Essential (unknown mechanism): 90%
- Secondary:
Phaeochromocytoma
Primary Aldosteronism
Cushing’s syndrome
Renal (Bright’s diseases glomerulonephritis)
Name some smooth muscle vasodilators for hypertension:
Group: Thiazide diuretics
Names: Bendroflumethiazide (bendrofluazide)
Cautions: hypokalaemia
Glucose intolerance due to kATP channel
MOA: unknown
Vasodilation: reduces Ca2+ entry, consequence of Na depletion
Synthesis of PGE2 and PGI2 –> vasodilator prostaglandins
K channel opening
How do Diazoxide and minoxidil work and what do they affect?
MOA:
- Blocks the action of ATP on ATP sensitive K+ channels (KATP)
- ATP binding to these channels inhibits K+ conductance causing them to close
- When ATP blocked, the channels remain open
- Hyperpolarisation
- Close L-type Ca2+ channels
- Vasodilation
Affects:
- SM and cardiac muscle
- Pancreatic islet insulin-secreting cells
When are DIAZOXIDE and MINOXIDIL used?
DIAZOXIDE:
Non-diuretic congener of thiazide diuretics
I.V. Emergency hypertension
Caution: Produces hyperglycaemia (Diabetagenic)
Minoxidil: Used in severe hypertensive unresponsive to other drugs
Caution: Very potent and long acting
Causes hypertrichosis (overgrowth of hair)
How does hydralazine work? And when is it used? What does it act on?
MOA: unknown
activate guanylate cyclase (mimicking NO)
Acts:
Only on arteriolar smooth muscle
Cautions:
1. Systemic Lupus Erythematosus Syndrome - fever, arthalagia, malaise and hepatitis
- As BP goes down can activate baroreceptor reflex leading to refelx tachycardia (b1 adrenoreceptor mediated) and water retention through RAS
Can give b1 antagonists
Name a calcium antagonist
Nifedipine
Caution: Problem is short acting
Name a direct acting vasodilator
Group: Nitrovasodilators
Name:
Sodium Nitroprusside
Only used in special situations
Very short acting and no good for ambulatory patients
Name some indirect vasodilators
- a1 - adrenoreceptor antagonist:
Doxazosin, Prazosin - Adrenergic neurone blocking drugs:
Guanethidine - Ganglion blockers:
Hexamethonium (not used anymore)
How does Clonidine work?
Works by reducing methylNA which is potent a2 agonist
The action of these drugs is mediated via alpha2 adrenoceptors in the ventrolateral medulla and the rostroventral medulla, which reduces NA release.
Inhibits NA release pre-junctionally, but also causes post-junctional smooth muscle contraction.
Centrally it acts on the CVLM and RVLM to reduce sympathetic drive. Also acts on NTS.
What is the mechanism of alpha-methylDOPA?
1) Inhibition of catecholamine synthesis
2) Converted to methylnoradrenaline
MethylNA is a potent a2 agonist therefore inhibiting NA release
Unwanted actions: sedation, postural hypotension, dry mouth
Use: Pre-eclampsia
What is the mechanism of alpha-methylDOPA?
1) Inhibition of catecholamine synthesis
2) Converted to methylnoradrenaline
MethylNA is a potent a2 agonist therefore inhibiting NA release
Unwanted actions: sedation, postural hypotension, dry mouth
Use: Pre-eclampsia
What are the major contra-indications for beta blockers?
1) Asthmatics
2) Diabetics
3) peripheral vascular disease
How do beta blockers reduce hypertension?
1) central: reset baroreceptors and reduce sympathetic tone
2) cardiac effect reduces output
3) blocks renin release
4) pre-junctional receptors
What are side effects of ACE inhibitors?
1) hyperkalaemia due to reduced aldosterone synthesis
2) under stimulation of mineralcorticoid receptors results in net retention of potassium at collecting duct
What encompasses metabolic syndrome?
1) impaired insulin secretion
2) insulin resistance
3) microvascular
4) macrovascular
5) central obesity
6) dyslipidemia
7) hypertension
