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Possible essay questions:
Definition of different types of hypertension
Describe importance of high blood pressure as a risk factor for diseases of the
cardiovascular and renal systems
Highlight possible causes and mechanisms of high blood pressure
Review non-pharmacological treatment of hypertension
Review pharmacological options for the treatment of hypertension

Definition and causes of hypertension
Definition:
Sustained elevation of systolic and diastolic BP
>140/90 mmHg
Causes:
Primary (idiopathic/essential) - 90%
No identifiable cause
Secondary to - 10%
Renal disease (Salt/H2O imbalance)
Adrenal tumours (Aldosterone)
Aortic coarctation (aldosterone)
Steroid reactions
Hypertension is an 'artificial' concept - i
...
a cut-off value applied to a risk continuum

Hypertension related end organ disease
Cerebrovascular
Infarction: thrombotic
Intracranial haemorrhage
Hypertensive encephalopathy

Cardiac
Angina/MI
CHF
Systolic/diastolic dysfunction
Left ventricular hypertrophy
Sudden death
Renal
Chronic renal failure
End stage renal disease
Retinopathy
Sclerosis/Arterial
Hemorrhage/Exudate
Papilledema
Large artery disease
Carotid artery stenosis
Claudication
Aortic aneurysm
Organ damage by hypertension
Blood vessels
Contribute to all aspects of hypertensive organ damage
...
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...
g
...
g
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)
Heart diseases (aortic valve disease, LHF, Mitral valve disease)
Thromboembolic disease
High altitude living (low O2 conditions)
Genetic predisposition

Treatment of Pulmonary Hypertension
Depends on:
Severity
Likelihood of progression
Individual drug tolerance
Oxygen
Anticoagulants
Diuretics
Digoxin
Calcium channel blockers
Targeted Therapies:
Bosentan
Dual ET-R (Endothelin Receptor) antagonist
Ambrisentan
Selective ET-RA antagonist
Sildenafil
Relaxes smooth muscle cells
Can be used for Angina, Erectile dysfunction and pulmonary hypertension
Endothelin signalling in Pulmonary Hypertension

Endothelin-axis

Learn Red box (Pre-pro-ET-1
mRNA)

G-protein coupled receptors --->

Differences in ET receptors
ET-A
Located on Smooth Muscle cells
Mediate vasoconstriction
ET-B
Located on endothelial and smooth muscle cells
SMCs mediate vasoconstriction
ECs mediate vasodilation

Endothelin and Drug targets

Extra information:
K+ Channel openers/agonists
Drugs:
Minoxidil
Diazoxide
Mechanism of action:
VSM hyperpolarisation
Reduction in VDCC activity
Reduction in [Ca2+]i
Increased relaxation

Nitrovasodilators
Drugs:
Nitroprusside
Hydralazine
Mechanism of action:
NO donors/NO enhancing effect
Activation of soluble guanylate cyclase activity
Increase in [cAMP]i
Reduction in VDCC activity
Reduction in [Ca2+]i
Increased relaxation

Inhibitors of the renin-angiotensin system - ACE inhibitors and Angiotensin II receptor blockers

ACE inhibitors
Enalapril
Ramipril
Some side effects - contraindications
Hyperkalaemia
Cough
Angioedema
Contraindicated in pregnancy

Angiotensin II receptor (type 1) antagonists
Losartan
Valsartan

Diuretics
Main effects:
Increase in Na+ and H20 excretion
Also direct effects on VSM tone
Main classes of diuretics:
Loop diuretics
Thiazides
Potassium Sparing
Major side effects:
Hypokalaemia
Loop and Thiazide but not K+ sparing)
Lipid abnormalities
Glucose intolerance/Hyperglycaemia

Drugs acting on sympathetic system and adrenergic receptors

Examples
Methyldopa, clonidine
Trimethapan
Reserpine, guanethidine

α1 receptor

Relaxation of
VSM

Prazosin

β1 receptor

Reduction in
cardiac output

Propranolol, atenolol

Inhibition of
renin release

Major side effects of beta-blockers:
Acute bronchospasm
Bradycardia
Raynaud’s syndrome
Claudication
Increased triglycerides
Decreased HDL
Glucose intolerance
Lethargy
Nightmares
Impotence
Ca2+ channel blockers



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