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Name some causes of essential hypertension?
- The cause is unknown but multifactorial. Risk factors include:
- Stress
- High cholesterol
- Diabetes
- Genetic predisposition
- Diet (high salt)
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What are the causes of identifiable cause hypertension?
- Renal artery constriction
- Narrowing of aorta
- Tumour of adrenal glands
- Cushings disease (hypercortisolism)
- Primary Aldosteronism (elevated aldesterone)
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What are the aims of drug treatment of hypertension?
- 1. To reduce the incidence of complications
- 2. To reuce the risk of coronary artery disease(buildup of placque) and stroke
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What is the ideal blood pressure?
120/80 mmHg
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What is the formula for determining blood pressure?
BP= Cardiac output x Peripheral vascular resistance
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What determines the cardiac output?
- Heart rate
- Stroke volume (volume of blood pumped in each beat)
- Amount of blood returning to the heart, which depends on venule and vein capacitance, and blood volume
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What determines the peripheral vascular resistance?
The arterioles
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What are the main sites of regulation of the blood pressure?
- Cardiac output
- Peripheral resistance
- Vein/venule capacitance
- The kidneys
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What are the tissue targets for hypertensive drugs?
- 1. Sympathetic nerves
- 2. Kidneys
- 3. Heart
- 4. Arterioles
- 5. Endothelial cells
- 6. Central nervous system
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What are the antihypertensive drugs that act on the heart and what do they acheive?
- beta blockers
- calcium channel blockers
They decrease the force of contraction and the heart rate.
This reduces cardiac output.
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What are the antihypertensive drugs that act on the kidney and what do they acheive?
- Diuretics
- ACE inhibitors
- beta blockers
They decrease the blood volume.
This causes a decrease in cardiac output.
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What are the antihypertensive drugs that act on the smooth muscle cells and what do they acheive?
- Calcium channel blockers
- Vasodilators
- ACE inhibitors
They relax vascular smooth muscle.
This causes a decrease in peripheral vascular resistance.
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What are the three main methods of reducing blood pressure?
- Reduce cardiac output
- Reduce plasma volume
- Reduce peripheral resistance
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Give an overview of the adrenergic receptors related to hypertension?
- Alpha mediated SM contraction
- alpha2 receptor in sympathetic nerve is activated.
- Noradrenaline released, activates alpha2 and alpha1 receptors on the SM cell.
- G protein is activated, produces IP3, muscle contraction occurs.
- = vasoconstriction.
- Beta1 mediated cardiac contraction
- Noradrenaline released from sympathetic nerve.
- Beta 1 receptor in the heart is activated.
- Gs protein produced cAMP, contraction occurs.
- =cardiac contraction increases
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What are the functions of beta blockers?
- Reduce cardiac output
- Reduce renin release
- Reduce sympathetic activity
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What are the side effects of beta blockers?
- Bronchocontriction
- Cardiac failure
- Fatigue
- Depression
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Give 2 examples of beta blockers.
- Propanolol
- Non selective
- Crosses BBB: nightmares, depression
- Atenolol
- Beta 1 selective
- Less risk of bronchoconstricion
- No central effects
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Give a summary of alpha blockers.
- Selective alpha 1 antagonist = Prazosin
- Used in severe hypertension
Causes vasodilation, reduces peripheral vascular resistance.
- Side effects:
- Postural hypotension
- Dizziness
- Weakness
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How do ACE inhibitors work?
Inhibit angiotensin converting enzyme, angiotensin 2 is not produced, blood pressure is not increased.
- Side effects:
- Bradykinin cough
eg Captopril
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Summarise angiotensin receptor antagonists.
eg Losartan
Used in patients intolerant to ACE inhibitors
No bradykinin cough
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Give an overview of calcium channel blockers?
- Used for mild to moderate hypertension.
- Bind ligand gated calcium channels
- Reduce intracellular calcium
Result: General arterial vasodilation
Example: Verapamil
- Side effects due to excessive dilation:
- Headache
- Ankle swelling
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