Drug treatment of Hypertension

  1. Name some causes of essential hypertension?
    • The cause is unknown but multifactorial. Risk factors include:
    • Stress
    • High cholesterol
    • Diabetes
    • Genetic predisposition
    • Diet (high salt)
  2. 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)
  3. 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
  4. What is the ideal blood pressure?
    120/80 mmHg
  5. What is the formula for determining blood pressure?
    BP= Cardiac output x Peripheral vascular resistance
  6. 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
  7. What determines the peripheral vascular resistance?
    The arterioles
  8. What are the main sites of regulation of the blood pressure?
    • Cardiac output
    • Peripheral resistance
    • Vein/venule capacitance
    • The kidneys
  9. What are the tissue targets for hypertensive drugs?
    • 1. Sympathetic nerves
    • 2. Kidneys
    • 3. Heart
    • 4. Arterioles
    • 5. Endothelial cells
    • 6. Central nervous system
  10. 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.
  11. 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.
  12. 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.
  13. What are the three main methods of reducing blood pressure?
    • Reduce cardiac output
    • Reduce plasma volume
    • Reduce peripheral resistance
  14. 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
  15. What are the functions of beta blockers?
    • Reduce cardiac output
    • Reduce renin release
    • Reduce sympathetic activity
  16. What are the side effects of beta blockers?
    • Bronchocontriction
    • Cardiac failure
    • Fatigue
    • Depression
  17. Give 2 examples of beta blockers.
    • Propanolol
    • Non selective
    • Crosses BBB: nightmares, depression

    • Atenolol
    • Beta 1 selective
    • Less risk of bronchoconstricion
    • No central effects
  18. 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
  19. 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
  20. Summarise angiotensin receptor antagonists.
    eg Losartan

    Used in patients intolerant to ACE inhibitors

    No bradykinin cough
  21. 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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Drug treatment of Hypertension