treatment of hypertension

Question 1

how is blood pressure controlled in the long and short term ?

Answer 1

Short term regulation:
* Baroreceptors
* Sympathetic and parasympathetic outflow
Long term:
* Hormonal control of total body sodium:
* Control of blood volume, via ECFV
* Degree of vasoconstriction

Question 2

what is the arbitrary measurement for hypertension ?

Answer 2

140/90 mm Hg

Question 3

what are the causes of hypertension ?

Answer 3

Secondary (identifiable cause, <10%):
* Renal disease
* Vascular – e.g., renal artery stenosis
* Hormonal – e.g., Conn’s syndrome, Cushing’s syndrome
* Monogenic genetic diseases – e.g., Liddle’s
Primary or essential (unknown cause, >90%):
* Genetic pre-disposition and environmental factors are proposed to cause essential hypertension through many mechanisms

Question 4

why treat hypertension ?

Answer 4

Risk reduction, e.g., 5 mm Hg drop in diastolic BP for 5 years:
* Reduce strokes by 42%
* Reduce heart attacks by 16%
* Reduce vascular mortality by 21%

Goals of anti-hypertensive treatment:
* Adequate blood pressure control - < 140/90 mmHg, alter relative risk
* Prevention of target organ damage
* Controlling other cardiovascular risk factors

Treatment pathways:
* Non-pharmacological: life-style modifications
* Pharmacological treatment
* Surgical (if known cause, e.g. Conn’s syndrome)

Question 5

describe ACE inhibitors and AT1 receptor blockers

Answer 5

Side effects: ACEi
* Cough (common) due to decrease in bradykinin breakdown
* Angioedema (rare but serious)
Side effects: both ACEi and ARBs
* Hyperkalaemia

Question 6

what are the sympathetic neural effects on the CVS ?

Answer 6

• β1 – increase HR and contractility → increase CO → increase BP
• α1 – vasoconstriction → TRP → increase BP
• Beta blockers (β1 blockers, e.g. atenolol): reduction in CO and renin release

Question 7

describe the mechanism of vasodilators - K channel openers

Answer 7

• ↑ K⁺ Efflux (via K⁺ channels activated by NO, PGI₂, EDHF)
• Hyperpolarization → Membrane potential becomes more negative
• ↓ VGCC Activity → Less Ca²⁺ entry into smooth muscle
• ↓ [Ca²⁺]ᵢ → Less activation of calmodulin & MLCK
• ↓ MLCK Activity → Less myosin phosphorylation → Relaxation (Vasodilation)

Key Vasodilators:
* NO (Nitric Oxide) → ↑ cGMP → PKG activation → K⁺ efflux
* PGI₂ (Prostacyclin) → ↑ cAMP → PKA activation → Ca²⁺ reduction
* EDHF → Direct K⁺ channel activation → Hyperpolarization

• Result: Smooth muscle relaxation → Vasodilation → ↓ Vascular resistance

Question 8

describe VGCC Blockers as Vasodilators

Answer 8

• VGCC Blockade → Prevents Ca²⁺ entry into vascular smooth muscle cells (VSMCs).
• ↓ [Ca²⁺]ᵢ → Less activation of myosin light chain kinase (MLCK).
• ↓ MLCK Activity → Less myosin phosphorylation → Smooth muscle relaxation (vasodilation).

🩸 Effects:
✔ Arteriolar dilation → ↓ Vascular resistance → ↓ Blood pressure.
✔ Improved blood flow → Used in hypertension, angina, Raynaud’s phenomenon.

🩸 Examples of VGCC Blockers:
🔹 Dihydropyridines (e.g., amlodipine, nifedipine) – Act mainly on blood vessels.
🔹 Non-dihydropyridines (e.g., verapamil, diltiazem) – Affect both heart and vessels.

Question 9

what are the considerations when selecting drug therapy ?

Answer 9

• Essential vs. secondary hypertension
• Evidence of efficacy
• Side effects of drug
• Drug interactions
• Individual demographics
• Co-existing diseases
• Quality of life
• Economic considerations