Drugs to control blood pressure

Question 1

Main groups of drugs used to lower blood pressure

Answer 1

• Diuretics
• Beta-adrenoceptor blockers
• Calcium channel blockers
• Angiotensin converting enzyme (ACE) inhibitors
• Angiotensin receptor blockers
• Alpha-adrenoceptor blockers
• Direct renin inhibitors

Question 2

Why should digoxin not be given with loop diuretics?

Answer 2

Digoxin is a competitive inhibitor of K+, act on the same site at the Na+/K+ pump. If extracellular K+ is high, digoxin will be less effective, low K+ enhances effects. Loop diuretics cause a reduction in plasma K+ levels and therefore potentiates it’s effects (lack of competition). Leads to loss of K+ and arrhythmias.

Question 3

Function of natriuretic hormones

Answer 3

ANP: released from atrial myocytes in response to stretch

BNP: released from ventricular myocytes in response to hypertrophy

CNP: endothelial factor released in atheroma

All bind to guanylate cyclase coupled receptors. Result in increased GFR and reduced Na+ reabsorption. Decreases RAAS and therefore lowers blood volume to reduce bp.

Question 4

Name three endothelium-derived vasoactive factors

Answer 4

Prostacyclin

Nitric oxide

Carbon monoxide

C-type natriuretic peptide

Endothelin-1

Angiotensin II

Question 5

Conn’s syndrome

Answer 5

Primary hyperaldosteronism caused by adrenal adenoma or adrenal hyperplasia. Aldosterone promotes increased Na+ reabsorption in principal cells (increasing water retention) and also promotes secretion of K+ and H+. Patients present with hypertension and hypokalaemia.

Question 6

Non-pharmacological treatment of bp

Answer 6

Weight
Exercise
Salt reduction
More potassium
Moderate alcohol intake
Quit smoking

Question 7

Why are smoking and obesity major CV risk factors?

Answer 7

Fat produces its own angiotensin, which increases blood pressure
Smoking impairs production and bioavailability of NO

Question 8

Difference between primary and secondary hypertension

Answer 8

Primary hypertension (95%) has no known cause but is associated with age, obesity, physical inactivity, smoking, alcohol, genetics

Secondary hypertension (5%) is caused by renal disease (activates RAAS) or endocrine disease

Question 9

Diuretics used in hypertension

Answer 9

Thiazides, loop diuretics, K+-sparing diuretics

Question 10

Use of thiazides in hypertension

Answer 10

Thiazides are the most powerful anti-hypertensives (e.g. bendroflumethiazide). Preferred as they are weak and long acting. They act at the DCT and inhibit the Na/Cl co-transporer in the luminal membrane. Increased Na+ and water is excreted and K+ secretion is increased. Reduced blood volume reduces filling of the heart

Adverse effects: hypokalemia (muscle weakness), hyponatremia (causes confusion) hyperuricaemia (gout), raised glucose and cholesterol

Question 11

K+-sparing diuretics in hypertension

Answer 11

Produce mild diuresis and cause excretion of 2-3% sodium. Used in combination with other drugs, useful in excess aldosterone. Contraindicated in renal patients

• Spironolactone: aldosterone antagonist. Competitive antagonist of receptor and reduces Na+ absorption and therefore K+ and H+ secretion
• Triamterene and Amiloride: Ep Na+ channel blocker. Block Na+ reabsorption by principal cells, reducing membrane potential and reducing K+ secretion. Decreased H+ secretion.

Side effects: High K+ and low Na+ Interact with ACEi to increase hyperkalemia. Aldosterone similar to oestrogen, causes gynaecomastia.

Question 12

Use of beta blockers in hypertension

Answer 12

Atenolol: cardioselective (b1)
Propanolol: non-selective (b1,b2)
Decrease cardiac output and prevent fatal arrhythmias, heart attack and stroke. Also blocks adrenal system (sympathetic innervation direct to adrenal gland)

Question 13

CV effects of calcium channel blockers

Answer 13

vascular smooth muscle relaxation
decreased myocardial force generation
decreased heart rate
natriuresis & diuresis

Question 14

Chemical classes of calcium channel blockers

Answer 14

Dihydropyridines: nifedipine, amlodipine (arterioselective - vascular effects, relaxes arteries and increases excretion of Na+ and water but increases HR)

Benzothiazepine: diltiazem (cardioselective, relaxes arteries, decreases HR and SV)

Phenylalkalamine: verapamil (cardioselective, relaxes arteries, decreases HR and SV)

Question 15

Cardioselective calcium channel blockers

Answer 15

Verapamil and diltiazem

Side effects:
Heart failure
Heart block
Peripheral oedema
Constipation
Facial flushing, headaches

Question 16

Side effects of dihydropyridines

Answer 16

Marked facial flushing
Headaches
Peripheral oedema
Polyuria (exacerbate prostatism)

Question 17

Adverse effects of angiotensin II

Answer 17

Excess Ang II stimulates NADPH oxidase to produce superoxide
Superoxide is a potent oxygen free radical
Oxidation by superoxide impairs protein & DNA function
Superoxide also inactivates nitric oxide:

Question 18

Action of ACEi

Answer 18

Inhibit the formation of angiotensin II, also inhibit the breakdown of bradykinin (vasodilator)

Side effects:
Dry cough Angioedema Hyperkalemia

Contraindicated in asthmatics

Question 19

Why are ACEi and ARBs contraindicated in renal artery stenosis?

Answer 19

Patients with bilateral renal artery stenosis may experience renal failure if ARBs are administered.

The reason is that the elevated circulating and intrarenal angiotensin II in this condition constricts the efferent arteriole more than the afferent arteriole within the kidney, which helps to maintain glomerular capillary pressure and filtration.

Removing this constriction by blocking angiotensin II receptors on the efferent arteriole can cause an abrupt fall in glomerular filtration rate.

Question 20

Action of ARBs

Answer 20

Receptor antagonists that block type 1 angiotensin II (AT1) receptors on blood vessels and other tissues such as the heart. These receptors are coupled to the Gq-protein and IP3 signal transduction pathway that stimulates vascular smooth muscle contraction

Question 21

Effect of NorA on arterial pressure

Answer 21

Acts via alpha1 to cause constriction of the arteries and beta1 receptors to produce mroe forceful contractions. This causes an increase in HR, systolic and diastolic pressure.

This is detected by baroreceptor reflexes which lower the hear rate in reponse.

Overall effect: raised systolic & diastolic pressure, lower HR

Question 22

Alpha-adrenoreceptor blockers

Answer 22

α1-adrenoceptor antagonists cause vasodilation by blocking the binding of norepinephrine to the smooth muscle receptors.

Non-selective α1 and α2-adrenoceptor antagonists block postjunctional α1 and α2-adrenoceptors, which causes vasodilation.

Alpha-blockers dilate both arteries and veins because both vessel types are innervated by sympathetic adrenergic nerves; however, the vasodilator effect is more pronounced in the arterial resistance vessels.

Question 23

Phaeochromocytoma

Answer 23

Neuroendocrine tumour of the adrenal medulla. Results in excess production of catecholamines, particularly NorA

Patients suffer with elevated HR and bp, palpitations, anxiety, headaches and elevated blood glucose.

Question 24

Classification of blood pressure in adults

Answer 24

Normal: 120-140 systolic, 80-90 diastolic

Mild: 140-150 systolic, 90-100 diastolic

Moderate: 160-180 systolic, 100-110 diastolic

Severe: >180 systolic, >120 diastolic