Pharmacological Treatment of Hypertension

Question 1

DIAGNOSIS of hypertension

Answer 1

• Clinic BP

* AND ambulatory blood pressure monitoring (ABPM) or home blood pressure monitoring (HBPM) average day time

Question 2

STAGE 1 HYPERTENSION: if there is no cardiovascular disease

Answer 2

then treat with lifestyle modifications and monitor BP

Question 3

STAGE 1 HYPERTENSION: if there is cardiovascular disease

Answer 3

there should be lifestyle modification and therapeutic interventions

Question 4

if it is stage 2 hypertension

Answer 4

treat with lifestyle modifications and therapeutic intervention

Question 5

types of lifestyle modifications

Answer 5

weight loss
reduced salt intake which is less than 6g a day

increased fruit and vegetable intake which increases potassium intake

reduce alcohol consumption

increase aerobic exercise

smoking cessation

stress reduction/relaxation techniques

Question 6

Antihypertensive therapeutics

Answer 6

• Angiotensin converting enzyme (ACE inhibitors)
• Angiotensin II receptor blockers (ARBs)
• Diuretics
• Calcium channel blockers (CCBs)
• a-adrenergic receptor blockers
• b-adrenergic receptor blockers
• Spironolactone / potassium-sparing diuretics

Question 7

THE KIDNEYS AND BP

Answer 7

•Kidneys control body water and salt balance

This determines extracellular fluid volume (ECF) and hence arterial BP

Kidneys filter 180L plasma/day

Reabsorb ~99% Na+ and H2O 1.5-2L urine produced

Question 8

THE KIDNEYS AND BP - what is this mechanism mediated by

Answer 8

• Mediated via nephrons
• glomerulus – filters plasma

tubules –absorption/secretion of water and solutes

Question 9

ACE INHIBITORS

Answer 9

• First or second line anti-hypertensive treatment

* e.g. captopril, enalapril, perindopril, lisinopril, ramipri

Question 10

ACE is involved in another process:

Answer 10

the kinin-kallikrein system:

• Kallikrein cleaves kininogen to Bradykinin
• Bradykinin is a vasodilator
• ACE breaks down bradykinin into an inactive metabolite

Question 11

DIURETICS

Answer 11

substances that help the body get rid of water (target Na+ absorption to do this)

• Reduce blood pressure by decreasing ECV
• 1. LOOP DIURETICS
     
     2. THIAZIDE DIURETICS
     3. K+ SPARING DIURETICS

Question 12

LOOP DIURETICS

Answer 12

• Most powerful diuretics (15-25% Na+) • “torrential urine flow”

• e.g. Furosemide, Bumetanide
• Inhibit the NKCC (Na+/K+/2Cl- co-transporter) in
the thick ascending limb of the Loop of Henlé

• reduction in reabsorption of Na+, K+, Cl-
• Absorbed in the GI tract, but bound tightly to plasma protein (cannot pass glomerular filter)
• Are secreted by PCT via organic anion transporters
• Secreted portion excreted with urine, remainder mainly metabolised in liver

Question 13

LOOP DIURETICS: Used to relieve salt and water overload:

Answer 13

• Acute pulmonary oedema
• Chronic heart failure
• Cirrhosis of the liver
• Nephrotic syndrome
• Renal failure

Question 14

loop diuretics Only used in treatment of

Answer 14

hypertension where renal function is impaired

• Thiazides are preferred when renal function preserved

Question 15

THIAZIDE DIURETICS

Answer 15

• Less powerful than loop diuretics
• e.g. Bendroflumethiazide,
Hydrochlorothiazide
• Inhibit the NCC (Na+/Cl- co-transporter)
• reduction in Na+ and Cl- reabsorption
• Also cause vasodilation
• Well tolerated, effective orally
• Common 2nd/3rd line treatment for hypertension
• Can cause erectile dysfunction

• Excreted in urine via tubular secretion (organic anion transporters)

Question 16

K+ SPARING DIURETICS

Answer 16

Limited diuretic action alone, but powerful antihypertensive agents in combination with loop/thiazide diuretics

Question 17

1. Aldosterone antagonists

Answer 17

e.g. Spironolactone, eplerenone

• competitively inhibit the mineralocorticoid receptor

Question 18

2. ENaC inhibitors

Answer 18

e.g. Amiloride, triamterene
• block the epithelial Na+ channel (ENaC)
• Reduce driving force for K+ secretion in CT, would cause hyperkalaemia alone
• Combined with loop diuretics balances plasma [K+]

Question 19

CALCIUM CHANNEL BLOCKERS side effects

Answer 19

Flushes Headaches Ankle oedema Dizziness

Question 20

ACE inhibitors side effects

Answer 20

Persistent dry cough
Dizziness
Tiredness
Headaches
Risk of angioedema (Afro-Caribbean )
Risk of hyperkalaemia Renal impairment
Avoid in bilateral artery stenosis teratogenic

Question 21

THIAZIDE DIURETICS side effects

Answer 21

Hypokalaemia Hyponatraemia Gout Impotence Monitor for dehydration
Ineffective in moderate to severe renal impairement

Question 22

K+ SPARING DIURETICS side effects

Answer 22

Hyperkalaemia Renal impairment GI upset

Spironolactone – oestrogen related side effects

Question 23

ARBs side effects

Answer 23

Dizziness
Headaches
Back/leg pain
Hyperkalaemia
Renal impairment
Avoid in bilateral artery stenosis
Teratogenic