Pharmacology of Hypertension Flashcards
What are some examples of Angiotensin converting enzyme inhiitors?
Ramipril
Lisinopril
Perindopril
What is the mechanism of action of ACE inhibitors?
Inhibit the angiotensin converting
enzyme.
Prevent the conversion of
angiotensin I to angiotensin II
by ACE.
What are the main side effects of ACE inhibitors?
Cough
Hypotension
Hyperkalaemia (care with K+ supplements or K+-sparing diuretics)
Foetal Injury (AVOID IN PREGNANT WOMEN)
Renal failure (in patients with renal artery stenosis)-
Urticaria/Angioedem
What do most ACE inhibitors require to reap therapeutic effects?
Most ACE inhibitors (not lisinopril) are pro-drugs. They require hepatic activation to generate the active metabolites required for therapeutic effects.
What must be regulated when prescribing ACE inhibitors?
eGFR and serum potassium
What are some examples of Calcium channel blockers?
Amlodipine
Felodipine
What is the mechanism of action of calcium channel blockers?
Block L-type calcium channels – predominantly on vascular smooth muscle. This results in a decrease in calcium influx, with downstream inhibition of myosin light chain kinase and prevention of cross-bridge formation. The resultant vasodilation reduces peripheral resistance.
What is the primary target for Calcium channel blockers?
L-type calcium channels
What are the main side effects of Calcium channel blockers?
Ankle oedema
Constipation
Palpitations
Flushing/Headaches
Which type of calcium channel blockers demonstrate greater vascular selectivity?
Dihydropyridine type calcium channel blockers
What are some examples of thiazide/thiazide-like diuretics?
They block the Na+, Cl- co-transporter in the early DCT.
Therefore, Na+ and Cl- reabsorption is inhibited.
As a result, the osmolarity of the tubular fluid increases, decreasing the osmotic gradient for water reabsorption in the collecting duct.
What is the primary target for thiazide/thiazide-like diuretics?
Sodium/chloride co-transporter
What are the main side effects of thiazide/thiazide-like diuretics?
Hypokalemia
Hyponatremia.
Metabolic alkalosis (increased hydrogen ion excretion)
Hypercalcemia.
Hyperglycemia (hyperpolarised pancreatic beta cells).
Hyperuricemia
What happens after 1-2 weeks of treatment with thiazide/thiazide-like diuretics?
Thiazide and thiazide-like diuretics both lose their diuretic effects within 1-2 weeks of treatment. Continuing anti-hypertensive action appears to be due to vasodilating properties (these are more pronounced for the thiazide-like diuretics)
What are some examples of Angiotensin receptor blockers?
Losartan
Irbesartan
Candesartan
What is the mechanism of action of Angiotensin receptor blockers?
These agents act as insurmountable (i.e. non-competitive) antagonists at AT1 receptor (found on kidneys and on the vasculature)
What are the major side effects of Angiotensin receptor blockers?
Hypotension
Hyperkalaemia (care with K+ supplements or K+-sparing diuretics)
Foetal Injury (AVOID IN PREGNANT WOMEN)
Renal failure (in patients with renal artery stenosis)-
NOT AS EFFECTIVE AS OTHER HYPERTENSIVES.
What do Losartan & Candesartan require to reap the desired therapeutic effects?
Losartan and candesartan are pro-drugs. They require hepatic activation to generate the active metabolites required for therapeutic effects.
What can Felodipine result in ?
dose-dependent decrease in systolic+diastolic blood pressure. reflex tachycardia
How does Amlodipoine mitigate the reflex tachycardia seen in many patients?
Slow onset
longer half life
What is used prior to Angiotensin 2 blockers?
ACE inhibitors, partially due to cost/ACE is more effective
What is the effect of thiazide like diuretics?
Decrease blood volume
Decrease venous return
Decrease cardiac output
How can thiazide diuretic access the NaCl transporter on the apical side of the distal tubule?
diuretic needs to travel from the blood to the basolateral side to the transporter on the apical side
How long does the diuretic effect of thiazides last?
1-2 weeks
kidney becomes tolerant, rebound activation of the renin angiotensin system which counteracts the diuretic effect due to Na reabsorption
What causes the continued anti-hypertensive effect of thiazides?
less well understood vasodilating action
