Hypertension Flashcards
What are the 4 types of drugs that can be prescribed for hypertension?
- Angiotensin converting enzyme inhibitors
- Calcium channel blockers
- Thiazide or thiazide-like diuretics
- Angiotensin receptor blockers
Name 3 ACE inhibitors.
Ramipril
Lisinopril
Perindopril
What is the primary mechanism of action of ACE inhibitors?
Inhibit the angiotensin converting enzyme (ACE).
This prevents the conversion of angiotensin I to angiotensin II by ACE.
What do ACE inhibitors target?
Angiotensin converting enzyme (found in high conc in lungs)
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/Angioedema
Most ACE inhibitors (except lisinopril) are pro-drugs. Where are they metabolised /activated?
Liver
What needs to be constantly monitored in patients being treated with ACE inhibitors?
- eGFR
- serum Potassium
Why does serum potassium need to be monitored?
- ACE inhibitors will reduce Ang II.
- This will cause a reduction in Aldosterone.
- Less Potassium will be excreted and more will remain in plasma -> hyperkalaemia.
Why do ACE inhibitors cause coughs?
- Ang II usually stimulates the breakdown of bradykinin in the lungs. Bradykinin is responsible for causing the cough reflex.
- ACE inhibitors reduce Ang II so there is bradykinin accumulates and causes coughing.
Drugs ending in -dipine are likely to be….
Calcium channel blockers
Name some calcium ion channel blockers.
Amlodipine
Felodipine
Describe the mechanism of action of calcium channel blockers.
- Block L-type calcium channels – predominantly on arteriolar 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 target of calcium channel blockers?
L-type calcium channels on arteriolar smooth muscle cells
What are the side effects of using calcium channel blockers?
Ankle oedema
Constipation
Palpitations
Flushing/Headaches
What are the 2 types of calcium channel blockers?
- Dihydropyridines
- non-dihydropyridines
Where do dihydropyridines act?
On smooth muscle cells in arterioles
Name some dihydropyridines.
- amlodipine
- Felodipine
Where do non-dihydropyridines act?
On smooth muscle cells but they have a more direct effect on the heart.
Which type is most effective at reducing hypertension?
dihydropyridines -> they show greater selectivity and have fewer side effects
Why is amlodipine preferred over felodipine?
- It is longer acting (long half life and is cleared away from the plasma much slower)
- reflex tachycardia is not seen with this drug because it reaches its peak action much slower (slower onset so body can adjust to the slow reduction in BP). Felodipine acts much quicker so the body feels like it needs to compensate for the low BP thus causing reflex tachycardia.
Name some Thiazide or thiazide-like diuretics.
Bendro-flumethiazide (thiazide)
Indapamide (thiazide-like)
How do Thiazide or thiazide-like diuretics work?
- They block the Na+, Cl- co-transporter in the early DCT.
- Therefore Na+ and Cl- reabsorption into the blood is inhibited.
- As a result the osmolarity of the tubular fluid increases, decreasing the osmotic gradient for water reabsorption in the collecting duct.
- More water remains in the kidney collecting ducts and is excreted.
- Reduction in blood volume, reduction in BP.
What is the target for thiazide diuretics?
Sodium/chloride cotransporters on the apical side of the DCT.
What are the side effects of using thiazide diuretics?
- Hypokalemia
- Hyponatremia.
- Metabolic alkalosis (increased hydrogen ion excretion)
- Hypercalcemia.
- Hyperglycemia (hyperpolarised pancreatic beta cells).
- Hyperuricemia
Why do Thiazide and thiazide-like diuretics both lose their diuretic effects within 1-2 weeks of treatment?
The kidneys become tolerant because there is a rebound activation in the RAAS system which counteracts the diuretic effect due to increasing sodium reabsorption.
How do Angiotensin receptor blockers work?
These agents act as insurmountable (i.e. non-competitive) antagonists at AT1 receptor.
Name some Angiotensin receptor blockers.
Losartan
Irbesartan
Candesartan
What do Angiotensin receptor blockers target?
Angiotensin receptors found on kidneys and on the vascular smooth muscle.
What are the 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)
Why don’t angiotensin receptor blockers cause coughs (like ACE inhibitors)?
Angiotensin receptor blockers don’t affect ACE -> they allow Ang II to be produced so that can still stimulate breakdown of bradykinin.
Which are more effective: angiotensin receptor blockers or ACE inhibitors?
ACE inhibitors -> these are usually the first line anti-hypertensive drugs
When are CCBs prescribed before ACE-I or ARBs?
- for Patients of African or Caribbean descent.
- >55 yrs
Losartan and candesartan are pro-drugs. Where are they activated?
In the liver
