Pharmacology of hypertension Flashcards by Tania Ahmed

What are the core drugs of hypertension?

Ramipril, Lisinopril, Perindopril (ACE-i)
Amlodipine, Felodipine (Ca2+ channel blockers)
Bendro-flumethiazide (thiazide), Indapamide (thiazide-like) (Thiazide or thiazide-like diuretics)
Losartan, Irbesartan, Candesartan (Angiotensin receptor blockers)

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What is the drug class of Ramipril/ Lisinopril/ Perindopril?

There are Angiotensin converting enzyme inhibitors

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What is the primary mechanism of action of Ramipril, Lisinopril, Perindopril

Inhibit the angiotensin converting enzyme.
Prevent the conversion of angiotensin I to angiotensin II by ACE.

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What is the drug target of Ramipril, Lisinopril, Perindopril

Angiotensin converting enzyme

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What are the main side effects of Ramipril, Lisinopril, Perindopril

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

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Why is hepatic activation required with the use of Ramipril, Lisinopril, Perindopril

Most ACE inhibitors (not lisinopril) are pro-drugs. They require hepatic activation to generate the active metabolites required for therapeutic effects.

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What must be monitored when prescribing Ramipril, Lisinopril or Perindopril?

eGFR and serum potassium must be regularly monitored when prescribing ACE inhibitors.

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What is the drug class of Amoldipine and Felodipine?

Calcium channel blockers

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What is the primary mechanism of action of Amoldipine and Felodipine?

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.

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What are the drug targets of Amoldipine and Felodipine?

L-type calcium channel

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What are the main side effects of Amoldipine and Felodipine?

Ankle oedema
Constipation
Palpitations
Flushing/Headaches

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Dihydropyridine type calcium channel blockers demonstrate a higher degree of vascular selectivity, true or false?

TRUE

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What is the drug class of Bendro-flumethiazide (thiazide) and Indapamide (thiazide-like)

Thiazide or thiazide-like diuretics

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What is the primary mechanism of action of Bendro-flumethiazide (thiazide) and Indapamide (thiazide-like)

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.
- decreases blood volume
- decreases venous return/ cardiac output
- decreases b.p

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What are the drug targets of Bendro-flumethiazide (thiazide) and Indapamide (thiazide-like)?

Sodium/chloride cotransporter

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What are the main side effects of Bendro-flumethiazide (thiazide) and Indapamide (thiazide-like)?

Hypokalemia
Hyponatremia.
Metabolic alkalosis (increased hydrogen ion excretion)
Hypercalcemia.
Hyperglycemia (hyperpolarised pancreatic beta cells).
Hyperuricemia.

How long can you use the diuretics Bendro-flumethiazide (thiazide) and Indapamide (thiazide-like)

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 is the drug class of Losartan, Irbesartan and Candesartan?

Angiotensin receptor blockers

What is the primary mechanism of action of Losartan, Irbesartan and Candesartan?

These agents act as insurmountable (i.e. non-competitive) antagonists at AT1 receptor (found on kidneys and on the vasculature)

What is the drug target of Losartan, Irbesartan and Candesartan?

Angiotensin receptor

What are the main side effects of Losartan, Irbesartan and Candesartan?

Hypotension
Hyperkalaemia (care with K+ supplements or K+-sparing diuretics)
Foetal Injury (AVOID IN PREGNANT WOMEN)
Renal failure (in patients with renal artery stenosis)

What is more effective for hypertension, angiotensin receptor blockers or ACEi?

Most trials indicate that angiotensin receptor blockers are not as effective anti-hypertensive agents as ACE inhibitors.

What drugs require hepatic activation before use?

Losartan and candesartan are pro-drugs. They require hepatic activation to generate the active metabolites required for therapeutic effects.

What are the “seven steps” taken when prescribing drugs?

Identify the patient’s problem
Specify the therapeutic objective
Select a drug on the basis of comparative efficacy, safety, cost and suitability
Discuss choice of medication with patient (and carer) and make a shared decision about treatment
Write a correct prescription
Counsel the patient on appropriate use of the medicine
Make appropriate arrangements for follow up (Monitor/stop the treatment)

What is the mechanism of action of calcium channel blockers in the treatment of hypertension?

1. Reduced vascular smooth muscle contractions= 2. Reduced cardiac contraction= reduced cardiac output= reduced b.p 3. Reduced vasoconstriction of blood vessels= reduced peripheral resistance= reduced b.p

What is the mechanism of action of ACE inhibitors in the treatment of hypertension?

- ACE enzyme catalyses the conversion of angiotensin I into angiotensin II - Angiotensin II is a vasoconstrictor and stimulates aldosterone secretion (causes water to be reabsorbed along with sodium; this blood pressure) - Inhibition decreases vasoconstrictor, decreasing blood pressure

Why are ACEi associated with the side effects of cough whereas angiontensin receptor blockers are not?

- ACE enzyme also converts bradykinin ( causes contraction of smooth muscle and dilation of blood vessels) into inactive metabolites - ACEi cause a build up of bradykinin- too much becomes irritative= COUGH

What is more ideal to use ACEi or ARBs for the treatment of hypertension

DEPENDS: - generally ACEi are used ahead of angiotensin 2 receptor blockers (ARBs) partly due to cost - Evidence also shows the ACEi's are more effective BUT: - ARBs are more suitable for patients of African or Caribbean descent

Why might ACEi's have a negative effect on eGFR and serum potassium?

- ACE enzyme catalyses the conversion of angiotensin I into angiotensin II - Angiotensin II is a vasoconstrictor and stimulates aldosterone secretion DECREASED VASOCONSTRICTION= * Increased dilation of efferent arterioles * Glomerular pressure decreases * eGFR regulation is lost * Ability to filter decreases * Causes build up of toxins in the blood= acute renal failure DECREASED ALDOSTERONE= * No sodium retention & reduced potassium lose * High K+ in the cell * leads to cardiac rhythm abnormality

Two of the most commonly prescribed ACE inhibitors are ramipril and lisinopril. Ramipril (like most ACE inhibitors) is a pro-drug whereas lisinopril is not. What does this mean?

"Pro-drug"= the drug is inactive before metabolism - requires metabolism via liver - if liver function decreases and you take a pro drug, you won't get any active drug - Whereas lisinopril is an "active drug"= drug takes effect directly

Indapamide (and other thiazide-like diuretics) are excreted unchanged in the urine. Why is this a vital part of the therapeutic action of thiazide-like diuretics?

The diuretics need to move from the blood -> transported on basolateral side, and only then can it access the sodium chloride transporter on the apical side of distal tubule

Why do the diuretic effect of thiazides only last 1-2 weeks?

The kidney becomes tolerant to the diuretics because there is a rebound activation of the renin angiotensin system which counteracts the diuretic effect due to increasing sodium reabsorption.

Why do thiazides continue to have an anit-hypertensive effect, when their diuretic effect only lasts 1-2 weeks?

The continuing anti-hypertensive effect of thiazides is due to a further (less well understood) vaso-dilating action.