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Year 2 - BRS > 1.8 - Pharmacology of hypertension (core drugs) > Flashcards

1.8 - Pharmacology of hypertension (core drugs) Flashcards

1
Q

What are the main types of anti-hypertensive drugs? (4)

A
  • angiotensin converting enzyme inhibitors
  • calcium channel blockers
  • thiazide / thiazide-like diuretics
  • angiotensin receptor blockers
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2
Q

What are some examples of ACE inhibitors? (3)

A
  • ramipril
  • lisinopril
  • perindopril
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3
Q

What is the primary mechanism of action of ACE inhibitors?

A
  • inhibit ACE
  • prevent conversion of angiotensin I –> angiotensin II
  • angiotensin II increases BP
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4
Q

What is the drug target of ACE inhibitors?

A

ACE

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5
Q

What are the main side effects of ACE inhibitors?

A
  • cough
  • hypotension
  • hyperkalaemia (care with K+ supplements or K+ sparing diuretics)
  • foetal injury (AVOID IN PREGNANT WOMEN)
  • renal failure (in renal artery stenosis patients)
  • urticaria (hives) / angioedema (swelling under skin)
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6
Q

What is some extra information about ACE inhibitors?

A
  • most (not lisonopril) are prodrugs so require hepatic activation to have an effect
  • eGFR and serum K+ must be regularly monitored when prescribing ACE inhibitors
  • typically used ahead of angiotensin II receptor blockers (cost and effectiveness)
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7
Q

What are some examples of calcium channel blockers?

A
  • amlodipine
  • felodipine
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8
Q

What is the primary mechanism of action of calcium channel blockers?

A
  • block L-type calcium channels, predominantly on vascular smooth muscle
  • results in decrease in calcium influx and downstream inhibition of myosin light chain kinase –> prevention of cross-bridge formation
  • resultant vasodilation reduces peripheral resisatance
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9
Q

What is the drug target for calcium channel blockers?

A

L-type calcium channel

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10
Q

What are the main side effects of calcium channel blockers?

A
  • ankle oedema
  • constipation
  • palpitations
  • flushing/headache
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11
Q

What do dihydropyridine type calcium channel blockers do differently?

A

Demonstrate a higher degree of vascular sensitivity

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12
Q

What are some examples of thiazide or thiazide-like diuretics?

A
  • bendro-flumethiazide (thiazide)
  • indapamide (thiazide-like)
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13
Q

What is the primary mechanism of action of thiazide or thiazide-like diuretics?

A
  • block Na+/Cl- cotransporter in early DCT
  • therefore Na+ and Cl- reabsorption is inhibited
  • as a result the osmolarity of the tubular fluid increases, decreasing osmotic gradient for water reabsorption in collecting duct
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14
Q

What is the drug target of thiazide or thiazide-like diuretics?

A

Sodium/chloride cotransporter

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15
Q

What are the main side effects of thiazide or thiazide-like diuretics?

A
  • hypokalaemia
  • hyponatraemia
  • metabolic alkalosis (increased H+ excretion)
  • hypercalcaemia
  • hyperglycaemia (hyperpolarised pancreatic beta cells)
  • hyperuricaemia
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16
Q

What is some extra information about thiazide or thiazide-like diuretics?

A
  • these drugs lose diuretic effects in 1-2 weeks of treatment
  • continuing anti-hypertensive action appears to be due to vasodilating properties (more pronounced for thiazide-like diuretics)
17
Q

What are some examples of angiotensin receptor blockers (ARBs)?

A
  • losartan
  • irbesartan
  • candesartan
18
Q

What is the primary mechanism of action of ARBs?

A

These act as insurmountable (non-competitive) antagonists at angiotensin I receptor (found on kidneys and on vasculature)

(AT-II acts via both AT1 and AT2 receptors)

19
Q

What is the drug target of ARBs?

A

Angiotensin receptor

20
Q

What are the main side effects of ARBs?

A
  • hypotension
  • hyperkalaemia (care with K+ supplements and K+ sparing diuretics)
  • foetal injury (AVOID IN PREGNANT WOMEN)
  • renal failure (in patients with renal artery stenosis)
21
Q

What is some extra information about ARBs?

A
  • not as effective anti-hypertensives as ACEi (ACEi typically used first partly due to cost, partly due to effectiveness)
  • losartan and candesartan are prodrugs so require hepatic activation to have effects
  • ARBs for patients of African/Caribbean descent
22
Q

What would you do if a patient had a BP of under 135/85, 135/85 to 149/94 and 150/95+?

A
  • <135/85 = monitor at least every 5 years
  • 135/85 to 149/94 = ABPM/HBPM offered, reduce CVD risk, start drug treatment if there is any of the following:
    • target organ damage
    • CVD
    • renal disease
    • diabetes
    • 10 year CVD risk >10%
  • > 150/95 = start drug treatment
23
Q

What is drug clearance?

A
  • clearance is the measure of the ability of the body to eliminate a drug
  • clearance by means of various organs of elimination is additive
  • elimination of drug may occur as a result of processes that occur in the liver, kidney and other organs
24
Q

What is elimination half-life of a drug?

A

Elimination half-life is the length of time required for the concentration of a particular drug to decrease to half of its starting dose in the body

25
Q

What is the time to peak plasma levels of a drug?

A
  • time to peak concentration is the time required for a drug to reach peak concentration in plasma
  • the faster the absorption rate, the lower the time to peak plasma concentration
26
Q

What can felodipine (Ca2+ channel blocker) result in? (2)

A
  • dose-dependent decrease in systolic and diastolic blood pressure
  • causes a reflex increase in heart rate (reflex tachycardia)
27
Q

Compare the onset and half-life of amlodipine to felodipine. (Calcium channel blockers)

A

Amlodipine has a slow onset and a much longer half-life

28
Q

What are the main effects of thiazide-like diuretics? (3 + 1)

A
  • decrease blood volume (and therefore BP)
  • decrease venous return
  • decrease cardiac output
  • (less well-understood vasodilating action)
29
Q

How long does the diuretic effect of thiazide-like diuretics last?

A
  • the diuretic effect of thiazides only lasts for 1-2 weeks
  • the kidney becomes tolerant to the diuretics because there is a rebound activation of the RAAS which counteracts the diuretic effect due to increasing Na+ reabsorption
  • the continuing anti-hypertensive effect of thiazides is due to a further (less well understood) vasodilating action
30
Q

When are ACE inhibitors contraindicated?

A

Bilateral renal artery stenosis

Year 2 - BRS (84 decks)

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