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Sophie - Applied Physiology & Pharmacology Year 2 > 52.4.1 Main Drug Classes Used in the Treatment of Hypertension > Flashcards

52.4.1 Main Drug Classes Used in the Treatment of Hypertension Flashcards

1
Q

What are the main drug classes used in the treatment of hypertension?

A

*Diuretics
*Vasodilators
*Cardio-inhibitory drugs
*Centrally acting sympatholytic drugs

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2
Q

What are the different types of diuretics?

A

Thiazide. loop, and potassium sparring

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3
Q

What are the different types of vasodilators?

A

*Alpha-adreno antagonists (alpha blockers)
*ACE inhibitors
*ARBs
*Ganglionic blockers
*NO donors
*Ion channel modulators (Ca2+ channel blockers and K+ channel openers)
*Renin inhibitors

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4
Q

When are ganglionic blockers and NO donors used?

A

In acute hypertensive emergencies

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5
Q

What are the cardio-inhibitory drugs?

A

*Beta blockers
*Ca2+ channel blockers

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6
Q

What is the most common class of diuretics used to treat diuretics?

A

Thiazides

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7
Q

How do thiazide diuretics work?

A
  • Inhibit the Na+-Cl- co-transporter in the distal convoluted tubule.
  • This leads to greater excretion of salt and therefore less water retention, lowering blood pressure.
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8
Q

What are some examples of thiazide diuretics?

A
  • Bendroflumethiazide
  • Chlorothiazide
  • Structurally unrelated drugs e.g. metolazone
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9
Q

Is the diuresis produced by thiazide diuretics strong?

A

It is weaker than with loop diuretics, but this is usually sufficient for treatment.

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10
Q

How do loop diuretics work?

A

Inhibit the NKCC (Na/K/2Cl transporter) in the thick ascending limb of the loop of Henle.

Additional effects include that they are vasodilators of:

  • Systemic resistance arterioles -> Useful in lowering arterial pressure in hypertension and in reducing peripheral resistance in cardiac failure
  • Renal resistance arterioles -> Useful in increasing GFR and so potentially increasing diuresis
  • Vasa recta of the renal medulla -> Resulting in a “washout” of the accumulated osmotically active substances of the medullary interstitium, and so further reducing the osmotic potential there and increasing the potency of the diuresis
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11
Q

Give some examples of loop diuretics.

A

Furosemide

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12
Q

Compare the effects of loop and thiazide diuretics in terms of their effects on calcium.

A
  • Loop diuretics increase calcium excretion
  • Thiazide diuretics reduce calcium excretion -> This can be used in treatment of conditions such as stone formation in the urinary tract
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13
Q

What are some side effects of thiazide and loop diuretics?

A
  • Metabolic alkalosis and hypokalemia
  • Hypovolemia
  • Hypercalcaemia (thiazides) or hypocalcaemia (loop)
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14
Q

How do potassium-sparing diuretics work?

A

There are two main classes:

  • Aldosterone antagonists
  • Inhibitors of the epithelial Na+ channel in the collecting duct
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15
Q

What are some examples of potassium-sparing diuretics?

A
  • Aldosterone antagonists -> Spironolactone
  • Inhibitors of the epithelial Na+ channel in the collecting duct -> Amiloride
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16
Q

When are potassium-sparing diuretics used?

A

They are used when:

  • Aldosterone levels are too high in disease, such as:
    • Cardiac failure
    • Hypertension
  • Aldosterone levels are too high as a natural response to diuretic therapy (sinc aldosterone conserves water indirectly by conserving salt)
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17
Q

Why may aldosterone levels be raised in diuretic therapy?

A
  • Diuresis activates the juxtaglomerular apparatus, which releases renin and causes the production of aldosterone.
  • Potassium-sparing diuretics may be used in these cases.
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18
Q

Describe how the kidney adapts to diuretics.

A

During diuretic action:

  • Downstream nephron segments increase NaCl reabsorption as delivered NaCl load increases.

Post-diuretic NaCl retention (short term):

  • As diuretic concentrations in the tubule decline, Na+ retention increases until the next dose of diuretic is administered.

Chronic increase in Na+ retention (the ‘braking phenomenon’):

  • Ability to increase renal NaCl excretion declines over time. Due to both depletion of the extracellular fluid volume and structural (hyperplasia, hypertrophy) and functional (include increase in Na/K ATPase in basolateral membrane) changes in the kidney tubules.
19
Q

How do beta-blockers work in treating hypertension?

A
  • Block of β1-adrenergic receptors in the kidney, reducing renin release (remember that the juxtaglomerular cells receive sympathetic innervation)
  • May also have a CNS effect to reduce sympathetic outflow to the heart and reduce cardiac output
20
Q

What are some examples of beta-blockers used to treat hypertension?

A

‘Cardioselective’ β blockers -> e.g. Atenolol

21
Q

How do alpha-blockers work in treating hypertension?

A

They block alpha-1 receptors in the vasculature, causing vasodilation.

22
Q

What is the limitation of using alpha-blockers in treating hypertension?

A

Sympathetic innervation of the vasculature is important in everyday life, such as when standing up.

23
Q

What are some examples of alpha-blockers?

A
  • Prazosin
  • Terazosin
24
Q

How do potassium channel opener drugs work in treating hypertension?

A
  • They open KATP channels on smooth muscle cells in the arteries
  • This leads to hyperpolarisation and therefore vasodilation of the vessels
25
Q

What are some examples of potassium channel opener drugs?

A
  • Diazoxide
  • Minoxidil
  • Hydralazine (maybe)
26
Q

How do nitric oxide donors work in treating hypertension?

A
  • They are drugs that lead to the production or release of NO
  • This NO is responsible for the dilation of blood vessels, especially the venous system
27
Q

What are some example of nitric oxide donor drugs?

A

Nitroprusside

28
Q

How do ganglionic blockers work in treatment of hypertension?

A
  • They lead to decreased activity of post-ganglionic nerves
  • Therefore, in theory, they should reduce both sympathetic and parasympathetic activity
  • However, since arteries receive only sympathetic innervation, this means that vasodilation is favoured
29
Q

What are some examples of ganglionic blockers used in treating hypertension?

A

Pentamethonium (C5) and hexamethonium (C6) found to be selective, non-depolarising ganglion blockers.

30
Q

What are sympatholytic drugs and what are the main types?

A

Drugs that block the sympathetic nervous system at different points:

  • Peripheral sympatholytic drugs (e.g. alpha-adrenoceptor and beta-adrenoceptor antagonists) block the influence of noradrenaline at the effector organ
  • Ganglionic blockers block impulse transmission at the sympathetic ganglia
  • Centrally acting sympatholytic drugs block sympathetic activity within the brain
31
Q

How do centrally acting sympatholytic drugs work in treating hypertension?

A
  • They are agonists of α2-adrenoceptors primarily in the brainstem.
  • This reduces sympathetic outflow to the heart and vasculature.
32
Q

What are some examples of centrally acting sympatholytic drugs?

A
  • Clonidine
  • Methyldopa
33
Q

What are the three main classes of anti-hypertensive drugs that modulate the RAA axis that you need to know about?

A
  • ACE inhibitors
  • Angiotensin receptor blockers
  • Renin inhibitors
34
Q

What are some examples of ACE inhibitors?

A
  • Captopril was the first
  • Lisinopril, ramapril, enalapril, benazepril, cilazapril, fosinopril all have a slower onset of action that captopril
  • Some are pro-drugs converted in the body: ramipril to ramiprilat, enalapril to enalaprilat
35
Q

How do ACE inhibitors work?

A
  • Block conversion of angiotensin I to angiotensin II (so that aldosterone is also not secreted)
  • This reduce peripheral resistance (passive dilatation) and sodium retention.
  • No direct effect on the heart.
36
Q

Aside from hypertension, when are ACE inhibitors used?

A

They can also be used to treat congestive heart failure.

37
Q

What are some examples of angiotensin receptor blockers?

A

Losortan

38
Q

How do angiotensin receptor blockers work?

A
  • They block the AT1 receptors that bind angiotensin II.
  • Angiotensin II usually causes vasoconstriction and aldosterone release (which leads to salt retention).
39
Q

What are some examples of renin inhibitors?

A

Aliskerin

40
Q

How do renin inhibitors work?

A
  • They block the enzymatic activity of renin in converting angiotensinogen to angiotensin I.
  • Thus, they reduce peripheral resistance (passive dilatation) and sodium retention (thus reduce blood volume).
41
Q

What are the main classes of calcium-channel blocker?

A
42
Q

What are some examples of calcium channel blockers used to treat hypertension?

A
  • Dihydropyridine calcium channel blockers, a group that includes amlodipine, felodipine and lacidipine, are a common choice for treatment.
  • Verapamil (more cardiac-specific tbf)
43
Q

How do calcium channel blockers work as antihypertensive drugs?

A
  • Block calcium entry into cells
  • This prevent contraction of smooth muscles, which leads to vasodilation
  • They also inhibit cardiac contraction, which lowers cardiac ouput
  • In the kidney, the afferent arteriole appears to be more affected than the efferent, so that GFR is maintained despite the falling blood pressure

Sophie - Applied Physiology & Pharmacology Year 2 (32 decks)

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