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RBF > Dawes: Antihypertensive Drugs > Flashcards

Dawes: Antihypertensive Drugs Flashcards

1
Q

What is essential hypertension?

A

This is the level of BP above which treatment does more good than harm.

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2
Q

What is hypertension a risk for?

A

It is a major risk for stroke, coronary artery disease and renal disease. The risk of CVS death doubles for each 20mmHg systolic rise and 10mmHg of diastolic rise.

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3
Q

What is the problem with hypertension in the general population?

A

The prevalence of hypertension increases with age with over 50% of people aged 65 and above suffering from it. This is especially common in the developing world where it accounts for 80% of the CVS disease burden and 90% of the $50 billion of global expenditure on antihypertensives.

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4
Q

What is the problem with hypertension in the general population?

A

It is poorly diagnosed and treated with 30% of people being undiagnosed, 50% of patients being diagnosed but untreated and only 25% of patients on treatment actually being controlled.

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5
Q

What is the differing influence of hypertension on the absolute risk of stroke and MI?

A

As Systolic Blood Pressure increases the risk of stroke and myocardial infarction increase exponentially.

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6
Q

What is the differing influence of hypertension on the relative risk of stroke and MI?

A
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7
Q

Does treatment help?

A

10 mmHg systolic BP fall means that the risk of…

  • CVA falls 20%
  • MI falls 40%
  • Reduced Mortality
    • CVS death risk falls 25%
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8
Q

What is the treatment for hypertension?

A
  • Lifestyle Changes
    • Diet - Sodium < 80mmol/day = 5g NaCl
    • Weight loss (1kg roughly equates to 1mmHg)
    • Exercise
    • Reduce Alcohol
  • Drug Therapy
    • Polypharmacy (30% need 3 or more)
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9
Q

What is the problem with the treatment of hypertension?

A

It is a lifelong disease that results in concurrent diseases. There are perceived benefits of treatment but most people are asymptomatic.

The trouble with therapy is that it needs to be taken daily (adherence) and has side effects.

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10
Q

What is the target for hypertension treatment?

A

Blood Pressure below 140/90 normally

In young people or those with target organ damage like diabetes, renal damage, heart attacl then aim for closer to 130/80

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11
Q

What drugs are available for the treatment of hypertension?

A
  • ACEi and Angiotensin II antagonists
  • Beta-Blocker
  • Calcium Channel Blockers
  • Diuretics
    • Thiazide
    • Loop
    • Aldosterone Antagonists
  • Alpha Blockers
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12
Q

What ACEi are used in the treatment of hypertension?

A

Generally 1st line treatment

Cilazapril 1-5mg o.d. is used as it induces hypotension. it also leads to the development of a cough, angioedema and hyperkalemia.

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13
Q

What AII antagonists are used in the treatment of hypertension?

A

1st line for those with contraindications to ACEi

Candesartan 4-32mg o.d. as it induces hypotension and hyperkalemia.

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14
Q

What are the effects of Angiotensin II binding to Type 1 AII receptors?

A
  • Vasoconstriction
  • Increased Sympathetic Tone
  • Oxidant Stress
  • VSM hypertrophy
  • Vascular Fibrosis
  • Increased release of endothelin
  • Increased release of aldosterone
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15
Q

What is the effect of Angiotensin II binding to Type II AII Receptors?

A
  • Antiproliferation
  • Tissue Repair
  • Apoptosis
  • Vasodilation
  • Kidney Development
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16
Q

What are the contraindications of ACEi / Angiotensin Antagonists?

A
  • Bilateral Renovascular Disease
    • AII acts to maintains perfusion gradient and therefore ACEi/AII antagonists lead to marked hypotension.
    • Ultimately causes the deterioration of renal function.
  • Pregnancy
    • They cross the placenta and reduce renal development.
17
Q

What are the mechanisms of how beta-blockers reduce blood pressure?

A

It is unclear but it is thought that they act to reduce cardiac output, reset baroreceptors, inhibit renin, reduce sympathetic activity and reduce norepinephrine release from the presynaptic terminal.

18
Q

What are the side effects of beta-blockers?

A
  • Fatigue
  • Bradycardia
  • Negative Inotropy
  • Erectile Dysfunction
  • Wheeze/Asthma Exacerbation
  • Cold Peripheries
19
Q

What is the function of nifedipine?

A

A dihydropyridine that acts as an L-type calcium channel blocker on resistance vessels. As a result, it causes flushing, headaches and oedema.

20
Q

What is the function of verapamil?

A

It acts as an L-type calcium channel blocker that effects cardiac tissue and the GI tract. As a result, it can cause heart block, negative inotropy and constipation. (not used to lower BP)

21
Q

What is the mechanism of action for thiazide diuretics such as bendrofluazide or chlorthalidone?

A

It acts by inhibiting Na+/Cl- in DCT (we pee out salt)

It acts to reduce BP with subdiuretic doses

causes vasodilation as it opens vascular K+ channels (this is how they lower BP)

The effects of diuretics may take 12 weeks to start.

22
Q

How do thiazide diuretics work?

A

They act to inhibit renal tubular reabsorption resulting in a reduction of body salt and water. The mechanism of long-term blood pressure reduction still is not completely clear but is thought to be through their vasorelaxcation through K+ channels.

  • The RAAS system will actually counter the diuretic effects producxed by the low amount of drug given.
23
Q

What are the side effects of thiazide diuretics?

A
  • Metabolic
    • Increased glucose (reduce glucose tolerance)
    • Increased urate (reduced urate clearance) - think gout!
    • Decreased K+, Na+ and Mg2+
  • Diuresis (very rarely recognised)
  • Erectile Dysfunction
24
Q

What are the mechanisms behind the action of loop diuretics such as frusemide?

A

They act by inhibiting Na+/K+/Cl-cotransporters in the ascending Loop of Henle. These diuretics are potent and have little antihypertensive effects alone. As a result, they are used in severe/resistant hypertension and have a potent effect if used with ACEi (blocking the RAAS compensation)

Better for fluid overload

25
Q

What are the pharmacokinetics of frusemide?

A

These drugs are secreted in the proximal tubule and concentrated. They act on the ascending limb and effect the Na+/K+/2Cl- cotransporters on the luminal side.

26
Q

What are the pharmacodynamics of frusemide?

A

It has a steep dose-response curve and is the most effective diuretic.

27
Q

What are the side effects of loop diuretics?

A
  • Dehydration/polyuria
  • Metabolic
    • Reduced Na+, K+ and Mg2+
28
Q

What are the properties of spironolactone (K+-sparing diuretics)?

A

Spironolactone acts as aldosterone antagonist that inhibits the distal N+/K+ exchange in the collecting duct. Its use can lead to gynecomastia, hyperkalemia and dehydration.

Has a role in people with resistant hypertension but due to causing retaining of K+ can lead to Hyperkalaemia.

29
Q

How do alpha-1 blockers such as doxazosin reduce hypertension?

A

Blocks tonic sympathetic activity on resistance vessels.

30
Q

What are the properties of doxazosin?

A

It is a reversible alpha blocker that acts as a vasodilator, reduces prostatic symptoms and can cause postural hypotension. As a result, it is taken once daily and patients need to be started on a low dose and titrated.

31
Q

What are the miscellaneous antihypertensive drugs used?

A
  • Vasodilators such as minoxidil (K+ channel opener)- makes you very hairy! and Hydralazine.
  • Centrally acting that act to reduce sympathetic tone such as methyldopa, clonidine and minoxidine.
32
Q

When do you start to use drugs to treat hypertension?

A
  • persistent BP > 160/100
  • BP > 140/90 + Target Organ Damage/Comorbities
    • 10 year CVS risk > 20%
33
Q

How do doctors decide which antihypertensive drugs to prescribe?

A

Young person whose hypertension is often defined by increased renin activity should take an ACEi or a Beta Blocker as 1st line

An older person who has hypertension independent of renin should take a Ca Channel blocker or Diuretic

2nd line is swapping over to one of the other class not already used

ACEi, vasodilator and diuretic (eg. cilazapril, felodipine and bendrofluazide)

34
Q

What are the sensible drug prescriptions?

A
35
Q

What is special about pregnancy and hypertension?

A

There are both maternal and fetal complications and it is defined as a BP > 140/90 mmHg

36
Q

When should beta-blockers be used?

A

Usually, 2nd/3rd line in hypertension but should be used if patient has MI, CCF and/or AF.

37
Q

What is the polypill?

A

This is a pill that combines all four drugs that target hypertension at levels lower than what causes side effects. As a result, they all combine in their little amounts to achieve reduced BP.

  • There are thoughts being put forward that these should be prescribed to everyone over a certain age to reduce the prevalence of MI, CCF and AF.

RBF (32 decks)

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