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Pharmacology - Year 2 AC > Week 7 - Hypertension Treatments > Flashcards

Week 7 - Hypertension Treatments Flashcards

1
Q

Why treat hypertension?

A
  • major risk factor for stroke

- major risk factor for ischaemic heart disease - e.g. angina, MI

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2
Q

When is hypertension treated?

A

-sustained systolic BP of >160mmHg
OR
-sustained diastolic BP of >100mmHg

If known CV disease, diabetes or organ damage:
-sustained systolic 140-159mmHg
OR
-sustained diastolic BP of 90-99mmHg

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3
Q

What are the types of anti hypertensive drugs?

A

Diuretics

Vasodilators (calcium antagonists, a1-blockers, angiotensin antagonists)

B-blockers

ACE inhibitors

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4
Q

How is BP calculated?

A

BP = CO (cardiac output) X TPR (total peripheral resistance)

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5
Q

How can cardiac output be reduced?

A
  • HR
  • stroke volume
  • plasma volume
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6
Q

How can total peripheral resistance be reduced?

A

-dilating arterioles

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7
Q

What do diuretics do?

A
  • reduce plasma volume then gradually TPR

- act on the kidney to increase diuresis

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8
Q

What do vasodilators do?

A

Directly lower TPR

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9
Q

What do B-blockers do?

A

Reduce cardiac output and kidney renin secretion

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10
Q

What do ACE inhibitors do?

A

Inhibit endogenous vasoconstrictor production

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11
Q

What do a-blockers do?

A

Reduce TPR by inhibiting noradrenaline action

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12
Q

What do angiotensin antagonists do?

A

Reduce TPR by inhibiting angiotensin action

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13
Q

What are the actions of diuretics?

A
  • increase Na+ excretion (reduce salt reabsorption from glomerular filtrate)
  • water loss follows
  • reduce plasma volume
  • reduce cardiac output
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14
Q

What are the types of diuretics?

A
  • thiazide diuretics

- loop diuretics

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15
Q

Describe thiazide diuretics

A
  • moderately potent diuretics
  • reduce systolic and diastolic pressure
  • widely used antihypertensive, suitable for most patients
  • inhibit Na+, Cl- co-transport in distal tubule
  • additional vasodilator action
  • potentiate effects of other antihypertensives
  • increase renin release (may counteract effects on BP)
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16
Q

What is the mechanism of action of thiazide diuretics?

A

Inhibit Na+, Cl- co-transport in distal tubule

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17
Q

Name some examples of thiazide diuretics

A

Derived from benzothiadiazine:

  • chlorothiazide
  • hydrochlorothiazide
  • bendrofluazide

Thiazide like structure:

  • chlorthalidone
  • metolazone
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18
Q

What are the side effects of thiazides?

A

-more frequent urination
but
-high safety
-low profile of side effects

19
Q

Describe loop diuretics

A
  • very potent diuretics
  • no more effective than thiazides at reducing BP
  • reserved for use in patients with renal insufficiency, resistant hypertension or heart failure
20
Q

Name the different types of vasodilator drugs

A

Calcium antagonists (main type)

A1-blockers 
Angiotensin antagonists (both used but less often)

Potassium channel activators
Sodium nitroprusside
Hydralazine (others used in special circumstances)

21
Q

What is the action of vasodilators?

A
  • act directly on the smooth muscle cells of arteries and arterioles
  • lower the intracellular calcium concentration
  • cause muscle cell relaxation
  • results in vasodilation
22
Q

Name some caccium channel antagonists

A

Dihydropyridines

  • amlodipine
  • nicardipine
  • nifedipine

Benzothiazepine
-diltiazem

-verapamil

23
Q

What are calcium channel antagonists mechanism of action?

A

Block Ca2+ entry through voltage-operated calcium channels in arterial smooth muscle cells - vasodilation

24
Q

Describe how Dihydropyridines act

A

-highly selective for smooth muscle but affect most smooth muscle

  • nifedipine
  • amlodipine - longer acting (once daily dose)
  • nicardipine - some selectively for cerebral and coronary arteries
25
Q

Describe how benzothiazepines act

A
  • also block calcium channels in the conducting tissue of the heart
  • diltiazem - slows heart rate, potentiate a B-blocker action
26
Q

What are the side effects of calcium antagonists?

A

All:

  • flushing
  • ankle oedema

Diltiazem:

  • cardiac depression
  • interaction with B-blockers
27
Q

What is the mechanism of action of a1-blockers?

A
  • drugs used for hypertension are selective blockers of a1-adrenoceptors
  • prevent vasoconstrictor action of endogenous noradrenaline
28
Q

Name some examples of alpha receptor antagonists/a1-blockers

A
  • doxazosin - once daily
  • terazosin - once daily
  • prazosin - shorter acting, 3X daily
29
Q

What are the adverse effects of a1-blockers

A

-postural hypertension (dizziness, light headedness)
-possible severe hypotension after first dose
but
-generally well tolerated

30
Q

Name some examples of B-blockers

A
  • atenolol

- metoprolol

31
Q

What is the mechanism of action of B-blockers?

A
  • bind to and block B1-adrenoreceptors in the heart (sino atrial node and ventricular muscle)
  • block action of noradrenaline released from sympathetic nerves and circulating adrenaline
32
Q

What is the initial effect of B-blockers?

A
  • reduce rate and force of heart beat

- decrease cardiac output

33
Q

What is the effect of bB-blockers after continued treatment?

A
  • CO returns to normal but BP remains low

- TPR reset at lower level

34
Q

What are the adverse effects of B-blockers?

A

Common:

  • cold hands
  • fatigue

Less common but serious:

  • can provoke asthma attack in asthmatic
  • heart failure
  • conduction block in heart

Also:
-may affect blood lipids

35
Q

Name some examples of ACE inhibitors

A

Angiotensin-converting enzyme inhibitors

  • captopril - 2x daily dose
  • enalapril -single daily dose
  • lisinopril - lysine analogue of enalapril
  • ramipril
36
Q

What system do ACE inhibitors have an effect on?

A

Renin angiotensin system

Angiotensinogen–> (renin helps convert to) angiotensin I –> (angiotensin converting enzyme (ACE helps convert to)) angiotensin II –> vasoconstriction

37
Q

What is the mechanism of action of ACE inhibitors?

A

-prevent conversion of angiotensin I to angiotensin II (potent vasoconstrictor, stimulates aldosterone secretion - which inhibits salt and H2O excretion)

  • causes vasodilation
  • reduces plasma volume
38
Q

What are the adverse effects of ACE inhibitors?

A
  • dry cough
  • hypotension initially, especially if given with a diuretic
  • these effects usually wear off with time
39
Q

Name some angiotensin II receptor antagonists

A
  • losartan
  • candesartan
  • eprosartan
  • valsartan
40
Q

What is the mechanism of action of angiotensin II receptor antagonists?

A
  • block the action of angiotensin II (vasoconstriction) at its receptors
  • competes for binding to AT receptors
  • so vasodilation
41
Q

How and when are angiotensin II receptor antagonists used?

A
  • in combination with an ACE inhibitor (improved mortality and morbidity vs. ACE inhibitor alone)
  • alternative to ACE inhibitor in intolerant patients
42
Q

How are antihypertensive drugs chosen for patients?

A
  1. Thiazide diuretic
    - effective, safe history and few side effects
  2. If thiazide ineffective
    - add ACE inhibitor or calcium antagonist
  3. Until recently B-blockers were first line choice but now:
    - less effective at reducing risk of stroke
    - more side effects
43
Q

What is hypertension?

A

Blood pressure is above normal level

Pharmacology - Year 2 AC (14 decks)

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