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ESA 5 - Pharmacology > Treatment of Hypertension > Flashcards

Treatment of Hypertension Flashcards

1
Q

How is blood pressure physiologically controlled?

A
  • Autonomic nervous system
  • Renin-angiotensin system
  • Bradykinin
  • Endothelin
  • Nitric oxide
  • Atrial natriuretic peptide
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2
Q

What organs might be damaged by high blood pressure?

A
  • Heart
  • Kidneys
  • Brain
  • Eyes
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3
Q

How does high blood pressure lead to organ damage?

A

Increased arterial thinking caused by smooth muscle cell hypertrophy and accumulation of vascular matrix causes loss of arterial compliance, and thus organ damage

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4
Q

What is hypertension defined as?

A

140/90mmHg

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5
Q

What are the categories of hypertension causes?

A
  • Primary (essential) hypertension
  • Secondary hypertension
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6
Q

What is primary hypertension?

A

High BP without any single evident cause

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7
Q

What % of the hypertensive population have primary hypertension?

A

90%

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8
Q

What is secondary hypertension?

A

High BP with discrete, identifiable underlying cause

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9
Q

What % of the hypertensive population have secondary hypertension?

A

10%

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10
Q

How should hypertension be treated?

A
  • Identify and treat underlying cause if present
  • Identify and treat other cardiovascular risk factors or co-morbidities
  • Lifestyle advice and non-pharmacological therapy
  • Pharmacological therapy
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11
Q

What is the optimal blood pressure?

A

<120/<80mmHg

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12
Q

What is considered to be normal blood pressure?

A

<130/<85mmHg

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13
Q

What is considered to be high normal blood pressure?

A

130-139/85-89mmHg

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14
Q

What is considered to be grade 1 (mild) hypertension?

A

140-159/90-99mmHg

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15
Q

What is considered to be grade 2 (moderate) hypertension?

A

160-179/100-109mmHg

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16
Q

What is grade 3 (severe) hypertension?

A

>180/>110mmHg

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17
Q

What is considered to be grade 1 isolated systolic hypertension?

A

140-159/<90mmHg

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18
Q

What is considered to be grade 2 isolated systolic hypertension?

A

>160/<90mmHg

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19
Q

What lifestyle therapy can be used in hypertension?

A
  • Patient education
  • Maintain normal body weight
  • Reduce salt intake to <6g/day
  • Limit alcohol consumption to <3units/day for men, <2units per day for women
  • Engage in regular aerobic physical exercise for >30min/day
  • Consume >5 portions of fresh fruit/veg daily
  • Reduse intake of total and saturated fat
  • Smoking cessation
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20
Q

What are the first line pharmacological therapies in the treatment of hypertension?

A
  • Angiotensin Converting Enzyme (ACE) inhibitiors/angiotensin receptor blockers
  • Calcium channel blockers
  • Diuretics
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21
Q

What are ACE inhibitiors?

A

Competitive inhibitiors of angiotensin converting enyzme

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22
Q

What are the effects of ACE inhibitors?

A
  • They reduce the formation of angiotensin II
  • Cause arteriolar vasodilation, with some venodilation
  • Circulating aldosterone reduced
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23
Q

Give two examples of ACE inhibitors

A
  • Lisinopril
  • Ramipril
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24
Q

What is the main side effect of ACE inhibitors?

A

Dry cough, which occurs in 10-15% of people

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25
Q

What are the important side effects of ACE inhibitors?

A
  • Angio-oedema
  • Renal failure
  • Hyperkalaemia
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26
Q

In whom is angio-oedema caused by ACE inhibitors more common?

A

Black populations

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27
Q

Give two examples of angiotensin receptor blockers

A
  • Lorsartan
  • Valsartan
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28
Q

How do angiotensin receptor blockers work>

A

They bind to the angiotensin AT1 receptor, and inhibit vasoconstriction and aldosterone stimulation caused by angiotensin II

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29
Q

What are the side effects of angiotensin receptor blockers?

A

They are well tolerated, so few side effects, but important side effects are;

  • Renal failure
  • Hyperkalaemia
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30
Q

What is the mechanism of action of calcium channel blockers?

A

They bind to specific alpha subunits of L-type calcium channels, reducing cellular calcium entry

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31
Q

What are the main groups of calcium channel blockers?

A
  • Dihydropyridines
  • Benzothiazepines
  • Phenylalkylamines
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32
Q

Give two examples of dihydropyridines

A
  • Nifedipine
  • Amlodipine
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33
Q

Give an example of a benzothiazepine

A

Dilitiazem

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34
Q

Give an example of a phenylalkylamine

A

Verapamil

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35
Q

What vessels do calcium channel blockers cause vasodilation in?

A

Peripheral, coronary, and pulmonary arteries

No significant effect in veins

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36
Q

What effect on the heart rate do short acting dihydropyridines have?

A

Cause baroreflex mediated tachycardia

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37
Q

What effect does verapamil have on the heart?

A

Depresses SA node and slows AV conduction

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38
Q

What are the pharmacokinetic properties of dihydropyridine calcium channel blockers?

A
  • Good oral absorption
  • Protein bound >90%
  • Metabolised by liver
  • Few have active metabolite
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39
Q

What are the adverse effects of dihydropyridine calcium channel blockers?

A
  • Sympathetic nervous system activation, leading to tachycardia and palpitations
  • Flushing
  • Sweating
  • Throbbing headaches
  • Oedema
  • Gingival hyperplasia
40
Q

What are the actions of verapamil?

A
  • Impedes calcium transport across the myocardial and vascular smooth muscle cell membrane
  • Prolongs the action potential/effective refractory period, therefore acts as a class IV anti-arrythmic agent
  • Cause peripheral vasodilation and a reduction in cardiac preload and myocardial contractility
41
Q

What are the adverse effects of verapamil?

A
  • Constipation
  • Risk of bradycardia
  • Reduce myocardial contractility, which can worsen heart failure
42
Q

What are the actions of dilitazem?

A
  • Impedes calcium transport across the myocardial and vascular smooth muscle cell membrane
  • Prolongs the action potential/effective refractory period
  • Peripheral vasodilation, and a reduction in cardiac preload and myocardial contractility
43
Q

What are the adverse effects of dilitizem?

A
  • Risk of bradycardia
  • Can worsen heart failure
44
Q

Give an example of a thiazide diuretic

A

Bendoflumethiazide

45
Q

How do thiazide/thiazide like diuretics act in hypertension?

A

They reduce tubular sodium reabsorption and therefore reduce blood pressure

46
Q

By what mechanisms to thiazide diuretics reduce blood pressure?

A
  • Initially, cause total blood volume to decrease
  • Later, cause total peripheral resistance to fall
47
Q

Describe the dose-blood pressure response with thiazide diuretics

A

Flat

48
Q

What are the adverse effects of bendoflumethiazide?

A
  • Hypokalaemia
  • Increased urea and uric acid levels
  • Impaired glucose tolerance, especially with beta blockers
  • Increase in cholesterol and triglyceride levels
  • Actives renin-angiotensin system
49
Q

What is used in step 1 treatment of hypertension?

A
  • In patients younger than 55 years, ACE inhibitors, or angiotensin-II receptor antagonist if ACE intolerant
  • In patients 55 years or older, or black patients of any age, use calcium-channel blocker or thiazide-type diuretic
50
Q

What is used in step 2 of hypertension treatment?

A

ACE inhibitor and calcium channel blocker, or ACE inhibitor and thiazide-type diuretic

51
Q

What is used in step 3 of hypertension treatment?

A

ACE inhibitors, calcium-channel blockers, and thiazide type diuretics

52
Q

What is used in step 4 of hypertension treatment?

A

Add further diuretic therapy, or an alpha blocker, or a beta-blocker, and consider seeking specialist advice

53
Q

What are the indications for the use of thiazide diuretics in the treatment of hypertension?

A
  • Elderly
  • ISH
  • Heart failure
54
Q

What are the contraindiciations for the use of thiazide diuretics in treating hypertension?

A

Gout

55
Q

What are the indications for the use of beta-blockers in the treatment of hypertension?

A

MI/angina

56
Q

When should caution be taken when giving beta-blockers in the treatment of hypertension?

A
  • Heart failure
  • PVD
  • Diabetes, except with CHD
57
Q

What are the contraindications for treatment of hypertension with beta blockers?

A
  • Asthma
  • COPD
  • Heart block
58
Q

What are the indications for treatment of hypertension with CCB (dihydropyridines)?

A
  • Elderly
  • ISH
59
Q

What are the indications for treatment of hypertension with CCB (rate limiting)?

A

Angina

60
Q

When should caution be taken when treating hypertension with CCB (rate limiting)?

A

When in combination with beta-blockade

61
Q

What are the contraindiciations for treatment of hypertension with CCB (rate limiting)?

A
  • Heart block
  • Heart failure
62
Q

What are the indiciations for treatment of hypertension with ACE inhibitors?

A
  • Heart failure
  • LV dysfunction
  • MI
  • Type I diabetes
  • Neuropathy
63
Q

When should caution be taken when treating hypertension with ACE inhibitors?

A
  • Renal impairment
  • PVD
64
Q

What are the contraindications for the treatment of hypertension with ACE inhibitors?

A
  • Pregnancy
  • Renovascular disease
  • Hypertension
65
Q

What are the indications for the treatment of hypertension with ARBs?

A
  • ACE inhibitor intolerance
  • Hypertension with LVH
  • Type 2 DM
66
Q

When should caution be taken when treating hypertension with ARBs?

A
  • Renal impairment
  • PVD
67
Q

What are the indications for treatment of hypertension with alpha blockers?

A

Benign prostatic hyperplasia

68
Q

When should caution be taken when treating hypertension with alpha blockers?

A
  • Postural hypertension
  • Heart failure
69
Q

What are the contraindications for treatment of hypertension with alpha blockers?

A

Urinary incontinence

70
Q

What are the types of adrenoceptor blockers that can act as anti-hypertensive drugs?

A
  • Alpha
  • Beta
71
Q

Give an example of a direct renin inhibitor

A

Aliskirin

72
Q

Give three examples of centrally acting anti-hypertensive agents?

A
  • Methyl dopa
  • Clonidine
  • Moxonidine
73
Q

Give three examples of vasodilator anti-hypertensives

A
  • Hydralazine
  • Minoxidil
  • Sodium nitroprusside
74
Q

What is the mechanism of action of alpha blockers?

A

Selective antagonists at post-synaptic alpha-1 adrenoceptors, antagonising the contractile effects of noradrenaline on vascular smooth muscle, reducing peripheral resistance

75
Q

In what position do alpha blockers have more effect?

A

The upright position

76
Q

Are alpha blockers safe in renal disease?

A

Yes

77
Q

What are the adverse effects of alpha blockers?

A
  • Postural hypotension
  • Dizziness
  • Headache and fatigue
  • Oedema
78
Q

Give three examples of beta-blockers

A
  • Atenolol
  • Bisoprolol
  • Nebivolol
79
Q

What are the effects of beta-blockers?

A
  • Reduce heart rate and cardiac output
  • Inhibit renin release
  • Initially TPR increases, but later falls to normal

​

80
Q

What are the adverse effects of beta-blockers?

A
  • Lethargy, impaired concentration
  • Reduced exercise tolerance
  • Bradycardia
  • Cold hands
  • Impaired glucose tolerance
81
Q

How does aliskiren work?

A

It binds to a pocket in the renin molecule, blocking cleavage of angiotensinogen to angiotensin I

82
Q

What is the bioavailability of aliskiren?

A

2.6%

83
Q

What is the half life of aliskiren?

A

40 hours (ranges from 25-45)

84
Q

What is the advantage of the relatively long half life of aliskiren?

A

It supports once daily dosing

85
Q

How long does a steady state of aliskiren take?

A

5-8 days

86
Q

How is aliskiren eliminated?

A
  • Mainly eliminated as unchanged compound in faeces (78%)
  • Less than 1% renall excreted
87
Q

Is aliskiren metabolised by the cytochrome P450 system?

A

No

88
Q

When should caution be taken in administered aliskiren?

A
  • Patients at risk of hyperkalaemia
  • Patients at risk of sodium depletion
  • Patients at risk of volume depletion
  • Heart failure
  • Severe renal impairment
  • Renal stenosis
89
Q

What initial dosage adjustment is required in elderly patients?

A

None

90
Q

Where is aliskeren contraindicated?

A

Pregnancy

91
Q

What significant drug interactions does aliskiren have?

A

Furosemide

92
Q

What happens do methyldopa in the body?

A

It is converted to alpha-methyl-noradrenaline

93
Q

What is the action of alpha-methyl-noradrenaline?

A

It is a potent alpha2-adrenoceptor agonist

94
Q

What is the action of clonidine?

A

It is a direct pre-synaptic alpha-2 adrenoceptor agonist

95
Q

What is moxonidine?

A

An I1 receptor agonist, which has some alpha2 agonist effect

96
Q

What are the side effects of centrally acting anti-hypertensive agents?

A
  • Tiredness/lethargy
  • Depression

ESA 5 - Pharmacology (28 decks)

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