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
2
Q
What organs might be damaged by high blood pressure?
A
- Heart
- Kidneys
- Brain
- Eyes
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
4
Q
What is hypertension defined as?
A
140/90mmHg
5
Q
What are the categories of hypertension causes?
A
- Primary (essential) hypertension
- Secondary hypertension
6
Q
What is primary hypertension?
A
High BP without any single evident cause
7
Q
What % of the hypertensive population have primary hypertension?
A
90%
8
Q
What is secondary hypertension?
A
High BP with discrete, identifiable underlying cause
9
Q
What % of the hypertensive population have secondary hypertension?
A
10%
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
11
Q
What is the optimal blood pressure?
A
<120/<80mmHg
12
Q
What is considered to be normal blood pressure?
A
<130/<85mmHg
13
Q
What is considered to be high normal blood pressure?
A
130-139/85-89mmHg
14
Q
What is considered to be grade 1 (mild) hypertension?
A
140-159/90-99mmHg
15
Q
What is considered to be grade 2 (moderate) hypertension?
A
160-179/100-109mmHg
16
Q
What is grade 3 (severe) hypertension?
A
>180/>110mmHg
17
Q
What is considered to be grade 1 isolated systolic hypertension?
A
140-159/<90mmHg
18
Q
What is considered to be grade 2 isolated systolic hypertension?
A
>160/<90mmHg
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
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
21
Q
What are ACE inhibitiors?
A
Competitive inhibitiors of angiotensin converting enyzme
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
23
Q
Give two examples of ACE inhibitors
A
- Lisinopril
- Ramipril
24
Q
What is the main side effect of ACE inhibitors?
A
Dry cough, which occurs in 10-15% of people
25
What are the important side effects of ACE inhibitors?
* Angio-oedema
* Renal failure
* Hyperkalaemia
26
In whom is angio-oedema caused by ACE inhibitors more common?
Black populations
27
Give two examples of angiotensin receptor blockers
* Lorsartan
* Valsartan
28
How do angiotensin receptor blockers work\>
They bind to the angiotensin AT1 receptor, and inhibit vasoconstriction and aldosterone stimulation caused by angiotensin II
29
What are the side effects of angiotensin receptor blockers?
*They are well tolerated, so few side effects, but important side effects are;*
* Renal failure
* Hyperkalaemia
30
What is the mechanism of action of calcium channel blockers?
They bind to specific alpha subunits of L-type calcium channels, reducing cellular calcium entry
31
What are the main groups of calcium channel blockers?
* Dihydropyridines
* Benzothiazepines
* Phenylalkylamines
32
Give two examples of dihydropyridines
* Nifedipine
* Amlodipine
33
Give an example of a benzothiazepine
Dilitiazem
34
Give an example of a phenylalkylamine
Verapamil
35
What vessels do calcium channel blockers cause vasodilation in?
Peripheral, coronary, and pulmonary arteries
## Footnote
*No significant effect in veins*
36
What effect on the heart rate do short acting dihydropyridines have?
Cause baroreflex mediated tachycardia
37
What effect does verapamil have on the heart?
Depresses SA node and slows AV conduction
38
What are the pharmacokinetic properties of dihydropyridine calcium channel blockers?
* Good oral absorption
* Protein bound \>90%
* Metabolised by liver
* Few have active metabolite
39
What are the adverse effects of dihydropyridine calcium channel blockers?
* Sympathetic nervous system activation, leading to tachycardia and palpitations
* Flushing
* Sweating
* Throbbing headaches
* Oedema
* Gingival hyperplasia
40
What are the actions of verapamil?
* 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
What are the adverse effects of verapamil?
* Constipation
* Risk of bradycardia
* Reduce myocardial contractility, which can worsen heart failure
42
What are the actions of dilitazem?
* 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
What are the adverse effects of dilitizem?
* Risk of bradycardia
* Can worsen heart failure
44
Give an example of a thiazide diuretic
Bendoflumethiazide
45
How do thiazide/thiazide like diuretics act in hypertension?
They reduce tubular sodium reabsorption and therefore reduce blood pressure
46
By what mechanisms to thiazide diuretics reduce blood pressure?
* Initially, cause total blood volume to decrease
* Later, cause total peripheral resistance to fall
47
Describe the dose-blood pressure response with thiazide diuretics
Flat
48
What are the adverse effects of bendoflumethiazide?
* 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
What is used in step 1 treatment of hypertension?
* 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
What is used in step 2 of hypertension treatment?
ACE inhibitor and calcium channel blocker, or ACE inhibitor and thiazide-type diuretic
51
What is used in step 3 of hypertension treatment?
ACE inhibitors, calcium-channel blockers, and thiazide type diuretics
52
What is used in step 4 of hypertension treatment?
Add further diuretic therapy, or an alpha blocker, or a beta-blocker, and consider seeking specialist advice
53
What are the indications for the use of thiazide diuretics in the treatment of hypertension?
* Elderly
* ISH
* Heart failure
54
What are the contraindiciations for the use of thiazide diuretics in treating hypertension?
Gout
55
What are the indications for the use of beta-blockers in the treatment of hypertension?
MI/angina
56
When should caution be taken when giving beta-blockers in the treatment of hypertension?
* Heart failure
* PVD
* Diabetes, *except with CHD*
57
What are the contraindications for treatment of hypertension with beta blockers?
* Asthma
* COPD
* Heart block
58
What are the indications for treatment of hypertension with CCB (dihydropyridines)?
* Elderly
* ISH
59
What are the indications for treatment of hypertension with CCB (rate limiting)?
Angina
60
When should caution be taken when treating hypertension with CCB (rate limiting)?
When in combination with beta-blockade
61
What are the contraindiciations for treatment of hypertension with CCB (rate limiting)?
* Heart block
* Heart failure
62
What are the indiciations for treatment of hypertension with ACE inhibitors?
* Heart failure
* LV dysfunction
* MI
* Type I diabetes
* Neuropathy
63
When should caution be taken when treating hypertension with ACE inhibitors?
* Renal impairment
* PVD
64
What are the contraindications for the treatment of hypertension with ACE inhibitors?
* Pregnancy
* Renovascular disease
* Hypertension
65
What are the indications for the treatment of hypertension with ARBs?
* ACE inhibitor intolerance
* Hypertension with LVH
* Type 2 DM
66
When should caution be taken when treating hypertension with ARBs?
* Renal impairment
* PVD
67
What are the indications for treatment of hypertension with alpha blockers?
Benign prostatic hyperplasia
68
When should caution be taken when treating hypertension with alpha blockers?
* Postural hypertension
* Heart failure
69
What are the contraindications for treatment of hypertension with alpha blockers?
Urinary incontinence
70
What are the types of adrenoceptor blockers that can act as anti-hypertensive drugs?
* Alpha
* Beta
71
Give an example of a direct renin inhibitor
Aliskirin
72
Give three examples of centrally acting anti-hypertensive agents?
* Methyl dopa
* Clonidine
* Moxonidine
73
Give three examples of vasodilator anti-hypertensives
* Hydralazine
* Minoxidil
* Sodium nitroprusside
74
What is the mechanism of action of alpha blockers?
Selective antagonists at post-synaptic alpha-1 adrenoceptors, antagonising the contractile effects of noradrenaline on vascular smooth muscle, reducing peripheral resistance
75
In what position do alpha blockers have more effect?
The upright position
76
Are alpha blockers safe in renal disease?
Yes
77
What are the adverse effects of alpha blockers?
* Postural hypotension
* Dizziness
* Headache and fatigue
* Oedema
78
Give three examples of beta-blockers
* Atenolol
* Bisoprolol
* Nebivolol
79
What are the effects of beta-blockers?
* Reduce heart rate and cardiac output
* Inhibit renin release
* *Initially TPR increases, but later falls to normal*
## Footnote
**
80
What are the adverse effects of beta-blockers?
* Lethargy, impaired concentration
* Reduced exercise tolerance
* Bradycardia
* Cold hands
* Impaired glucose tolerance
81
How does aliskiren work?
It binds to a pocket in the renin molecule, blocking cleavage of angiotensinogen to angiotensin I
82
What is the bioavailability of aliskiren?
2.6%
83
What is the half life of aliskiren?
40 hours (ranges from 25-45)
84
What is the advantage of the relatively long half life of aliskiren?
It supports once daily dosing
85
How long does a steady state of aliskiren take?
5-8 days
86
How is aliskiren eliminated?
* Mainly eliminated as unchanged compound in faeces (78%)
* Less than 1% renall excreted
87
Is aliskiren metabolised by the cytochrome P450 system?
No
88
When should caution be taken in administered aliskiren?
* 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
What initial dosage adjustment is required in elderly patients?
None
90
Where is aliskeren contraindicated?
Pregnancy
91
What significant drug interactions does aliskiren have?
Furosemide
92
What happens do methyldopa in the body?
It is converted to alpha-methyl-noradrenaline
93
What is the action of alpha-methyl-noradrenaline?
It is a potent alpha2-adrenoceptor agonist
94
What is the action of clonidine?
It is a direct pre-synaptic alpha-2 adrenoceptor agonist
95
What is moxonidine?
An I1 receptor agonist, which has some alpha2 agonist effect
96
What are the side effects of centrally acting anti-hypertensive agents?
* Tiredness/lethargy
* Depression
