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Pharmacology B > Lecture 1 - Antihypertensives > Flashcards

Lecture 1 - Antihypertensives Flashcards

1
Q

List some thiazide diuretics

A

hycrochlorothiazide

chlorthalidone

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2
Q

List some loop diuretics

A

furosemide

ethacrynic acid

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3
Q

List a potassium sparing diuretic

A

spironolactone

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4
Q

List some ACEi’s

A

enalapril

fosinopril

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5
Q

List some ARB’s

A

losartan

candesartan

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6
Q

List some vascular CCB’s (calcium channel blockers)

A

nifedipine - long-acting

amlodipine

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7
Q

List some cardiac CCB’s (calcium channel blockers)

A

verapamil

diltiazem

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8
Q

List some B blockers

A

propranolol

metoprolol

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9
Q

List some alpha 1 receptor antagonists

A

prazosin

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10
Q

List some alpha 2 receptor agonists

A

clonidine

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11
Q

List some vasodilators

A

hydralazine
minoxidil
nitroprusside

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12
Q

What is the formula for BP?

A

BP = CO x TPR

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13
Q

What does CO (cardiac output) depend on?

A
  • venous return
    • venous tone
    • blood volume
  • heart rate
  • contractility
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14
Q

What does TPR (total peripheral resistance) depend on?

A
  • resistance vessel diameter

- arterial tone

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15
Q

What are chronic increases in BP usually due to?

A

normally due to increased arterial resistance

-total peripheral resistance (TPR)

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16
Q

90% is ______ hypertension

A

essential

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17
Q

10% has a _______ cause

A

definable

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18
Q

What OTC & Rx drugs can cause hypertension?

A
  • estrogens (oral contraceptives)
  • NSAIDs
  • antidepressants, cyclosporin, amphetamines (stimulants)
  • decreased compliance
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19
Q

What conditions can cause hypertension?

A
  • renal artery stenosis (renovascular hypertension)
  • coarctation of the aorta
  • phaeochromocytoma (catecholamine secreting tumor), primary hyperaldosteronism
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20
Q

What are the three major compensatory responses to a decrease in blood pressure?

A

1) Decreases RPP (renal profusion pressure)
Increase sodium retention

2) RAAS
Aldosterone

3) SNA (sympathetic nervous activity)
norepinephrine

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21
Q

List some potential causes of a drop in BP?

A
  • hypovolemia (hemorrhage, dehydration)
  • postural (orthostatic hypotension)
  • heart failure
  • antihypertensive
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22
Q

What does an increase in SNA do to raise BP??

A

increase HR
increase ionotropy (muscle contraction)
increase venous preload

*All 3 increase CO

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23
Q

What does an increase in RAAS do?

A 
increase venous preload
-leads to increased CO
increase arterial afterload
-leads to increased TPR
increase sodium retention in the kidney
-leads to increased blood volume
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24
Q

Non-pharms for hypertension?

A
  • sodium restriction
  • weight loss
  • exercise
  • reduced alcohol intake
  • smoking cessation
  • relaxation
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25
Q

List the 1st line pharmacological treatments for hypertension

A
  • ACEi’s, ARB’s
  • diuretics
  • CCB (calcium channel blocker)
  • B blocker (but not in uncomplicated hypertension)
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26
Q

List the other pharmacological treatments for hypertension

A
  • alpha 1 antagonist
  • alpha 2 agonist
  • vasodilator
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27
Q

____ used to be first line single therapy in uncomplicated hypertension (but this is changing now!)

A

thiazides

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28
Q

Thiazides:

Dose response for blood pressure lowering is relatively ____

A

flat

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29
Q

Thiazides:

Increasing dose produces little ______ in effect

A

improvement

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30
Q

Thiazides:

What complications can increase with dose?

A 
hypokalemia
glucose intolerance
increased LDL (low density lipoprotein)
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31
Q

Loop diuretics:

Useful in ____ impairment and edematous states

A

renal

GFR < 50 mL/min

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32
Q

Loop diuretics:

Greater diuretic but weaker ______

A

antihypertensive

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33
Q

Loop diuretics:

Extreme _____ imbalance possible

A

electrolyte

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34
Q

Loop diuretics:

____ onset and _____ acting

A

fast

short

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35
Q

Loop diuretics:

Are they a good choice for long term treatment?

A

No

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36
Q

Potassium sparing diuretics:

Useful with ____ to decrease potassium loss

A

thiazides

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37
Q

Potassium sparing diuretics:

Are effective when increased BP due to ??

A

mineralocorticoid excess

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38
Q

Major problem with thiazides and loop diuretics?

A

electrolyte problems

  • hypokalemia
  • hypercalcemia (thiazides)
  • hypocalcemia (loop)
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39
Q

Problems with thiazide diuretics?

A
  • decreased insulin release (hyperglycemia)
  • increased LDL levels (bad)
  • increased incidence of erectile dysfunction
  • vascular volume contraction (decrease blood volume)
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40
Q

Problems with loop diuretics?

A
  • deafness (if given with aminoglycoside antibiotic)

- vascular volume contraction (decreased blood volume)

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41
Q

Problems with potassium sparing diuretics?

A
  • hyperkalemia

- estrogenic effects - gynecomastia, impotence

42
Q

Where do thiazide and loop diuretics work?

A

they decrease sodium retention in the kidney

43
Q

What are the 2 renin angiotensin system inhibitors?

A

ACEi’s

ARB’s

44
Q

MOA of ACEi’s

A
  • decrease AII levels (angiotensin 2)
  • decrease TPR
  • decrease aldosterone
  • increase in plasma potassium
45
Q

MOA of ARBs

A
  • blocks AII receptors (angiotensin 2)
  • decrease TPR
  • decrease aldosterone
  • increase in plasma potassium
46
Q

List some points about renin angiotensin system inhibitors (ACEi’s and ARBs)

A
  • effective even with low renin levels
  • metabolically neutral (glucose, lipids not altered)
  • first line in hypertension, CHF and or diabetic nephropathy
  • little or no reflex increase in cardiac output
  • possible problems
    • rash, cough (ACEi’s), hyperkalemia, proteinuria, angioedema
47
Q

What is currently the first line single therapy in uncomplicated hypertension?

A

renin angiotensin system inhibitors (ACEi’s and ARBs)

48
Q

ACEi’s and ARBs are _____ in benefits and side effects

A

similar

49
Q

When do you recommend renin angiotensin system inhibitors ?

A
  • heart failure
  • left ventricle dysfunction
  • post myocardial infarction
  • diabetes
  • systolic dysfunction
  • proteinuria (chronic kidney disease)

*suggested these agents may have benefits in addition to their blood pressure lowering

50
Q

Renin Angiotensin System Inhibitors (ACEi’s and ARBs):

____ reflex tachycardia

A

little

  • baroreceptors reset
  • decrease in NE release
51
Q

Renin Angiotensin System Inhibitors (ACEi’s and ARBs):

Contraindicated in _______

A

pregnancy

52
Q

List the medications involved in CHF

A

ACEi, B-Blocker, diuretic, digitalis:

  • low plasma potassium increases digitalis toxicity
  • increased aldosterone may decrease Pk
  • diuretic may decrease Pk
  • ACEi and B-blocker may increase Pk

*Pk = plasma potassium

53
Q

Where do ACEi work?

A
  • inhibit angiotensin converting enzyme
  • decrease RAAS (because ACEi’s are renin angiotensin aldosterone system inhibitors)
  • decrease sodium retention
  • decrease arterial afterload
  • decrease venous preload
54
Q

Describe calcium channel blockers

A

Block L-type calcium channels - but really two sub-classes:

  • one predominately vascular
  • one predominately cardiac
55
Q

Vascular calcium channel blockers are known as ________

A

dihydropyridines

56
Q

Give examples of vascular calcium channel blockers (dihydropyridines)

A

amlodipine

nifedipine

57
Q

Give examples of vascular and cardiac (non-dihydropyridines)

A

verapamil

diltiazem

58
Q

Dihydropyridines (nifedipine and amlodipine):

Describe them

A
  • greater affinity for vascular calcium channels
  • used for angina, Raynauds and hypertension
  • reduce TPR without apparent cardiac actions
  • diuretics may block nifedipine effects on BP
  • used for hypertensive crisis
59
Q

What are non-dihydropyridines used for?

A

used in hypertension if also concern about heart rate control in atrial fibrillation or in patients with angina

60
Q

Describe diltiazem

A
  • used to treat angina and hypertension

- both vascular and cardiac effects

61
Q

Describe verapamil

A
  • blocks mainly in the heart (limited vascular tissue)
  • should not be combined with a beta blocker (both drug classes block AV node)
  • contraindicated in heart failure
62
Q

Why can’t you combine Verapamil with a beta blocker?

A

it will slow the heart way too much since both drug classes block AV node (both drugs decrease HR)

63
Q

____ _____ blockers are another first line single therapy in uncomplicated hypertension

A

calcium channel

64
Q

When are calcium channel blockers useful?

A

Where beta blockers are contraindicated

65
Q

Calcium channel blockers are not contraindicated in ??

A

obstructive airway diseases
or
diabetes

66
Q

Why are calcium channel blockers useful in african americans?

A

Because they are resistant to ACEi

67
Q

List some more points about calcium channel blocker?

A
  • low incidence of side effects - but expensive

- neutral metabolic profile

68
Q

Calcium channel blockers:

What are the adverse effects related to?

A

Vasodilation

69
Q

Calcium channel blockers:

adverse effects?

A

headache
flushing
edema
constipation

70
Q

Calcium channel blockers can be used in the presence of what other coexisting conditions?

A
  • angina pectoris
  • Raynaud’s phenomenon
  • asthma or COPD
71
Q

Where do dihydropyridines work?

A

-decrease arterial afterload

72
Q

Where do non-dihydropyridines work?

A
  • decrease ionotropy (muscle contraction)

- decrease HR

73
Q

Propranolol and metoprolol are ??

A

beta-blockers

74
Q

MOA for beta blockers

A

unknown but they work

75
Q

Are beta-blockers recommended as single therapy?

A

No

  • good as a second drug to block reflex activation of the heart by SNS
  • not recommended as single therapy in uncomplicated hypertension
  • given for hypertension when concomitant diseases also benefit
  • post-MI
  • heart failure
76
Q

Problems with beta blockers?

A
  • NOT metabolically neutral - may increase TGs/decrease HDLs
  • avoid sudden withdrawal
  • increased incidence of ED
  • increased incidence of type 2 diabetes
  • doesn’t protect against stroke
77
Q

When would you avoid beta blockers?

A

asthma, COPD, peripheral vascular disease, insulin dependent diabetes (use with caution)

78
Q

When are beta blockers a good choice?

A

In patients with:

  • glaucoma
  • supraventricular arrhythmia
  • heart failure (ALWAYS)
  • MI
  • angina
79
Q

Where do beta blockers work?

A
  • decrease RAAS
  • decrease isotropy
  • decrease HR
80
Q

Prazosin is an _______

A

alpha 1 antagonist

81
Q

Prazosin:

Not effect as a single agent for chronic _______

A

hypertension

82
Q

What does prazosin do?

A
  • vasodilates arteries and veins

- decreases insulin resistance (good)

83
Q

Where is prazosin useful?

A

in BPH (benign prostatic hyperplasia)

84
Q

Prazosin:

Shown to decrease nightmares in _____

A

PTSD

85
Q

Problems with prazosin?

A
  • fluid retention with long-term treatment (give with a diuretic)
  • first dose effect (initial large drop in BP)
  • orthostatic hypotension
86
Q

Where does an alpha 1 blocker work?

A

-decreases arterial afterload therefore decreases TPR

87
Q

Clonidine is an ________

A

alpha 2 agonist

88
Q

Describe clonidine

A
  • acts on central vasomotor centers
  • decreases sympathetic nerve activity from CNS
  • autonomic system remains intact - reflexes intact
  • orthostasis rare
  • give as two unequal doses (high dose at night to cause sedation)
  • limited use due to sedation and dry mouth
  • rebound hypertension upon rapid cessation of drug
89
Q

Where do alpha 2 agonists work?

A

decrease SNA (sympathetic nerve activity)

  • decrease arterial afterload
  • decrease venous preload
  • increase isotropy
  • increase HR
90
Q

Are vasodilators used alone for chronic blood pressure lowering?

A

No

91
Q

What is an example of a vasodilator?

A

hydralazine
minoxidil
sodium nitroprusside

92
Q

Describe hydralazine?

A
  • greater arteriolar effect
  • give with B-blocker and diuretic
  • can be used in pregnancy (safe and works)
93
Q

Problems with hydralazine?

A
  • may cause lupus like syndrome
  • may increase SNA - myocardial stimulation
  • headache, flushing nausea, hypotension, tachycardia, angina pectoris
94
Q

Describe Minoxidil (vasodilator)

A
  • arteriolar dilator
  • give with B blocker and diuretic
  • for severe hypertension (refractory)
  • may cause pericardial effusion
  • hirsutism (growth of unwanted male pattern hair in women) - problem?
  • *this drug is now marketed for male pattern baldness
  • problems similar to hydralazine
95
Q

Describe sodium nitroprusside

A
  • venous and arteriolar dilator
  • rapid onset (1 min)
  • rapid offset (5 min)
  • blood pressure titratable
  • for hypertensive encephalopathy
  • potential for cyanide toxicity
  • If it used for more than a day or two, cyanide toxicity is a worry
96
Q

Where do arterial vasodilators work?

A

decrease arterial afterload

97
Q

Where do venous vasodilators work?

A

decrease venous preload

98
Q

Where do arterial and venous vasodilators work?

A
  • decrease arterial afterload

- decrease venous preload

99
Q

Target BP for patients below 80 years of age if uncomplicated

A

140/90 mmHg or less

100
Q

If patient has other conditions like atherosclerotic cardiovascular disease, diabetes mellitus, chronic kidney disease (proteinuria) it is better if target BP is ??

A

below 140/90

101
Q

What do younger patients respond best to?

A

ACEi, ARB or B blockers

*But B blockers may be inferior to protect from stroke

102
Q

What do black patients and elderly patients respond best to?

A
  • respond best to thiazide diuretics or long-acting CCB

- however, patients may have other indications (heart failure, post-MI) suggesting need for ACEi or ARB

Pharmacology B (21 decks)

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