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Pharmacology > Unit 2: Drugs Used in Hypertension > Flashcards

Unit 2: Drugs Used in Hypertension Flashcards

0
Q

Diuretics: Classification

A

Thiazide Diuretics
Loop (high-ceiling) diuretics
Potassium-sparing diuretics

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1
Q

Diuretics

A

Action: Deplete sodium stores
Effect: Lowers BP during rest, exercise, regardless of posture; prevents sodium retention; reduces plasma and extracellular fluid volume; decrease peripheral resistance; enhances effects of other hypotensive drugs and takes care of the compensatory effect; well tolerated;

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2
Q

Thiazide diuretics

A

Initial drug of choice for hypertension

Cheap

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3
Q

Thiazide Diuretics: Drugs

A

Hydrochlorothiazide

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4
Q

Hydrochlorothiazide: Mechanism

A

Mechanism: Reduces blood volume; reduces arterial peripheral resistance; some have direct vasodilating effects

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5
Q

Thiazide Toxicities

A

Hypokalemia
Dehydration, hyperglycemia, hyperuricemia
Increase levels of LDL cholesterol, total cholesterol and TG

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6
Q

Thiazide contraindications

A

Ineffective when GFR is low

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7
Q

Loop (high-ceiling) diuretics: Drugs

A

Furosemide, ethacrynic acid, bumetanide, torsemide

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8
Q

Loop (High-ceiling) diuretics: Diuresis

A

Produce much greater diuresis than thiazides

Reserved for patients with a low GFR

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9
Q

Loop (high-ceiling) diuretics: adverse effects

A

Dehydration, hyperglycemia, hyperuricemia

Hearing-loss

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10
Q

Potassium sparing diuretics: Drugs

A

Spironolactone
Triamterene
Amiloride

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11
Q

Potassium-Sparing Diuretics: Features

A 
Poor diuresis (modest hypotensive effect)
Conserves K (combination with thiazides)
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12
Q

Potassium-Sparing Diuretics: Toxicity

A

Hyperkalemia

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13
Q

Potassium-Sparing Diuretics: C/I

A

K supplements
ACE inhibitorso
angiotensin II receptor blockers

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14
Q

Sympatholytics: Sites of Action

A

Decrease outflow of SNS activity from the brain
Antagonism of alpha or beta adrenergic receptors
Availability of neurotransmitter released from adrenergic neurons
Blockade of SNS neurotransmission at the level of autonomic ganglia

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15
Q

Centrally acting sympatholytics: Drugs

A

Methyldopa

Clonidine

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16
Q

Methyldopa: MOA

A

Decreases SNS outflow from brainstem
Must first be converted (metabolite)
- Alpha-methyl norepinephrine

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17
Q

Methyldopa: Therapeutic Use

A

Treatment of essential hypertension

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18
Q

Methyldopa: Side Effects and Toxicity

A

Bradycardia, diarrhea, failure of ejaculation
Edema
Postural hypotension but less than with reserpine or other; reduces BP in supine and standing position
- Venous pooling
Effects on the dopaminergic system (sedation, drowsiness, vertigo, EPS)
Lactation
Dry mouth and decrease in saliva
Idiosyncratic reactions

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19
Q

Methyldopa: What causes lactation

A

high prolactin in plasma

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20
Q

Methyldopa: What are the symptoms of dry mouth

A

Pain in the salivary glands

Difficulty swallowing

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21
Q

Methyldopa: What are the idiosyncratic reactions

A

Drug fever
Liver damage
Hemolytic anemia

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22
Q

Methyldopa: Pharmacokinetics

A

Excreted through the kidney primarily

Absorbed well from GIT

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23
Q

Clonidine: Mechanism

A

Decrease in Central sympathetic outflow
Alpha2 agonist
- stimulate alpha2 receptors in vasomotor centers of brainstem

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24
Q

Clonidine: Use

A

Treatment of essential hypertension
Analgesia
Withdrawal from opioids, alcohol, tobacco
Migraine; Tourette’s syndrome

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25
Q

Clonidine: Pharmacological Effects

A

Bradychardia
- Decreased sympathetic nerve activity
Decreased tone thus decrease in CO
Decreased SNS to vessels causing vasodilation
- Occurs with reduction of PR, especially when patient upright
Light orthostatic hypotension

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26
Q

Clonidine: Side effects

A 
Similar to those seen with methyldopa
Bradycardia
Fluid and sodium retention
Occasionally impotence or postural hypotension
Sudden withdrawal
      - Hypertensive crisis
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27
Q

Clonidine: Pharmacokinetics

A

Absorbed well from GIT

Largely excreted by kidney

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28
Q

Adrenoreceptor Antagonists

A 
Propranolol 
Beta-blockers
      - Timolol
      - Nadolol
      - Metoprolol
      - Atenolol
Combined beta and alpha blockade
      - Labetalol
      - Carvedilol
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29
Q

Propranolol: Mechanism

A

Beta-adrenergic blocking agent
Decreases CO via beta1 blockade
Beta1 blockade inhibits renin production by juxtaglomerular cells in kidney
- decreases cascade

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30
Q

Propranolol: Use

A 
Mild-Moderate hypertension
Reduce morbidity and mortality in HF
Supraventricular and ventricular arrhythmias
CHF
Migraines
Decrease remodeling
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31
Q

Propranolol: Side Effects

A 
HF
Rebound hypertension from sudden continuation
AV block
Hypotension
Exacerbation of asthmatic symptoms
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32
Q

Propranolol: Toxicity

A

May be detrimental to diabetics
- Masks tachycardia which usually signals hypoglycemia intensified hypoglycemic response because of suppression of glycogenolysis
Elevated TG
Decreased HDL-cholesterol
Diminished exercise tolerance
- Skeletal muscle needs vasodilation
- Blocked beta-2 does not allow vasodilation

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33
Q

Metoprolol: type of drug (what is it preferred for as well)

A

Selective beta-1 blockade

Preferred for patients with asthma or diabetes

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34
Q

Beta blockers with “Intrinsic Sympathomimetic Activity”

A

Less effect on resting HR and CO

Less likely to cause decrease in HDL/LDL

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35
Q

Labetalol

A

Combined beta and alpha receptor blockade
- Predominance of beta blockade (3:1)
Lowers BP without much alteration of HR or CO
Pheochromocytoma and hypertensive emergencies

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36
Q

Carvedilol

A

Combined beta and alpha receptor blockade

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37
Q

Adrenoreceptor Antagonists (alpha blockers)

A

Prazosin

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38
Q

Prazosin: Mechanism

A

Blocks postsynaptic alpha adrenoreceptors in arterioles and venules
Allows NE to act on presynaptic alpha2 receptor negative feedback on its own release
Less reflex tachycardia than non-selective alpha-blockers
Block of presynaptic alpha2 “auto-receptors” by nonselective blockers allows more NE release following nerve stimulation

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39
Q

Prazosin: Use

A

Essential hypertension
- Could be increased by combination
Dilates both resistance and capacitance vessels (decreases both afterload and preload)
- BP reduced more in upright than supine

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40
Q

Prazosin: Side effects

A

Well tolerated
“First-dose phenomenon”
- Postural hypotension and syncope occurring shortly after the first dose
First dose should be given at bedtime
Dizziness, palpitations, lassitude, headache

41
Q

Adrenergic Neurons (presynaptic)

A

Reserpine

Guanethidine

42
Q

Reserpine: Mechanism

A

Depletion of catecholamines
Depletion of serotonin in CNS and PNS
Crosses the BBB
Antagonizes the uptake and binding of NE by storage granules
NE then metabolized by MAO in neuron
Once NE depleted, sympathetic discharge is decreased

43
Q

Reserpine: Use

A

Antihypertensive agent

Once used as an antipsychotic

44
Q

Reserpine: Side Effects

A 
Sedation
Parkinson's like symptoms
Nightmares
Depression
GIT (Increase tone, motility and secretion)
Severe diarrhea
Miosis, flushing, congestion
Orthostatic hypotension
45
Q

Guanethidine: Mechanism

A

Taken up by adrenergic neuron and replaces NE in vesicle
Concentrated in vesicle where it displaces NE and causes gradual NE depletion
Prevents release of NE from vesicles
Primarily peripheral
- Doesn’t cross BBB

46
Q

Guanethidine: Use

A

Moderately severe to severe hypertension

47
Q

Guanethidine: Side effects

A

Postural hypotension
Dizziness
Intestinal cramping and diarrhea
Ejaculatory failure

48
Q

MAO inhibitors: Effects

A

Produce severe postural hypotension

No longer used for hypertension, but sometimes used for action on the CNS

49
Q

MAO: Mechanism

A

Related to formation of false neurotransmitter

 - Tyramine
 - Octopamine replaces NE
 - Octopamine is ineffective in stimulating alpha receptors
50
Q

Drugs acting on Autonomic Ganglia

A

Mecamylamine (hypertensive emergency)

51
Q

Vasodilators

A 
Hydralazine
Minoxidil
Diazoxide (Hyperstat IV)
Nitroprusside
Fenoldopam
52
Q

Hydralazine: Mechanism

A

Relaxation of vascular smooth muscle is major effect (arteriole effect greater than effect on veins)
Causes reflex cardiac stimulation
Increases renin secretion (due to stimulation of sympathetic and decrease in BP)
Sodium and water retention
Affects preload the most due to effect on arteries

53
Q

Hydralazine: Use

A

Hypertensive emergency

Essential hypertension

54
Q

Hydralazine: Side effects

A

Headache, palpitation, anorexia, nausea, dizziness, sweating
Myocardial stimulation
Drug fever, urticaria, skin rash
Drug-induced lupus-like syndrome occurs in 10-20% of patients receiving prolonged therapy with high doses

55
Q

Minoxidil: Mechanism

A

Direct vasodilator

Like hydralazine, it dilates arterioles but not veins

56
Q

Minoxidil: Use

A

More reflex sympathetic stimulation and sodium and water retention than hydralazine
Used in combination with a beta-blocker and a diuretic

57
Q

Minoxidil: Side Effects

A

Tachycardia, palpitations, angina and edema when doses of beta-blockers and diuretics are inadequate

58
Q

Minoxidil: other uses

A

Rogaine for hair growth

59
Q

Diazoxide: mechanism

A

Arteriolar dilator used for hypertensive emergencies
Structurally related to diuretics but is devoid of diuretic activity
Hypotensive effects greater if given with a beta-blocker to prevent reflex tachycardia

60
Q

Nitroprusside:Mechanism

A

Decrease pre-load and after-load
- Dilates both arterioles and venules resulting in decreased peripheral resistance and venous return
Parenterally administered
Complex of iron, cyanide groups and a nitroso moiety; metabolized to cyanide
Solutions are light sensitive
Sodium thiosulfate used to prevent or treat cyanide poisoning during infusion

61
Q

Nitroprusside: Use

A

Hypertensive emergency and severe cardiac failure

62
Q

Fenoldopam: Mechanism

A

Dopamine receptor agonist

63
Q

Fenoldopam: Administration

A

Continuous IV infusion

64
Q

Fenoldopam: Use

A

Hypertensive emergency

65
Q

Calcium Channel Blockers (vasodilators):Mechanism

A

Calcium antagonists
Inhibits calcium influx in arterial smooth muscle causing dilation of peripheral arterioles and reduction of blood pressure
Inhibits movement of calcium through channels in myocardial and specialized conducting tissues of the heart

66
Q

Calcium Channel Blockers: Agents

A

Verapamil
Diltiazem
Nifedipine
Amlodipine

67
Q

Cardioactive CCB: Drugs

A

Verapamil

Diltiazem

68
Q

Vasoactive CCB (Dihydropyridines): Drugs

A

Nifedipine

Amlodipine

69
Q

CCB: Drug Interactions

A

Do not use with beta-blocker (additive effect)
Grape fruit juice (can increase serum level of calcium channel blockers)
Digoxin
- Levels will be increased with verapamil
- Verapamil will cause a prolongation of AV conduction velocity
- Digoxin does as well

70
Q

CCB: Use

A

Treatment of hypertension
Treatment of angina
Antiarrhythmic
Can be vasogenic to decrease stroke

71
Q

Actions of Angiotensin II

A

Vasoconstriction
Release of aldosterone
- From the adrenal cortex
Alteration of cardiac and vascular structure (remodeling)

72
Q

Actions of aldosterone

A

Regulation of blood volume and blood pressure
Sodium and water retention
Pathologic cardiovascular effects
involved in remodeling

73
Q

Renin: What does it do?

A

Catalyzes the formation of angiotensin I from angiotensinogen
regulation of renin release

74
Q

Angiotensin- converting enzyme (kinase II): Action

A

catalyzes the conversion of angiotensin I (inactive) into angiotensin II (highly active)

75
Q

Regulation of blood pressure by the RAA system: operation

A

Help regulate blood pressure in the presence of hemorrhage, dehydration, or sodium depletion

76
Q

Regulation of blood pressure by the RAA system: how it acts

A

Constricts renal blood vessels

Acts on the kidney to promote retention of sodium and water and excretion of potassium

77
Q

Angiotensin- Converting Enzyme Inhibitors: Mechanism

A

Reducing levels of angiotensin II

Increasing levels of bradykinin

78
Q

Captopril (ACE Inhibitor): Mechanism

A

Prevents formation of angiotensin II and reduces blood levels of aldosterone
Inhibition of the enzyme (ACE; kinase II) also inhibits inactivation of the vasodilator bradykinin
- Can cause increase in prostaglandins
- Increase in bradykinin
- Can cause dry cough

79
Q

Captopril: Use

A 
Hypertension
Heart failure
Myocardial infarction
Diabetic and nondiabetic nephropathy
Prevention of MI, stroke, and death in patients at high cardiovascular risk
80
Q

Captopril: Adverse effects

A 
First-dose hypotension
Fetal injury
Cough
Angioedema
Hyperkalemia
Rash/ Dysguesia
Renal failure
Neutropenia
81
Q

Captopril: Drug Interactions

A

Diuretics
- Can increase possibility of first-dose hypertension
Antihypertensive agents
Drugs that raise potassium levels
Lithium
Nonsteroidalanti- inflammatory drugs
- will counter the effectiveness of many antihypertensives
- prostaglandins cause dilation of the renal vessels

82
Q

Other ACE Inhibitors

A

Enalapril

83
Q

Angiotensin II Receptor Blockers [ARB]: Drugs

A

Losartan
Candesartan
Olimesartan
Valsartan

84
Q

Losartan: Mechanism

A

Competitive receptor antagonist of angiotensin II

Lower BP almost as effectively as ACEI with fewer side effects such as cough

85
Q

Losartan: Pharmacologic effects

A 
Block access of angiotensin II
Cause dilation of arterioles and veins
Prevent angiotensin II from inducing pathologic changes in cardiac structure
Reduce excretion of sodium and water
No inhibition of Kinase II
Do not increase levels of bradykinin
86
Q

Renin Inhibitors

A

Aliskiren

87
Q

Aldosterone Antagonists

A

Spironolactone

Eplerenone

88
Q

Spironolactone: Mechanism

A

Blocks aldosterone receptors

Binds with receptors for other steroid hormones

89
Q

Spironolactone: Therapeutic uses

A

Hypertension

Heart failure

90
Q

Spironolactone: Adverse effects

A 
Hyperkalemia
Gynecomastia
Menstrual irregularities
Impotence
Hirsutism
Deepening of the voice
91
Q

Eplerenone: Mechanism

A

Selective blockade of aldosterone receptors

92
Q

Eplerenone: Therapeutic

A

Hypertension

HF

93
Q

Eplerenone: Pharmacokinetics

A

Absorption is not affected by food

94
Q

Eplerenone: Adverse effects

A

Hyperkalemia

95
Q

Eplerenone: Drug interactions

A

Inhibitors of CYP3A4
Drugs that raise potassium levels
Caution when combined with lithium

96
Q

Stage I hypertension: Drug of choice

A

Thiazide diuretics

97
Q

Stage II hypertension drug of choice

A

Combination of ACEI, ARB, CCB, beta-blocker and a diuretic

98
Q

Don’t use these drugs if you have:

A

chronic kidney disease

bilateral renal stenosis

99
Q

Which hypertension drug is most effective on African Americans

A

Diuretics

Pharmacology (13 decks)

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