Unit 2: Drugs Used in Hypertension Flashcards
(100 cards)
0
Q
Diuretics: Classification
A
Thiazide Diuretics
Loop (high-ceiling) diuretics
Potassium-sparing diuretics
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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Q
Thiazide diuretics
A
Initial drug of choice for hypertension
Cheap
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Q
Thiazide Diuretics: Drugs
A
Hydrochlorothiazide
4
Q
Hydrochlorothiazide: Mechanism
A
Mechanism: Reduces blood volume; reduces arterial peripheral resistance; some have direct vasodilating effects
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Q
Thiazide Toxicities
A
Hypokalemia
Dehydration, hyperglycemia, hyperuricemia
Increase levels of LDL cholesterol, total cholesterol and TG
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Q
Thiazide contraindications
A
Ineffective when GFR is low
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Q
Loop (high-ceiling) diuretics: Drugs
A
Furosemide, ethacrynic acid, bumetanide, torsemide
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Q
Loop (High-ceiling) diuretics: Diuresis
A
Produce much greater diuresis than thiazides
Reserved for patients with a low GFR
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Q
Loop (high-ceiling) diuretics: adverse effects
A
Dehydration, hyperglycemia, hyperuricemia
Hearing-loss
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Q
Potassium sparing diuretics: Drugs
A
Spironolactone
Triamterene
Amiloride
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Q
Potassium-Sparing Diuretics: Features
A
Poor diuresis (modest hypotensive effect) Conserves K (combination with thiazides)
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Q
Potassium-Sparing Diuretics: Toxicity
A
Hyperkalemia
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Q
Potassium-Sparing Diuretics: C/I
A
K supplements
ACE inhibitorso
angiotensin II receptor blockers
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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
15
Q
Centrally acting sympatholytics: Drugs
A
Methyldopa
Clonidine
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Q
Methyldopa: MOA
A
Decreases SNS outflow from brainstem
Must first be converted (metabolite)
- Alpha-methyl norepinephrine
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Q
Methyldopa: Therapeutic Use
A
Treatment of essential hypertension
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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
19
Q
Methyldopa: What causes lactation
A
high prolactin in plasma
20
Q
Methyldopa: What are the symptoms of dry mouth
A
Pain in the salivary glands
Difficulty swallowing
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Q
Methyldopa: What are the idiosyncratic reactions
A
Drug fever
Liver damage
Hemolytic anemia
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Q
Methyldopa: Pharmacokinetics
A
Excreted through the kidney primarily
Absorbed well from GIT
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Q
Clonidine: Mechanism
A
Decrease in Central sympathetic outflow
Alpha2 agonist
- stimulate alpha2 receptors in vasomotor centers of brainstem
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Clonidine: Use
Treatment of essential hypertension
Analgesia
Withdrawal from opioids, alcohol, tobacco
Migraine; Tourette's syndrome
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Clonidine: Pharmacological Effects
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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Clonidine: Side effects
```
Similar to those seen with methyldopa
Bradycardia
Fluid and sodium retention
Occasionally impotence or postural hypotension
Sudden withdrawal
- Hypertensive crisis
```
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Clonidine: Pharmacokinetics
Absorbed well from GIT
| Largely excreted by kidney
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Adrenoreceptor Antagonists
```
Propranolol
Beta-blockers
- Timolol
- Nadolol
- Metoprolol
- Atenolol
Combined beta and alpha blockade
- Labetalol
- Carvedilol
```
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Propranolol: Mechanism
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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Propranolol: Use
```
Mild-Moderate hypertension
Reduce morbidity and mortality in HF
Supraventricular and ventricular arrhythmias
CHF
Migraines
Decrease remodeling
```
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Propranolol: Side Effects
```
HF
Rebound hypertension from sudden continuation
AV block
Hypotension
Exacerbation of asthmatic symptoms
```
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Propranolol: Toxicity
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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Metoprolol: type of drug (what is it preferred for as well)
Selective beta-1 blockade
| Preferred for patients with asthma or diabetes
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Beta blockers with "Intrinsic Sympathomimetic Activity"
Less effect on resting HR and CO
| Less likely to cause decrease in HDL/LDL
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Labetalol
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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Carvedilol
Combined beta and alpha receptor blockade
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Adrenoreceptor Antagonists (alpha blockers)
Prazosin
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Prazosin: Mechanism
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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Prazosin: Use
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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Prazosin: Side effects
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
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Adrenergic Neurons (presynaptic)
Reserpine
| Guanethidine
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Reserpine: Mechanism
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
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Reserpine: Use
Antihypertensive agent
| Once used as an antipsychotic
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Reserpine: Side Effects
```
Sedation
Parkinson's like symptoms
Nightmares
Depression
GIT (Increase tone, motility and secretion)
Severe diarrhea
Miosis, flushing, congestion
Orthostatic hypotension
```
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Guanethidine: Mechanism
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
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Guanethidine: Use
Moderately severe to severe hypertension
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Guanethidine: Side effects
Postural hypotension
Dizziness
Intestinal cramping and diarrhea
Ejaculatory failure
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MAO inhibitors: Effects
Produce severe postural hypotension
| No longer used for hypertension, but sometimes used for action on the CNS
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MAO: Mechanism
Related to formation of false neurotransmitter
- Tyramine
- Octopamine replaces NE
- Octopamine is ineffective in stimulating alpha receptors
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Drugs acting on Autonomic Ganglia
Mecamylamine (hypertensive emergency)
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Vasodilators
```
Hydralazine
Minoxidil
Diazoxide (Hyperstat IV)
Nitroprusside
Fenoldopam
```
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Hydralazine: Mechanism
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
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Hydralazine: Use
Hypertensive emergency
| Essential hypertension
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Hydralazine: Side effects
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
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Minoxidil: Mechanism
Direct vasodilator
| Like hydralazine, it dilates arterioles but not veins
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Minoxidil: Use
More reflex sympathetic stimulation and sodium and water retention than hydralazine
Used in combination with a beta-blocker and a diuretic
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Minoxidil: Side Effects
Tachycardia, palpitations, angina and edema when doses of beta-blockers and diuretics are inadequate
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Minoxidil: other uses
Rogaine for hair growth
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Diazoxide: mechanism
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
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Nitroprusside:Mechanism
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
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Nitroprusside: Use
Hypertensive emergency and severe cardiac failure
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Fenoldopam: Mechanism
Dopamine receptor agonist
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Fenoldopam: Administration
Continuous IV infusion
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Fenoldopam: Use
Hypertensive emergency
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Calcium Channel Blockers (vasodilators):Mechanism
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
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Calcium Channel Blockers: Agents
Verapamil
Diltiazem
Nifedipine
Amlodipine
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Cardioactive CCB: Drugs
Verapamil
| Diltiazem
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Vasoactive CCB (Dihydropyridines): Drugs
Nifedipine
| Amlodipine
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CCB: Drug Interactions
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
CCB: Use
Treatment of hypertension
Treatment of angina
Antiarrhythmic
Can be vasogenic to decrease stroke
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Actions of Angiotensin II
Vasoconstriction
Release of aldosterone
- From the adrenal cortex
Alteration of cardiac and vascular structure (remodeling)
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Actions of aldosterone
Regulation of blood volume and blood pressure
Sodium and water retention
Pathologic cardiovascular effects
involved in remodeling
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Renin: What does it do?
Catalyzes the formation of angiotensin I from angiotensinogen
regulation of renin release
74
Angiotensin- converting enzyme (kinase II): Action
catalyzes the conversion of angiotensin I (inactive) into angiotensin II (highly active)
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Regulation of blood pressure by the RAA system: operation
Help regulate blood pressure in the presence of hemorrhage, dehydration, or sodium depletion
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Regulation of blood pressure by the RAA system: how it acts
Constricts renal blood vessels
| Acts on the kidney to promote retention of sodium and water and excretion of potassium
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Angiotensin- Converting Enzyme Inhibitors: Mechanism
Reducing levels of angiotensin II
| Increasing levels of bradykinin
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Captopril (ACE Inhibitor): Mechanism
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
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Captopril: Use
```
Hypertension
Heart failure
Myocardial infarction
Diabetic and nondiabetic nephropathy
Prevention of MI, stroke, and death in patients at high cardiovascular risk
```
80
Captopril: Adverse effects
```
First-dose hypotension
Fetal injury
Cough
Angioedema
Hyperkalemia
Rash/ Dysguesia
Renal failure
Neutropenia
```
81
Captopril: Drug Interactions
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
Other ACE Inhibitors
Enalapril
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Angiotensin II Receptor Blockers [ARB]: Drugs
Losartan
Candesartan
Olimesartan
Valsartan
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Losartan: Mechanism
Competitive receptor antagonist of angiotensin II
| Lower BP almost as effectively as ACEI with fewer side effects such as cough
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Losartan: Pharmacologic effects
```
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
Renin Inhibitors
Aliskiren
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Aldosterone Antagonists
Spironolactone
| Eplerenone
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Spironolactone: Mechanism
Blocks aldosterone receptors
| Binds with receptors for other steroid hormones
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Spironolactone: Therapeutic uses
Hypertension
| Heart failure
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Spironolactone: Adverse effects
```
Hyperkalemia
Gynecomastia
Menstrual irregularities
Impotence
Hirsutism
Deepening of the voice
```
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Eplerenone: Mechanism
Selective blockade of aldosterone receptors
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Eplerenone: Therapeutic
Hypertension
| HF
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Eplerenone: Pharmacokinetics
Absorption is not affected by food
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Eplerenone: Adverse effects
Hyperkalemia
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Eplerenone: Drug interactions
Inhibitors of CYP3A4
Drugs that raise potassium levels
Caution when combined with lithium
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Stage I hypertension: Drug of choice
Thiazide diuretics
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Stage II hypertension drug of choice
Combination of ACEI, ARB, CCB, beta-blocker and a diuretic
98
Don't use these drugs if you have:
chronic kidney disease
| bilateral renal stenosis
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Which hypertension drug is most effective on African Americans
Diuretics
