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Phcol 402 > 02/01/16 > Flashcards

02/01/16 Flashcards

1
Q

USA HTN Stats

A
  • >20 years old: ~33% hypertensive
  • >40 million ambulatory care visits
  • >50% nursing home patients
  • ~30% unaware
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2
Q

HTN Diagnosis

A
  • Hypertension: an elevation of arterial blood pressure above an arbitrarily defined normal value
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3
Q

HTN Symptoms

A
  • Stage 1:
    • No symptoms
  • Stage 2:
    • Headache
    • Somnolence
    • Confusion
    • Vision disturbances
    • nausea
    • vomiting
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4
Q

Consequences of chronic hypertension

A
  • peripheral vascular disease
  • myocardial infarction
  • heart failure
  • aneurysm
  • renal failure
  • retinopathy
  • stroke
  • atherosclerosis
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5
Q

Primary (or Essential) HTN

A
  • ~90-95%: causes unknown
  • Due to multiple genetic/environmental factors:
    • nutrition
    • SNPs
    • age
    • obesity: 85% in BMI>25
    • renin levels
    • substance abuse
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6
Q

Secondary HTN

A
  • ~5% of all cases of hypertension
  • Due to identifiable secondary conditions
    • renal disease: nephritis
    • anatomical CVS defects
    • CAD
    • adrenal disorders
    • tumors
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7
Q

Mean Arterial Pressure equation

A
  • MAP=CO*(TPR/SV)
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8
Q

Strategies to treat HTN

A
  1. Decrease cardiac output
    • Beta adrenergic receptor antagonists
    • Cardiac Ca2+ channel blockers
    • alpha-2 adrenergic receptor agonists
  2. Decrease plasma volume
    • thiazides
    • loop diuretics
    • ACE inhibitors/angiotensin II receptor antagonists
  3. Decrease TPR
    • alpha-2 adrenergic receptor agonists
    • ACE inhibitors/angiotensin II receptor antagonists
    • Vasodilators
    • alpha-1 adrenergic receptor antagonists
    • endothelin receptor antagonists
    • vascular smooth muscle Ca2+ channel blockers
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9
Q

HTN Drug Summary: Figure

A
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10
Q

Thiazides: Name, MOA, toxicity

A
  • Hydrochlorothiazide: Microzide
  • MOA:
    • inhibit apical Na+/Cl- transporter (NCC) in DCT
  • Toxicity:
    • hypokalemic metabolic alkalosis
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11
Q

Thiazides use in HTN

A
  • Initial therapy for Stage 1 HTN
    • Decrease SBP ~10-15 mmHg
  • Advised for patients with normal renal function
  • Combination therapies
    • Aldactazide: HCT, spironolactone
    • Zestoretic: HCT, lisinopril
    • Diovan HCT: HCT, valsartan
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12
Q

Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)

A
  • 42,418 participants
  • Thiazide>>>ACE-I/ARB>>>Ca2+ channel blocker>>>alpha 1 blocker
  • Thiazide for stage I/II HTN
  • Diuretic intolerant patients: Ca2+ channel blocker or RAAS blockers
  • Use>1 drug
  • Exercise, change diet, stress
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13
Q

Loop Diuretics: Name, MOA, toxicities

A
  • Furosemide: Lasix
  • MOA:
    • inhibit apical Na+/K+/2Cl- transporter (NKCC2) in TALOH
  • Toxicity:
    • hypokalemic metabolic alkalosis
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14
Q

Loop use in HTN

A
  • Moderate to severe HTN
    • Decrease SBP ~30 mmHg
  • HTN crisis
  • begin with low dose
  • shorter duration of action than thiazides
  • enhance urinary Ca2+ loss- consideration when treating elderly
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15
Q

RAAS Inhibitors: MOA Figure

A
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16
Q

Macula Densa regulates Renin release: Big Picture Figure

A
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17
Q

Macula Densa regulates Renin Release: Up Close Figure

A
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18
Q

Macula Densa regulates renin release

A
  • Decrease BP→Decrease GFR→Decrease [Na+Cl-] in distal tubule→Increase PGE2/I2
    • Stimulate EP2/EP4/IP receptors→increase renin→increase BP
  • Increase BP→Increase GFR→Increase [Na+Cl-] in distal tubule→increase ATP/adenosine
    • Stimulate A1 receptors→decrease renin→decrease BP
  • Angiotensin-II inhibits renin release in JG cells (negative feedback loop)
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19
Q

Renin release mechanisms in JG cells: Figure

A
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20
Q

Renin levels in HTN

A
  • Renin levels can vary between patients
  • Important for therapy decision
  • ~60%: normal renin
  • ~15%: increased renin
    • young, caucasian, males
    • increase SNS activity, stress
    • treat with ACE-I, ARBS
  • ~25%: decreased renin
    • old, AA, females
    • increase Na+ retention
    • treat with diuretics, Ca2+ channel blockers
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21
Q

ACE-I: Drug names

A
  • Captopril: Capoten
  • Fosinopril: Monopril
  • Enalapril: Vasotec
  • Lisinopril: Prinivil
  • Ramipril: Altace
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22
Q

ACE-I: MOA

A
  • inhibit ACE
  • Decrease conversion of ATI→ATII
  • Decrease TPR→decrease BP
  • decrease aldosterone/VP→decrease plasma volume→decrease BP
  • decrease CVS remodeling
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23
Q

ACE-I: PK

A
  • Oral; most are pro-drugs
  • captopril t1/2=2 h, lisinopril=12-24 h
  • excreted in urine
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24
Q

ACE-I: Toxicity

A
  • severe hypotension/acute renal failure
  • decrease ACE=increase BK/substance P→cough reflex
  • angioedema
  • hyperkalemia
  • teratogenic
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25
Q

ARBs: Drugs

A
  • Losartan: Cozaar
  • Omesartan: Benicar
  • Telmisartan: Micardis
  • Valsartan: Diovan
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26
Q

ARB: MOA

A
  • 2 ATII GPCR subtypes;
    • ATII-1→Gq/11→vasocontriction
    • ATII-2→Gi2/3→vasodilation
  • ARBs antagonist ATII-1
    • decrease TPR, decrease BP
  • ATII-2 active
    • Increase vasodilation
    • Decrease TPR, decrease BP
  • Decrease aldosteron/VP
    • Decrease plasma volume, decrease BP
  • Decrease CVS remodeling
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27
Q

ARB: PK

A
  • Oral; some are pro-drugs
  • losartan t1/2= 2 h, telmisartan= ~24 h
  • excreted in urine
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28
Q

ARB: toxicity

A
  • severe hyoptension/acute renal failure
  • no cough!
  • less angioedema
  • hyperkalemia
  • teratogenic
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29
Q

Renin Inhibtors: Drug Name

A
  • Aliskiren: Tekturna
  • Remikiren
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30
Q

Renin Inhibitors: MOA

A
  • inhibit renin
    • decrease ATII production
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31
Q

Renin Inhibitors: Clincal uses/toxicities

A
  • Clinical uses:
    • HTN secondary to renal failure of diabetes
    • High-renin HTN
  • Toxicity:
    • Angioedema
    • Renal impairment
32
Q

Beta-adrenergic receptor antagonists: 3 main types

A
  1. Non-selective
    • Antagnoize beta-1 and beta-2 adrenergic receptors
    • Propranolol (Inderal)
  2. Selective
    • antagonize one beta adrenergic receptor subtype
    • Metoprolol (Lopressor): beta-1 AR selective
  3. Mixed
    • antagonize alpha and beta adrenergic receptors
    • Carvedilol (Coreg)
    • Labetalol (Trandate)
33
Q

Beta-adrenergic receptor antagonists: MOA

A
  • Block cardiac beta-1 ARs
    • Decrease CO
  • Block JG cell beta-1 ARs
    • Decrease renin
    • Decrease RAAS
  • Enter CNS, decrease SNS activity
34
Q

Beta-adrenergic receptor antagonists: Use in HTN

A
  • Propranolol:
    • Original beta-blocker for HTN
    • Antagonizes beta 1 and beta 2 ARs
    • Contraindicated with asthma, bradycardia
  • Metoprolol
    • commonly used for stage I/II HTN
    • 50-100x higher affinity for beta 1-AR
    • t1/2=4-6 h, CYP2D6, 50-100 mg/day
35
Q

Pregnancy Induced HTN

A
  • >140/90 mmHg
  • Increase protein in urine (>300 mg)
  • week 20 to 6 weeks post partum
  • organ damage to mother and child
  • edema in hands/face
  • ~10% of pregnancies
  • no known cause or cure
36
Q

Labetolol

A
  • Recommended therapy for pregnancy induced HTN/eclampsia
  • racemic mix of 4 stereoisomers:
    • (R,R) is beta1-AR selective
    • (S,R) is alpha1-AR selective
  • block beta1-ARs and alpha1-ARs: decrease CO/TPR
37
Q

Pulmonary HTN

A
  • Increase BP in pulmonary artery/vein, lung vasculature
  • SOB, dizziness, fainting, cough, angina
  • decrease exercise tolerance, heart failure
  • Risk factors: family history, stimulant/alcohol abuse, tobacco
  • survival: 2-3 years post diagnosis
38
Q

Endothelin Receptor Antagonists

A
  • Bosentan: Tracleer
    • competitive antagonist for endothelin-A/B
  • Ambrisentan: Letairis
    • 100x selective for endothelin-A receptor
  • Macitentan: Obsumit
    • approved in 2013, decreases aberrant liver function
39
Q

Endothelin Receptor Antagonists: MOA

A
  • GPCRs
    • Endothelin A=vasocontrictor
    • Endothelin B= vasodilator
  • Decrease pulmonary vasoconstriction
    • Increases blood flow through pulmonary vasculature
40
Q

Endothelin Receptor Antagonists: Clinical Uses

A
  • Pulmonary HTN
41
Q

Endothelin Receptor Antagonists: SE

A
  • Headache
  • Aberrant liver function
42
Q

Cardiac selective Ca2+ channel blockers

A
  • Verapamil (Calan, Isoptin)
  • Diltiazem (Cardizem)
43
Q

Cardiac selective Ca2+ channel blockers: MOA

A
  • inhibit voltage gated L-type Ca2+ channels in cardiac myocytes
  • Decrease force and rate of cardiomyocyte contraction
    • decrease cardiac output
44
Q

Cardiac selective Ca2+ channel blockers: toxicity

A
  • hypotension
  • excessive cardiac depression
  • constipation
45
Q

Cardiac selective Ca2+ channel blockers: MOA figure

46
Q

Vascular selective Ca2+ channel blockers

A
  • Dihydropyridines
    • Nifedipine (Procardia)
    • Amlodipine (Norvasc)
47
Q

Vascular selective Ca2+ channel blockers: MOA

A
  • Inhibit L-type Ca2+ channels on vascular smooth muscle cells
  • Decrease arterial and venous contraction
    • Decrease TPR
48
Q

Vascular selective Ca2+ channel blockers: toxicity

A
  • hypotension
  • flushing, dizziness
49
Q

Vascular selective Ca2+ channel blockers: MOA figure

50
Q

alpha-1 adrenergic receptor antagonists

A
  • Prazosin (Minipress, Vasoflex)
  • Doxazosin (Cardura)
51
Q

alpha-1 adrenergic receptor antagonists: MOA

A
  • alpha-1 ARs on VSM
    • Activated by epi/ne
      • Vasocontriction
  • alpha-1 AR anatgonists inhibit epi/ne
    • Decrease TPR
52
Q

alpha-1 adrenergic receptor antagonists: clinical use

A
  • hypertension unresponsive to diuretetics, CCB
  • BPH
53
Q

alpha-1 adrenergic receptor antagonists: Toxicity

A
  • orthostatic hypotension
  • reflex tachycardia
54
Q

Drugs for HTN crisis

A
  • SBP >180 or DBP>110
    • drugs used are vasodilators
      • decrease TPR
    • short duration of action
  • Nitroprusside (Nipride)
    • nitric oxide donors
  • Hydralazine (Apresoline)
  • Diazoxide (Proglycem)
  • Minoxidil (Loniten)
    • open K+ channels on vascular smooth muscle cells
  • Toxicity:
    • excessive hypotension
    • tachycardia
55
Q

alpha-2 adrenergic receptor agonists

A
  • Clonidine (Catapress)
  • alpha-methyldopa
56
Q

alpha-2 adrenergic receptor agonists : MOA

A
  • alpha-2 ARs on sympathetic nerve terminal
    • Decrease NE release
  • Decrease CO, TPR
57
Q

alpha-2 adrenergic receptor agonists: clinical uses

A
  • hypertension unresponsive to diuretics, CCD
  • diagnose pheochromocytoma
  • ADHD
58
Q

alpha-2 adrenergic receptor agonists : toxicity

A
  • Severe withdrawal
  • Sedation
59
Q

alpha-2 adrenergic receptor agonists: MOA figure

60
Q

Peripheral Sympatholytics: Drugs

A
  • Metyrosine (1a)
    • inhibit tyrosine hydroxylase
      • decrease NE production
  • Bretylium, guanetidine (3)
    • uptake 1
    • inhibit Na+ ATPase pump/VGKC
    • decrease NE release
  • Reserpine (2)
    • inhibit VMAT
    • decrease NE transport into vessicle
61
Q

Peripheral Sympatholytics: Uses

A
  • experimental tools
  • rarely used clinically
  • dyskinesia in Huntington disease
  • CVS emergencies
    • severe HTN, ventricular tachycardia
62
Q

Peripheral Sympatholytics: SE

A
  • hypotension
  • CNS
  • GI
  • sexual dysfunction
  • diarrhea
63
Q

Hydrochlorothiazide: Drug card

A
  • Brand Name:
    • Microzide
  • MOA:
    • inhibit NCC in DCT
  • Clinical uses:
    • hypertension
    • CHF
    • idiopathic hypercalciuria
  • Toxicity:
    • hypokalemic metabolic alkalosis
    • hyponatremia
    • hyper-lipidemia, uricemia, calcemia
  • Extra info:
    • “low ceiling diuretic”
    • component of many combination therapies
64
Q

Furosemide: Drug Card

A
  • Brand Name:
    • Lasix
  • MOA:
    • Inhibit NKCC2 in TALOH
  • Clinical Uses:
    • edema in CHF, cirrhosis, nephrotic syndrome
    • HTN
    • hypercalcemia
  • Toxicity:
    • hypokalemia
    • ototoxicity
    • dehydration
  • Extra info:
    • “high ceiling diuretic”
    • rapid onset of action (min)
65
Q

Catopril: Drug Card

A
  • Brand Name:
    • Capoten
  • MOA:
    • ACE
  • Clincal Uses:
    • Stage I/II HTN
    • CHF
    • diabetic renal disease
  • Toxicity:
    • bradykinin cough reflex
    • hyperkalemia
    • teratogenic
  • Extra info:
    • oral
    • effective up to 12 h
66
Q

Losartan: Drug card

A
  • Brand Name:
    • Cozaar
  • MOA:
    • ARB
  • Clinical Uses:
    • Stage I/II HTN
      CHF
  • Toxicity:
    • hyperkalemia
    • teratogenic
  • Extra info:
    • oral
    • no cough reflex
67
Q

Aliskiren: Drug Card

A
  • Brand Name:
    • Tekturna
  • MOA:
    • renin inhibitor
  • Clinical Uses:
    • HTN secodary to renal failure or diabetes
    • “high renin” HTN
  • Toxicity:
    • angioedema
    • renal impairement
  • Extra info:
    • no significant advantage over other RAAS inhibitors for most types of HTN
68
Q

Propranolol: Drug Card

A
  • Brand Name:
    • Inderal
  • MOA:
    • non-selective beta adrenergic receptor antagonist
  • Clinical uses:
    • HTN
    • CHF
    • angina
    • arrhythmias
  • Toxicity:
    • bradycardia, atrioventricular block
    • bronchospasm
    • CNS sedation
  • Extra info:
    • contraindicated in asthma
    • also used for performance anxiety and migraine
    • cross BBB
69
Q

Metoprolol: Drug Card

A
  • Brand Name:
    • Lopressor
  • MOA:
    • selective beta-1 adrenergic receptor antagonist
  • Clinical uses:
    • CHF
    • HTN
  • Toxicity:
    • bradycardia, atrioventricular block
    • CNS sedation
  • Extra info:
    • show to reduce mortality in heart failure patients
    • widely used for stage I/II HTN
70
Q

Labatelol: Drug Card

A
  • Brand Name:
    • Trandate
  • MOA:
    • mixed alpha-1 and beta adrenergic receptor antagonist
  • Clinical uses:
    • preganancy induced HTN, eclampsia, pre-eclampsia
    • HTN crisis
  • Toxicity:
    • bradycardia, atrioventricular block
    • CNS sedation
    • less bronchospasm
  • Extra info
    • composed of 4 stereoisomers
    • (R,R) isomer: beta-1 adrenergic receptor antagonist
    • (S,R) isomer: alpha-1 adrenergic receptor antagonist
71
Q

Carvedilol: Drug Card

A
  • Brand Name:
    • Coreg
  • MOA:
    • mixed alpha-1 and beta adrenergic receptor antagnoist
  • Clinical uses:
    • CHF
    • HTN
  • Toxicity:
    • bradycardia, atrioventricular block
    • CNS sedation
    • less bronchospasm
  • Extra info:
    • composed of 4 stereoisomers
    • shown to reduce mortality in heart failure patients
72
Q

Ambrisentan: Drug Card

A
  • Brand Name:
    • Letairis
  • MOA:
    • selective endothelin-a receptor antagonist
  • Clinical uses:
    • pulmonary HTN
  • Toxicity:
    • hepatic impairment
    • headache
  • Extra info:
    • 100x selective for endothelin-a receptor
    • Bosentan antagnoizes endothelin a and b receptors
73
Q

Verapamil; Drug Card

A
  • Brand Name:
    • Calan
  • MOA:
    • cardioselective L-type CCB
  • Clinical Uses:
    • HTN
    • angina
    • arrhythmias
  • Toxicity:
    • excessive cardiac depression
    • constipation
  • Extra info:
    • strong cardiac blocking effect
    • weak vascular smooth muscle blocking effect
74
Q

Nifedipine: Drug Card

A
  • Brand Name:
    • Procardia
  • MOA:
    • Vascular selective L-type CCB
  • Clinical uses:
    • HTN
    • angina
    • arrhythmias
  • Toxicity:
    • hypotension
    • flushing
    • dizziness
  • Extra Info:
    • strong vascular smooth muscle blocking effect
    • weak cardiac muscle blocking effect
75
Q

Prazosin: Drug Card

A
  • Brand Name:
    • Minipress
  • MOA:
    • selective alpha-1 adrenergic receptor antagonist
  • Clinical uses:
    • HTN
    • BPH
  • Toxicity:
    • orthostatic hypotension
    • reflex tachycardia
  • Extra info:
    • used in HTN patients unresponsive to other therapies
76
Q

Clondine: Drug Card

A
  • Brand Name:
    • Catapress
  • MOA:
    • selective alpha-2 adrenergic receptor agonist
  • Clinical uses:
    • HTN
    • ADHD
  • Toxicity:
    • severe withdrawal
    • sedation
  • Extra info:
    • penetrates CHS and inhibits sympathetic nervous system NE release
    • available as a transdermal patch
77
Q

Hydralazine: Drug Card

A
  • Brand Name:
    • Apresoline
  • MOA:
    • K+ channel activator
  • Clinical uses:
    • HTN crisis
    • pregnancy induced HTN
    • heart failure
  • Toxicity:
    • tachycardia
    • salt and water retention
  • Extra info:
    • MOA not completely understood
    • Can also cause lupus-like syndrome

Phcol 402 (11 decks)

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