Phcol 402 > 02/01/16 > Flashcards

02/01/16 Flashcards

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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
ARBs: Drugs
* Losartan: Cozaar * Omesartan: Benicar * Telmisartan: Micardis * Valsartan: Diovan
26
ARB: MOA
* 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
27
ARB: PK
* Oral; some are pro-drugs * losartan t1/2= 2 h, telmisartan= ~24 h * excreted in urine
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ARB: toxicity
* severe hyoptension/acute renal failure * no cough! * less angioedema * hyperkalemia * teratogenic
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Renin Inhibtors: Drug Name
* Aliskiren: Tekturna * Remikiren
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Renin Inhibitors: MOA
* inhibit renin * decrease ATII production
31
Renin Inhibitors: Clincal uses/toxicities
* Clinical uses: * HTN secondary to renal failure of diabetes * High-renin HTN * Toxicity: * Angioedema * Renal impairment
32
Beta-adrenergic receptor antagonists: 3 main types
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
Beta-adrenergic receptor antagonists: MOA
* Block cardiac beta-1 ARs * Decrease CO * Block JG cell beta-1 ARs * Decrease renin * Decrease RAAS * Enter CNS, decrease SNS activity
34
Beta-adrenergic receptor antagonists: Use in HTN
* 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
Pregnancy Induced HTN
* \>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
Labetolol
* 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
Pulmonary HTN
* 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
Endothelin Receptor Antagonists
* 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
Endothelin Receptor Antagonists: MOA
* GPCRs * Endothelin A=vasocontrictor * Endothelin B= vasodilator * Decrease pulmonary vasoconstriction * Increases blood flow through pulmonary vasculature
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Endothelin Receptor Antagonists: Clinical Uses
* Pulmonary HTN
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Endothelin Receptor Antagonists: SE
* Headache * Aberrant liver function
42
Cardiac selective Ca2+ channel blockers
* Verapamil (Calan, Isoptin) * Diltiazem (Cardizem)
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Cardiac selective Ca2+ channel blockers: MOA
* inhibit voltage gated L-type Ca2+ channels in cardiac myocytes * Decrease force and rate of cardiomyocyte contraction * decrease cardiac output
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Cardiac selective Ca2+ channel blockers: toxicity
* hypotension * excessive cardiac depression * constipation
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Cardiac selective Ca2+ channel blockers: MOA figure
46
Vascular selective Ca2+ channel blockers
* Dihydropyridines * Nifedipine (Procardia) * Amlodipine (Norvasc)
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Vascular selective Ca2+ channel blockers: MOA
* Inhibit L-type Ca2+ channels on vascular smooth muscle cells * Decrease arterial and venous contraction * Decrease TPR
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Vascular selective Ca2+ channel blockers: toxicity
* hypotension * flushing, dizziness
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Vascular selective Ca2+ channel blockers: MOA figure
50
alpha-1 adrenergic receptor antagonists
* Prazosin (Minipress, Vasoflex) * Doxazosin (Cardura)
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alpha-1 adrenergic receptor antagonists: MOA
* alpha-1 ARs on VSM * Activated by epi/ne * Vasocontriction * alpha-1 AR anatgonists inhibit epi/ne * Decrease TPR
52
alpha-1 adrenergic receptor antagonists: clinical use
* hypertension unresponsive to diuretetics, CCB * BPH
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alpha-1 adrenergic receptor antagonists: Toxicity
* orthostatic hypotension * reflex tachycardia
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Drugs for HTN crisis
* 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
alpha-2 adrenergic receptor agonists
* Clonidine (Catapress) * alpha-methyldopa
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alpha-2 adrenergic receptor agonists : MOA
* alpha-2 ARs on sympathetic nerve terminal * Decrease NE release * Decrease CO, TPR
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alpha-2 adrenergic receptor agonists: clinical uses
* hypertension unresponsive to diuretics, CCD * diagnose pheochromocytoma * ADHD
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alpha-2 adrenergic receptor agonists : toxicity
* Severe withdrawal * Sedation
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alpha-2 adrenergic receptor agonists: MOA figure
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Peripheral Sympatholytics: Drugs
* 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
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Peripheral Sympatholytics: Uses
* experimental tools * rarely used clinically * dyskinesia in Huntington disease * CVS emergencies * severe HTN, ventricular tachycardia
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Peripheral Sympatholytics: SE
* hypotension * CNS * GI * sexual dysfunction * diarrhea
63
Hydrochlorothiazide: Drug card
* 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
Furosemide: Drug Card
* 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
Catopril: Drug Card
* 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
Losartan: Drug card
* Brand Name: * Cozaar * MOA: * ARB * Clinical Uses: * Stage I/II HTN CHF * Toxicity: * hyperkalemia * teratogenic * Extra info: * oral * no cough reflex
67
Aliskiren: Drug Card
* 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
Propranolol: Drug Card
* 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
Metoprolol: Drug Card
* 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
Labatelol: Drug Card
* 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
Carvedilol: Drug Card
* 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
Ambrisentan: Drug Card
* 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
Verapamil; Drug Card
* 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
Nifedipine: Drug Card
* 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
Prazosin: Drug Card
* 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
Clondine: Drug Card
* 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
Hydralazine: Drug Card
* 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
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