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
2
Q
HTN Diagnosis
A
- Hypertension: an elevation of arterial blood pressure above an arbitrarily defined normal value

3
Q
HTN Symptoms
A
- Stage 1:
- No symptoms
- Stage 2:
- Headache
- Somnolence
- Confusion
- Vision disturbances
- nausea
- vomiting
4
Q
Consequences of chronic hypertension
A
- peripheral vascular disease
- myocardial infarction
- heart failure
- aneurysm
- renal failure
- retinopathy
- stroke
- atherosclerosis
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
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
7
Q
Mean Arterial Pressure equation
A
- MAP=CO*(TPR/SV)

8
Q
Strategies to treat HTN
A
- Decrease cardiac output
- Beta adrenergic receptor antagonists
- Cardiac Ca2+ channel blockers
- alpha-2 adrenergic receptor agonists
- Decrease plasma volume
- thiazides
- loop diuretics
- ACE inhibitors/angiotensin II receptor antagonists
- 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
9
Q
HTN Drug Summary: Figure
A

10
Q
Thiazides: Name, MOA, toxicity
A
- Hydrochlorothiazide: Microzide
- MOA:
- inhibit apical Na+/Cl- transporter (NCC) in DCT
- Toxicity:
- hypokalemic metabolic alkalosis
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
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
13
Q
Loop Diuretics: Name, MOA, toxicities
A
- Furosemide: Lasix
- MOA:
- inhibit apical Na+/K+/2Cl- transporter (NKCC2) in TALOH
- Toxicity:
- hypokalemic metabolic alkalosis
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
15
Q
RAAS Inhibitors: MOA Figure
A

16
Q
Macula Densa regulates Renin release: Big Picture Figure
A

17
Q
Macula Densa regulates Renin Release: Up Close Figure
A

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)
19
Q
Renin release mechanisms in JG cells: Figure
A

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
21
Q
ACE-I: Drug names
A
- Captopril: Capoten
- Fosinopril: Monopril
- Enalapril: Vasotec
- Lisinopril: Prinivil
- Ramipril: Altace

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
23
Q
ACE-I: PK
A
- Oral; most are pro-drugs
- captopril t1/2=2 h, lisinopril=12-24 h
- excreted in urine
24
Q
ACE-I: Toxicity
A
- severe hypotension/acute renal failure
- decrease ACE=increase BK/substance P→cough reflex
- angioedema
- hyperkalemia
- teratogenic
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
28
ARB: toxicity
* severe hyoptension/acute renal failure
* no cough!
* less angioedema
* hyperkalemia
* teratogenic
29
Renin Inhibtors: Drug Name
* Aliskiren: Tekturna
* Remikiren
30
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
40
Endothelin Receptor Antagonists: Clinical Uses
* Pulmonary HTN
41
Endothelin Receptor Antagonists: SE
* Headache
* Aberrant liver function
42
Cardiac selective Ca2+ channel blockers
* Verapamil (Calan, Isoptin)
* Diltiazem (Cardizem)
43
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
44
Cardiac selective Ca2+ channel blockers: toxicity
* hypotension
* excessive cardiac depression
* constipation
45
Cardiac selective Ca2+ channel blockers: MOA figure

46
Vascular selective Ca2+ channel blockers
* Dihydropyridines
* Nifedipine (Procardia)
* Amlodipine (Norvasc)
47
Vascular selective Ca2+ channel blockers: MOA
* Inhibit L-type Ca2+ channels on vascular smooth muscle cells
* Decrease arterial and venous contraction
* Decrease TPR
48
Vascular selective Ca2+ channel blockers: toxicity
* hypotension
* flushing, dizziness
49
Vascular selective Ca2+ channel blockers: MOA figure

50
alpha-1 adrenergic receptor antagonists
* Prazosin (Minipress, Vasoflex)
* Doxazosin (Cardura)
51
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
53
alpha-1 adrenergic receptor antagonists: Toxicity
* orthostatic hypotension
* reflex tachycardia
54
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
56
alpha-2 adrenergic receptor agonists : MOA
* alpha-2 ARs on sympathetic nerve terminal
* Decrease NE release
* Decrease CO, TPR
57
alpha-2 adrenergic receptor agonists: clinical uses
* hypertension unresponsive to diuretics, CCD
* diagnose pheochromocytoma
* ADHD
58
alpha-2 adrenergic receptor agonists : toxicity
* Severe withdrawal
* Sedation
59
alpha-2 adrenergic receptor agonists: MOA figure

60
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

61
Peripheral Sympatholytics: Uses
* experimental tools
* rarely used clinically
* dyskinesia in Huntington disease
* CVS emergencies
* severe HTN, ventricular tachycardia
62
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