1
Q
Staging of BP: normal
A
<120/80
2
Q
Staging of BP: prehypertension
A
120-135/80-89
3
Q
Staging of BP: Stage I HTN
A
140-159/90-99
4
Q
Staging of BP: Stage II HTN
A
>/= 160/100
5
Q
BP target for >/=60yo
A
<150/90mmHg
6
Q
BP target for <60yo
A
140/90 mmHg
7
Q
BP targets for all adults w/CKD or DM
A
<140/90 mmHg
8
Q
AHA/ASA position on higher BP targets for older adults?
A
Do not endorse
9
Q
Recommended 1st line treatment for non black, all ages, +/- DM
A
thiazide, ACEi, ARB, CCB
10
Q
Recommended 1st line treatment for Black +/- DM
A
thiazide, CCB
11
Q
Recommended 1st line treatment for CKD, any race, +/- DM
A
ACEi, ARB
12
Q
Why is HTN a risk for AAs?
A
not higher risk of mortality
higher risk of EOD
13
Q
HTN mgmt guidelines: what if goal is not reached in 1mth?
A
Increase dose or add recommended drug
14
Q
HTN mgmt guidelines: can ACEis and ARBs be used concomitantly?
A
No!
15
Q
HTN mgmt guidelines: what if goal is not achieved w/2 drugs?
A
add and titrate 3rd recommended drug
16
Q
HTN mgmt guidelines: what if goal is not achieved even w/3rd drug?
A
- Consider referral to HTN specialist
- Use drugs from other classes
17
Q
Non first line HTN drugs
A
- Loop diuretics
- K-sparing diuretics including aldosterone receptor antagonists
- Direct renin inhibitors
- Central-acting alpha2 agonists
- Beta-blockers including those with alpha-blocking or vasodilating effects*
- Alpha-blockers**
- Nitrates
- Direct vasodilators
- Peripherally-acting adrenergic antagonists
18
Q
*Beta blocker vs. ARB study: outcome
A
Atenolol (Beta blocker) associated with increased risk of composite CV death, MI, stroke compared to Losartan (ARB)
19
Q
Alpha blocker vs. Thiazide Diuretics study
A
Doxazosin associated with increased rate of cerebrovascular events, heart failure and composite CVD events
20
Q
Thiazide-type diuretics: Agents
A
- Microzide (hydrochlorothiazide)
- Chlorthalidone
- Indapamide
- Zaroxolyn (metolazone)
21
Q
Thiazide-type diuretics: MOA/PK
A
Early: depletes sodium stores by blocking Na/CL transporter in renal distal convoluted tubule –> decreases blood vol. & CO
Late: CO normalizes, systemic vasc. Resistance decreases
22
Q
Thiazide-type diuretics: ADRs
A
- Hyponatremia
- Hypokalemia
- Metabolic alk
- Photosensitivity
- Hyperuricemia
- Hyperglycemia
- Weakness
23
Q
Thiazide-type diuretics: monitor
A
electrolytes, BP, fluid status
24
Q
Thiazide-type diuretics: special considerations (e.g., renal impairment, possible allergies, dose timing)
A
- *Less effective in setting of renal impairment
- *Sulfa drug!
- *counsel patient to avoid taking close to bedtime (or they will get up all night to pee!)
25
Loop diuretics: agents
Lasix (furosemide)
Demadex (torsemide)
Bumex (bumetanide)
26
Loop diuretics: MOA
Block Na/K pump in renal loop of Henle
27
Loop diuretics: ADRs
* Hyponatremia
* Hypokalemia
* Hypomagnesemia
* Dehydration
* Hyperuricemia
* Oxtotoxicity!
* Photosens.
* Rash
28
Loop diuretics: are they sulfa drugs?
All are sulfa drugs (EXCEPT Edecrin)
29
Loop Diuretics: PT counseling
\* Counsel patients to avoid taking close to bedtime (or they will get up all night to pee!)
30
Loop diuretics: considerations for lasix, demadex, bumex
\*Lasix-also available IV (2:1 conversion from PO)
\*Demadex-CYP2C9 substrate
\*Bumex-also available IV (1:1 conversion from PO)
31
Potassium Sparing diuretics: Agents
## Footnote
Aldactone (spironolactone)
Inspra (eplerenone, also CYP3A4 substrate)
Amiloride
Triamterene
32
Potassium Sparing diuretics: MOAs
* Aldosterone receptor antagonist (aldactone & eperenone)
* Epithelial sodium channel blocker (amiloride, triameterene)
33
Potassium Sparing diuretics: ADRs
Hyponatermia
Hyperkalemia
Gynecomastia (spironolactone)
**Amiloride & Triamterene**
Hyponatremia
Hyperkalemia
Metabolic acidosis
34
Special considerations: aldactone
aldosterone antagonist
| (K+ sparing)
35
Special considerations: Eplerenone
aldost. antag. CYP3A4 substrate
| (K+ sparing)
36
Angiotensin-converting enzyme inhibitor (ACEI): Agents
* Capotan (captropril)
* Accupril (quinapril)
* Prinivil (lisinopril)
* Alface (rarripril)
* Lotensin (benezapril)
* Vasotec (enalapril, enalaprilaf)
37
ACEi: MOA
Prevent conversion of angiotensin I \> angiotensin II, thereby inhibiting angiotensin II induced vasoconstriction and aldosterone secretion
38
ACEi: ADRs
* Hyperkalemia
* Dry cough
* Angioedema
* Rash
* Dysgeusia
39
ACEis: metabolism
\*most oral forms are pro-drugs requiring hepatic activation through hydrolysis
40
ACEis and AAs
\* AA’s diminished efficacy increased risk for angioedema
41
ACEis and pregnancy
avoid in pregnancy, women of childbearing potential
42
ACEi: cough
\*if dry cough occurs, trial another ACEI or switch to ARBs (less associated with cough d/t lack of effects on bradykinin)
43
ACEi: what to do if angioedema
angioedema occurs, avoid all ACEI and ARBs
44
ACEi: what to do if kidney issues
\* hold in setting of AKI, however have beneficial effect on CKD (dx stabilization and decreased proteinuria)
45
ACEi: what is important about captopril? (duration, SEs, PK)
short-acting; rare neutropenia, CYP2D6 substrate
46
ACEi: which is IV formulation
enalopril (Vasotec)
47
Angiotensin-receptor blockers (ARB): agents
* Cozaar (losartan)
* Diovan (valsartan)
* Teveten (eprosartan)
* Avapro (irbesartan)
* Mcards (teimisartan)
* Atacand (candesartan)
* Benicar (oimesartan)
48
ARBs: MOA
Blocks angiotensin receptor therby inhibiting vasoconstriction and aldosterone secretion
49
ARBs: ADRs
* Fatigue
* Diarrhea
* Hyperkalemia
* Cough
* Angioedema
50
ARBs & AAs
AA’s diminished efficacy increased risk for angioedema
51
ARBs: what to do if cough or angioedema assoc w/ACEi?
\* not associated with cough
\* avoid in pts with anaphylaxis or angioedema to ACEI less associated with cough & angioedema than ACEI
52
ARBs and pregnancy
Contraindication in pregnancy
53
ARBs: concomitant use w/ACEi or renin inhibitor?
increases risk of hypotension, hyperkalemia and renal dysfunction
54
Losartan metabolism
CYP3A4 substrate; CYP2C9 substrate & inhibitor
(ARB)
55
Irbesartan (Avapro): metabolism
CYP2C8 and CYP2C9 inhibitor
| (ARB)
56
Renin Inhibitors: Agents
Tekturna (Allskiren)
57
Tekturna (Allskiren): MOA
Inhibits renin therapy reducing angiotensin I, II and aldosterone
(Renin Inhibitor)
58
Tekturna (Allskiren): ADRs
Hyperkalemia
Diarrhea
(Renin Inhibitor)
59
Tekturna (Aliskiren): and renal impairment, diabetes, pregnancy
\*avoid in pts with renal impairment (CrCl \<80 ml/min) diabetes, or pregnancy
60
Sympathoplegic Central Acting: Agents
## Footnote
Clonidine, methyldopa
61
Clonidine: MOA
Central alpha 2 agonist decreases sympathetic and increases parasympathetic tone à reduced perpheral vascular resistance, bradycardia and reduced CO
(Sympathoplegic Central Acting)
62
Clonidine: ADRs
Abrupt withdrawal can result in hypertensive crisis
63
Sympathoplegic Central Acting: ADRs
* Sedation
* Depression
* Xerostomia
* Confusion
* Dizziness
* Hallucinations
* Nausea/vomiting
* Tinnitus
* Diaphoresis
* Sedation
* Confusion
* Nightmares (yuck!)
* Depression
* Vertigo
* Hemolytic anemia
* Hepatitis
* Drug fever
64
Methyldopa: MOA
Reduces peripheral vascular resistance
| (Sympathoplegic Central Acting)
65
Methyldopa: special consideration
\* primarily used in pregnancy
66
Adrenoreceptor Antagonists: Agents
Beta Blockers
Alpha Blockers
67
Adrenoreceptor Antagonists: BBs, agents
* Inderal (propranolol)
* Lopressor (metropolol)
* Tenomin (atenolol)
* Brevibloc (esmolol)
* Coreg (carvedilol)
* Transdate (labetalol)
* Bystolic (nebivolol)
68
BBs: MOA
Beta 1 antagonists reduce HR, myocardial contractility, peripheral vasc. Resistance, reduce renin release, some also have alpha-blocking effects (labetalol)
69
BBs: ADRs
Bradycardia
Bronchoconstriction (beta2 effects)
Contribute to hypoglycemia unawareness
Depression
Sexual dysfunction
70
BBs: efficacy
\*Agents w/direct vasodilating properties or alpha-block effects may be more effective for hypertension
\*Reduce mortality after MI, some in heart failure as well
71
BBs: discontinuation
Result in tachycardia
72
BBs: when to avoid
pts with depression, asthma
73
BBs: dosing consideration - who to dose differently, which most effective for BP
\*Chinese ancestry pts can require lower doses
usually ones w/alpha activity, like carvedilol, for BP
74
BB most likely to have CNS effects
propanolol -lipophillic. most likely to have central effects!
(BB)
75
BB that is Cardioselective
Atenolol, 1x daily PO
Esmolol, ultra-fast acting cont. IV infusion
76
Coreg (Carvedilol): formulations
avail as extended-release tab (not 1:1 conversion)
(BB)
77
Labetalol: formulations
available as extended-release tab, IV form
78
What distinguishes Nebivolol MOA from other BBs?
Nebivolol, unlike other beta-blockers, also produces an endothelium-derived nitric oxide-dependent vasodilation resulting in a reduction of systemic vascular resistance.
79
Alpha Blockers: Agents
## Footnote
* Cardura (doxazosin)
* Hytrin (terazosin)
* Minipress (prazosin)
80
Alpha Blockers: MOA
Alpha 1 receptor antagonists --\> vasodilation of veins and arterioles resulting in decreased peripheral vasc. resistance
81
Alpha Blockers: ADRs
* Ortho. Hypotension
* Dizziness
* Fatigue
* HA
* Rare priapism
82
Alpha Blockers: considerations in elderly
\*Most associated with orthostatic hypotension—avoid in elderly!
83
Alpha blockers: pt counseling
\*Titrate slowly, give dose at bedtime, advise patient to get up slowly from bed
84
Alpha blockers: other uses
Effective in tx of symptoms of BPH
85
Alpha blocker that is CYP3A4 substrate; longer 1/2 (22hr)
Cardura (doxazosin)
| (alpha blocker)
86
Terazosin: dosing consideration
may need to divide dose q12h combat wearing off or peak related hypotension
(alpha blocker)
87
Prazosin: dosing considerations & other use
short-acting; requires frequent dose admin. may be effective adjunct for PTSD-related nightmares
(alpha blocker)
88
Vasodilators - CCBs: agents
CCB:
Dihydropyridine
Norvasc (amlodipine)
Sular (nisoldipine)
Adalat CC (Nifedipine)
Cardene (nicardipine)
Cleviprex (clevidipine)
NON-dihydropyridine
Cardizem (dilitiazem)
Veralan (verapamil)
89
Dihydropyridine: MOA
Relax arterial smooth muscle resulting in peripheral vasodilation w/o significantly affecting cardiac rate or output
(Vasodilators: CCBs)
90
Dihydropyridine: ADRs
* Peripheral edema
* Flush!
* HA!
* Dizziness
(Vasodilators: CCBs)
91
Nifedipine for acute tx of hypertensive crisis?
\*Avoid immediate-release rifedipine for acute tx of hypertensive crisis d/t increased risk of heart attack, stroke and death! Avoid Nifedipine SL.
(Vasodilators: CCBs, dihydropyridine)
92
Vasodilators -CCB - NON-dihydropyridine: MOA
* Non-selective antagonism of L-type CC results in relaxation of arterial smooth muscle and peripheral vasodilation as well as depression of myocardial contractility thru decreased conduction rate of sinoatrial node and slowing of AV conduction
* \*Inhibit P-glycoprotein and CYP450 isoenzymes
(Vasodilators: CCBs, dihydropyridine)
93
Vasodilators -CCB - NON-dihydropyridine: ADRs
Bradycardia
Heart block
Constipation
Peripheral edema
94
Vasodilators -CCB - NON-dihydropyridine: Avoid in
\*Avoid in pts with heart failure secondary to systolic dysfunction d/t negative inotropic effects
\*Increased risk of complete heart block when used in conjunction with beta-blockers
95
Amlodipine, nisoldipine, Nifedipine, diltiazem: PK
CYP3A4 substrate
diltiazem is also 3A4 inhibitor
(Vasodilators: CCBs)
(diltiazem is dihydropyridine)
96
Clevidipine: formulations
only IV, ultra-short acting
| (Vasodilators: CCBs, dihydropyridine)
97
\*Verapamil: Formulations
-immediate sustained, extended-release and IV form. avail.(Vasodilators: CCBs, dihydropyridine)
98
Vasodilators - direct-acting: Agents
Hydralazine, Minoxidil
99
Hydralazine: MOA
Direct vasodilation of arterioles thru stimulation of nitric oxide release which results in decreased systemic resistance
(Vasodilators: direct-acting)
100
Hydralazine: ADRs
* Flush
* HA
* Dizziness
* Reflex tachycardia
* anorexia
* Diaphoresis
* Rare peripheral neuropathy
* Drug fever
(Vasodilators: direct-acting)
101
Hydralazine: Special considerations for Rxing - how and with whom
* \*Tachyphylaxis develops rapidly, more effective when used in combo with other agenst such as nitrates
* \*Can be particularly beneficial to AA pts with both HTN and heart failure
(Vasodilators: direct-acting)
102
Minoxidil: MOA
Direct vasodilation of arterioles --\> decreased systemic resistance
(Vasodilators: direct-acting)
103
Minoxidil: ADRs
* Flush
* HA
* Dizziness
* ECG changes (T wave)
* Peripheral edema
* Pericardial effusion
* Tachycardia
* Hypertrichosis
* Fluid retention
(Vasodilators: direct-acting)
104
Minoxidil: Special considerations: administer with..., can exacerbate...
* \*must administer w. diuretic to prevent edema
* \*can exacerbate heart failure!
(Vasodilators: direct-acting)
105
Vasodilators: Nitrates - agents
Nitroglycerin
Nitroprusside
106
Nitrates: MOA
Cause vasodilation of both venous and arteriolar vessels: increase cardiac output by decreasing afterload
107
Nitrates: ADRs
* Flush
* Tachycardia
* Palpitations
* Dizziness/HA
* Methemoglobinemia (nitroprusside)
* Delayed hypothyroidism (nitroprusside)
108
Nitrates: C/Is
\*Contraind. with PDE-5 inhibitors like Viagra (sildenafil)
(Vasodilator)
109
Nitrates: longterm use
\*Not appropriate for long term mgmt of HTN d/t rapid dev. of tolerance
\*When used for angina-require 10-12 hr nitrate free interval to avoid tolerance
110
Nitroglycerin: Indication
-used for tx of hypertensive emergency in pts w/o IV access
(Nitrates, Vasodilators)
111
Nitroprusside: dosing concern
ultra short-acting; risk of **cyanide toxicity** with prolonged/high doses!
(Vasodilator, nitrate)
112
Angioedema -- absolute C/I
ACEi
113
Bronchospastic Dz: Absolute C/I
BB
114
Depression: absolute C/I
Reserpine
115
Liver Dz: Absolute C/I
Methyldopa
116
Pregnancy: Absolute C/I
ACEi, ARB
117
Second or Third Degree Heart Block: Absolute C/I
BB, Nondihydropyridine CCB
