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28 - Hypertension
Terms in this set (125)
Drugs that can increase BP
-Amphetamines and ADHD drugs
-decongestants (e.g., pseudoephedrine, phenylephrine)
-immunosuppressants (e.g., cyclosporine)
What natural products have some evidence for reducing blood pressure and overall cardiovascular risk?
Fish oil, coenzyme Q10, L-arginine, garlic
What are the four preferred drug classes recommended for initial and/or titration of treatment for hypertension?
ACE inhibitors, ARBs, CCBs, or thiazide diuretics
BP goal for hypertensive patients
Initial hypertensive drug selection for blacks?
thiazide or CCB
ACEI or ARBs are first line only when the patient has __________ or _____________.
CKD or albuminuria
What hypertensive drugs have a boxed warning for fetal toxicity in pregnancy and should be stopped immediately?
ACE inhibitors, ARBs and the direct renin inhibitor aliskiren
Pregnant patients with chronic hypertension should receive drug treatment if SBP is >/= ______ mmHg or DBP >/= _______ mmHg.
What drugs does ACOG recommend as first-line treatments for pregnant patients with hypertension?
Labetalol and nifedipine extended-release. Methyldopa is recommended but may be less effective at BP lowering.
Maxzide, Maxzide-25, Dyazide
Thiazide diuretics MOA
Inhibit sodium reabsorption in the distal convoluted tubules, causing increased excretion of sodium, chloride, water and potassium
12.5-25 mg daily
Hydrochlorothiazide (Microzide) dosing
12.5-50 mg daily
Contraindications to thiazide diuretics
Hypersensitivity to sulfonamide-derived drugs
What electrolytes are decreased with thiazide diuretics?
K, Mg, Na
What electrolytes are increased with thiazide diuretics?
Ca, UA (monitor this in a pt with gout), LDL, TG, BG
Photosensitivity is a side effect for what BP drug class?
Thiazide diuretics are not effective when CrCl <_____ml/min.
What is a clinical pearl for thiazide diuretics?
Take early in the day to avoid nocturia
Which thiazide diuretic is the only medication in this class available IV?
Drugs that cause sodium and water retention (e.g., ____________) can decrease the effectiveness of antihypertensive medications. Do not use in combination.
Thiazide diuretics can decrease ________ renal clearance and increase the risk of ____________ toxicity. Do not use in combination if possible.
What are dihydropyridine CCBs used for?
Hypertension, chronic stable angina and Prinzmetal's angina
Dihydropyridine CCBs MOA
Inhibit Ca ions from entering vascular smooth muscle and myocardial cells; this causes peripheral arterial vasodilation (which decreases SVR and BP) and coronary artery vasodilation. The peripheral vasodilation leads to common side effects of reflex tachycardia/palpitations, headache, flushing and peripheral edema.
What are the DHP CCBs?
Nicardipine IV (Cardene IV)
Nifedipine ER (Adalat CC, Procardia XL)
Clevidipine (Cleviprex) injection
Warnings for DHP CCBs?
Hypotension, worsening angina and/or MI, severe hepatic impairment, use caution in heart failure
Warnings for nifedipine IR
Do not use for chronic hypertension or acute BP reduction in non-pregnant adults (profound hypotension, MI and/or death has occurred)
Side effects of DHP CCBs
Peripheral edema/headache/flushing/palpitations/reflex tachycardia/fatigue, gingival hyperplasia (more gingival hyperplasia with non-DHPs)
What drugs are considered the safest if a CCB must be used to lower BP in heart failure with reduced ejection fraction?
Amlodipine and felodipine
What DHP CCB is considered a drug of choice in pregnancy?
DHP CCBs (e.g., nifedipine ER) are used to prevent peripheral vasoconstriction in ____________(i.e., cold/blue fingers)
Which BP drug has a contraindication to patient's with allergies to soybeans, soy products or eggs
Clevidipine (Cleviprex) injection
Warnings for Clevidipine (Cleviprex) DHP CCB injection?
Hypotension, reflex tachycardia, infections (use strict aseptic technique due to infection risk; maximum time of use after vial puncture is 12 hours)
Hypertriglyceridemia is a side effect of which DHP CCB? This drug is also a lipid emulsion (provides 2 kcal/mL); it is milky-white in color.
The non-DHP CCBs, verapamil and diltiazem, are primarily used to control ______ in certain arrhythmias (e.g., atrial fibrillation), and are sometimes used for hypertension and angina.
Non-DHP CCBs MOA
Inhibit Ca ions from entering vascular smooth muscle and myocardial cells, but they are more selective for the myocardium than the DHP CCBs
The decrease in BP produced by non-DHP CCBs is due to negative ____________ (decrease force of ventricular contraction) and negative ________________ (decrease HR) effects.
Warnings with non-DHP CCBs
Heart failure (may worsen symptoms), bradycardia
Side effects with non-DHP CCBs
Edema, constipation (more with verapamil) gingival hyperplasia
___________________ are used to reduce rapid heart rate in atrial fibrillation
CCBs should be cautiously used with other drugs that decrease HR, including ____________, _____________, ______________, ____________ and dexmedetomidine (Precedex).
Beta-blockers, digoxin, clonidine, amiodarone
All CCBs are major substrates of CYP450 3A4. Do not use with _________________.
Diltiazem and verapamil are substrates and inhibitors of P-gp and moderate inhibitors of CYP3A4, increasing the concentration of many other drugs. Patients who take statins should use lower doses of _____________ or ________________ or use a statin that is not metabolized by CYP3A4 (e.g., pitavastatin, pravastatin, rosuvastatin).
What drugs have been shown to slow the progression of kidney disease in patients with albuminuria?
ACE inhibitors and ARBs
How do ACE inhibitors and ARBs work in heart failure?
Protect the myocardium from the remodeling effects of Ang II.
RAAS inhibitors should not be used in combination (e.g, ACE inhibitor + ARB +______________+____________) due to an increased risk for adverse effects.
(T or F) angioedema is a potentially fatal adverse effect that can occur with use of ANY drug.
True; it is more common with ACE inhibitors, than with ARBs or aliskiren, and black patients have a higher risk
For testing purposes, if a patient develops angioedema with any RAAS inhibitor, other drugs in the class should be __________.
ACE inhibitor MOA
Block the conversion of angiotensin I (Ang I) to Ang II, resulting in decreased vasoconstriction and decreased aldosterone secretion. The block the degradation of bradykinin, which is thought to contribute to the vasodilators effects (and side effects of a dry and hacking cough and angioedema).
What is the boxed warning for ACE inhibitors?
Can cause injury and death to the developing fetus when used in the 2nd and 3rd trimesters; discontinue as soon as pregnancy is detected.
ACE inhibitor contraindications
-Do not use with history of angioedema
-Do not use within 36 hours of sacubitril/valsartan (Entresto)
Warnings for ACE inhibitors
Angioedema, hyperkalemia, hypotension, renal impairment, bilateral renal artery stenosis (avoid use)
Side effects of ACE inhibitors?
Can cause cough, hyperkalemia, increased SCr, hypotension/dizziness
Monitoring of ACE inhibitors
BP, K, renal function
ACEi, ARBs and direct renin inhibitors should not be used in patients with ______________________________.
Bilateral renal artery stenosis
What are the ACE inhibitor drugs?
-enalaprilat (Vasotec IV)
-lisinopril (Prinivil, Zestril)
Block Ang II from binding to the angiotensin II type-1 (AT1) receptor on vascular smooth muscle, preventing vasoconstriction
Compared to ACE inhibitors, ARBs are associated with what?
-no washout period required with sacubitril/valsartan (Entresto)
What are the ARBs?
What is the warning associated with olmesartan (Benicar)?
Sprue-like enteropathy - severe, chronic diarrhea with substantial weight loss; can occur months to years after drug initiation
MOA of aliskiren (Tekturna)
Directly inhibits renin, which is responsible for the conversion of angiotensinogen to Ang I. A decrease in the formation of Ang I results in a decrease in the formation of Ang II.
Contraindication to the use of direct renin inhibitor, aliskiren (Tekturna).
Do not use with ACE inhibitors or ARBs in patients with diabetes
If switching from an ACE inhibitor to Entresto, or vice versa, a ________ washout period is required.
_______________________ can decrease lithium renal clearance and increase the risk of lithium toxicity.
ACE inhibitors and ARBs
What drugs are the preferred add-on drugs in resistant hypertension (uncontrolled BP despite maximum tolerated doses of a CCB + thiazide diuretic + ACE inhibitor or ARB) and they are commonly used in heart failure.
Aldosterone receptor antagonists, spironolactone and eplerenone
This is a non-selective aldosterone receptor antagonist (also blocks androgen)
A selective aldosterone receptor antagonist that does not exhibit endocrine side effects
Where do potassium sparing diuretics act?
Distal convoluted tubule and collecting ducts of the nephron
Boxed warnings with potassium-sparing diuretics
Amiloride and triamterene: hyperkalemia (K > 5.5 mEq/L) - more likely in patients with diabetes, renal impairment, or elderly patients
contraindications to potassium-sparing diuretics
Do not use if hyperkalemia, severe renal impairment, Addison's disease (spironolactone) or taking strong CYP3A4 inhibitors (eplerenone)
Side effects of potassium-sparing diuretics
Hyperkalemia, increased serum creatinine, dizziness
Spironolactone side effects
Gynecomastia, breast tenderness, impotence
Monitoring of potassium-sparing diuretics
BP, K, renal function, fluid status, s/sx of HF
What are the potassium sparing diuretics?
Beta-blockers are no longer recommended first-line for ___________________ _____________ unless the patient has a comorbid condition for which the beta-blockers are recommended first-line (e.g., post-MI, stable ischemic heart disease, heart failure).
For most conditions, any beta-blocker can be selected, but ______________, _______________ or __________ should be used if treating chronic heart failure.
Bisoprolol, carvedilol, metoprolol succinate
Competitively blocks beta-1 and/or beta2 adrenergic receptors resulting in decreases in HR and myocardial contractility
Beta blockers with intrinsic sympathomimetic activity (ISA) (such as acebutolol, penbutolol, and pin do lol) do not decrease HR to the same degree as beta-blockers without ISA and are not recommended in _______________ patients.
Beta-1 selective blockers (atenolol, esmolol, metoprolol tartrate, metoprolol succinate ER, bisoprolol) are preferred in ________________ disease.
What are the beta-1 selective beta blockers?
What are the beta-1 selective blocker with nitric-oxide dependent vasodilation?
What are the beta-1 and beta-2 blockers (non-selective)?
Propanolol (Inderal LA, Inderal XL)
What are the non-selective beta-blocker and alpha-1 blockers?
Carvedilol (Coreg, Coreg CR)
What is the boxed warning with beta-1 selective blockers? (Atenolol, metoprolol, esmolol, bisoprolol, beta o lol, acebutolol)
Do not discontinue abruptly (particularly in patients with CAD/IHD); gradually taper dose over 1-2 weeks to avoid acute tachycardia, hypertension, and/or ischemia
Warnings for beta-1 selective blockers (atenolol, metoprolol, esmolol, bisoprolol, betaxolol, acebutolol)?
Use caution in patients with diabetes: can worsen hyperglycemia or hypoglycemia and mask hypoglycemic symptoms
What are the side effects for beta-1 selective blockers (atenolol, metoprolol, esmolol, bisoprolol, betaxolol, acebutolol)?
Bradycardia, fatigue, hypotension, dizziness, depression, impotence (less than thiazides), cold extremities (can exacerbate Raynaud's)
Metoprolol tartrate IV is not equivalent to PO! What is the IV:PO ratio?
All forms of ____________ and _____________ should be taken with or immediately following food.
Carvedilol and metoprolol
Which beta-blocker has high lipid solubility (lipophilic) and crosses the blood-brain barrier; it is associated with more CNS side effects but this makes it useful for other conditions (e.g., migraine prophylaxis, essential tremor)?
Non-selective beta-blockers (propanolol and nadolol) are used in ___________ _________________.
Carvedilol CR has less bioavailability than carvedilol IR; dosing conversions are not 1:1 (e.g., Coreg _______ mg BID = Coreg CR ____ mg daily
Dizziness is associated with ___________, which is the drug of choice in pregnancy.
What are the centrally-acting alpha-2 adrenergic agonists?
clonidine, guanfacine, methyldopa
Centrally-acting alpha-2 adrenergic agonists (clonidine, guanfacine, methyldopa) MOA?
Stimulate alpha-2 adrenergic receptors in the brain and reduce sympathetic outflow of norepinephrine, which decreases SVR and HR
What is clonidine commonly used for?
-patients who cannot swallow (e.g., due to dysphasia, dementia) since it is available as a patch formulation
Contraindications to the use of methyldopa
Concurrent use with MAO inhibitors and active liver disease
Warnings for centrally-acting alpha-2 adrenergic agonists
Do not discontinue abruptly(can cause rebound hypertension, sweating, anxiety, tremors); must taper gradually over 2-4 days
Warnings with methyldopa
risk for hemolytic anemia (detected by a positive Coombs test)
Side effects of centrally-acting alpha-2 adrenergic agonists
Dry mouth, somnolence, fatigue, dizziness, constipation, decrease HR, hypotension
Side effects with methyldopa
Hypersensitivity reactions [e.g., drug induced lupus erythematous (DILE)]
What are the instructions for the clonidine patch?
Apply weekly to a clean, dry and hairless area of skin on the upper outer arm or upper chest; remove before MRI; can apply the adhesive cover over the patch if it loosens
Which centrally-acting alpha-2 adrenergic agonist is a preferred drug in pregnancy?
What is the MOA of direct vasodilators (hydralazine, minoxidil)?
Cause direct vasodilation of arterioles, with little effect on veins. The result is a decrease in SVR and a reduction in BP
Drug-Induced Lupus Erythematosus (DILE) is a warning for which direct vasodilator?
What are the side effects of hydralazine?
Peripheral edema, headache, flushing, palpitations, reflex tachycardia
Which drug has a boxed warning for potent antihypertensive?
Side effects of minoxidil
Fluid retention, tachycardia, hair growth
Minoxidil is a direct vasodilator that is also available OTC for .....
Topical hair growth
(T or F) Alpha-blockers (e.g., doxazosin, prazosin, terazosin) are not recommended for hypertension.
MOA of alpha-blockers (doxazosin, prazosin, terazosin).
Bind to alpha-1 adrenergic receptors which results in peripheral vasodilation of arterioles and veins
Alpha-blockers (e.g., doxazosin, prazosin, terazosin) may be used in men who have hypertension and ___________________.
Benign prostatic hyperplasia
A rapidly accelerating BP (generally >/= 180/120 mmHg)
Patient has acute target organ damage that may be life-threatening (e.g., encephalopathy, stroke, acute kidney injury, acute coronary syndrome)
No evidence of acute target organ damage
Hypertensive emergency treatment
-treat with IV medications
-decrease BP by no more than 25% (within the first hour)
Hypertensive urgency treatment
-treat with any oral medication that has a short onset of action (e.g., 15-30 minutes).
-decrease BP gradually over 24-48 hours
Key IV hypertension medications
Chlorothiazide, Clevidipine, diltiazem, enalaprilat, esmolol, hydralazine, labetolol, metoprolol tartrate, nicardipine, nitroglycerin (vasodilator), nitroprusside (vasodilator), propanolol, verapamil
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