Hypertension

Question 0

AHA goals

Answer 0

Most with CVD :<140/90

Question 1

Drugs that cause or worsen hypertension

Answer 1

ACTH, alcohol, amphetamines, appetite suppressants, caffeine, Calcineurin antagonists (cyclosporine, tacrolimus), corticosteroids, decongestants, erythropoietin stimulating agents, estrogen, herbals (ginseng, guarana, St. John’s wort), mirabegron (mybetriq), NSAIDs, oncology drugs, SNRIs, thyroid hormone

Question 2

Lifestyle modifications

Answer 2

1. Weight control
2. Eating: DASH (high in fruits and veggies, low fat dairy, reduced sat. And total fat, reduced salt)
3. Reduced sodium intake: <2.4g /day
4. Inc. Physical activity
5. Alcohol limits 1/day women and 2/day men
6. Smoking cessation
7. CONTROL GLUCOSE AND LIPIDS TO REDUCE CV RISK

Question 3

First line per JNC8

Answer 3

1. African Americans and elderly: CCB or thiazide
2. White: ACE, ARB, CCB, THIAZIDE
3. CKD/Diabetes: ACE or ARB

Question 4

Goals per JNC 8

Answer 4

REVIEW

Question 5

Thiazides

Answer 5

Inexpensive, effective

MOA: work on DCT of the nephron and cause vasodilation (inhibit Na re absorption in the DCT causing inc. Sodium , potassium, H+ and water excretion)

Drugs: chlorthalidone (thalitone), HCTZ (microzide), metolazone (zaroxolyn), indapamide

Contra: hypersensitivity to Sulfa, anuria, and renal decompensation

Warning: sulfa allergy, electrolyte disturbances

Side effects: hypokalemia, hyperuricemia, elevated lipids, hyperglycemia, hypercalcemia, hyponatremia, hypomag, dizziness, photosensitivity, rash

Notes: May not be effective in pts with CrCl <30

Pregnancy category B

Question 6

Loops

Waste more potassium than others (May need supplement)

Answer 6

Mostly used for fluid in HF

MOA: inhibit reabsorption of Na and Cl in the thick ascending loop of Henle thus inc water excretion

Drugs: furosemide (lasix), bumetanide, torsemide (demadex), ethacrynic acid (edecrin)

Equivalency: (40:1:20:50)

BBW: profound dieresis

Warnings: sulfa allergy on all but ethacrynic acid

Side effects: hypokalemia, orthostatic hypotension, dec (Na, Mg, Cl, Ca), metabolic alkalosis, hyperuricemia, hyperglycemia, inc cholesterol, photosensitivity, ototoxicity, including hearing loss, tinnitus and vertigo (most with ethacrynic acid)

Monitoring: renal function, fluid status, BP, electrolytes, hearing

Notes: IV formulations are light sensitive (amber bottle); IV:PO for torsemide and bumetanide 1:1

Question 7

Potassium Sparing Diuretics

Answer 7

MOA: compete with aldosterone in DCT and collecting ducts increasing Na and water excretion while conserving potassium and H+

Drugs: amiloride (midamor), triamterene (dyrenium)(+ HCTZ is maxzide or dyazide), spironolactone (aldactone), eplerenone (inspra)

BBW: tumor risk (spironolactone)

Contra: renal impairment (CrCl <30), hyperkalemia

Side effects: hyperkalemia, inc. SCr

Spironolactone specific SE: gynecomastia, breast tenderness, impotence

Monitoring: check K+ before starting, BP, Scr/BUN

Question 8

Diuretic drug interactions

Answer 8

Loops can inc the ototoxic potential of other ototoxic drugs such as aminoglycosides and vancomycin and should not be used in comb with ethacrynic acid

Monitor if used win lithium as can inc toxicity

Avoid with NSAIDs as they inc Na & h2o retention

Question 9

RAAS inhibitors

Answer 9

Reduce vasoconstriction, decrease aldosterone release, and some agents have shown benefit in renal protection and heart failure

Caution if using two RAAS agents together such as an ace inhibitor, ARB, and Aliskiren. (monitor renal function, BP and potassium carefully)

Question 10

Major side effects with an ACE inhibitor or an ARB

Answer 10

Cough and angioedema (more common with an ace inhibitor)

Angioedema is a contraindication to any other agent in this class

Angioedema is most common in black patients and signs and symptoms include swelling of the lips, mouth, tongue, face, or neck

Question 11

Pregnancy considerations with RAAS inhibitors

Answer 11

Contraindicated

Question 12

ACE-Inhibitors

Answer 12

MOA: inhibit the angiotensin-converting enzyme preventing the conversion of angiotensin I to angiotensin II a potent vasoconstrictor thereby reducing blood pressure

Drugs: benazepril (Lotensin), captopril (Capoten), enalapril (Vasotec), lisinopril (prinivill, zestril), quinapril (accupril), Ramipril (Altace)

Benazepril and enalapril are twice-daily dosing most others are once daily

Blackbox warning: discontinue in pregnancy

Contraindications: angioedema, bilateral renal artery stenosis, cannot use concurrently with Aliskiren in patients with diabetes

Warning: caution when using more than one RAAS agent at the same time due to risk of hypertension, hyperkalemia, renal dysfunction

Side effects: cough, hyperkalemia, angioedema, hypotension, dizziness and acute renal insufficiency (captopril has many more SEs such as taste perversion and rash)

Monitoring: blood pressure, potassium, renal function

Notes: pregnancy category D

Question 13

ARBs

Answer 13

MOA: block angiotensin II from binding to the angiotensin II receptor on vascular smooth muscle and thus preventing vasoconstriction

Drugs: valsartan (Diovan), losartan (Cozaar), irbesartan (Avapro), candesartan (Atacand), Olmesartan (Benicar), telmisartan (micardis), azilsartan (Edarbi)

Blackbox warning: do not use in pregnancy

Contraindications: angioedema, bilateral renal artery stenosis, do not use with Aliskiren in patients with diabetes

Warning: caution with other RAAS agents; (Olmesartan only: spruce like enteropathy (severe diarrhea))

Side effects: angioedema, hyperkalemia, hypertension, dizziness and acute renal insufficiency

Monitoring: BP, potassium, renal function

Notes: pregnancy category D

Question 14

Direct Renin Inhibitor

Answer 14

MOA: directly inhibits renin which is responsible for the conversion of angiotensinogen to angiotensin one a potent vasoconstrictor thereby reducing BP

Drug: Aliskiren (Tekturna)

Blackbox warning: discontinue in pregnancy

Question 15

Beta blocker considerations

Answer 15

MOA: inhibits the effects of catecholamines especially norepinephrine at the beta-1 and beta-2 adrenergic receptors causing BP and HR reduction

Used for HTN, post-MI, angina, HF, and migraine prophylaxis (1st line in HTN no longer recommended)

Metoprolol and carvedilol often used for both HF and HTN (note dosage difference)

Beta-blockers with intrinsic sympathomimetic activity (cartelol, acebutolol, penbutolol, pindolol) show both stimulation and blockade at the beta receptor and thus are useful in patients with excessive bradycardia to meet beta blocker therapy

Beta-1 selective agents: (AMEBBA) atenolol, metoprolol, esmolol, bisoprolol, betaxolol and acebutolol

Propranolol has hives look at solubility and therefore penetrates the CNS called and C&S side effects such a sedation, depression, cognitive effects

Carvedilol: must be taken with food and is not milligram per milligram switch between CR and IR

Labetolol: first-line for hypertension in pregnancy

Caution when used in patients with a history of hypoglycemia as it can mask the symptoms (in these patients look for sweating and hunger as these are not masked)

Caution in patients with breathing problems such as asthma /COPD choose beta-1 selective agents in these patients at lower selective dosing

Question 16

Beta-1 selective beta blockers

Answer 16

Drugs: acebutolol (sectral), atenolol (tenormin), bisoprolol (zebeta), metoprolol tartrate (Lopressor), metoprolol succinate (Toprol XL)

Blackbox warning: do not withdraw abruptly particularly in patients with CAD, gradually taper over 1 to 2 weeks to avoid a cute tachycardia, hypertension, and or ischemia

Contraindications: sinus bradycardia, second or third degree heart block, sick sinus syndrome, or cardiogenic shock

Side effects: decreased HR, hypertension, fatigue, dizziness, depression, decreased libido, impotence, hyperglycemia, hypertriglyceridemia, weight gain, edema

Monitoring: HR, BP

Notes: caution and diabetes with recurrent hypoglycemia, asthma, severe COPD or resting limb ischemia

Caution: IV doses are not equivalent to oral doses

Question 17

Beta-1 selective blocker and nitric oxide dependent vasodilation

Answer 17

BBW, CONTRA, MONITORING: same for all BB

Drug: Nebivolol (Bystolic)

Side effects: headache, fatigue, dizziness, diarrhea, nausea, bradycardia, hypertriglyceridemia and decreased HDL

Notes: nitric oxide causes peripheral vasodilation

Question 18

Beta-1 and beta-2 nonselective beta blockers

Answer 18

Drugs: Nadolol (cogard), pentbutolol (levatol), pindolol, propranolol (Inderal LA, InnoPran XL), Timolol

Same considerations as other beta blockers

Question 19

Nonselective Alpha and beta blockers

Answer 19

Drugs: carvedilol (coreg, coreg CR), labetalol (Trandate)

Same considerations as other beta blockers

Carvedilol must be taken with food

Coreg 3.125=coreg CR 10mg, coreg 6.25=20mg, etc.

Question 20

Beta blocker drug interactions

Answer 20

1. Can enhance the effects of insulin and oral hypoglycemic agents therefore monitor BG carefully
2. Carvedilol: inc. digoxin and cyclosporine levels

Question 21

Dihydropyridine Calcium Channel Blocker

Answer 21

Uses: HTN and angina

MOA: inhibit calcium ions from entering the slow channels or voltage sensitive areas of vascular smooth muscle resulting in peripheral arterial vasodilation and decreasing peripheral resistance

Drugs: amlodipine (Norvasc), nifedipine ER (Adalat CC, Procardia XL, afeditab CR), nifedipine IR (Procardia), nicardipine (Cardene)

Side effects: peripheral edema, headache, Flushing, tachycardia/reflex tachycardia, gingival hyperplasia (least likely with amlodipine)

Monitoring: BP, HR, peripheral edema

Notes: do not use sublingual nifedipine as it may increase the risk of MI

Some capsule shells will be seen in the Feces

Question 22

Inpatient acute-care dihydropyridine CCB

Answer 22

Drugs: Clevidipine (cleviprex) IV only

other drugs that can be used IV: diltiazem, verapamil, nicardipine

Contraindications: do not using soy or egg allergy, acute pancreatitis, severe aortic stenosis

Side effects: headache, nausea/vomiting and other rare side effects such as hypertriglyceridemia and infections

Monitoring: BP, HR

Notes: in a lipid emulsion therefore it is milky white in color

Question 23

Non-dihydropyridine calcium channel blockers

Answer 23

Uses: primarily for arrhythmias to control/slow heart rate and sometimes for hypertension and angina

Class effect: negative inotropes that decrease contraction force and Negative chronotopes that decrease heart rate

MOA: inhibit calcium ions from entering the slow channels or voltage sensitive areas of the vascular smooth muscle and myocardium, resulting in coronary vasodilation

Drugs:

1. Diltiazem (Cardizem, Cardizem CD, Cardizem LA, Dilacor XR, Dilt – CD, Dilt-XR, Cartia XT, Tiazac, Taztia XT)
2. Verapamil (Calan, Calan SR, Covera HS, Verelan)

Contraindications: severe hypotension, second or third degree heart block, sick sinus syndrome, cardiogenic shock, acute MI and pulmonary congestion

Side effects: Adema, headache, AV block, bradycardia, hypertension, arrhythmias, HF constipation (more with verapamil), gingival hyperplasia

Monitoring: BP, HR, ECG

Question 24

Calcium channel blocker drug interactions

Answer 24

Diltiazem and verapamil are both CYP3A4 substrates and moderate three A4 inhibitors and they will raise the concentration of many other drugs and 3A4 inducers and inhibitors will affect their concentration Avoid grapefruit juice

Question 25

Centrally acting alpha-2 adrenergic agonist

Answer 25

MOA: stimulate alpha to adrenergic receptors in the brain which results in reduced sympathetic outflow from the CNS Drug: clonidine (Catapres, Catapres TTS patch), guanfacine (tenex (for ADHD intuniv)), methyldopa Clonidine is used commonly for resistant hypertension and patient you cannot swallow due to dysphasia or dementia sets it comes as a patch APPLIED WEEKLY (to upper/outer arm or chest) Side effects: bradycardia, dry mouth, drowsiness, sedation, lethargy, hypertension, depression, psychotic reactions, nasal stuffiness, sexual dysfunction Notes: rebound hypertension if stopped abruptly therefore do not stop abruptly you must taper

Question 26

Direct vasodilators: hydralazine

Answer 26

MOA: calls direct vasodilation on arterioles with little effect veins Side effects: headache, reflex tachycardia, palpitations, anorexia; rare: lupus like syndrome

Question 27

Direct vasodilator: minoxidil

Answer 27

Side effects: fluid retention, tachycardia, aggravation of angina, pericardial effusion, hirsutism

Question 28

Alpha Blockers

Answer 28

MOA: bind to alpha-1 adrenergic receptors which result in vasodilation of arterioles and veins; use mostly from BPH; not first line for hypertension Drugs: prazosin (minipress), terazosin (hytrin), doxazosin (cardura, cardura XL) Side effects: orthostatic hypotension, syncope with first dose, dizziness, fatigue, headache, fluid retention, priapism Notes: caution with concurrent use with a PDE five inhibitors such as sildenafil, vardenafil and avanafil due to additive effects on BP and dizziness

Question 29

Hypertensive urgency and emergency

Answer 29

Urgency: BP generally >/= 180/110-120 without acute target organ damage Emergency: urgency plus acute target organ damage such as encephalopathy, myocardial infarction, unstable angina, pulmonary edema, eclampsia, stroke, aortic dissection Treatment of urgency: oral medication with the onset of action of 15 to 30 minutes; reduced BP gradually over 24 to 48 hours Treatment of emergency: reduce mean arterial pressure by no more than 25% within minutes to one hour, then if stable, 260/100 with in the next 2 to 6 hours. use IV medication.

Question 30

Drugs used for hypertensive urgency

Answer 30

Captopril, clonidine, labetalol

Question 31

Drugs used in hypertensive emergencies

Answer 31

Clevidipine, sodium nitroprusside (Nitropress), nicardipine (Cardene), fenoldopam (corlopam), nitroglycerin, enalaprilat (vasotec IV), hydralazine, labetalol (trandate), esmolol (brevibloc)