An#hypertensives. Drugs for Med Students. Presented by Eric Campbell & Jen Chen

Transcription

1 An#hypertensives Drugs for Med Students Presented by Eric Campbell & Jen Chen

2 Lifestyle Modifica#ons to Prevent and Manage HTN Modifica(on Recommenda(on Approximate Systolic Blood Pressure Reduc(on (mm Hg) a Weight loss DASH- type dietary paverns Reduced salt intake Physical ac#vity Modera#on of alcohol intake Maintain normal body weight (body mass index kg/m 2) Consume a diet rich in fruits, vegetables, and low- fat dairy products with a reduced content of saturated and total fat Reduce daily dietary sodium intake as much as possible, ideally to 65 mmol/ day (1.5g/day sodium or 3.8g/day sodium chloride) Regular aerobic physical ac#vity (at least 30 min/day, most days of the week) Limit consump#on to 2 drinks/day in men and 1 drink/day in women and lesser- weight persons 5 20 per 10- kg weight loss DASH, Dietary Approaches to Stop Hypertension a Effects of implemen#ng these modifica#ons are #me- and dose- dependent and could be greater for some pa#ents. Data from Chobanian et al., 1 and Kos6s et al. 24

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6 Diure#cs Subclass Drug (Brand Name) Usual Dose Range (mg/day) Daily Frequency Thiazides Chlorthalidone (Hygroton) Hydrochlorothiazide (Microzide) Indapamide (Lozol) Metolazone (Zaroxolyn) Loops Bumetanide (Bumex) Furosemide (Lasix) Torsemide (Demadex) Potassium sparing Amiloride (Midamor) or 2 Amiloride/hydrochlorothiazide (Modure#c) 5 10/ Triamterene (Dyrenium) or 2 Triamterene/hydrochlorothiazide (Dyazide) / Aldosterone antagonists Epleronone (Inspra) or 2 Spironolactone (Aldactone) or 2 Spironolactone/Hydrochlorothiazide (Aldactazide) 25 50/

7 Diure#cs: Side Effects HCTZ High: Calcium, uric acid, glucose, cholesterol, TG Low: Na, K, Mg, Zn Rash Photosensi#vity Furosemide Tinnitus Low: Na, K, Mg Spironolactone Hyperkalemia Gynecomas#a Eplerenone Hyperkalemia

8 Diure#cs: Contraindica#ons HCTZ Sulfa allergy Electrolyte disturbances Gout Ocular abnormali#es Furosemide Sulfonamide allergy Anuria Spironolactone Anuria Hyperkalemia Addison s disease or other condi#ons associated with hyperkalemia

9 Diure#cs Diure#cs are effec#ve in lowering BP by 10-15mmHg in most pa#ents Ohen provide adequate tx for mild- moderate essen#al HTN When HCTZ is used as monotherapy, lower doses (25-50mg) exert as much an#hypertensive effect as do higher doses In contrast to thiazides, BP response to loop diure#cs con#nue to increase at doses many #mes greater than the usual tx dose Chlorthalidone is more potent and longer ac#ng than HCTZ, and has the best outcome evidence But is used less than HCTZ for some reason!

10 ACEI / ARB Class Drug (Brand Name) Usual Dose Range (mg/day) Daily Frequency ACE inhibitors Benazepril (Lotensin) or 2 Captopril (Capoten) or 3 Enalapril (Vasotec) or 2 Fosinopril (Monopril) Lisinopril (Prinivil, Zestril) Moexipril (Univasc) or 2 Perindopril (Aceon) Quinapril (Accupril) or 2 Ramipril (Altace) or 2 Trandolapril (Mavik) ARBs Candesarten (Atacand) or 2 Eprosartan (Teveten) or 2 Irbesartan (Avapro) Losartan (Cozaar) or 2 Olmesartan (Benicar) Telmisartan (Micardis) Valsartan (Diovan)

11 Approved indications for ACEIs (2009) literature review for the purpose of formulary additions ACE Inhibitor Hypertension CHF Post MI Increased risk for CV Events Diabe(c Nephropathy Benazepril Captopril Cilazapril Enalapril Fosinopril Lisinopril Perindopril Quinapril Ramipril Trandolapril

12 ACE inhibitor- induced angioedema % of recipients. Incidence is up to 5X greater in people of African descent Can occur with any ACEI and is not dose- related. Lips, tongue, face, and upper airway. Less ohen, intes#ne. In >50% of cases, angioedema occurs during the 1st week of exposure, although it may occur any #me during the course of therapy from hours to years aher treatment.

13 How do I recognize angioedema?

14 ACE inhibitor- induced angioedema

15 ACE inhibitor- induced angioedema Tx: D/C ACEI. Airway management as needed. Addi#onal therapies may be helpful for severe or persistent symptoms. Some ps experience 1 recurrent angioedema episodes in the months aher the ACEI has been discon#nued % rate of recurrent angioedema in pts with a hx of ACEI- induced angioedema that were switched to an ARB. may be misleading and avributable to pts having addi#onal episodes of angioedema in the weeks to months aher the ACEI is discon#nued. UpToDate: Given the current evidence, we do not feel that use of ARBs should be avoided in pa#ents with ACE inhibitor- induced angioedema, if ARBs offer an advantage over other an#hypertensives for that individual pa#ent. Clinical judgment

16 ACEI/ARB: Side Effects Dry cough (ACEI) Higher incidence in East Asian, female Hypotension Hyperkalemia ARF (High Scr) However, expect to see an increase of Scr up to 30% within 2 weeks of star#ng ACEI/ARB Angioedema (esp in blacks) Rash (esp Captopril) Headache (ACEI > ARB) Dizziness (ACEI > ARB)

17 ACEI/ARB: Contraindica#ons Pregnancy Hx of angioedema Concern pre- contrast Hyperkalemia Bilateral renal artery stenosis not an absolute contraindica#on Solitary kidney stenosis if only 1 kidney Not an absolute contraindica#on

18 More on Renal Artery Stenosis Manufacturers of ACEI and ARBs cau#on against use of these agents for the pharmacologic management of hypertension in pa#ents with renal artery stenosis; however, such treatment is not absolutely contraindicated in these pa#ents. If ACEI/ARB interrupted RAAS in a pt with renal artery stenosis, blood flow through the kidney would decrease, eventually leading to renal failure. Thus, both ACEI and ARBs theore#cally can contribute to the development of acute renal failure in pa#ents with renal artery stenosis. Literature supports being cau#ous with the use of ACEI in this clinical sewng, but literature is lacking in its support of using such cau#on with ARBs.

19 ACEI/ARB Less effec#ve in blacks but s#ll use for compelling indica#ons (MI, HF, CKD) Combina#on of ACEI + ARB: No bever CV benefit Increased SE (hypotension, hyperkalemia, worse renal outcome) Small benefit in proteinuria and persistent HF

20 Calcium Channel Blockers Subclass Drug (Brand Name) Usual Dose Range (mg/day) Daily Frequency Dihydropyridines Amlopidine (Norvasc) Felopidine (Plendil) Isradipine (DynaCirc) Isradipine SR (DynaCirc SR) Nicardipine (Cardene SR) Nifedipine long- ac#ng (Adalat CC, Procardia XL) Nisoldipine (Sular) Nondihydropyridines Dil#azem SR (Cardizem SR) Dil#azem SR (Cardizem CD, Car#a XT, Dilacor XR, Dil#a XT, Tiazac, Taz#a XT) Dil#azem ER (Cardizem LA) (morning or evening) Verapamil SR (Calan SR, Isop#n SR, Verelan) or 2 Verapamil ER (Covera HS) (in the evening) Verapamil oral drug absorp#on system ER (Verelan PM) (in the evening)

21 CCB: Side Effects Edema (DHP > Non- DHP) Cons#pa#on (esp Verapamil) Dizziness Headache Flushing Rash Dyspnea & pulmonary edema

22 CCB: Contraindica#ons Avoid dil#azem & verapamil if WPW HF Systolic dysfunc#on Recent MI with pulmonary edema, SSS with 2 nd or 3 rd deg AV block, severe hypotension

23 CCB Preferred for pts >55yo and blacks Preferred in vasospas#c angina Alternate in diabe#cs, CAD (with ACEI), and angina Non- DHP useful for AF and SVT s Other uses: esophageal disorders, migraine, panic avack, Raynaud s, thyrotoxicosis, tardive dyskinesia, ToureVe s

24 FYI: Nimodipine CCB NOT used as an an#hypertensive Indica#on: Subarachnoid Hemorrhage greater effect on cerebral arterials than other arterials due to increased lipophilicity and cerebral distribu#on Dose: 60 mg every 4 hours for 21 consecu#ve days, start within 96 hours of onset of SAH

25 Beta- Blockers Subclass Drug (Brand Name) Usual Dose Range (mg/day) Daily Frequency Cardioselec(ve Atenolol (Tenormin) Betaxolol (Kerlone) Bisoprolol (Zebeta) Metoprolol tartrate (Lopressor) Metoprolol succinate (Toprol XL) Nonselec(ve Nadolol (Corgard) Propranolol (Inderal) Propranolol long- ac#ng (Inderal LA, InnoPran XL) Timolol (Blocadren) Intrinsic sympathomime(c ac(vity Acebutolol (Sectral) Carteolol (Cartrol) Penbutolol (Levatol) Pindolol (Visken) Mixed α- and β- blockers Carvedilol (Coreg) Carvedilol phosphate (Coreg CR)

26 Cardioselec#ve Beta- Blockers Cardioselec#ve BB is advantageous in tx hypertensive pts who also suffer from asthma, diabetes, or PVD. Eg. Metoprolol causes less bronchial constric#on than propranolol at doses that produce equal beta blockade. HOWEVER, cardioselec#vity is not complete, and asthma#c symptoms have been exacerbated by metoprolol Cardioselec#vity may be lost at higher dosages.

27 ISA Beta- Blockers BB with intrinsic sympathomime#c ac#vity (ISA) are par#al agonists that lower BP by decreasing vascular resistance They depress CO or HR less than other BB Beneficial for pts with bradyarrhythmias or PVD

28 Bradycardia Bronchospasm Mask & delay hypoglycemia Increase TG Decrease HDL Fa#gue Insomnia Vivid dream Impotence Decreased exercise tolerance Dizzy Cold extremity Hallucina#on Depression BB: Side Effects

29 BB: Contraindica#ons Asthma (selec#ve BB may be safe in mild- mod asthma) 2 nd or 3 rd degree heart block, or PR >0.24sec Uncompensated HF Severe PAD Pheochromocytoma (if no alpha blockade first)

30 BB BB are inferior for first- line HTN tx in the elderly who do not have HF or angina Pts > 60yo with IHD or HF should s#ll be prescribed BB In older pts, BB could be added as a 3 rd or 4 th agent for HTN Metoprolol is a good choice, as it is inexpensive and proven to reduce mortality in pa#ents with a history of MI or heart failure. Taper over 2-4 weeks if discon#nuing Sudden withdrawal can increase angina/mi BB overdose: glucagon IV, calcium gluconate IV, epinephrine, insulin, sodium bicarb

31 FYI: The Many Uses of BB Propranolol Essen#al tremor Migraine headache prophylaxis Pheochromocytoma Thyroid storm Variceal hemorrhage prophylaxis Nadolol Thyrotoxicosis Variceal hemorrhage prophylaxis

32 Alterna#ve An#hypertensive Agents Class Drug (Brand Name) Usual Dose Range (mg/day) Daily Frequency α 1 - blockers Doxazosin (Cardura) Prazosin (Minipress) or 3 Terazosin (Hytrin) or 2 Direct renin inhibitor Alikiren (Tekturna) Central α 2 - agonists Clonidine (Catapres) Clonidine patch (Catapres- TTS) weekly Methyldopa (Aldomet) Peripheral adrenergic antagonist Reserpine (generic only) Direct arterial vasodilators Minoxidil (Loniten) or 2 Hydralazine (Apresoline) to 4

33 FYI: Prazosin PTSD- related nightmares and sleep disrup#on BPH Raynaud s Topical Minoxidil (Rogaine) Alopecia Clonidine Nico#ne withdrawal symptoms Chronic pain management

34 Treatment of Chronic HTN in Pregnancy Methyldopa β- blockers Labetalol Clonidine Drug/Class Calcium channel blockers Diure(cs Angiotensin- conver(ng enzyme inhibitors, angiotensin II receptors, and direct renin inhibitors Comment Preferred agent based on long- term followup data suppor#ng safety Generally safe, but intrauterine growth retarda#on reported Increasingly preferred over methyldopa becayse of fewer side effects Limited data available Limited data available; no increase in major teratogenicity with exposure Not first- line agents but probably safe in low doses if used chronically prior to concep#on Contraindicated; major teratogenicity reported with exposure (fetal toxicity and death)

35 Parenteral An#hypertensives for Hypertensive Emergency Sodium nitroprusside Drug Dose Onset (min.) Dura(on (min.) mcg/kg/min intravenous infusion (requires special delivery system) Immediate 1 2 Nicardipine hydrochloride 5 15 mg/h intravenous ; may exceed 240 Fenoldopam mesylate mcg/kg/min intravenous infusion <5 30 Nitroglycerin mcg/kg intravenous infusion Hydralazine hydrochloride mg intravenous; mg intramuscular Labetalol hydrochloride mg intravenous bolus every 10 min; mg/min intravenous infusion Esmolol hydrochloride mcg/kg/min intravenous bolus, then mcg/kg/min intravenous infusion; may repeat bolus aher 5 minutes or increase infusion to 300 mcg/kg/min 10 20; ;

36 Monitoring Class Diure(cs Aldosterone antagonists Angiotensin- conver(ng enzyme blockers Angiontensin receptor blockers Calcium channel blockers β- blockers Parameters Blood pressure, blood urea nitrogen (BUN)/serum crea#nine, serum electrolytes (potassium, magnesium, sodium), uric acid (for thiazides) Blood pressure, BUN/serum crea#nine, serum potassium Blood pressure, BUN/serum crea#nine, serum potassium Blood pressure, BUN/serum crea#nine, serum potassium Blood pressure; heart rate Blood pressure; heart rate

37 Fixed- Dose Combina#on Products Combina(on ACE inhibitor with a thiazide diure(c ARB with a thiazide diure(c β- blocker with a thiazide diure(c ACE inhibitor with calcium channel blocker ARB with calcium channel blocker

38 Fixed- Dose Combina#on Products Advantages Less pill burden Combina#on products with ACEI/ARB and a diure#c - > synergis#c low- dose combos - > decreases BP more than doubling the ACEI/ARB dose Disadvantages Can t #trate dose $$$

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