1. Antianginal Agents and Hypotensive Agents
馬偕紀念醫院藥劑室
林育成藥師

2. Amlodipine besylate (Norvasc)
Form: Tab:5mg
Dosage:
Hypertension: Initial 2.5-5mg qd, MD 5-10mg qd, Max. 10mg/day
Angina: 5-10mg qd, MD 10mg qd

3. Amlodipine besylate (Norvasc)
Precautions
aortic stenosis
CHF
exacerbation of angina during initiation of therapy, after dose increases, or withdrawal of beta blocker therapy
hypotension (initially or after dose increases)
liver impairment
persistent progressive dermatologic reactions

4. Amlodipine besylate (Norvasc)
Dose adjustments:
renal impairment: NOT recommended in patients with severe renal impairment (CrCl below 30 mL/min/1.73m(2), serum creatinine >/=3 mg/dL)
liver disease: starting dose, 2.5 mg/10 mg
geriatrics: starting dose, 2.5 mg/10 mg

5. Isosorbide dinitrate (Isordil, Sorbitrate tab, Isoket inj)
Dose:
Oral, initial 5-20 mg q6h, MD 10-40mg q6h ac,
IV infusion, 2-7mg/hr, up to 10mg/hr
Note:
Dosing interval may be bid or tid and last dose no later than 7 PM to minimize nitrate tolerance

6. Isosorbide mononitrate (Imdur CR)
Form: Tab: 60mg (extended release)
Dose:
Initial 30mg qd for 2-4 days then mg qd
Note:
should be taken in the morning
should be swallowed whole not chewed, but it can be administered half of a tablet at a time

7. Isosorbide monotrate (ISMO-20, Isormol)
Form: Tab:20mg
Dose:
Initial 10mg bid for 2 days then 20-30mg bid
Note:
Asymmetrical dosing regimen of 7AM and 3PM or 9AM and 5PM to allow for a nitrate-free dosing interval to minimize nitrate tolerance
Do not crush or chew but can cut half

8. Isosorbide monotrate (ISMO-20, Isormol)
Administration:
administer 0.5 hr before or 1 hr after meals
do not crush or chew extended release dosage forms
dose to provide a hr drug-free interval

9. Drug-drug interaction: Organic nitrate and Sildenafil (Viagra)
SILDENAFIL inhibits phosphodiesterase type 5 (PDE5) which is responsible for the metabolic degradation of cyclic guanosine monophosphate (cGMP).
Organic nitrates exert their action by activation of guanylate cyclase, which increases cGMP. Because of the potential for excessive hypotensive effects as a result of increased cGMP, the concomitant use of sildenafil and organic nitrates is contraindicated

10. Diltiazem HCl (Herbesser, Cartil)
Form: Tab:30mg
Dose:
angina: start with 30mg qid ac, increase dosage gradually until optimal response, average mg/ day divide into 3-4 doses

11. Diltiazem HCl (Diltelan SR)
Form: Cap: 90mg (controlled release)
Dose: Initial 90mg bid for 2 wks, may increase gradually to 360mg/day div. into 2 dose
Hypertension: mg/day
Angina: 240mg/day
Note: Swallow whole; do not open, chew or crush the capsules

12. Nicorandil (Sigmart)
Form: Tab:5mg
Dose: 5-20 mg bid, Max. 30mg bid

13. Mechanism of Nicorandil (Sigmart)
Nicorandil : potassium channel openers or activators, which produce vascular smooth muscle relaxation by increasing potassium flux through adenosine triphosphate (ATP)-sensitive sarcolemmal potassium channels
This leads to hyperpolarization of the cell membrane, and subsequent decreases in levels of cytoplasmic calcium (calcium channel blockade) and dilation of arterial resistance vessels

14. Nifedipine (Adalat OROS)
Form: Tab:30 mg (extended release)
Dose: initial 30mg once daily, may be increased to 120mg once daily if needed
Note: Swallow whole; do not crush or chew

15. Nitroglycerin (Glyceryl trinitrate, NTG, Nitrostat tab, Tridil inj)
Form: Tab:0.6mg, inj:50 mg/10ml amp
Dose:
Sublingal, mg every 5 min for max. of 3 doses in 15 min
IV infusion, initial 5mcg/min then increased by 5mcg/min at 3-5 min intervals until a response is noted or the rate is 20mcg/min

16. Nitroglycerin lingual aerosol
Form: Aerosol: 0.4mg/spray, 200 sprays/set
Dose:
Acute relief of angina pectoris: 1-2 srpays ( mg) every 3-5min if necessary , Max. of 3 doses in 15 min
Prophylaxis angina pectoris: 1-2 sprays, 5-10min before situations

17. Antiadrenergic agents-centrally acting
Clonindine HCl (Catapres)
Methyldopa (Aldomet)

19. Captopril (Capoten) Form: Tab:25mg
Dose: Hypertension : Initial mg bid-tid ac, the dosage being increased to 50mg bid-tid if necessary after 1 or 2 wks CHF: Initial 25mg tid ac, the dosage being increased up to 50mg tid; if further increased in dosage, it is made after an interval of 2 wks, MD mg bid-tid, Max. 450mg/day

20. Cotraindication of Capoten
A. Angioedema induced by other angiotensin converting enzyme (ACE) inhibitors during prior exposure
B. Anuric renal failure during prior exposure to ACE inhibitors
C. Hypersensitivity to this or any other ACE inhibitor
D. Hereditary or idiopathic angioedema
E. Pregnancy (second and third trimesters particularly

21. Enalapril maleate (Renitec)
Form: Tab:20mg
Dose:
Hypertension: Initial 2.5~5mg/day, MD 10-40mg/day divide into 1-2 doses
CHF: initial 2.5mg qd-bid, MD 5-20mg/day divide into 1-2 doses, Max. 40mg/day

22. Enalapril maleate (Renitec)
MECHANISM :
Enalapril is a weak angiotensin-converting enzyme inhibitor; however, hepatic activation of enalapril to enalaprilat being 10 to 20 times as potent as captopril

23. Enalapril maleate (Renitec)
Precautions:
ACE-inhibitor induced angioedema
apheresis (low-density lipoprotein) with dextran sulfate
CHF, severe (oliguria and/or progressive azotemia may occur)

24. Fosinopril Sodium (Monopril)
Form: Tab: 10mg
Hypertension: initial 10mg qd, MD 20~40mg/day qd or bid up to 80mg/day
CHF: initial 10mg qd, MD 20~40mg/day

25. Fosinopril Sodium (Monopril)
Mechanism :
Fosinopril is a prodrug and must undergo reesterification to its biologically active diacid metabolite, fosinoprilat. Fosinopril has a phosphinic acid binding site and lacks the sulfhydryl group characteristic of captopril

26. Fosinopril Sodium (Monopril)
Precautions
ACE-inhibitor induced angioedema
apheresis (low-density lipoprotein) with dextran sulfate
CHF, severe (oliguria and/or progressive azotemia may occur)
collagen vascular disease, especially in presence of renal impairment (risk of neutropenia, agranulocytosis)

27. Perindopril tert-butylamine (Acertil)
Form: Tab: 4mg
Dose:
Hypertenision: Initial 2mg qd, MD 4mg/day, Max. 8mg/day, Max. 8mg/day ac CHF: Initial 2mg qd, MD 4mg/day ac

28. Perindopril tert-butylamine (Acertil)
Mechanism:
Perindopril is an ester prodrug, requiring in vivo hydrolysis to its active diacid metabolite, perindoprilat
Perindoprilat is a long-acting, non-thiol angiotensin converting enzyme (ACE) inhibitor

29. Rampril (Tritace) Form: Cap: 2.5mg
Dose: Hypertension: initial mg qd, MD 2.5-5mg as a single dosage or in 2 divided doses. Max. 10mg/day CHF post-MI: initial 2.5mg bid, if hypotension occurs,dosage should be reduced to 1.25mg bid. MD 5mg bid

30. Rampril (Tritace) Mechanism :
Ramipril is a prodrug that undergoes enzymatic saponification by esterases in the liver to its biologically active metabolite, ramiprilat. Ramipril is a long active angiotensin converting enzyme inhibitor with hypotensive effects lasting a full 24 hours with single daily dosing.

32. Clonidine (Catapres) Form: Tab:75mcg Dose:
Initial mg bid, may be increase by mg/day,
MD mg/day divide into 2-4 doses,
Max. 2.4mg/day

33. Methyldopa (Aldomet) Form: Tab:250mg Dose:
Initial 250mg bid-tid for 2 days then being adjusted until the desired response is obtained,
MD 500mg-2g/day divide into 2-4 doses

35. Alfuzosin HCl (Xatral XL)
Indication:
Benign prostatic hyperplasia
Form: Tab:10mg (prolonged release)

36. Alfuzosin HCl (Xatral XL)
A. Alfuzosin: a selective -1 adrenoceptor antagonist.
B. dosing information:
benign prostatic hyperplasia :7.5 to 10 mg daily;
hypertension, 5 to 10 mg twice daily.
Dose reductions are suggested in patients with liver disease, and in the elderly.

37. Alfuzosin HCl (Xatral XL)
CONTRAINDICATIONS
A. Concomitant use of potent CYP3A4 inhibitors (eg, ketoconazole, itraconazole, ritonavir)
B. Hepatic insufficiency (moderate to severe)
C. Hypersensitivity to alfuzosin or other quinazolines

38. Alfuzosin HCl (Xatral XL)
Precautions:
A. Carcinoma of the prostate and benign prostatic hyperplasia may cause the same symptoms and frequently coexist. Prostate cancer should be ruled out prior to treatment.
B. Concomitant use of other alpha-blockers
C. Congenital or acquired QT prolongation syndromes
D. Coronary artery disease

39. Alfuzosin HCl (Xatral XL)
Precautions:
E. General anesthesia
F. Hepatic disease (mild)
G. Dizziness, lightheadedness
H. Orthostatic hypotension
I. Renal dysfunction (severe)
J. Syncope (First-dose effect)

40. Doxazosin (Doxaben) Indications Form: Tab: 1mg
Benign prostatic hyperplasia
Hypertension
Form: Tab: 1mg
Dose: Initial 1mg qd, MD 2mg qd, if necessary subsequent dosage adjustments can be made by doubling the dose every 2 wks, Max. 16mg/day

41. Doxazosin (Doxaben) Precautions carcinoma of the prostate
concomitant use of other antihypertensives (additive hypotensive effects)
first dose syncope/ sudden loss of consciousness
liver disease
orthostatic hypotension, syncope
recent cerebrovascular accident

42. Doxazosin (Doxaben) Administration
first dose phenomenon characterized by excessive postural hypotension, palpitations, syncope, and tachycardia can be minimized by limiting the initial dose to 1 mg, administering the first dose at bedtime, and increasing the dosage slowly

43. Terazosin Form: Tab: 2mg Dose:
Hypertension: Initial 1mg hs, may be increased gradually to 5mg/day, Max. 20mg/day
Benign prostatic hyperplasia: Initial 1mg hs, may be increased in a stepwise manner to 2,5 and 10mg/day as necessary, Max. 20mg/day

45. Acebutolol Hydrochloride (Sectral)
Angina: mg ORALLY daily (divided 2-3 times/day)
Arrhythmias: initial, 400 mg ORALLY daily (divided twice a day); maintenance, mg ORALLY daily (divided 2-3 times/day)
Hypertension: initial, 400 mg ORALLY daily; maintenance, mg ORALLY daily (may be divided twice a day); MAX 1200 mg/day (divided twice a day)

46. Acebutolol Hydrochloride (Sectral)
Dose Adjustments
geriatric: may require lower maintenance doses (specific guidelines unavailable); doses above 800 mg/day should be avoided
renal impairment: CrCl less than 50 mL/min - reduce usual adult dose by 50%
renal impairment: CrCl less than 25 mL/min - reduce usual adult dose by 75%

47. Acebutolol Hydrochloride (Sectral)
FDA labeled indications
Arrhythmia
Hypertension
Non-FDA labeled indications
Angina pectoris

48. Acebutolol Hydrochloride (Sectral)
Contraindications
cardiogenic shock
hypersensitivity to acebutolol
overt cardiac failure
second and third degree AV block
severe sinus bradycardia

49. Atenolol (Tenormin) Form: Tab: 50mg
Hypertension (HTN): mg ORALLY once daily

50. Atenolol (Tenormin) Dose Adjustments:
hemodialysis: mg after each dialysis session
renal impairment: CrCl 35 mL/min or greater - normal dosing
renal impairment: CrCl mL/min - MAX dose 50 mg once daily
renal impairment: CrCl less than 15 mL/min - MAX dose 25 mg once daily

51. Atenolol (Tenormin) Contraindications cardiogenic shock
hypersensitivity to atenolol
overt cardiac failure
second and third degree AV block
severe sinus bradycardia

52. Atenolol (Tenormin) Precautions(1):
anesthesia/surgery (myocardial depression)
avoid abrupt withdrawal
bronchospastic disease
congestive heart failure
diabetes mellitus
hyperthyroidism/thyrotoxicosis

53. Atenolol (Tenormin) Precautions(2):
patients receiving clonidine - discontinue atenolol several days prior to withdrawal of clonidine
peripheral vascular disease
pregnancy
renal impairment

54. Betaxolol HCl (kerlone)
FDA labeled indications
Glaucoma/Ocular hypertension
Hypertension
Non-FDA labeled indications
Angina pectoris

55. Betaxolol HCl (kerlone)
Dosage, Adult (usual)
Angina: 5-80 mg once daily
Glaucoma/ocular hypertension: 1-2 drops (0.25% suspension) twice daily
Hypertension: initial, 10 mg once daily, maintenance, mg once daily

56. Bisoprolol fumarate (Concor 5)
Form: Tab: 5mg
Dosage:Dosage, Adult (usual)
Angina: 5-20 mg once daily
CHF: initial, 1.25 mg once daily, titrate to maximum dose of 10 mg once daily
HTN: initial, mg once daily, maintenance, mg once daily, maximum dose, 40 mg once daily

57. Bisoprolol fumarate (Concor 5)
Dose adjustment:
hemodialysis: dose replacement is not necessary
liver disease: initial, 2.5 mg once daily
liver disease: maximum dose, 10 mg once daily
renal impairment: initial, 2.5 mg once daily
renal impairment: maximum dose, 10 mg once daily

59. Carvedilol (Dilatrend)
Form: Tab: 6.25mg, 25mg
Dose:
Hypertension: Initial 6.25mg bid for 1-2 wks, then increased to 12.5mg bid, Max. 50mg/day

60. Carvedilol (Dilatrend)
Dose Adjustments:
hemodialysis: dosing adjustments are NOT required
liver disease: initial, 20% of the normal dose

61. Carvedilol (Dilatrend)
FDA labeled indications
Congestive heart failure
Hypertension
Postmyocardial infarction with left ventricular dysfunction
Non-FDA labeled indications
Angina pectoris

62. Carvedilol (Dilatrend)
Contraindications
bronchial asthma or chronic obstructive pulmonary disease
cardiogenic shock
hypersensitivity to carvedilol
overt cardiac failure
second and third degree AV block
severe liver failure
severe sinus bradycardia
sick sinus syndrome

63. Labetalol HCl (Trandate)
Indications
FDA labeled indications
Hypertension
Non-FDA labeled indications
Angina pectoris

64. Labetalol HCl (Trandate)
Dosage:
Oral, initial 100mg bid; may increase as needed every 2-3 days by 100mg bid until desired response is obtained; MD, mg bid, Max. 2-4g/day
IV, 20 mg over 2 min , additional 40mg or 80 mg may be given at 10 min intervals until the desired BP is achieved or to a total dose of 300mg
Infusion, 200 mg is added to ml of IV fluid administered at rate of 2mg/ min, the dosage is adjusted according to BP response

65. Calcium channel blocking agents
1.Benzothiazepine gr.
2. Didydropyridine gr.
3. Phenylalkylamine gr.

68. Nimodipine (Nimotop) Form: Inj: 0.2mg/ml, 50ml/vial
Dose:Neurological deficits following subarachonoid hemorrhage: IV infusion, initial 1mg/h for 2hrs then increased to 2mg/h; if patients<70kg o r with unstable BP, initial dose<0.5mg/h, infusion should be continued for at least 5 days and nor more than 14 days/

69. Isardipine (Dynacirc SRO)
Form: Cap: 5mg (sustained release)
Dose: Initial, 5mg qd, may be adjusted in increasements of 5mg/day at 2-4 wks intervals, Max. 20mg/day
Note: swallow whole

70. Felodipine (Plendil) Form: Tab: 5mg (extended release)
Hypertension: initial 5mg qd, MD 5-10mg qd, Max. 20mg qd
Note: Swallow whole; do not crush or chew

71. Hydralazine HCl (Apresoline, Aprezin)
Form: Tab: 10mg, 50mg, Inj: 20mg powder in amp
Dose: oral: initial 10mg qid for the first 2-4 days then increased by 10-25mg with meals, Max. 300mg/day divide into 4 doses
IM, slow iv, 20-40mg

72. Hydralazine HCl (Apresoline, Aprezin
Contraindication:
A. Previous hypersensitivity to hydralazine, dihydralazine, or cadralazine
B. Dissecting aortic aneurysm

73. Hydralazine HCl (Apresoline, Aprezin
Precautions
A. Coronary artery disease
B. History of cerebrovascular disease or stroke
C. Renal insufficiency
D. Hydralazine-induced systemic lupus erythematosus

74. Hydralazine HCl (Apresoline, Aprezin
Precautions:
E. Resulting peripheral neuropathy may be related to pyridoxine deficiency.
F. Hydralazine may reduce the pressor responses to epinephrine.
G. Apresoline(R) tablets may contain FD+C yellow 5 (tartrazine).

75. Minoxidil (Loniten) Form: Tab:10mg
Dose; Initial 2.5-5mg qd, can be increased at least 3 days intervals to 10,20 then 40mg in single or divided doses; ususal dose 10-40mg/day, Max. 100mg/day

76. Minoxidil (Loniten) Contraindications:
hypersensitivity to minoxidil products
pheochromocytoma (systemic use)

77. Minoxidil (Loniten) Precautions: angina pectoris (exacerbation)
cerebrovascular disease
concomitant use of guanethidine (profound orthostatic effects)
malignant hypertension
may cause congestive heart failure (without adequate diuretic therapy)
myocardial infarction (recent)

79. Nitroprusside sodium dihydrate (Nipride)
Form: inj. 50mg powder in vial
Dosage: IV infusion (50mg in ml of D5W), 3mcg/kg/min (range:0.3-10mcg/kg/min)
Note: protect from light

80. Dose Adjustment of Nitroprusside
hepatic insufficiency: consideration should be made for cyanide toxicity since cyanide is converted to thiocyanate by the liver; dosage adjustments may be required (specific guidelines unavailable)
renal impairment: nitroprusside's metabolite thiocyanate accumulates during renal failure and should be monitored to ensure levels remain less than 10 mg/dL

81. Nitroprusside sodium dihydrate (Nipride)
PRECAUTIONS
A. Excessive hypotension
B. Cyanide toxicity
C. Methemoglobinemia
D. Pre-existing anemia and/or hypovolemia

83. Angiotensin II receptor (type AT1) antagonist
[C] 1st trimester; [D] 2nd and 3rd trimester
Drugs acting directly on the renin-angiotensin- aldosterone system are documented to cause fetal harm.
ACE inhibitors may cause fetal or neonatal injury or death when used during the second or third trimester of pregnancy. Hypotension, neonatal anemia, hyperkalemia, neonatal skull hypoplasia, anuria, and renal failure have occurred in fetuses and neonates.
Oligohydramnios  decreased fetal renal function,
limb contractures, craniofacial deformities, and hypoplastic lung development

84. Irbesartan (Aprovel) Form: Tab:150mg Dosage, adult (usual)
Hypertension: 150 mg once daily, MAX 300 mg once daily

85. Irbesartan (Aprovel) contraindications
A. Hypersensitivity to irbesartan
B. Pregnancy

86. Losartan potassium (Cozzar)
Form: Tab:50mg
Dose:25-100mg/day divide into 1-2 doses
FDA labeled indications
Nephropathy, diabetic II patients with a history of hypertension
Hypertension

87. Losartan potassium (Cozzar)
Precautions:
angioedema (present or past)
excessive hypotension - volume-depletion
hepatic or renal impairment
hyperkalemia
renal artery stenosis
severe CHF

88. Telmisartan (Micardis)
Form: Tab:40mg
Dose: Initial 40mg once daily; usual dose mg once daily

89. Telmisartan(Micardis)
Contraindication:
A. Hypersensitivity to telmisartan
B. Pregnancy

90. Valsartan (Diovan) Form: Cap:80mg
Dose: 80mg/day; may be increased to 160mg if needed

91. Valsartan (Diovan) Administration:
may be administered without regard to food
may be given with other antihypertensive agents
avoid potassium supplements or potassium-containing salt substitutes

92. Valsartan (Diovan) avoid lithium electrolyte imbalance
Precautions :
avoid lithium
electrolyte imbalance
hepatic or renal impairment
hyperkalemia
pregnancy

93. Valsartan (Diovan)
Precautions:
sensitivity reactions may occur with or without a history of allergy or asthma
systemic lupus erythematosus
volume-/salt-depletion - excessive hypotension