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INTRODUCTION OF DRUG-DRUG INTERACTION OF ANTIHYPERTENSIVE

A drug interaction is a situation in which a substance (usually another

drug) affects the activity of a drug when both are administered

together.

Important drug-drug interaction of antihypertensive agent can be

caused by sharing of metabolic pathways with other drugs, either

inducing or inhibiting the metabolism. Most of effects are through

hepatic cytochrome p450. E.g. CYP3A is responsible for 40-60% of

traditional type hepatic drug-drug interaction.

The chance of drug-drug interaction increases, as increase in age

because elderly patient receive large number of drugs, and also due to

impaired renal excretion of some therapeutic agents as a result of

kidney impaired.

All beta blocker interfere with digitalis preparations and NSAIDs.

Orthostatic hypotension with beta blocker can be exacerbated by

ethanol or CNS depressants. Catecholamine-depleting drugs and beta

blocker can lead to bradycardia and heart attack. The cardiac effect of

nondihydropyridine calcium antagonists and lidocaine can be

potentiated by beta blocker. The effect of propranolol are potentiated

by ethanol, antithyroid drugs, tricyclic antideprassants and monoamine

oxidase inhibitor. likewise propranolol increase the effect of other

drugs e.g lidocaine, diazepam warfarin, theophylin, rizatriptan.

ACE inhibitor and angiotensin receptor blocker, these two classes of

antihypertensive drugs share their pathway to be adversely affected by

NSAIDs. Both classes of drug increase the risk of lithium toxicity and

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hyperkalemia. Diuretics increase blood pressure lowering effects of

both ACEI and ARBs. Telmisartan has drug interaction with digoxin that

increases the concentration of digoxin.

When patient takes alpha1 blocker and phosphodiesterase 5 inhibitors

the BP: Lowering effect of alpha1 inhibitor is affected. Both tadalafil

and vardenafil are contraindicated when patient is taking alpha1

blocker. The combination of verapamil and alpha blocker produce more

orthostatic hypotension and dizziness than either drug given alone.

Alpha2 agonist’s effect is interfered by NSAID and MAOIs, effect is

hypotension and sedation. Hypotensive effect of alpha2 agonist is

antagonized/inhibited by tricyclic antidepressant. Methyl dopa can

potentiate digoxin and lithium toxicity and antagonize effect of oral

hypoglycemic agents.

Antihypertensive agents also interact with cough and cold medication.

Many cough and cold medication contains NSAIDs for pain relief. NSAID

may increase blood pressure. Cough and cold medicine also contain

decongestant. Decongestant make blood pressure worse in 2 ways

1 Decongestant may increase blood pressure and heart rate.

2 Decongestant may prevent antihypertensive drug to function

properly.

ACE inhibitor enhanced hypotensive effect when sodium nitroprusside

given with ACEI.

Adrenergic neuron blocker enhanced hypotensive effect when given

with sodium nitroprusside.

ACE inhibitor enhance hypotensive effect when given with hydralazine.

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DRUG-DRUG INTERACTION WITH MECHANISM

DRUG

DRUG INTERACT . WITH

MECHANISM

propranolol Multivitamin with minerals

Minerals may decrease the effect of propranolol

propranolol

Alcohol

Additive effect in lowering your BP.

Bisoprolol

Theophylline

Combination causes bisoprolol less effective and increase effect of theophylline. bisoprolol reduce the CYP450 hepatic metabolism.

Metoprolol

Diltiazem

Additive reduction in heart rate cardiac conduction, cardiac contractility may occur when calcium channel blocker specially verapamil and diltiazem used with beta blocker.

Bepridil

Ciprofloxacin

Quinolones may cause dose related prolongation of QT intervals in some pt. that may result in elevated risk of arrhythmias, ventricular tachycardia.

Verapamil

fentanyl

Coadministration with inhibitors of CYP450 3A4 may increase plasma concentration of fentanyl, increase concentration could increase

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ADRs that may be fatal

Furodemide

Amikacin

Combination may cause nephrotoxicity due to additive or synergistic effect.

Furosemide

Lithium

Combination increase serum concentration of lithium. And cause lithium toxicity

Buemetanide Neomycin Combination may increase oto/ nephrotoxicity due to additive or synergistic effect.

Spironolactone quinapril Combination increase risk of hyperkalemia.

Nitroprusside Avanafil Combination causes sever hypotension and myocardial ischemia.

Spironolactone

candesartan

Combination increase risk of hyperkalemia. Life threatening and fatal hyperkalemia can occur especially when combination given to person who have renal impairment , diabetes, old age and sever heart failure.

Hydrochlorthiazide

Sodium biphosphate

Combination effect renal function/perfusion

Aliskiren

captopril

Combination causes renal complication,hyperkalemia,hypotension

Triamterene valsartan Increase serum concentration of potassium

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Lisinopril

leflunomide

Induce hepatotoxicity may potentiate liver injury associated with leflunomide.

Amlodipine Rifampicin Using amlodipine with rifampicin can decrease the effect of amlodipine.

Felodipine

Itraconazole

Itraconazole increase plasma level of felodipine

Isradipine

Dolasetron

Cause prolongation of PR and QRS intervals. Cardiac arrest and ventricular arrhythmias

Nisoldipine

Mifepristone

Mifepristone significantly increase plasma concentration of nisoldipine

Eplerenone clarithromycin Increase plasma concentration of eplerenone

Clonidine

Desipramine

Potentially life threatening elevation in BP when tricyclic antidepressant given with clonidine, enhancement of pressor response by TCA.

Guanfacine

Tizanidine

Tizanidine has alpha2 adrenergic activity and may potentiate hypotensive effect of other alpha2 adrenergic agonist.

Azilsartan medoxomil

Zolpidem Azilsartan and zolpidem have additive effect in lowering BP

Olmesartan

Pregabalin

Pregabalin is associated with development of angioedema. And when administered with olmesartan may increase the risk of angioedema. Specific

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symptoms include swelling of face , mouth and neck

Prazosin

Grastek

Immunotherapy with timothy grass pollen allergen extract can sometimes cause severe, even potentially life threatening allergic rxn that require emergency treatment with epinephrine, and prazocin can interfere with body’s response to epinephrine and significantly reduce its effect.

Benazepril

Ibuprofen

NSAID induced inhibition of renal prostaglandin synthesis which results in unopposed pressor activity producing hypertension in addition NSAID can cause fluid retention which also effects BP

Captopril furosemide These combination have additive effect. Coadministration cause hypotension and hypovolemia.

Ethacrynic acid

dronedarone

Dronedarone may cause dose related prolongation of QT interval. Hypokalemia and hypomagnesemia are known risk factor for arrhythmia associated with QT prolongation.

Nicardipine

Rifampin

Nicardipine together with rifampin can decrease the effects of nicardipine

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INTERACTON FOUND IN PRESCRIPTION

CORSAFE- NAVIDAT

Corsafe contains active ingredient amlodipine besylate and navidat

contains ciprofloxacin. when these 2 drugs are given in combination then

ciprofloxacin will interact with amlodipine and will increase plasma

concentration of amlodipine. In 8 elderly hypertensive pt. administration of

a single 5 mg dose of amlodipine in combination with moderate CYP450

3A4 inhibitor (ciprofloxacin 180mg orally daily for 3 days) resulted in nearly

60% increase in amlodipine peak plasma concentration and systemic

exposure.

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NAVIDAT- SURBEX,Z

As we know navidat contains amlodipine which is calcium channel blocker.

And surbex contains vitamins and minerals. Using amlodipine together with

multivitamin with minerals can decrease effect of calcium channel blocker.’

RENITEC-COXLAN

Renitec contains enalapril (ACEI) and coxlan contains meloxicam (NSAID).

When these are given in combination then NSAID will decrease

antihypertensive effect of ACEI. NSAID also cause fluid retention which

also affects blood pressure.

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LASORIDE – COXLAN

Lasoride is combination of furosemide and amiloride. And coxlan contains

meloxicam. when these medication are given in combination cause

interaction, NSAID and diuretic may adversely affect renal function due to

NSAID inhibition of prostaglandin that help renal perfusion in dehydrated

state. Hypotensive effect of diuretic may decrease because inhibition of

prostaglandin and can cause pressor activity and consequently elevation in

BP

TASMI – EPHAROX

Tasmi contain telmisartan and epharox contain piroxicam.

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Combination may reduce kidney function particularly in elderly or volume

depleted individual.

TASMI – PANADOL

There was no interaction found between them.

CIPEX –ENALAPRIL

Cipex contain ciprofloxacin . There was no interaction found between

ciprofloxacin and enalapril.

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CORSAFE- kARDURA

Corsafe contains amlodipine and kardura contains doxazosin. Both

increase blood pressure lowering effect. So should be given with precation

and with low doses otherwise it may cause hypotension.

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30 BRAND NAMES OF ANTIHYPERTENSIVE WITH

INDICATION, FREQUENCY, DOSAGE, SIDE EFFECT

COZAR (LOSARTAN )

FREQUENCY:-

Initial dose : 50mg orally once a day

Maintenance dose: 25 to 100 mg orally per day in 1 or 2 divided

doses

6 year or older,

Initial dose: 0.7mg/kg orally once a day (upto 50mg total)

DOSAGE = tablet,Film coated

INDICATIONS:-

Treatment of hypertension

To reduce the risk of stroke in patient with hypertension and left

ventricular hypertrophy.

Treatment of diabetic nephropathy with elevated serum creatinine

and proteninuria (urinary albumin to Creatinine ratio 300mg/g or

greater) in patients with 2 type diabetes and a history of hypertension.

ADR’S

Dizziness

Dry Cough

Back pain

Cold symptoms such as stuffy nose, sneezing,sore throat

In rare cases, cozaar cn cause a condition that results in the

breakdown of Skeletal muscle tissue, leading to kidney failure.

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TEVETEN (eprosartan)

Frequency

Initial dose: 600mg orally once a day

Maintenance dose 400 to 800 mg orally per day in 1 or 2 divided

doses

DOSAGE.

400mg pink,non-scored ,oval tablets

600mg white ,non-scored ,capsule-shaped tablets.

INDICATIONS

Teveten is indicated for the treatment of hypertension,it may be used

alone or in combination with other antihypertensives such as

diurentics and calcium channel blockers.

ADR’S

Burning or painful urination or changes in urinary frequency.

Cough

Fever

Sore throat

Abdominal or stomach pain

Joint pain

Unusual tiredness

CARDURA (doxazosin)

FREQUENCY

FOR HYPERTENSION

Initial dose: 1mg orally once a day

Maintenance dose: 1 to 16 mg orally once a day.

For Prostatic Hyperplasia

Initial Dose : 1mg orally once a day.

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Maintenance dose: Immediate-release: 1 to8mg orally once a day

.Depending on patient’s Symptomatic response and tolerability,the

dose may be increased to 8mg(the maximum recommended

dose).

DOSAGE = Tablet

INDICATIONS

Cardura is used to treat hypertension (high blood pressure), or to

improve urination in men with benign prostatic hyperplasia(enlarges

prostate)

ADR”S

Dizziness or lightheadedness

Blurred vision

Confusion

Dizziness,faintness, or lightheadedness when getting up form a lying

or sitting position

Fainting(sudden)

MINIPRESS (PRAZOSIN HYDROCHLORIDE)

FREQYENCY

Initial dose: 1mg or three times a day

Dosage may be slowly increased to a total daily dose of 20 mg given

in divided doses. The therapeutic dosages most commonly employed

have ranged from 6mg daily given in divided doses

INDICATIONS

Minipress is indicated for the treatment of hypertension,to lower blood

pressure.Lowering blood pressure reduces the rosk of fatal and

nonfatal cardiovascular events,primarily strokes and myocardial

infarctions.

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ADR’S

Dizziness or lightheadedness,especially when hetting up from a lying

or sitting position

Fainting(Sudden)

Loss of bladder control

Pounding heartbeat

Swelling of the feet or lower legs

Dryness of the mouth

Nervousness

Unusual tiredness or weakness

EDARBI (azilsartan)

FREQUENCY

INITIAL DOSE : 80mg orally once a day.It may be appropriate to

initiate dosage at 40mg orally once daily for patients who are treated

with high doses of diuretics.

MAINTANCE DOSE : 80mg orally once a day

DOSAGE “TABLET”

INDICATIONS

Edrabi is used to treat high blood pressure.

ADR’S

Hives ,Diffuculty Breating,swelling of your face,lips,tongue,or throat

Swelling in your feet or ankles

Diarehea

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BENICAR HCT (olmesartan/hydrochlorothiazide)

FREQUENCY

The recommended starting dose of BENICAR HCT is 40/12.5mg

once a day to patients whose blood pressure is not adequateley

controlled with olmesartan monotherapy.Dose can be titrated upto

40/25mg if necessary.

DOSAGE “FILM COATED TABLET

INDICATION

Treating high blood pressure.

ADR’S

Difficult ,burning,or painful urination

Flushed, dryskin.

Frequent urge to urinate

Fruit-like breath odor

Increased hunge

DIOVAN HCT (hydrochlorothiazide and valsartan)

FREQUENCY

The usual starting dose is diovan HCT160/12.5 mg once daily.The

dosage can be increased after 1 to 2 weeks of therapy to a maximum

of one 320/25 tablet once daily

DOSAGE “Tablet, film coated”

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INDICATION

Hydrochlorothiazide and valsartan is combination medicine used to

treat high blood pressure (hypertension).

ADR’S

Common(1 to 10)% Headache,fatigue,dizziness

Rare(less than 0.1%). Veryigo tinnitus.

INSPRA (eplerenone)

Frequency

The recommended starting dose of INSRA is 50mg administered

once daily.Increase the dosage of INSPRA to 50mg twice daily.

DOSAGE “Film Coated tablet”

INDICATION

Eplerenone os used to treat congestive heart failure after a heart

attack. Eplerenone is used to treat high blood pressure.

ADR’S

Cough,diarrhea,flu-like symptoms,and fatigue ,excess of cholesterol

in the blood

Excess of triglycerides in the blood.

LOTENSIN (benazepril)

FREQUENCY

10mg orally once a day

Maintenance dose: 20 to 40mg/day orally as a single dose or in two

equally divided doses

Maximum dose: 80mg/day

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DOSAGE “tablet”

INDICATION

Lotensin is used to treat high blood pressure.

ADR’S

Chills

Cold sweats

Confusion

Fast, irregular,pounding,or racing heartbeat or pulse

Feeling of warmth

CAPOTEN (capropril)

FRIQUENCY

The initial dose is 25mg b.i.d or t.i.d . If satisfactory reduction of blood

pressure has not been achieved after one or two weeks ,the dose

may be increased to 50mg b.i.d or t.i.d

DOSAGE “tablet 12.5mg

INDICATION

Capoten is used to treat high blood pressure ,congestive heart

failure,kidney problems caused by diabetes,and to improve survival

after a heart attack

ADR’S

Chest pain

Cloudy urine

Fast ,pounding, or irregular heartbeat or pulse

Dilated neck veins

MONPRIL (fosinopril)

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FREQUENCY

Initial dose 10mg orally once a day alone or in combination with

diuretic.

Maintenance dose: 20 to 40 mg orally once a day.

DOSAGE “ORAL TABLET

INDICATION

Monopril is used to treat high blood pressure or Heart failure.

ADR”S

Blurred vision

Chest pain or discomfort

Chills

Cold sweats

Confusion

Fast, slow, irregular heartbeat.

ACCUPRIL (quinapril)

FREQUENCY

Initial dose 10 or 20mg orally once a day in patient not on

diuretics

Maintenance dose 20 to 80mg orally per day,administered as a

single dose or in two equally divided doses.

DOSAGE “ORAL TABLET”

INDICATION

Accupril is used to treat high blood pressure and heart failure.

ADR’S

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Abdominal or stomach pain

Blurred vision

Chest pain

Confusion

Diarrhea

Difficult or labored breathing

PRINIVIL (Lisinopril)

FREQUENCY

Initial dose 10mg orally once a day,5mg orally once a day

Maintenance dose 20 to 40 mg orally once a day

Maximum dose 80 mg orally once a day

DOSAGE” ORAL TABLET & ORAL SOLUTION

INDICATION

Prinivil is used to treat high blood pressure or congestive heart

failure. It is also used to improve survival after a heart attack.

ADR’S

Dizziness

Hypotension

Hyperkalemia

Increased blood urea nitrogen

Increased serum creatinine

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TRANDATE (labetalol HCL)

FREQUENCY

The recommended initial dosage is 100mg twice daily whether used

alone or added to a diuretic regimen.After 2 or 3 days,using standing

blood pressure as an indicator,dosage may be titrated in increments

of 100 mg b.i.d. every 2 or 3 days.The usual maintenance dosage of

labetalol HCL is between 200 and 400mg twice daily.

DOSAGE “TABLET

INDICATION

Treating high blood pressure.It may be used alone or in combination

with other medicines, such as diuretics.

ADR’S

Orthostatic Hypotension,tightness in chest

Wheezing

TENORMIN (atenolol)

FREQUENCY

50 mg given as one tablet a day either alon or added to diuretic

therapy.Dose can be increase upto 100mg

DOSAGE = “IV SOLUTION & ORAL TABLET”

INDICATION

Tenormin is used to treat angina (chest pain) & hypertension

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ADR’S

Cardic failure

Dizziness

Fatigue

Bradycardia

Cold extremities

KERLONE (betaxolol HCL)

FREQUENCY

The initial dose of kerlone in hypertension is ordinarily 10mg once

daily either alone or added to diuretic therapy.The full

antihypertensive effect is usually seen within 7 to 14 days.If the

desired response is not achieved the dose can be doubled after 7 to

14 days.

DOSAGE “TABLET”

INDICATION

Betaxolol is used to treat hypertension

ADR’S

Headache

Bradycardia chest pain or discomfort

Lightheadedness ,dizziness or fainting

ZEBETA (bisoprolol FUMARATE)

FREQUENCY

The usual startin dose is 5mg once daily.The dose may be increased

to 10mg and then,If necessary,to 20 mg once daily.

DOSAGE “FILM COATED TABLET”

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INDICATION

Zebeta is used to treat hypertension

ADR’S

Body aches

Chest pain

Chills

Cough

Difficult or labored breathing

LOPRESSOR (metoprolol tartrate)

FREQUENCY

Initial 100mg Dailly in single or divided doses.The effective dosage

range of Lopressor tablets is 100-450 mg per day.

DOSAGE “TABLET,INJECTION”

INDICATION

Treating high blood pressure,alone or with other medicines.long term

treatment of chest pain,and reducing the risk of death because of

heart problems in patients who have a heart attach.

ADR’S

Cardiac failure and hypotension

Blurred vision

Chest pain or discomfort

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BYSTOLIC (nebivolol)

FREQUENCY

Starting dose is 5mg once daily, with or without food

DOSAGE = ORAL TABLET

INDICATION

BYSTOLIC IS USED TO TREAT HYPERTENSION

ADR’S

Tingling of the hands or feet

Unusual tiredness or weekness

Unususal weight gain or loss

Wheezing

VASCOR (bepridi)

FREQUENCY

100mg twice daily

DOSAGE = Available as film-coated tablets for oral use

INDICATION

Bepridil is used to treat hypertension and to treat angina (chest pain).

ADR’S

Palpitations and edema have been reported in 1% to 2% of patients.

Exacerbation of congestive heart failure has been associated with the

use of bepridil in 1% of patients.

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CARDIZEM (diltiazem)

FREQUENCY

Extended Release Tablets.

Initial dose 180 to 240mg orally once a day.increasing the dose as

needed

Maximum dose540 mg/day

DOSAGE

Oral capsule extended release,oral capsule extended release 12

hr,oral capsule extended release 24 he,oral tablet extended release

INDICATION

Cardizem is used to treat hypertension Cardizem is also used to treat

chronic

Stable angina (chest pain)and angina due to coronary artery spasm.

ADR’S

Hoarseness

Tender or swollen glands in the neck

Trouble swallowing

Voice changes

VERALAN PM (verapamil)

FREQUENCY

Oral 200 mg orally once a day at bedtime

Maximum dose 400 mg/day

DOSAGE Extended Release Capsule

INDICATION

Verapamil is used to treat hypertension,angina and certain heart

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rhytm disorders.

ADR’S

Sinus bradycardia

Severe hypotension

Pulmonary edema

LASIX (furosemide)

FREQUENCY

Oral for hypertension

Initial 20 to 80mg per dose

Maintenance dose

Increase in increments of 20 to 40 mg/dose every 6 to 8 hours toi

desired effect the usual interval in once or twince daily,with maximum

daily dose of 600mg,

DOSAGE = Injection ,oral solution,oral tablet

INDICATION

Lasix is used to treat fluid retention (edema) in people with

congestive heart failure,liver disease,or a kidney disorder such as

nephrotic syndrome.

Lasix is also used to treat high blood pressure.

ADR’S

Sores,ulcers,or white spots on the lips or in the mouth

Swollen or painful glads

Tightness in chest

Unusual bleeding or bruising

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BUMEX (bumetanide)

FREQUENCY

The usual total daiy dosage of bumex is 0.5mg to 2 mg and in most

patients is given as a single dose .

DOSAGE TABLET

INDICATION

Bumetanide trears fluid retention in people with congestive heart

failure,liver disease,or a kidney disorder such as nephrotic

syndrome,hypertension

ADR’S

Hypokalemia

Hyperurucemia

AIDACTONE (spironolactone)

FREQUENCY

50 to 100 mg of ALDACTONE administered in either single or divided

doses is recommended

DOSAGE Film coated tablet

INDICATION

Aldosterone is a hormone produced by your adrenal glands to help

regulate the salt and water balance in your body .Idactone alsi treat

fluid retention (edena) in people with congestive heart Failer ,cirrhosis

of the liver,or a kidney disorder called nephrotic syndrome.

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ADR’S

Abdominal or stomach cramping,burning,or tendetness

Bleeding gums

Bloody or black ,tarry stools

Bloody urine

Breast pain

Chest pain

NITROPRESS (Nitroprusside)

FREQUENCY

Initial dose 0.3mcg/kg/min IBW administered by continuous IV

infusion.

Mantenance dose The dose may be titrated upward to a maximum of

mcg/kg/min IBW

DOSAGE = I v powder for injection .iv solution

INDICATION

Nitroprusside is used to treat congestive heart failure and lift-threating

high blood pressure (hypertension). Nitroprusside is also used to

keep blood pressure low during a surgery.

ADR’S

Hypotension

Cyanide toxicity

Thiocyanate toxicity

LOTENSIN HCT (hydrichlorothiazide and benazepril)

FREQUENCY

Dose once daily. The dosage may then be increased after 2 to 3

weejs as needed to help achieve blood pressure goals.The maximum

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recommended dose is 20mg/25mg.

DOSAGE oral tablet

INDICATION

Hydrochlorothiazide and benazepril us a combination medicine used

to treat hypertension

ADR’S

Rapid breathing

Selzures

Sweating

Thirst

Trembling

Unusual tiredness or weakness

VALTURNA (aliskiren and valsartan)

FREQUENCY

The recommended initial once daily dose of valturna is

150/160mg.Titrate as needed to a maximum of 300/320 mg.

DOSAGE Oral tablet

INDICATION

Valturna is used to treat high blood pressure

ADR’S

Bladder Pain

Bloody or cloudy urine

Body aches or pain

Chills

Cough

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Diarehea

Difficult,Burning.or Painful urination

TARKA (trandolapril and verapamil)

FREQUENCY

Tarka have explored only once a day doses 4/240mg

DOSAGE = Oral tablet extended release

INDICATION

Trandolapril and verapamil is a combination medicine used to treat

high blood pressure.

ADR”S

Bradtcardia, first degree atrioventricular block,and second degree

atrioventricular block.

REFRENCE

FROM RIMINGTON

FROM LIPPINCOTT 4TH

EDITION

https://www.ncbi.nlm.nih.gov/pubmed/9397294

http://onlinelibrary.wiley.com/doi/10.1111/j.1524-

6175.2006.05939.x/full

https://www.drugs.com/