introduction of Anti-hypertensive drug, 30 brands of anti-hypertensive, their uses,ADRs, frequency, 30 drug interactions,

1. 1
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

2. 2
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.

3. 3
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

4. 4
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.
Hydrochlorthiazid
e
Sodium
biphosphate
Combination effect renal
function/perfusion
Aliskiren captopril
Combination causes renal
complication,hyperkalemia,hyp
otension
Triamterene valsartan Increase serum concentration
of potassium

5. 5
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

6. 6
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

7. 7
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.

8. 8
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.

9. 9
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.

10. 10
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.

11. 11
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.

12. 12
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.

13. 13
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.

14. 14
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.

15. 15
 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

16. 16
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”

17. 17
 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

18. 18
 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)

19. 19
 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

20. 20
 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

21. 21
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

22. 22
 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”

23. 23
 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

24. 24
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.

25. 25
 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

26. 26
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

27. 27
 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.

28. 28
 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

29. 29
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

30. 30
 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/