1 Macaraeg, Allen B.

ANTIHYPERTENSIVES
Dr. Paguirigan Part 1/2014
FOUR CATEGORIES
Diuretics
o Deplete the body Na
o Indirectly reduce the blood volume
Sympathoplegic Agents
o Reduce the peripheral vascular resistance
o Inhibits cardiac function
o Increase the venous pooling in the capacitance
vessels
Direct Vasodilators
o Relax the vascular smooth muscles,
o Dilates the resistance vessel (artery)
Angiotensin Antagonists
o Blocks production or action of angiotensin
o Reduce peripheral vascular resistance and blood
volume

SYMPATHOPLEGIC AGENTS
Drugs that alter the sympathetic nervous system function
Centrally acting
o Methyldopa
o Clonidine
Ganglion blocking agents
o Obsolete, due to toxic effects
Adrenergic Neuron Blocking Agents
o Guanethidine
Guanadrel
Bethanidine
Debrisoquin
o Reserpine
Adrenoceptor antagonist
o Alpha Receptor Antagonist Drugs
Phenoxybenzamine
Phentolamine
Prasozin
Terazosin
Doxasozin
Tamsulosin
o Beta Receptor Antagonist Drugs
Propanolol Oxprenolol
Metoprolol Celiprolol
Atenolol Penbutolol
Nebivolol Labetolol
Nadolol Carvidelol
Timolol medroxalol
Levobunolol Bacindolol
Betaxolol Esmolol
Carteolol Butoxamine
Pindolol
Acetobutolol
o Other Alpha Receptor Antagonist
Alfuzosin Silodosin
Indoramin Urapidil
Labetalol Chlorpromazine
Haloperidol Trazodone
Yohimbine
VASODILATORS
Hydralazine
Sodium Nitroprusside
Minoxidil
Diazoxide
Fenoldopam
Calcium Channel Blockers
o Verapamil
o Diltiazem
o Dihydropyridine family
Amlodipine
Felodipine
Isradipine
Nicardipine
Nifedipine
Nisoldepine
Clevidipine

ANGIOTENSIN INHIBITORS
ACE Inhibitors
o Captopril
o Enalapril
o Benazepril
o Fosinopril
o Moexipril
o Perindopril
o Quinapril
o Ramipril
o Trandolapril
Angiotensin II Receptor Blocking Agents
o Losartan
o Valsartan
o Candesartan
o Eprosartan
o Irbesartan
o Telmisartan
o Olmesartan

CLASSIFICATION OF ANTIHYPERTENSIVE DRUGS
ACCORDING TO PRIMARY SITE OF ACTION
There are also other 2 ways of classifying antihypertensive agents
1. Classify it as
Diuretics
o Thiazides
Hydrochlorothiazide
chlorthalidone
o Loop diuretics
Furosemide
Bumethanide
Tarsemide
Ethacrinic acid
o Postassium sparing diuretics
Amiloride
Triamterine
Spironolactone
Sympatholytic drugs which are also centrally acting
o Alpha adrenergic antagonist
Prazosin
Terazosin
Doxazosin
Phenoxbenzamine
phentolamine
o Beta adrenergic antagonist
Metoprolol
Atenolol
2 Macaraeg, Allen B.

Mixed antagonist
o Betalol
Adrenergic neuron blocking agents
o Labetalol, Cardivelol
Ganglionic blocking agents
Vasodilators
o Arterial
Hydralazine
Minoxidil
Diazoxide
Fenoldopan
o Arterial and venous
Angiotensin converting enzyme inhibitor

2. Another way of classifying will be:
Diuretics also, both thiazides and the loop
Sympathoplegics
o Baroreceptor active agents
o CNS active drugs, these are alpha 2 selective
agonist
Ganglionic blockers
Post ganglionic sympathetic nerve terminal blockers
o Reserpine
o Guanethidine
o Mao inhibitors
Adrenoceptor blockers these are the alpha 1 and alpha 2
blockers
Vasodilators
Calcium channel blockers examples are Nefidipine,
Verapamil and Deltiazem,
ACE inhibitors
Angiotensin 2 receptor blockers

INDIVIDUAL DRUG DISCUSSION
DIURETICS
THIAZIDES, And other related compounds
If given in acutely in reasonably large doses :
o (100 mg hydrochlorothiazide),
o they will decrease the plasma volume, cardiac
output, and glumelular filtration rate, because
o they decrease the renal blood flow and mean
arterial pressure.
In chronic administration :
o Cardiac output and glumerular filtration rates will
return to near normal
o MAP remains reduced
o Systemic vascular resistance will fall
Potentiates antihypertensive effects of other
antihypertensive agents that have different MOA, thus they
are commonly used with other antihypertensives
More effective antihypertensive than loop diuretics
(furosemide, bumethamide)
Spironolactone in doses up to 100 mg / day is equivalent to
hydrocholothiazide in its hypotensive effect.
When GFR is reduced by 50% or more, thiazides will loose
most of their effectiveness both as a diuretic and
antihypertensive agent.
when this happens, loop diuretics can be given as substitute
SYMPATHOLYTIC AGENTS
ALPHA ADRENERGIC ANTAGONISTS .
METHYLDOPA
Mechanism of Action
o Exerts hypotensive effects within the central
nervous system
o Once it reaches CNS, converted to alpha methyl
norepinephrine, a potent alpha 2 adrenergic
agonist
o Leads to sympathetic outflow
Absorption:
o Variable, incomplete
Bioavaliability:
o 25%
Peak plasma concentration: reached in
o 2 to 3 hours
Elimination:
o 2/3 of the administered dose is eliminated by
renal excretion
Preparation:
o Aldomet 125, 250, 500 mg tablet
Initial Dose: 250 mg BID
If given in OD, should administer it at night
o to minimize effects of sedation and postural
hypotension
Side Effects:
o Sedation
o Postural hypotension,
o Dizziness
o Dryness of the mouth
o Head ache
o Decreased mental acuity
o Sleep disturbances
o Depression
o Impotence limits its use for younger patients
o Anxiety
o Blurred vision
o Parkinsionian signs
o Nasal stuffiness

CLONIDINE
Mechanism of action
o Major action: centrally acting alpha 2 adrenergic
agonist
o Resembles MOA of methydopa
o Partial agonist
o Effect at a given site are dependent on the
endogenous concentration of norepinephrine
o If NE concentration if high:
Acts as antagonist
Pharmacologic effects
o Reduction in HR and stroke volume in the supine
position.
o Total peripheral resistance is reduced if the
patient is standing
o Hypotensive effect will generally parallel to
reduction of concentration of circulating NE
Absorption:
o Rapid and almost complete
Bioavailability: High
Peak plasma concentration: reached within
o 1 to 3 hours

3 Macaraeg, Allen B.

Plasma Half life:
o 9 hours
Preparation:
o Catapres 0.1, 0.2, 0.3 mg
Dose: 0.2 to 0.8 mg daily in two or more divided dose
Side effects:
o Xeropthalmia
o Sedation
o Dry mouth
o Impotence
o Nightmares
o Depression
o Urticaria
o Alophecia
Sudden withdrawal may produce hypertensive crisis
o Advise patients to discontinue the drug gradually

GUANABENZ, GUANFACINE
MOA
o Centrally acting alpha 2 adrenergic agonist
Pharmacological properties
o Similar to clonidine
Availability
o 4 and 8 mg tablets
Dose: 4 mg BID
Maximal effect: reached within
o 2 to 4 hours
Half life : 6 hours

PRAZOSIN
MOA
o Peripheral alpha 1 adrenergic antagonist
o Competitive blocking action on vascular post
synaptic alpha 1 adrenergic receptor
o At rest: can reduce MAP and peripheral resistance
o Produces very minimal tachycardia (advantage)
o Hypotensive effect is greater when the patient is
standing
o Relative tolerance to the hypotensive effects can
develop
Absorption and elimination
o First pass metabolism by the liver
Peak plasma concentration: reached in
o 1 to 3 hours
o 90% of the drug is bound to alpha 1 acid
glycoprotein
Plasma Halflife
o 2-3 hours
Elimination
o Metabolites are eliminated though the bile
Toxic Reaction
o First Dose Phenomenon
o Hypotension, sudden LOC, experience 30 to 90
mins after the initial dose
Side Effects
o Faintness
o Palpitation
o Tachycardia
o Head ache
o Urinary urgency
o Polyrthritis
o Pedal edema
Indication
o Mild to moderate hypertension
More effective if combined with
diuretic, and beta blocker than when it
is used alone
o Congestive heart failure
o Pheochromocytoma
o Hypertensive crisis
Availability
o Minipress 1, 2, 5 mg capsule
Dose: 1 mg BID or TID

BETA ADRENERGIC ANTAGONIST .

MOA
o Combination of reduction of cardiac output
o Inhibition of renin secretion
o Both are due to effects of beta 1 adrenergic
receptor blockage

PROPANOLOL, METOPROLOL
More lipid soluble agents
Rapidly and completely absorbed in the GI tract
Extensively metabolized in the liver
Substantially distributed in the CNS
Rapidly eliminated
Bioavailability :
o sensitive to changes in the hepatic bloodflow, and
o to drugs that alter hepatic blood flow, or
o to drug that inhibits hepatic drug metabolism
(Cimetidine)
Interaction
o Not to be given with cimetidine
o Tends to inhibit drug metabolism

ATENOLOL, NADOLOL
Less lipid soluble agents
Not metabolized appreciably
Has longer half life
Dose are adjusted esp in patients with renal insufficiency
Can cross the blood brain barrier only to limited extent
Untoward Effects
o Sudden withdrawal will cause a syndrome
characterized by:
Ventricular arrhythmias
Sever angina
Myocardial infaction
Death
o Incidence is as high as 5% of patients, esp with the
uses of relatively short acting beta blockers
(propanolol)
o Incidence with these SE are lower with longer
acting beta blocker (atenolol)
o Gradual withdrawal from use, atleast for period of
7 t0 14 days
ATENOLOL
o Has been found to be safe and effective
CONTRAINDICATIONS
o Bronchial asthma
o Chronic obstructive lung disease
o Pulmonary disease
o Peripheral resistance abnormalities
o CHF
o IDDM/ Type 1 DM



4 Macaraeg, Allen B.

RESERPINE
Effective antihypertensive when used together with
thiazides
Used for long term treatment with uncomplicated mild
hypertension
Side Effect
o Depression in 25 % of patients
Contraindication
o History of depression

GUANETHEDINE
Severe hypertension
Causes severe orthostatic hypotension
Does not enter the CNS in significant quantity

TRIMETOPHAN
Ganglionic blocking agent
Not anymore popular
Occasional useful in the treatment of hypertension
associated with dissecting aneurism of the aorta

VASODILATORS
HYDRALAZINE
Many of its unwanted effects are minimized when used
together with diuretics, and beta adrenergic antagonists or
other sympathoplegic agents.
MOA
o Causes direct relaxation of the arteriolar and
vascular smooth muscles
o Achieved through the activation of Guanylate
cyclase and guanosine monophosphate (cyclic
GMP)
Peak plasma concentration reached within:
o 30 to 120 mins
Duration of effect: 6-8 hours
Marketed as: Apresoline 10, 25, 50, 100 mg
Dose: 25 to 100 mg BID
Toxic effects
o Tachycardia
o Palpitation
o Headache
o Nausea
o Vomiting
o Dizziness
o Weakness
o Fatigue
o Postural hypotension
Indication
o Severe hypertension during pregnancy
o Toxemia of pregnancy

MINOXIDIL
MOA
o Same as hydralazine
o Arteriolar dilatation effect
o Decreases arteriolar resistance
o Lowers systolic and diastolic blood pressure
o Minimal hypotensive activity in normal subjects
o Can improve renal function in uncontrolled
malignant hypertension
Rapidly and completely absorbed if given orally
Peak concentration reached within
o 1 hour
Maximal effect within 2 hours
Half life: 3 hours
Antihypertensive effect may persist for 1 to 3 days
Metabolized in the liver
Excreted by the kidneys
Availability
o Lonetin 2, 5, 10 mg tablet
Dose: 2 mg OD, can be given as high as 40 mg OD or BID
Side effects:
o Fluid retention
o Hypertrichosis (peculiar SE)
Hair growth in the temporous forehead,
face, pinna of the ear, eyebrows,
forearms, all hairy body surfaces
o Rebound hypertension
o tachycardia
Indication
o Severe hypertension refractory to the
conventional drug regimens like
Diuretics
Sympatholytics
Vasodilators

CALCIUM CHANNEL BLOCKERS

VERAPAMIL, NIFEDIPINE, DILTIAZEM
A group, they are potent arterial vasodilators
MOA. In contrast to agent like hydralazine, CCB
o causes dilatation of coronary arteries
o accelerate relaxation of ventricles
o improve the endocardial perfusion

SODIUM NITROPRUSSIDE
Directly relaxes both arterial and venous smooth muscles
Decreases the cardiac preload, and after load
MOA
o Same with other nitrates
o Hypotensive effects occurs in supine and standing
position
o Venous pooling is more extensive when the
patient is upright.
o Renal blood flow and GFR are maintained
o Rennin plasma activity is increased
o By reducing the preload, myocardial workload will
be decreased, ischemic changes like angina will be
less likely than with more selective arterial
vasodilators (hydralazine and minoxidil)
ROA: parenterally
Onset of action: within 1 -2 mins
Toxic reactions are secondary to severe hypotension and
vasodilation
Indication
Severe hypertensive emergencies.
Preparation
o Vial, with 50 mg
o Dissolved with 3 ml D5W
o Added to 500 ml of D5W
o This combination will produce 100 mg/ml
Rate of infusion:
o 0.5 -10 nanogram/kg/min





5 Macaraeg, Allen B.

DIAZOXIDE
Both with antidiuretic action and
Capacity to relax the arteriolar smooth muscles directly
Striking increase in HR and Cardiac Output accompanied by
Hypotensive effect
Unlike Na Nitroprusside, has no substantial effect of venous
capacitance
Causes marked retention of Na and water
o This compensatory reactions may reduce or blunt
or reduce the hypotensive effect of diazoxide.
o Countered by the use of potent diuretics
Plasma halflife: 20 to 60 hours
10% of the drug not bound to plasma protein
Patients with renal dysfunction will
o exhibit decreased binding of diazoxide to plasma
albumin.
o have greater than normal hypotensive effect to
the drug
about 1/3 of the drug is eliminated unchanged through the
kidney, metabolized by the liver into inactive metabolites.
Availability/ preparation
o Hyperstat IV, 20 ml ampuole
Indication
o Hypertensive crisis
Bolus injection of 0.5 to 1 mg/kg over 5 to 10 sec will
produce maximal reduction in MAP in 2 mins
If a beta blocker and diuretic is being given prior to adm of
diazoxide, it should be be given in slow infusion over at
least 30 mins, not as a bolus.
Contraindication
o Should not be used to treat hypertension
associated with aortic coarctation, AV shunt,
aortic dissection.
Side effects
o Fluid retention
o Hyperglycemia
o Tachycardia
o Myocardial, cerebral ischemia, caused by
hypotension
o Azotemia
o Hypersensitivity reaction
o Rare SE
Salivation
Dyspnea
Altered taste and smell
Considerations
o If given for more than 12 to 24 hours,
give potent diuretic
restrict Na intake
Contraindication
o not used during labor
o can cause uterine relapsation

Classification of Hypertensive drugs by their primary cycle or
mechanism of action
Diuretics
o lower blood pressure by reduction of blood
volume and direct vascular effects
Sympathoplegic
o interfere with the sympathetic nerve function in
several ways.
o This will result in reduction of one or more of the
following:
Venous tone,
Heart rate
Contractile force of the heart
Cardiac output
Total peripheral resistance.
Baroreceptor active agents
o veratrum alkaloids
sensitize the carotid sinus
baroreceptors.
CNS active agents
o alpha2 selective agonists
o (Eg. Clonidine/Methyldopa)
Ganglion Blocking Agents
o Trimetharphan
o Hexamethonium
Post ganglionic Sympathethic Nerve terminal Blockers
o Reserpine and Guanethidine
MAO Inhibitors
o cause formation of a false transmitter in
sympathetic postganglionic neuron terminals and
lower blood pressure.
Adrenoreceptor blockers
o An alpha 1 selective agent
o Prazosin and Propanolol
Vasodilators
o Hydralazine
o Minoxidil
Calcium Channel Blockers
o Nifedipine
o Verapamil
o Sodium Nitroprusside

ACE INHIBITORS
THREE BROAD GROUPS
1. Sulfhydryl-containing ACE Inhibitors
2. Dicarboxylate-containing ACE Inhibitors
3. Phosphorus-containing ACE Inhibitors

SULFHYDRYL CONTAINING ACE INHIBITOR
Are structurally related to Captopril,
o Zofenopril
o Alocepril

DICARBOXYLATE CONTAINING ACE INHIBITOR
Structurally related to Enalapril
o Ramipril
o Quinapril
o Perindopril
o Lisinopril
o Benazepril
o Imidapril
o Trandolapril
o Cilazapril

PHOSPHORUS CONTAINING ACE INHIBITOR
Structurally related to Fosinopril

11 ACE INHIBITORS AVAILABLE FOR CLINICAL USE
1. Benazepril
2. Captopril
3. Enalapril
4. Enalaprilat
5. Fosinopril
6. Liconapril
7. Moexipril
6 Macaraeg, Allen B.

8. Perindropril
9. Quinalapril
10. Lamipril
11. Landolopril

CAPTOPRIL (Capoten)
Contains sulphydril molecule
Given orally
Absorbed rapidly
Bioavailability 75%
Peak plasma concentration: within 1 hour
Half life: 2 hours
Most of the drug is eliminated in the urine
40 to 50% as captopril, the rest as metabolite captopril
disulfide, captopril cystiene disulfide
Oral dose: 6.25 - 150 mg BID or TID
Most appropriate dosage: 6.25 mg TID, or 25 mg BID
Indication
o Antihypertensive
o CHF
patients should not receive daily doses in excess of 150 mg
Food reduces the oral bioavailability as much as 25 % or
30%
o Should be given 1 hour before meal

ELAPRIL (Vasotech)
Prodrug
Hydrolyzed by esterases in the liver in order to produce an
active dicarboxylic acid ENALAPRILAT.
ENALAPRILAT
o Is a highly potent inhibitor of ACE.
o Contains a proline, sulphate.
o Differs from Captopril that it is an analogue of a
tripepdtide rather than a dipeptide.
Bioavailability
o Oral BA 60%
o Absorbed rapidly when given orally.
o Bioavailability is not reduced by food
o can be taken with meal
Peak concentration:
o occurs within 1 hour,
o concentration of Enalaprilat (metabolite), reaches
its peak only after 3-4 hours
Half life:
o Enalapril 1.3 hours
o Enalaprilat: 11 hours, because of its tight binding
to the ACE
Nearly all of the drugs are eliminated by the kidney as
either an intact enalapril or enalaprilat.
Oral Dose:
o 2.5 to 40mg daily either single or divided doses
o Most appropriate is 2.5 or 5mg daily especially
during the initiation therapy
Initial dose:
o 2.5 mg daily for Hypertensive patients who are
taking diuretics or patients who are water or
sodium depleted
Preparation:
o ENALAPRILAT as VASOTEC - Injection
o Enalaprilat is not absorbed orally, it is available for
intravenous administration. ( Oral therapy is not
appropriate)
Indication
o Hypertension
Dose of Enalprilat
o 0.625 upto 1.25mg given by I.V (5minutes)
o If blood pressure is not lowered after 6 hours it
can be repeated.

LISINOPRIL
It is an analogue of Enalaprilat
Active unlike Enalapril
o (Enalapril must be converted to Enalaprilat to
become Active)
Slightly more potent as an ACE inhibitor than Enalaprilat
Absorption
o slowly, variably and incompletely
o Only about 30% is absorbed after oral
administration.
o Absorption is not reduced by food.
Peak plasma concentration: reach within 7 hours
This is cleared by an intact compound by the kidney
Half life: 12hours

Consideration
o It does not accumulate in the tissues
Oral dose: 5-40mg daily either in single dose or divided
doses

BENAZEPRIL (Lotensin)
more potent than Captopril, Enalaprilat or Lisinopril
Absorption
o Rapidly although it is also incompletely,
o 37% of the orally administered dose is absorbed.
o Absorption is slightly reduced by food
Merely completely metabolized and excreted both through
the urine and the bile.
Peak plasma concentration: Reach in 30mins -1 hour
Half life: 10-11 hours
Consideration
o With an exception of the lungs, this drug does not
accumulate in the tissues
Average oral dose: 5-80mg daily either single or divided
doses

FOSINOPRIL
Is the only ACE inhibitor that is commonly used clinically
that contains a phosphonate group
o binds to the active site of the ACE.
Absorption
o slowly, incompletely
o 36% is absorbed after an oral dose
o Rate of absorption is reduced by food but
o the extent of absorption is not affected by food.
Largely metabolized into an active conjugate. Mother drug
together with the metabolites is excreted both in the urine
and in the bile
Peak plasma concentration: reach within 3hours
Half life in the plasma: 11.5 hours
Consideration
o Clearance of the drug is not significantly altered
by renal impairment/disease
Oral dose: 10 -80mg daily but the dose should be reduced
to 5mg daily in patient with sodium and water depletion or
those with severe renal failure.





7 Macaraeg, Allen B.

TRANDOLAPRIL
It is only 10-70% bioavailable.
Absorption rate is affected by food but its extent of
absorption is not affected by food.
Metabolite:TRANDOLAPRILAT
o About 8 times more potent than Trandolapril
itself as an inhibitor.
Excreted in the kidneys (urine) and feces.
Peak plasma concentration: reach within 4-10hours
Since it is metabolized: the initial half life of the parent drug
is 10 hours, but the metabolite drug has a more prolonged
half life.
Plasma clearance of the metabolite (Trandolaprilat) is
reduced by both renal and hepatic insufficiency.
Oral dose: 1-8mg daily

QUINAPRIL (Accupril)
Is also metabolized, is absorbed rapidly
Peak plasma concentration: reach within 1hour,
o this peak plasma concentration can be delayed by
food.
o It is the rate again that is affected and not the
extent of absorption.
Bioavailabilty is 60%.
It is excreted through the urine and feces.
Initial half life of Quinaprilat is about 2 hours while
Terminal half life is 25 hours because of high affinity
binding of the drug to the tissues.
Normal dosage range is 5-80mg daily

RAMIPRIL
Hepatic esterases will transform Ramipril into Ramiprilat, its
metabolite.
An ACE inhibitor that is about as potent as Benazeprilat and
Quinaprilat
Absorbed very rapidly
Peak plasma concentration is achieved in 1 hour
Rate of absorption is affected by food and not the extent of
absorption
Bioavailability is 50-60%
Excreted predominantly by the kidneys
Since it is absorbed in the tissues, it has 3 half life
Has an Initial half life, intermediate half life and because of
the dissociation of the metabolites from the tissues it has
also a terminal half life
Initial half life: 2-4hours
Intermediate half life: 9-18hours
Terminal half life: 50hours

MOEXIPRIL
A prodrug
Antihypersentensive activity is almost entirely due to its
metabolite, the Moexiprilat
Absorbed incompletely
Bioavailability is only 13%
Bioavailability is markedly decreased by food,
o the drug should be taken 1 hour before meal.
Peak plasma concentration is reached within 1.5 hours
Elimination half life varies between 2-12hours
Recommended dose: 7.5-30mg





PERINDOPRIL
Is also a prodrug, only 30-50% of the drug is bioavailable
This also transform into an active metabolite by hepatic
esterases
Bioavailabitlity is not affected by food, but the
bioavailability of its metabolite is reduced to approximately
35% by food.
Displace a biphasic elimination kinetic
Major component has a half life of 3-10 hours
Slow dissociation of its metabolite from the tissue ACE will
have a slower half life of 30-120 hours

NON-PEPTIDE ANGIOTENSIN II RECEPTOR
ANTAGONIST

CANDESARTAN
It is an inactive prodrug that is completely hydrolyzed to an
active form during absorption from the gastrointestinal
tract.
Peak plasma concentration: reached within 3-4hours after
oral administration
Plasma half life is 9 hours
Elimination is through the kidney and bile.
o 33% of the drug is eliminated through the urine
o 67% is through the bile.
Plasma clearance is affected by renal insufficiency but not
by mild to moderate hepatic insufficiency
Should be administered orally once or twice a day for a
total of daily dose of 4-30mg
EPROSARTAN
Peak plasma level is attained within 2-3 hours after oral
administration
Plasma half life is 5-9hours
Also metabolized and the parent compound together with
its metabolite are cleared by both renal and biliary
excretion.
Clearance is affected by both renal and hepatic insufficiency
Recommended is 400-800mg daily O.D or B.I.D

IRBESARTAN
Peak plasma level is 1 -2hours after oral administration
Plasma half life is 11-15hours
Also metabolized by Glucoronide conjugate and its
elimination is both renal and biliary. 20% is elimited though
the kidney and 80% through the bile.
Plasma clearance is not affected either by renal or mild to
moderate insufficiency
Daily dose: 150-300mg daily O.D















8 Macaraeg, Allen B.

LOSARTAN (Cozaar)
Very popular drug in clinical use and Marketed as COZAAR
Approximately 40% of the oral dose of Losartan is
converted to its metabolite which is Carbonic acid
metabolite
Metabolite is more potent than the parent compound as a
receptor antagonist
Peak plasma level is attained in 1-3 hours after oral
administration
Plasma half life: parent compound: 2 hours
Plasma half life: metabolite: 6-9 hours
Plasma Clearance is affected by Hepatic insufficiency but
not renal insufficiency.
Should be administered daily once or twice daily for the
dose of 25-100mg
Is also a competitive antagonist of Thromboxane A2
receptor therefore it tends to attenuate platelet
aggregation.
Metabolite also reduces the COX-2 up regulation
It can also affect the secretion of prostaglandin

OLMESARTAN
It is an inactive and so it has to be completely hydrolyzed to
an active form during its absorption in the gastrointestinal
tract
Peak plasma concentration level is reached in 1.4-2.8 hours
after oral dose
Plasma half life is 10-15 hours
Although renal impairment and hepatic disease will
decrease the plasma clearance of Olmesartan, there is no
need to adjust the dose in patient with mild to moderate
renal or hepatic impairment.
Oral dose: 20-40mg daily

TELMISARTAN
Plasma level is obtained in 30mins-1hour after oral dose
Plasma half life is about 24hours
Cleared from the circulation mainly by biliary excretion of
the intact drug
Its elimination however is affected by hepatic insufficiency
but with renal insufficiency
Recommended dose is 40-80mg O.D


VALSARTAN
Peak plasma level occurs in 2-4 hours after oral
administration
Plasma half life: 9 hours
Food markedly decreases the absorption of this drug.
It is cleared through hepatic elimination
Clearance is affected by hepatic insufficiency but not by
renal insufficiency
Dosage: 80-320mg once a day

Therapeutic Uses of Angiotensin Receptor Antagonist
Treatment of hypertension
Irbesartan and Losartan are also used for Diabetic
nephropathy
Losartan has also been used clinically for prophylaxis of
Stroke
Valsartan is used for Heart failure patients who are
intolerant to the ACE inhibitors



Angiotensin Receptor Antagonist Advantages over the ACE:
Unlike the Ace inhibitors, Angiotensin receptor blockers do
not cause cough.
The incidence of Angioedema with these Angiotensin
receptor blockers is much less than Ace inhibitor
ACE Inhibitors has the teratogenic potentials, they should
be discontinued before patient reaches the 2
nd
trimester of
pregnancy
Angiotensin Receptor antagonists should be used
continuously in patient whose arterial blood pressure or
renal function is highly depleted or the Renin angiotensin
system is compromised.
In such patients, the Angiotensin receptor blockers can
cause hypotension, oliguria and other signs of renal failures