CPT CASE NO 3

HYPERTENSION

BASIS OF THE PROBLEM

Prevent recurrence
Prevent complications

NON-PHARMACOLOGIC MANAGEMENT

3 mos PTC, pt sought consult at a local health center,

evaluation revealed type II DM
Family Hx of HPN (2 siblings with diagnosed HPN)
Social drinker
Current meds : Lisinopril 20 mg PO daily
BP 150/95 (stage I HPN)

THERAPEUTIC OBJECTIVES

JNC 7 recommendations to lower BP and decrease

cardiovascular disease risk include the following, with greater
results achieved when 2 or more lifestyle modifications are
combined :

Weight loss (range of approximate systolic BP reduction

[SBP], 5-20 mm Hg per 10 kg)

Limit alcohol intake to no more than 1 oz (30 mL) of

ethanol per day for men or 0.5 oz (15 mL) of ethanol per
day for women and people of lighter weight (range of
approximate SBP reduction, 2-4 mm Hg)
Reduce sodium intake to no more than 100 mmol/day (2.4
g sodium or 6 g sodium chloride; range of approximate
SBP reduction, 2-8 mm Hg)
Maintain adequate intake of dietary potassium
(approximately 90 mmol/day)
Maintain adequate intake of dietary calcium and
magnesium for general health
Stop smoking and reduce intake of dietary saturated fat
and cholesterol for overall cardiovascular health
Engage in aerobic exercise at least 30 minutes daily for
most days (range of approximate SBP reduction, 4-9 mm
Hg)

The AHA/ASA recommends a diet that is low in sodium, is high

in potassium, and promotes the consumption of fruits,
vegetables, and low-fat dairy products for reducing BP and
lowering the risk of stroke. Other recommendations include
increasing physical activity (30 minutes or more of moderate
intensity activity on a daily basis) and losing weight (for
overweight and obese persons).

Control hypertension

Deo adjuvante non timendum. Deo gratias.

The 2013 European Society of Hypertension (ESH) and the

European Society of Cardiology (ESC) guidelines recommend a
low-sodium diet (limited to 5 to 6 g per day) as well as reducing
body-mass index (BMI) to 25 kg/m2 and waist circumference .

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 Avoidance of cigarette smoking

Avoidance of the use of illicit drugs, such as cocaine
PHARMACOLOGIC MANAGEMENT

I.

DIURETICS
Lower blood pressure by depleting the body of sodium and
reducing blood volume. Sodium is believed to contribute
to vascular resistance by increasing vessel stiffness and
neural reactivity, possibly related to altered sodiumcalcium exchange with a resultant increase in intracellular
calcium.

THIAZIDE DIURETICS
Low-dose thiazide diuretics may be used alone or in
combination with other antihypertensive drugs.
Thiazides inhibit the Na+/Cl pump in the distal
convoluted tubule and hence increase sodium
excretion.
Thiazides are safe, efficacious, inexpensive, and
reduce clinical events. They provide additive blood
pressurelowering effects when combined with beta
blockers, angiotensin-converting enzyme inhibitors
(ACEIs), or angiotensin receptor blockers (ARBs). In
contrast, addition of a diuretic to a calcium channel
blocker is less effective.
HYDROCHLOROTHIAZIDE
Usual doses range from 6.2550 mg/d.
Due to an increased incidence of metabolic side
effects
(hypokalemia,
insulin
resistance,
increased cholesterol), higher doses generally are
not recommended.
CHLORTHALIDONE
a
diuretic
structurally
similar
to
hydrochlorothiazide,
and
like
hydrochlorothiazide, it blocks sodium-chloride
cotransport in the early distal tubule.
Has a longer half-life (4060 h vs. 915 h) and an
antihypertensive potency ~1.52.0 times that of
hydrochlorothiazide. Potassium loss is also
greater with chlorthalidone.
POTASSIUM SPARING DIURETICS
AMILORIDE AND TRIAMTERENE
Inhibits epithelial sodium channels in the distal
nephron.
Weak antihypertensive agents but may be used
in combination with a thiazide to protect against
hypokalemia.
Potassium-sparing diuretics are useful both to
avoid excessive potassium depletion and to
enhance the natriuretic effects of other diuretics.

Drug therapy is recommended for individuals with blood

pressures 140/90 mmHg.

Deo adjuvante non timendum. Deo gratias.

TOXICITY OF DIURETICS
In the treatment of hypertension, the most common
adverse effect of diuretics (except for potassiumsparing diuretics) is potassium depletion.
Potassium loss is coupled to reabsorption of sodium,
and restriction of dietary sodium intake therefore
minimizes potassium loss. Diuretics may also cause
magnesium depletion, impair glucose tolerance, and
increase serum lipid concentrations.
Diuretics increase uric acid concentrations and may
precipitate gout.

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 The use of low doses minimizes these adverse

metabolic
effects
without
impairing
the
antihypertensive action.
Potassium-sparing
diuretics
may
produce
hyperkalemia, particularly in patients with renal
insufficiency and those taking ACE inhibitors or
angiotensin receptor blockers; spironolactone (a
steroid) is associated with gynecomastia.
II.

The pressor response is due to direct stimulation of

adrenoceptors in arterioles.
The drug is classified as a partial agonist at
receptors because it also inhibits pressor effects of
other agonists.
Hypotensive effect of clonidine is exerted at
adrenoceptors in the medulla of the brain.
Clonidine reduces sympathetic and increases
parasympathetic tone, resulting in blood pressure
lowering and bradycardia.
Blood pressure lowering by clonidine results from
reduction of cardiac output due to decreased heart
rate and relaxation of capacitance vessels, as well as a
reduction in peripheral vascular resistance.
The reduction in pressure is accompanied by a
decrease in circulating catecholamine levels.
Toxicity:
Dry mouth and sedation are common.
Concomitant treatment with tricyclic antidepressants
may block the antihypertensive effect of clonidine. he
interaction is believed to be due to -adrenoceptorblocking actions of the tricyclics.
Withdrawal of clonidine after protracted use,
particularly with high dosages (more than 1 mg/d),
can result in lifethreatening hypertensive crisis
mediated by increased sympathetic nervous activity.
Patients exhibit nervousness, tachycardia, headache,
and sweating after omitting one or two doses of the
drug.
If the drug must be stopped, it should be done
gradually while other antihypertensive agents are
being substituted.
Treatment of the hypertensive crisis consists of
reinstitution of clonidine therapy or administration of
- and -adrenoceptor-blocking agents

SYMPATHOPLEGIC AGENTS

Lower blood pressure by reducing peripheral vascular

resistance, inhibiting cardiac function, and increasing venous
pooling in capacitance vessels thereby reducing cardiac output.
1.

CENTRALLY ACTING SYMPATHOPLEGIC DRUGS

These agents reduce sympathetic outflow from
vasomotor centers in the brainstem but allow these
centers to retain or even increase their sensitivity to
baroreceptor control.

METHYLDOPA
Antihypertensive action appears to be due to
stimulation of central adrenoceptors by methylnorepinephrine or -methyldopamine.
It lowers blood pressure chiefly by reducing
peripheral vascular resistance, with a variable
reduction in heart rate and cardiac output.
Postural (orthostatic) hypotension sometimes occurs,
particularly in volume-depleted patients.
One potential advantage of methyldopa is that it
causes reduction in renal vascular resistance.
Toxicity:
The most common undesirable effect of methyldopa is
sedation, particularly at the onset of treatment.
With long-term therapy, patients may complain of
persistent mental lassitude and impaired mental
concentration.
Nightmares, mental depression, vertigo, and
extrapyramidal signs may occur but are relatively
infrequent.
Lactation, associated with increased prolactin
secretion, can occur both in men and in women
treated with methyldopa. This toxicity is probably
mediated by inhibition of dopaminergic mechanisms
in the hypothalamus.
Other important adverse effects of methyldopa are
development of a positive Coombs test (occurring in
1020% of patients undergoing therapy for longer
than 12 months), which sometimes makes crossmatching blood for transfusion difficult and rarely is
associated with hemolytic anemia, as well as hepatitis
and drug fever.
Discontinuation of the drug usually results in prompt
reversal of these abnormalities.
CLONIDINE
After intravenous injection, clonidine produces a brief
rise in blood pressure followed by more prolonged
hypotension.

Deo adjuvante non timendum. Deo gratias.

2.

ADRENERGIC NEURON-BLOCKING AGENTS

These drugs lower blood pressure by preventing
normal physiologic release of norepinephrine from
postganglionic sympathetic neurons

GUANABENZ AND GUANFACINE

Centrally active antihypertensive drugs that share the
central -adrenoceptor stimulating effects of
clonidine.
They do not appear to offer any advantages over
clonidine and are rarely used.
GUANETHIDINE
In high enough doses, guanethidine can produce
profound sympathoplegia.
Guanethidine inhibits the release of norepinephrine
from sympathetic nerve endings.
Therapeutic use of guanethidine is often associated
with symptomatic postural hypotension and
hypotension following exercise, particularly when the
drug is given in high doses.
Guanethidine-induced sympathoplegia in men may be
associated with delayed or retrograde ejaculation (into
the bladder).
Guanethidine commonly causes diarrhea, which
results from increased gastrointestinal motility due to

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parasympathetic predominance in controlling the

activity of intestinal smooth muscle.
RESERPINE
Reserpine blocks the ability of aminergic transmitter
vesicles to take up and store biogenic amines,
probably by interfering with the vesicular membraneassociated transporter (VMAT).
This effect occurs throughout the body, resulting in
depletion of norepinephrine, dopamine, and serotonin
in both central and peripheral neurons. Chromaffin
granules of the adrenal medulla are also depleted of
catecholamines.
At lower doses used for treatment of mild
hypertension, reserpine lowers blood pressure by a
combination of decreased cardiac output and
decreased peripheral vascular resistance.
Reserpine rather often produces mild diarrhea and
gastrointestinal cramps and increases gastric acid
secretion.
The drug should not be given to patients with a
history of peptic ulcer.
Toxicity:
High doses of reserpine characteristically produce
sedation, lassitude, nightmares, and severe mental
depression; occasionally, these occur even in patients
receiving low doses (0.25 mg/d).
Much less frequently, ordinary low doses of reserpine
produce
extrapyramidal
effects
resembling
Parkinsons disease, probably as a result of dopamine
depletion in the corpus striatum.
3.

BETA-ADRENOCEPTOR-BLOCKING AGENTS
-Adrenergic receptor blockers lower blood
pressure by decreasing cardiac output, due to a
reduction of heart rate and contractility. Other
proposed mechanisms by which beta blockers
lower blood pressure include a central nervous
system effect and inhibition of renin release. Beta
blockers are particularly effective in hypertensive
patients with tachycardia, and their hypotensive
potency is enhanced by coadministration with a
diuretic,

PROPRANOLOL
In severe hypertension, blockers are especially
useful in preventing the reflex tachycardia that often
results from treatment with direct vasodilators
Propranolols efficacy in treating hypertension as well
as most of its toxic effects result from nonselective
blockade.
Propranolol decreases blood pressure primarily as a
result of a decrease in cardiac output.
Propranolol inhibits the stimulation of renin
production by catecholamines (mediated by 1
receptors).
When blockers are discontinued after prolonged
regular use, some patients experience a withdrawal
syndrome, manifested by nervousness, tachycardia,
increased intensity of angina, and increase of blood
pressure.

Deo adjuvante non timendum. Deo gratias.

METOPROLOL
Cardioselective,
The most widely used blockers in the treatment of
hypertension.
Approximately equipotent to propranolol in inhibiting
stimulation of 1 adrenoceptors such as those in the
heart but 50- to 100-fold less potent than propranolol
in blocking 2 receptors.
Relative cardioselectivity is advantageous in treating
hypertensive patients who also suffer from asthma,
diabetes, or peripheral vascular disease.
Although cardioselectivity is not complete, metoprolol
causes less bronchial constriction than propranolol at
doses that produce equal inhibition of 1adrenoceptor responses.
Metoprolol is extensively metabolized by CYP2D6
with high first-pass metabolism.
ATENOLOL
Atenolol is not extensively metabolized and is
excreted primarily in the urine with a half-life of 6
hours; it is usually dosed once daily.
Atenolol is reported to be less effective than
metoprolol in preventing the complications of
hypertension. A possible reason for this difference is
that once-daily dosing does not maintain adequate
blood levels of atenolol.
The usual dosage is 50100 mg/d. Patients with
reduced renal function should receive lower doses.
PINDOLOL, ACEBUTOLOL, & PENBUTOLOL
Partial agonists, ie, blockers with some intrinsic
sympathomimetic activity.
They lower blood pressure by decreasing vascular
resistance and appear to depress cardiac output or
heart rate less than other blockers, perhaps because
of significantly greater agonist than antagonist effects
at 2 receptors.
Beneficial for patients with bradyarrhythmias or
peripheral vascular disease.
These drugs have both -blocking and vasodilating
effect. Blood pressure is lowered by reduction of
systemic vascular resistance (via blockade) without
significant alteration in heart rate or cardiac output.
Because of its combined - and -blocking activity,
labetalol is useful in treating the hypertension of
pheochromocytoma and hypertensive emergencies.
Nebivolol is a 1-selective blocker with vasodilating
properties that are not mediated by blockade. The
vasodilating effect may be due to an increase in
endothelial release of nitric oxide via induction of
endothelial nitric oxide synthase.
Carvedilol reduces mortality in patients with heart
failure and is therefore particularly useful in patients
with both heart failure and hypertension.
ESMOLOL
Used for management of intraoperative and
postoperative hypertension, and sometimes for
hypertensive
emergencies,
particularly
when
hypertension is associated with tachycardia or when
there is concern about toxicity such as aggravation of
severe heart failure, in which case a drug with a short

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duration of action that can be discontinued quickly is

advantageous.
4.

PRAZOSIN & OTHER ALPHA1 BLOCKERS

PRAZOSIN, TERAZOSIN, AND DOXAZOSIN

Produce most of their antihypertensive effects by
selectively blocking 1 receptors inarterioles and
venules.
These agents produce less reflex tachycardia when
lowering blood pressure than do nonselective
antagonists such as phentolamine. Alpha blockers
reduce arterial pressure by dilating both resistance
and capacitance vessels.
Blood pressure is reduced more in the upright than in
the supine position.
Retention of salt and water occurs when these drugs
are administered without a diuretic.
The drugs are more effective when used in
combination with other agents, such as a blocker
and a diuretic, than when used alone.
Due to their beneficial effects in men with prostatic
hyperplasia and bladder obstruction symptoms, these
drugs are used primarily in men with concurrent
hyhypertension and benign prostatic hyperplasia.

III.
VASODILATORS
Reduce pressure by relaxing vascular smooth muscle, thus
dilating resistance vessels andto varying degrees
increasing capacitance as well.
1.

2.

CALCIUM CHANNEL BLOCKERS

Calcium antagonists reduce vascular resistance
through L-channel blockade, which reduces
intracellular calcium and blunts vasoconstriction.
Includes drugs in the following three classes:
phenylalkylamines (verapamil), benzothiazepines
(diltiazem), and 1,4-dihydropyridines (nifedipinelike).
Used alone and in combination with other agents
(ACEIs, beta blockers, 1-adrenergic blockers),
calcium antagonists effectively lower blood pressure.
Side effects of flushing, headache, and edema with
dihydropyridine use are related to their potencies as
arteriolar dilators; edema is due to an increase in
transcapillary pressure gradients, not to net salt and
water retention.
DIRECT VASODILATORS
Decrease peripheral resistance and concomitantly
activate mechanisms that defend arterial pressure,
notably the sympathetic nervous system, the reninangiotensin- aldosterone system, and sodium
retention.
Usually, they are not considered first-line agents but
are most effective when added to a combination that
includes a diuretic and a beta blocker.

Deo adjuvante non timendum. Deo gratias.

HYDRALAZINE
Hydralazine, a hydrazine derivative, dilates arterioles
but not veins.
A potent direct vasodilator that has antioxidant and
nitric oxide enhancing actions.
Toxicity:
The most common adverse effects of hydralazine are
headache, nausea, anorexia, palpitations, sweating,
and flushing.
In patients with ischemic heart disease, reflex
tachycardia and sympathetic stimulation may provoke
angina or ischemic arrhythmias.
With dosages of 400 mg/d or more, a syndrome
characterized by arthralgia, myalgia, skin rashes, and
fever that resembles lupus erythematosus. The
syndrome is not associated with renal damage and is
reversed by discontinuance of hydralazine
MINOXIDIL
Minoxidil is a very efficacious orally active
vasodilator. The effect results from the opening of
potassium channels in smooth muscle membranes by
minoxidil sulfate, the active metabolite.
Increased potassium permeability stabilizes the
membrane at its resting potential and makes
contraction less likely.
Like hydralazine, minoxidil dilates arterioles but not
veins.
Minoxidil is a particularly potent agent and is used
most frequently in patients with renal insufficiency
who are refractory to all other drugs.
Side effects:
Hypertrichosis and pericardial effusion.
SODIUM NITROPRUSSIDE
Sodium nitroprusside is a powerful parenterally
administered vasodilator that is used in treating
hypertensive emergencies as well as severe heart
failure.
Nitroprusside dilates both arterial and venous
vessels. There is activation of guanylyl cyclase, either
via release of nitric oxide or by direct stimulation of
the enzyme. The result is increased intracellular
cGMP, which relaxes vascular smooth muscle
resulting in reduced peripheral vascular resistance
and venous return.
Intravenous nitroprusside can be used to treat
malignant hypertension and life-threatening left
ventricular heart failure associated with elevated
arterial pressure.
DIAZOXIDE
An effective and relatively long-acting parenterally
administered arteriolar dilator that is occasionally
used to treat hypertensive emergencies.
IV. AGENTS THAT BLOCK PRODUCTION OR
ACTION OF ANGIOTENSIN
Reduce peripheral vascular resistance and (potentially)
blood volume.
ACEIs and ARBs improve insulin action and ameliorate
the adverse effects of diuretics on glucose metabolism.

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1.

Additional predisposing conditions to renal

insufficiency induced by these agents include
dehydration, CHF, and use of nonsteroidal antiinflammatory drugs.
Dry cough occurs in ~15% of patients, and
angioedema occurs in <1% of patients taking
ACEIs.
Hyperkalemia due to hypoaldosteronism is an
occasional side effect of both ACEIs and ARBs.

ANGIOTENSIN-CONVERTING ENZYME (ACE)

INHIBITORS
ACEIs decrease the production of angiotensin II,
increase bradykinin levels, and reduce sympathetic
nervous system activity.

CAPTOPRIL
Inhibit the converting enzyme peptidyl dipeptidase
that hydrolyzes angiotensin I to angiotensin II and
(under the name plasma kininase) inactivates
bradykinin, a potent vasodilator, which works at least
in part by stimulating release of nitric oxide and
prostacyclin.
The hypotensive activity results both from an
inhibitory action on the renin-angiotensin system and
a stimulating action on the kallikrein-kinin system.
Benazepril,
fosinopril,
moexipril,
perindopril,
quinapril, ramipril, and trandolapril are other longacting members of the class. All are prodrugs, like
enalapril, and are converted to the active agents by
hydrolysis, primarily in the liver.
Toxicity
Severe hypotension can occur after initial doses of any
ACE inhibitor in patients who are hypovolemic as a
result of diuretics, salt restriction, or gastrointestinal
fluid loss.
Other adverse effects common to all ACE inhibitors
include acute renal failure (particularly in patients
with bilateral renal artery stenosis or stenosis of the
renal artery of a solitary kidney), hyperkalemia, dry
cough sometimes accompanied by wheezing, and
angioedema.
Hyperkalemia is more likely to occur in patients with
renal insufficiency or diabetes. Bradykinin and
substance P seem to be responsible for the cough and
angioedema seen with ACE inhibition.
2. ANGIOTENSIN RECEPTOR-BLOCKING AGENTS
LOSARTAN AND VALSARTAN CANDESARTAN,
EPROSARTAN, IRBESARTAN, TELMISARTAN, AND
OLMESARTAN
They have no effect on bradykinin metabolism and are
therefore more selective blockers of angiotensin
effects than ACE inhibitors.
They also have the potential for more complete
inhibition of angiotensin action compared with ACE
inhibitors because there are enzymes other than ACE
that are capable of generating angiotensin II.
Adverse effects are similar to those described for ACE
inhibitors, including the hazard of use during
pregnancy. Cough and angioedema can occur but are
uncommon.
Angiotensin receptor-blocking drugs are most
commonly used in patients who have had adverse
reactions to ACE inhibitors.
Side effects of ACEIs and ARBs include functional
renal insufficiency due to efferent renal arteriolar
dilation in a kidney with a stenotic lesion of the
renal artery.

Deo adjuvante non timendum. Deo gratias.

3.

DIRECT RENIN INHIBITORS

ALISKIREN
A nonpeptide competitive inhibitors of the enzymatic
activity of renin.
Monotherapy with aliskiren seems to be as effective as
an ACEI or ARB for lowering blood pressure, but not
more effective. Further blood reductions may be
achieved when aliskiren is used in combination with a
thiazide diuretic or a calcium antagonist.
Currently, aliskiren is not considered a first-line
antihypertensive agent.
IV.

ALDOSTERONE ANTAGONISTS

SPIRONOLACTONE
A nonselective aldosterone antagonist that may be
used alone or in combination with a thiazide diuretic.
It may be a particularly effective agent in patients with
low-renin
primary
hypertension,
resistant
ypertension, and primary aldosteronism.
In patients with CHF, low-dose spironolactone
educes mortality and hospitalizations for heart failure
when given in addition to conventional therapy with
ACEIs, digoxin, and loop diuretics.
Spironolactone binds to progesterone and androgen
receptors, side effects may include gynecomastia,
impotence, and menstrual abnormalities. These side
effects are circumvented by a newer agent,
eplerenone, which is a selective aldosterone
antagonist.

DOC, PHARMACOKINETICS AND

PHARMACODYNAMICS
LOSARTAN/HYDROCHLOROTHIAZIDE
Hydrochlorothiazide increases renal excretion of sodium and
chloride and reduces cardiac load. Losartan is an angiotensin II
receptor (type AT1) antagonist hypertensive which acts by
blocking the actions of angiotensin II of RAAS. The drug and
its active metabolite selectively block the vasoconstrictor and
aldosterone secreting effects of angiotensin II. The two drugs
exert additive effects in hypertension.
ONSET
Hydrochlorothiazide diuresis : approx. 2 hr
Losartan : 6 hr

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DURATION
Hydrochlorothiazide : 6-12 hr
PHARMACOKINETICS
ABSORPTION
Hydrocholorothiazide : Oral absorption approx. 50-80%;
time to peak 1-2.5 hr; peak effect 4-6 hr; bioavailability 5080%.
Losartan : time to peak 1 hr; losartans active metabolite
(E-3174) time to peak 3-4 hr; bioavailability 25-33%.
DISTRIBUTION
Hydrochlorothiazide : 3.6-7.8 L/kg; protein binding 68%
Losartan: volume of distribution 34L; plasma protein
binding high. Losartans active metabolite (E-3174) volume of
distribution 12L.
METABOLISM
Hydrochlorothiazide : not metabolized.
Losartan : hepatic (14%) via CYP2CP and CYP3A4 to active
metabolite E-3174 (40 more times potent than losartan,
extensive 1st-pass effect.
EXCRETION
Hydrocholorothiazide : half life elimination 5.6-14.8 hr;
excretion via urine (as unchanged drug).
Losartan : excretion via urine (% as unchanged drug and
6% as active metabolite); plasma clearance 600 mL/min
(active metabolite 50 ml.min)
DOSAGE
Initial: 50 mg/12.5 mg PO qDay
If dose titrated upward, do not to exceed final titration of 100
mg/25 mg PO qDay or 50 mg/12.5 mg PO q12hr
Decrease losartan to 25 mg PO qDay initially if volume
depleted
DOSING CONSIDERATIONS
Replacement therapy: Combination may be substituted for the
individually titrated components
DOSING MODIFICATIONS
Renal impairment
CrCl 30 mL/min: Do not use thiazide-containing products;
loop diuretic preferred
CrCl >30 mL/min: No dosage adjustment required
DRUG INTERACTIONS
Aliskiren (contraindicated
Amisulpride
Benazepril
Captopril
Carbamazepine
Cisapride
Cyclosporine
Dofetilide
Enalapril
Fosinopril
Idelalisib
Isocarboxazid

Ivacaftor
Lisinopril
Lithium
Moexipril
Perindopril
Potassium phosphates, iv
Quinapril
Ramipril
Squill
Trandolapril
Tretinoin

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ADVERSE EFFECTS
LOSARTAN
Fatigue
Hypoglycemia
Chest pain
Cough, incidence higher in
previous cough related to ACE
therapy

HYDROCHLOROTHIAZIDE
Hypotension
Anorexia
Epigastric distress
Hypokalemia
Phototoxicity
Thrombocytopenia

CONTRAINDICATIONS
Hypersensitivity to losartan, hydrochlorothiazides, or
sulfonamides
Renal impairment (CrCl <30 mL/min)
Hepatic impairment
Anuria
Do not coadminister with aliskiren in patients with
diabetes
CAUTIONS
Intravascular volume depletion should be corrected prior
to use
Monitor serum lithium levels in patients receiving lithium
and hydrochlorothiazide
Monitor for signs of fluid or electrolyte imbalance,
including hyponatremia, hypochloremic alkalosis, and
hypokalemia
Acute transient myopia and acute angle-closure glaucoma
have been reported, particularly with history of
sulfonamide or penicillin allergy (hydrochlorothiazide is a
sulfonamide)
Coadministration with corticosteroids, ACTH, or
glycyrrhizin (found in liquorice) may intensify electrolyte
depletion, particularly hypokalemia
Dual blockade of the renin-angiotensin-aldosterone
system (ie, ARB plus an ACE inhibitor) in patients with
established atherosclerotic disease, heart failure, or with
diabetes with end organ damage is associated with a
higher frequency of hypotension, syncope, hyperkalemia,
and changes in renal function (including acute renal
failure) as compared with use of a single reninangiotensin-aldosterone system agent; closely monitor
blood pressure, renal function and electrolytes in patients
on losartan and other agents that affect the reninangiotensin system (RAS)

BLACK BOX WARNING:

Discontinue as soon as possible when pregnancy is
detected;
affects
renin-angiotensin
system,
causing
oligohydramnios, which may result in fetal injury and/or death
Since the patient is 55 y/o this may not be
applicable due to menopause.

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