TUTORIAL REPORT 1

PHARMACOLOGY AND THERAPY

Lecturer : Nurmawati Fatimah dr., M.Si

Medical Study Program

Faculty of Medicine Universitas Airlangga
2021
 Arranged By:
Group B8

Mutiara Rizqia Rivania (012011133247)

Diva Khansadea Fyamanda (012011133248)

Faris Dary Utama (012011133249)

Aldilla Afifie Putri Maridsky (012011133250)

Ariel Kevin K. Ginting (012011133251)

Machfud Fauzi (012011133252)

Nadhifa Arna (012011133253)

Tyaswara Endah Sayekti (012011133254)

Karfadimas Bima Putra Wiryono (012011133256)

Avisha Fakhira (012011133257)

Athalla Jeryco Julyando Putra (012011133259)

Anggita Annisa Wahyu Dewanti (012011133260)

 TABLE OF CONTENTS

I. SCENARIO ............................................................................................................................. 4
II. MAIN PROBLEM AND KEYWORDS .................................................................................. 4
III. LITERATURE REVIEW ........................................................................................................ 4
Definition .................................................................................................................................... 4
Classification ............................................................................................................................... 5
Pathophysiology .......................................................................................................................... 5
Drug Class ................................................................................................................................... 7
IV. P-DRUG TABLE.................................................................................................................. 24
V. ANALYSIS P-DRUG TABLE ............................................................................................. 25
DIURETICS GROUP ............................................................................................................... 25
CCB GROUP ............................................................................................................................ 27
VI. MIND MAP .......................................................................................................................... 32
VII. DRUG PRESCRIPTION...................................................................................................... 33
REFERENCES ............................................................................................................................. 34
 I. SCENARIO
A 45 years old woman came to the primary health care center complaining that her neck
had felt heavy and stiff since 1 week ago. Complaint was not accompanied by fever, nausea
as well as blurred vision. Medical history: bronchial asthma, taking salbutamol inhaler
whenever an asthma attack occurs. She gets an asthma attack approximately once in a
month. Physical examination: blood pressure 160/90 mmHg, pulse rate 88x/ minute,
respiratory rate 16x/minute, body temperature 36.8 ° C, meningeal sign (-).
Weight: 60 Kg; Height: 158 cm; Lung and heart auscultation normal.
Lab examination: lipid profile, blood glucose, uric acid within normal limit.

II. MAIN PROBLEM AND KEYWORDS

MAIN PROBLEMS :
- Grade II Hypertension
- History of bronchial asthma
- Stiff neck
- Feeling heavy since last week

KEYWORDS :
Hypertension, Bronchial asthma, No meningeal sign, stiff neck and weight, Salbutamol,
Respiratory rate 16x/minute, pulse 88x/minute

III. LITERATURE REVIEW

Definition
Blood pressure is the product of cardiac output and peripheral resistance. Maintenance of
normal blood pressure depends on a balance between cardiac output and peripheral vascular
resistance. At a younger age, cardiac output is often increased, whereas in older patients, increased
systemic vascular resistance and vascular stiffness predominate. Due to increased -adrenoceptor
stimulation or increased release of peptides such as angiotensin and endothelin, vascular tone may
also be increased. Another cause is an increase in cytosolic calcium in vascular smooth muscle
which causes vasoconstriction (Yonata & Pratama, 2016).
Hypertension in general is a condition where the systolic pressure is more than 140 mmHg
and the diastolic pressure is more than 90 mmHg (Manuntung, 2019). According to WHO, the
normal limit for blood pressure is 120-140 mmHg systolic pressure and 80-90 mmHg diastolic
pressure. A person is called hypertension when his blood pressure is more than 140/90 mmHg.
According to JNC VII 2003, blood pressure in adults aged over 18 years is classified as having
stage 1 hypertension if the systolic pressure is 140-159 mmHg and the diastolic pressure is 90-99
mmHg. Meanwhile, hypertension is stage/level 2 if the systolic pressure is more than 160 mmHg
and the diastolic pressure is more than 100 mmHg, and stage/level 3 hypertension is when the
systolic pressure is more than 180 mmHg and the diastolic pressure is more than 116 mmHg.

Classification
Based on the cause, hypertension is divided into 2, primary hypertension and secondary
hypertension. Hypertension with no known exact cause is called essential/primary hypertension.
Meanwhile, hypertension caused by other diseases is called secondary hypertension.
1. Essential/Primary Hypertension
This type occurs in the majority of cases of high blood pressure, about 95%. The cause is not
clearly known although it is associated with a combination of lifestyle factors such as diet and lack
of physical activity. However, increasing age, heredity, and psychological stress are thought to
have a role in causing this type of hypertension.
2. Secondary Hypertension
This type is less common, the article is only about 5% of all cases of hypertension. Hypertension
in this type is caused by other medical conditions or reactions to certain drugs, such as kidney
vascular disorders, thyroid gland disorders, adrenal gland diseases, and so on.

Pathophysiology
Various pathophysiologies and complications that can arise due to hypertension make
hypertension a major cause of death worldwide (WHO, 2019). Even so, complications due to
hypertension are not necessarily prevented. Therefore, it is necessary to treat hypertension in a
comprehensive manner as an effort to improve the patient's quality of life and reduce the risk of
death from hypertension.
According to WHO (1985), rational medicine is treatment in which the patient receives the
drug according to the patient's clinical needs, in doses appropriate for each patient, within a
sufficient period of time, and with the lowest cost for patients and their families or communities.
Treating patients rationally is an important thing for doctors to do so that the level of drug efficacy
can be achieved maximally, the patient can recover properly, and the patient is not burdened too
much, both in terms of cost and convenience.
Pathophysiology of hypertension is highly complex and can occur due to many things,
namely genetic factors, polymorphisms of gene loci involved in the regulation of angiotensin I
receptors and aldosterone synthase at risk of causing hypertension. In one study, in hypertensive
patients with Chinese ethnic participants, mutations in the -adducin gene were found that play a
role in the enzymatic activity of the Na+/K+/ATPase ion pump related to sodium absorption in the
kidneys resulting in increased sensitivity to salt.
Changes in the cardiovascular, neurohormonal and renal systems play a role. Increased
sympathetic nerve activity can trigger an increase in cardiac work resulting in an increase in
cardiac output. Abnormalities in blood vessels contribute to total peripheral resistance.
Vasoconstriction can be caused by increased sympathetic nerve activity, impaired regulation of
local factors (nitric oxide, natriuretic factor, and endothelin) that play a role in regulating vascular
tone. Abnormalities in the kidneys in the form of defects in the Na+/K+/ATPase ion channels,
abnormal regulation of the hormone renin-angiotensin-aldosterone and impaired blood flow to the
kidneys. Disturbances in pressure natriuresis can also interfere with the regulation of sodium
excretion, resulting in salt and fluid retention. Elevated levels of vasoconstrictors such as
angiotensin II or endothelin are associated with increases in total peripheral resistance and blood
pressure.
A high-salt diet, especially in patients with high salt sensitivity, contributes to high blood
pressure. Unhealthy lifestyles such as physical inactivity and the wrong diet can lead to obesity.
Obesity also plays a role in increasing the risk of essential hypertension as one study demonstrated
weight loss followed by a decrease in blood pressure. Obesity can trigger hypertension through
several mechanisms, including compression of the kidneys by retroperitoneal and visceral fat.
Increased visceral fat, especially retroperitoneal fat, can exert a compressive effect on the renal
veins and parenchyma, thereby increasing intrarenal pressure, interfering with pressure natriuresis
and causing hypertension.
In addition, increased sympathetic nerve activity can be triggered by leptin. Studies have
shown that the binding of leptin to its receptors, especially on proopiomelanocortin (POMC)
neurons in the hypothalamus and brainstem, plays a role in this increase. Sympathetic nerve
stimulation causes an increase in angiotensin II and aldosterone levels. In obesity, increased
adipose tissue and metabolic rate increase cardiac output in an attempt to meet the demands of
blood flow. Not only that, obesity is also associated with metabolic syndrome.
An increase in blood pressure in the long term will result in structural changes in blood
vessels. Structural changes include changes in macro and microvascular structures. Macrovascular
changes in the form of stiffening arteries and changes in central to peripheral pressure
amplification. Microvascular changes in the form of changes in the ratio of blood vessel walls and
lumens in large arterioles, abnormalities of vasomotor tone and 'structural rarefaction'
(microvascular loss due to not flowing blood in all microvascular in order to maintain perfusion to
certain capillaries).
These structural changes will interfere with tissue perfusion. Therefore, in the long term,
target organ damage can occur. Although the body's autoregulation of blood pressure will try to
maintain blood flow to meet metabolic needs, the ability of this regulation is decreased in
hypertensive patients. Target organs that can be damaged include the heart, kidneys, eyes and
brain.

Drug Class
Drug therapy is also needed for the efficacy of the treatment. Generally, the first-line
medications used in the treatment of hypertension, which includes diuretics, angiotensin-
converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), beta-blockers, and
calcium channel blockers (CCBs) (Nguyen et al, 2010).
1. Calcium Channel Blockers
Calcium Channel Blockers prevents calcium from entering the smooth muscle cells of the
heart and arteries. When calcium enters these cells, it causes a stronger and harder
 contraction, so by decreasing the calcium, the heart's contraction is not as forceful.
Calcium channel blockers relax and open up narrowed blood vessels, reduce heart rate
and lower blood pressure. Some of CCB drugs are Verapamil, Diltiazem, Amlodipine,
Felodipine, Nicardipine, Nifedipine, Nimodipine, etc. Calcium Channel blockers drug
also has a side effects. Which can cause palpitations, swollen ankles, constipation,
headache, and dizziness.
2. Diuretics
Diuretics work to increase the excretion of sodium, water and chloride thereby reducing
blood volume and extracellular fluid. As a result, there is a decrease in cardiac output and
blood pressure.
a) Thiazides
The mechanism of action is to inhibit the reabsorption of sodium or sodium
(Na +) and a decrease in plasma volume caused by a reflex increase in the secretion of
renin and aldosterone.
Thiazides can be used alone in mild to moderate hypertension, or in combination
with other antihypertensives when diuretics alone cannot reduce blood pressure. Thiazides
in high doses can cause hypokalemia which can be dangerous in patients receiving digitalis.
These side effects can be avoided when thiazides are given in low doses or in combination
with other drugs such as potassium-sparing diuretics, or angiotensin converting enzyme
inhibitors (ACE-inhibitors). While potassium supplements are not more effective.
Thiazides can also cause hyponatremia and hypomagnesemia and hypercalcemia.
In addition, thiazides can inhibit the excretion of uric acid from the kidneys, and in
hyperuricemic patients can trigger acute gout attacks. To avoid these metabolic effects,
thiazides should be used in low doses.
b) Loop diuretic
Loop diuretics work to lower blood pressure by inhibiting sodium and chloride
reabsorption in the ascending loop of Henie and in the renal tubules, affecting the chloride
binding transport system, causing increased excretion of water, sodium, chloride,
magnesium and calcium.
 The side effects of loop diuretics are similar to those of thiazides, except that loop
diuretics cause hypercalciuria and decrease blood calcium, whereas thiazides cause
hypocalciuria and increase blood calcium levels.
c) Potassium sparing diuretic
These diuretics are weak diuretics or aldosterone antagonists. Its mechanism of
action is by competing with aldosterone at the receptor site in the distal tubule, so that it
can inhibit the effect of aldosterone on arteriolar smooth muscle, increase salt and water
excretion, and prevent loss of potassium and hydrogen ions. Its use is mainly in
combination with other diuretics to prevent or reduce the hypokalemic effect of other
diuretics.
Potassium-sparing diuretics may cause hyperkalemia when administered to patients
with renal failure, or in combination with ACE inhibitors, ARBs, -blockers, NSAIDs or
with potassium supplements.
 1. Calcium Channel Blocker

NICARDIPINE
PK ● Absorption: fast through the GI tract, has a
bioavailability of 35% besides that
nicardipine has a fast onset of 5- 15
minutes. Plasma levels will rapidly
increase within the first 2 hours, but
decrease to 50% after discontinuation and
will stabilize within 24 - 48 hours.
● Distribution: rapidly distributed
throughout the body and 95% bound to
protein.
● Metabolism: nicardipine is rapidly
metabolized in the liver via the cytochrome
P450 enzymes mainly by the CYP3A4,
CYP2C8, and CYP2D6 isoenzymes.

Dosage Form Per oral > Capsule : 20 mg and 30 mg

Parenteral > by inject IV : 1 mg/ml

Method and Timing of Drug Administration
Nicardipine is given directly by the doctor through
an IV under the supervision of a doctor, and
medical staff will monitor the patient's body
response to the drug through the patient's blood
pressure and heart rate while nicardipine is given.
The administration of nicardipine is accompanied
by the application of a healthy lifestyle in order to
increase the effectiveness of treatment by:
● Consume low-fat and low-salt foods
● Maintain ideal body weight
● Do not smoke and consume alcohol
● Exercise regularly

Dosage IV: 3-5 mg/h by infusion over 15 minutes can be

adjusted according to blood pressure with an
increase of 0.5-2.5 mg/hour every 15 minutes if
blood pressure has decreased can be continued by
reducing the dose to a maintenance level of 2-4 mg
/ o'clock. Maximum 15mg/hour.
orally : 20-40 mg/kg 2-3dd

Drug interactions ● Increased risk of developing heart failure

or worsening heart failure if used with
 beta-blocking drugs, such as propranolol,
atenolol etc.
● Decreased blood levels of nicardipine
when used with carbamazepine or
rifampicin
● Increased blood levels of nicardipine when
used with cimetidine
● Increased blood levels of the drugs
ciclosporin, tacrolimus, sirolimus, or
digoxin.

Definition Nicardipine is a strong drug category in the

antihypertensive drug group and belongs to the
CCB (calcium channel blocker) or calcium
antagonist class, has the benefit of treating
hypertension and can prevent angina, including
category C which has AE in the fetus.

Pathophysiology Nicardipine is a dihydropyridine CCB (vasodilator)

antihypertensive drug that works by inhibiting and
controlling the flow of calcium into heart cells and
blood vessels, resulting in vasodilation of blood
vessels, thereby increasing the supply of blood and
oxygen to the heart, and reducing the workload of
the heart. Side effects In giving nicardipine to the
body, namely: constipation, dizziness, headache,
fatigue due to high blood pressure decreases.

PD ● Reduces systemic vascular resistance and

afterload so that through this mechanism
nicardipine can reduce systolic, diastolic,
and mean arterial blood pressure.
● Increase the supply of oxygen to the
myocardium so that nicardipine also has a
role as an antianginal.
● Minimal negative inotropic effect.
● Nicardipine does not affect the conduction
system, so it has no significant effect on the
PR interval, QRS complex, and QT
interval.
● Nicardipine also has the action of lowering
cerebrovascular resistance and renal
vascular resistance and does not affect
blood calcium levels.
DILTIAZEM
PK ● Absorption: Well absorbed orally, Oral
bioavailability 40-65%.
● Half-life: 3-4 hours.
● Distribution: body tissues except for the
central nervous system. Bind to plasma
protein about 25-30%.
● Metabolism: in the liver, oxidized by
CYP450.
● Elimination: 40-50% excreted in the
urine unchanged.

Dosage Forms Available in tablet, capsule, vial and powder

form for injection
● Tablets: 30 mg, 60 mg, 90 mg, 120 mg.
● Slow-release tablets: 120 mg, 180 mg,
240 mg.
● Slow-release capsules: 100 mg, 120 mg,
180 mg, 200 mg, 240 mg, 300 mg, 360
mg, 420 mg.
● Injection: 5 mg/mL, 25 mg/5 mL, 50
mg/10 mL, 125 mg/25 mL.
● Powder injection: 10 mg, 50 mg, 100
mg.

Method and Timing of Drug Administration

Follow the doctor's advice and read the
instructions for use on the packaging before
using diltiazem.

Diltiazem can be taken with or without food. Do

not crush, chew, or split this medicine, as this
may affect the effectiveness of the medicine.

● Tablets
Initial dose: 120 to 240 mg orally, 1 dd,
dose may be increased as indicated.
● Maintenance dose: 120 to 540 mg
orally, 1 dd.
● Maximum dose: 540 mg/day.

Taken at the same time every day

Dosage Oral : 30-80 mg 4dd

IV : 75-150 mcg/kg
Drug Interactions ● Anesthesia → negative inotropic
● Beta-blockers (atenolol, metoprolol,
atenolol, etc) and digoxin → risk of
bradycardia
● Buspirone →absorption rate increases
● Cimetidine → increased serum
diltiazem concentration
● Digitalis and Quinidine → risk of
increased arrhythmia
● Rifampin → increased diltiazem
metabolism

Definition DiltiazemDiltiazem is a calcium channel blocker

cardiovascular drug nondihydropyridine used to
treat hypertension, angina pectoris, and
arrhythmias.

Pathophysiology Diltiazem works by dilating blood vessels,

thereby lowering blood pressure and easing the
workload of the heart. Thus, blood can flow
easily, and increase the supply of blood and
oxygen throughout the body, including to the
heart.

PD ● Binds to Ca ion receptors thereby

inhibiting Ca influx during
depolarization of cardiac and smooth
muscle → causes muscle relaxation and
vasodilation of blood vessels, also
increases oxygen flow to heart muscle.
● Inhibits the work of the heart, reduces
output and heart rate.
● Can be used as antiarrhythmic and
angina drugs.

NIFEDIPINE
PK Absorption: influenced by food,
chewed/crushed, high absorption
on the GI tract. bioavailability: 45-56%
Distribution: binds to protein (92-98%) and also
penetrates breast milk.
 Metabolism: First pass high metabolism,
oxidation in liver by CYP3A4.
Half-life: 2 hours
Excretion: Via urine (85-90%) in the form of
inactive metabolites) and feces.

Dosage Form 10 mg tablets, 20 mg and 30 mg slow-release

tablets.

Method and Timing of Drug Administration Orally, 3 times a day, take after or after meals,
should not be chewed or crushed.

Dosage A single dose of 5 - 10 mg. The average dose is

5 - 10 mg, 3 times a day.

Interval every two doses at least 2 hours

Drug interactions - Concomitant use of nifedipine with fentanyl

during surgical procedures may cause severe
hypotension.
- The antihypertensive effect of nifedipine will
be increased if taken together with antipsychotic
drugs.
- Blood levels of nifedipine may increase if used
with cimetidine, erythromycin, fluoxetine, or
antifungal drugs.

Definition Nifedipine is a drug commonly used for people

with high blood pressure and also for certain
types of chest pain (angina). Nifedipine works
by relaxing blood vessels so that blood can flow
more easily. This medicine must be used
regularly to be effective. Nifedipine should not
be used to treat chest pain attacks. Nifedipine is
a drug with a generic name, which is produced
by several pharmaceutical companies.

Pathophysiology Nifedipine blocks the tension of L-type calcium

channels in vascular smooth muscle and
myocardial cells. This blockage prevents the
entry of calcium ions into cells during
depolarization, reduces peripheral arterial
vascular resistance and dilates coronary arteries.
This action lowers blood pressure and increases
the supply of oxygen to the heart thereby
 reducing angina.

PD CCB :
Prevents calcium ions from entering Ca
receptors in heart &
smooth muscle -> peripheral and coronary
vasodilation

AMLODIPINE
PK ● Absorption: bioavailability 65% with a
half-life of 35 hours.
● Distribution: high plasma protein
binding
● Metabolism: extensive

Dosage form Oral and characterized by high first pass

Method and Timing of Drug Administration This drug is taken orally, once a day, and
according to the doctor's instructions. This drug
is recommended by the Ministry of Health to be
taken after eating food and in the morning.

Dosage the recommended initial dose is 2.5 mg/day. The

usual maintenance dose range is 5-10 mg/day. no
dose reduction required in moderate renal
insufficiency

Drug interactions ● interactions The interactions between

amlodipine and hydrochlorothiazide are
not adverse. Amlodipine was found to be
effective (13/1 mmHg in lowering blood
pressure) when added with
hydrochlorothiazide. The
● interaction between amlodipine and
calcium carbonate was to decrease the
effect of amlodipine by calcium
carbonate. Calcium carbonate can reduce
the effectiveness of CCBs due to the
saturation of calcium channels by the
accumulation of calcium
https://media.neliti.com/media/publications/335
331-potensi-interaksi-obat-amlodipine-pada-pa-
9cc8c4fe.pdf
Definition Amlodipine is a drug that has proven efficacy for
hypertension. It has also shown moderate
efficacy for a variety of other diseases, including
hypertrophic cardiomyopathy, migraine, and
Raynaud's phenomenon.

Pathophysiology Amlodipine can decrease the force of contraction

of the myocardium which reduces the oxygen
demand of the myocardium. These drugs in
arterial smooth muscle can reduce arterial and
intraventricular pressure. Decreased stress on the
left ventricle. This drug also relieves and prevents
coronary artery spasm. The SA node and AV
node networks, which consist mainly of slow-
responding calcium-dependent cells, are mildly
affected by the dihydropyridine group.

PD ● muscle: decrease in blood pressure;

relaxes smooth muscle cells, the most
sensitive of which is vascular smooth
muscle, relaxation can be demonstrated
in smooth muscles of the bronchi,
gastrointestinal tract, and uterus;
arterioles are more sensitive so that
postural hypotension is less common
● cardiac muscle: reduces cardiac
contractility, cardiac output may also be
reduced in some cases, blocks smooth
muscle calcium channels at
concentrations below those required to
cause significant effects on the heart and
thus less stress on the heart than
verapamil and diltiazem
● other effects: interferes with stimulus-
secretion fusion in glands and nerve
endings due to differences in the type and
sensitivity of calcium channels in various
tissues
VERAPAMIL
PK Absorption: has a bioavailability of 20-30%
Distribution: half-life in adults 2-8 hours and
increases to 12 hours with multiple doses
Metabolism: This drug is extensively
metabolized by the liver.

Dosage form 80 mg tablet, 240 mg slow-release tablet, 2.5

mg/mL injection

Method and Timing of Drug Administration
Verapamil can be taken before or after meals.
Swallow the medicine whole with the help of a
glass of water. Do not crush, chew, or split the
medicine, as this may affect the effectiveness of
the medicine.

Dosage IV: 75-150 mg/kg, PO: 80-160 mg 3 dd

Drug interactions - Use with rifampin or phenobarbital will

increase the elimination of verapamil
thereby decreasing the bioavailability of
oral
- verapamil When verapamil is combined
with cardiodepressant drugs or drugs
that block the AV node, eg beta
blockers, Quinidine, it may cause
synergism

Definition verapamil is the drug of calcium

antagonists(calcium channel blockers),which
works by blocking the flow of calcium into heart
cells and blood vessel

Pathophysiology verapamil inhibits channel L-type active or

inactive

PD prevent entry of ionic Ca through slow channels

or selective voltage sensitive areas in cardiac
muscle and smooth muscle when depolarized,
causes vasodilation and increases oxygen flow
to heart muscle, and inhibits AV node
conduction.
 2. Diuretics
HYDROCHLOROTHIAZIDE (HCT)
PK Absorption : Affected by food consumed by
ingestion, bioavailability 65-75%, well absorbed
in the GI tract, duration of action ( The DOC) of
the drug Hydrochlorothiazide is 6-12 hours and
has a T1/2 for 6-15 hours.
Distribution : Has 68% protein binding and can
cross the placenta, but cannot cross the blood
brain barrier (BBB) and can be excreted in
breast milk
Metabolism : minimal metabolism and affects
the mechanism of electrolyte reabsorption in the
distal tubule of the
kidney ExcretionRapidlyintestines :eliminated in
the kidneys and at least 61% of the oral dose is
eliminated without any change in the drug for 24
hours.

Dosage form Available in tablet form of 12.5 mg, 25 mg, and

50 mg, orally

Method and timing of Drug Administration
In adult cases take 25 mg once a day as a single
dose and consume 2 hours before using other
drugs such as antacids, calcium supplements and
iron supplements because they can reduce
absorption of hydrochlorothiazide.

Dosage Oral, as much as 25 mg single dose

Drug interactions Foods with high fat content reduce drug

bioavailability, and may decrease the efficacy of
bivalirudin.

Definition Hydrochlorothiazide is a short-acting thiazide

diuretic. Hydrochlorothiazide is used to treat
hypertension and edema. This drug acts and
binds to red blood cells and is excreted through
the kidneys.

Pathophysiology Hydrochlorothiazide reduces absorption of

sodium and from the distal renal tubule

PD Inhibits NaCl cotransporter in distal tubule

SPIRONOLACTONE
PK Absorption: 90% bioavailability
Distribution: Crosses the blood placenta barrier,
enters breast milk in the form of canrenone.
Metabolism: extensively metabolized to several
active metabolites.
Excretion; Through urine and feces as
metabolites. Plasma half life is 1.3 hours
(spironolactone) and 2.8-11.2 hours (active
metabolite).

Dosage form Tablets 25 mg, 100 mg

Method and Time of Drug Administration Given by orally, 1 dsp or 2 dd

Dosage 50-100 mg/day, can be divided into 1 or 2

doses

Drug Interaction Definition Spironolactone is the most commonly used

potassium-sparing diuretic in children, it is an
aldosterone antagonist and increases potassium
retention and sodium excretion in the distal
tubule.

Definition Spironolactone is the most commonly used

potassium-sparing diuretic in children, it is an
aldosterone antagonist and increases potassium
retention and sodium excretion in the distal
tubule.

Pathophysiology Potassium-sparing diuretics are most useful in

the setting of mineralocorticoid excess or
hyperaldosteronism (also called aldosteronism)
because of primary hypersecretion (Conn's
syndrome, ectopic production of
adrenocorticotropic hormone) or secondary
hyperaldosteronism (triggered by heart failure,
liver cirrhosis, nephrotic syndrome, or other
disease associated with decreased effective
intravascular volume). In conditions of
increased mineralocorticoid secretion and
excessive delivery of Na+ to the distal nephrons,
the kidneys waste K+. Potassium-sparing
diuretics of both types can be used in this
 situation to reduce the K+ secretion response

PD Acts distal to the kidney as a competitive

antagonist of aldosterone, resulting in increased
excretion of NaCl and water.

FUROSEMIDE
PK Absorption : The duration of furosemide
absorption is usually 2-3 hours. The half-life
depends on kidney function.
Distribution : Because loop diuretics act on the
luminal side of the tubule, their diuretic activity
correlates with secretion by the proximal tubule.
Reduced secretion of loop diuretics may occur
due to the simultaneous administration of drugs
such as NSAIDs or probenecid, which compete
for fatty acid secretion in the proximal tubule
Metabolism : Metabolites of ethacrynic acid and
furosemide have been identified, but it is not
known whether they have diuretic activity
Excretion : Eliminated by the kidneys through
glomerular filtration and tubular secretion.

Dosage Form form of furosemide is orally and parenterally.

Method and Timing of Drug Administration Oral:

● Edema. Adult, initial dose 40 mg in the

morning, support 20-40 mg daily,
increase to 80 mg daily in resistant
edema. Children, 1-3 mg/kg daily,
maximum 40 mg daily.
● Oliguria. Initial dose 250 mg daily. If
larger doses are required, increase
gradually by 250 mg, may be given every
4-6 hours up to a maximum of a single
dose of 2 g (rarely used).

Intravenous or intramuscular injection:

● Edema. Adult >15 years, initial dose 20-

 40 mg, dose may be increased by 20 mg
every 2 hour interval until effect is
achieved. Individual doses are
administered 1-2 times a day.
Intravenous injection should be given
slowly at a rate not exceeding 4 mg/min.
Intramuscular administration is only
done when oral and intravenous
administration is not possible.
Intramuscular not for acute conditions
such as pulmonary oedema.
● Acute pulmonary edema. The initial dose
is 40 mg intravenously. If the expected
response is not achieved within 1 hour,
the dose may be increased to 80 mg
slowly intravenously.
● Brain edema. Intravenous injection 20-
40 mg 3 times daily.
● Urgent diuresis. Doses of 20-40 mg are
given with electrolyte fluid infusion.
Infants and children <15 years,
parenteral administration is only done
when the situation is urgent or life-
threatening (1 mg/kg BW up to a
maximum of 20 mg/day).

(Source: PIO Nas

<http://pionas.pom.go.id/monografi/furosemide
>)

Dosage The total daily dose of furosemide is usually 20-

80 mg (as a single dose or in two divided doses).

Drug interactions
● glucocorticoids, carbenoxolone, or
laxatives: increase potassium depletion
with risk of hypokalemia.
● Non-steroidal anti-inflammatory drugs
(NSAIDs), probenecid, methotrexate,
phenytoin, sucralfate: reduce the effect
of furosemide.
● Cardiac glycosides: increase the
sensitivity of the myocardium.
 ● Drugs that can prolong the QT interval:
increase the risk of ventricular
arrhythmias.
● Salicylates: increases the risk of
salicylate toxicity.
● Aminoglycoside antibiotics,
cephalosporins and polymyxins: enhance
nephrotoxic and ototoxicity effects.
● Cysplastin: allows a risk of hearing
damage.
● Lithium: enhances the effect of lithium
on the heart and is neurotoxic because
furosemide reduces lithium excretion.
● Antihypertensive: has the potential to
drastically lower blood pressure and
decrease kidney function.
● Probenecid, methotrexate: decreases the
elimination of probenecid and
methotrexate.
● Theophylline: enhances the effect of
theophylline or muscle relaxant agents.
● Sympathomimetic antidiabetics and
antihypertensives: reduces the effect of
sympathomimetic antidiabetic and
antihypertensive drugs.
● Risperidone: use with caution
concurrently.
● Cyclosporine: increases risk of gout.
Contrast media: risk of worsening kidney
damage.
● Chloral hydrate: fever, sweating,
restlessness, nausea, increased blood
pressure and tachycardia may occur

(Source: PIO Nas

<http://pionas.pom.go.id/monografi/furosemide
>)

Definition Furosemide is a prototype drug from Loop

Diuretic which selectively inhibits NaCl
reabsorption in Thin Ascending Limb.
Pathophysiology
Furosemide has a direct effect on blood flow
through several vascular tissues, namely
increasing renal blood flow through the effects of
prostaglandins on renal blood vessels. In
addition, furosemide has also been shown to
reduce pulmonary congestion and left ventricular
filling pressures in heart failure before a
measurable increase in urine output occurs.

PD
● Loop diuretics inhibit NKCC2 in the
Thin Ascending Limb of Henle by
reducing NaCl reabsorption and also
eliminating the positive lumen potential
from K+ cycling leading to increased
M2+ and Ca2+ excretion.
● Prolonged use can cause
hypomagnesemia significantin some
patients.
● Loop diuretics have also been shown to
induce the expression of one of the
cyclooxygenases (COX-2), which is
involved in the synthesis of
prostaglandins from arachidonic acid.
 IV. P-DRUG TABLE

Golongan DIURETIK
Efficacy Safety (20%) Suitability (20%) Cost (10%) Total
(50%)

Furosemide 50 x 50% = 25 40 x 20%= 8 40 x 20% = 8 40 x 10% = 4 45

Hydrochlorothiazide 60 x 50%= 30 60 x 20%= 12 50 x 20% = 10 60 x 10% = 6 58

Spironolactone 40 x 50% = 20 50 x 20% = 10 30 x 20% = 6 50 x 10% = 5 41

Golongan CCB
Efficacy (50%) Safety (20%) Suitability (20%) Cost (10%) Total

Nicardipine 40 x 50% = 20 60 x 20% = 12 60 x 20% = 12 70 x 10% = 8 52

Nifedipine 40 x 50% = 20 40 x 20% = 8 50 x 20% = 10 50 x 10% = 6 44

Amlodipine 70 x 50% = 35 70 x 20% = 14 60 x 20% = 12 50 x 10% = 5 68

Verapamil 60 x 50% = 30 30 x 20% = 6 40 x 20% = 8 50 x 10% = 5 49

Diltiazem 50 x 50% = 25 60 x 20% = 12 40 x 20% = 8 40 x 10% = 4 49

 V. ANALYSIS P-DRUG TABLE

DIURETICS GROUP
Efficacy
Efficacy is not just based on pharmacodynamics. The therapeutic objective is that the
drug should work as soon as possible. Pharmacokinetics are therefore important as well.
All groups contain drugs or dosage forms with a rapid effect.

Furosemide
Furosemide could reduce reabsorption of NaCl and KCl in loop Henle tight ascendent.
It could increase salt and water excretion, reduce heart preload and afterload, reduce
lung edema. Its clinical use is for acute heart failure, emergency hypertension.
Furosemide could be given by oral and IV with its duration of action 2-4 hours. Oral
bioavailability of this drug is 61%.

Hydrochlorothiazide
HCT could reduce reabsorption of NaCl in distal convoluted tubule. It has the same
effect as furosemide but the efficacy is lower than furosemide. Its clinical use is for
mild chronic heart failure, mild to moderate hypertension, hypercalciuria. HCT could
be given only by oral with its duration of action 10-12 hours and bioavailability 70%.

Spironolactone
Spironolactone could block aldosterone receptors in the cytoplasm of the collecting
ducts of the nephrons, increase salt and water excretion, reduce remodelling and
mortality. Its clinical use is for chronic heart failure and aldosteronisme (cirrosis,
adrenal tumor), hypertension. Spironolactone could be given by oral with duration of
action 24-48 hours. Spironolactone has a rather slow onset of action, requiring several
days before full therapeutic effect is achieved and the effects last for 2–3 days after the
drug is discontinued.
Safety
All drug groups have side effects, most of which are a direct consequence of the
working mechanism of the drug. In the three groups, the side effects are more or less
equally serious, although at normal dosages few severe side effects are to be expected.

Furosemide
Skin rash, eosinophilia and, less often, interstitial nephritis are occasional side effects
of
furosemide. Hypokalemic metabolic alkalosis, ototoxicity, hyperuricemia, and
hypomagnesemia are also the adverse effects of furosemide.

Hydrochlorothiazide
Adverse effects reported for HCT include ototoxicity, hypovolemia, hyperuricemia,
and hypomagnesemia.

Spironolactone
Adverse effects reported for spironolactone include hyperkalemia, cardiac arrhythmia,
menstrual abnormalities, gynecomastia, sedation, headache, gastrointestinal
disturbances, and skin rashes.

Suitability
This is usually linked to an individual patient and so not considered when making a list
of P-drugs. However, we need to keep some practical aspects in mind.

Furosemide
Increases the potential for hypokalemia (potassium deficiency), when used with
diuretics, such as furosemide, but for furosemide has side effects that are not too many
and severe.

Hydrochlorothiazide
 Increased risk of hypokalemia if used with salbutamol, HCT diuretics have fewer side
effects than furosemide and spironolactone.

Spironolactone
Spironolactone may also increase the risk of hypokalemia if used with salbutamol, has
the most side effects.

Cost
Prices different between countries, and are more linked to individual drug products
than to drug groups.

Furosemide
On the internet the price for furosemide has a cheaper price than the two diuretic drugs.

Hydrochlorothiazide.
HCT has the most expensive price among them.

Spironolactone
For the drug spironolactone is at the middle price.

CCB GROUP
Efficacy
Giving efficacy scores in the P-drug table is influenced by pharmacokinetic and
pharmacodynamic factors of each drug. Each class of drugs has almost the same
potential in achieving certain effects. Differences in pharmacokinetics of each drug
cause differences in half-life resulting in variations in drug efficacy. Nifedipine and
nicardipine have half-lives that allow them to be taken 3 times a day, while amlodipine,
verapamil, and diltiazem (slow-release) are sufficient once a day.
Nifedipine
Nifedipine absorption is influenced by food and mechanical digestive processes, so it
is highly absorbed in the GI tract. Nifedipine is distributed by binding to 92-98% protein
and penetrates breast milk, has a half-life of 2 hours, and is oxidized in the liver by
CYP3A4. Nifedipine also prevents calcium ions from entering Ca receptors in cardiac
and smooth muscle by peripheral and coronary vasodilation.

Amlodipine
Amlodipine has a bioavailability of 65% with a half-life of 35 hours, is distributed with
high plasma protein binding, and is extensively metabolized. Amlodipine lowers blood
pressure and relaxes smooth muscles, especially vascular smooth muscle, reduces
contractility and cardiac output, blocks smooth muscle calcium channels at
concentrations below those required to exert a significant effect on the heart and thus
puts less stress on the heart than verapamil and diltiazem. Amlodipine may also
interfere with stimulus-secretion fusion in glands and nerve endings because of
differences between the type and sensitivity of calcium channels in various tissues.

Verapamil
Verapamil has a bioavailability of 20-30%, and is extensively metabolized by the liver.
It has a half-life of 2-8 hours in adults and is increased to 12 hours with multiple doses.
It prevents the entry of Ca ions through selective voltage sensitive areas in cardiac and
smooth muscle during depolarization, causes vasodilation and increases oxygen flow
to cardiac muscle, and inhibits AV node conduction.

Nicardipine
Nicardipine is rapidly absorbed from the GI tract, has a bioavailability of 35% and a
half-life of 2 hours, and is rapidly distributed throughout the body. Nicardipine is
rapidly metabolized in the liver via cytochrome P450 enzymes, mainly by the enzymes
CYP3A4, CYP2C8, and CYP2D6. The use of nicardipine can reduce systemic vascular
resistance and also afterload so that it can lower blood pressure, increase oxygen supply
to the myocardium as an antianginal, and provide minimal negative inotropic effect.
Diltiazem
Diltiazem is well absorbed orally with a bioavailability of 40-65% and a half-life of 3-
4 hours, distributed throughout the body tissues except the central nervous system,
bound to plasma proteins about 25-30%, and metabolized in the liver by oxidation by
CYP450. Diltiazem inhibits Ca influx during depolarization so that it can cause muscle
relaxation and vasodilation of blood vessels, inhibiting work and reducing cardiac
output and rate. Diltiazem can also be used as an antiarrhythmic and antianginal drug.

Safety
The provision of safety scores in the P-drug table is influenced by side effects and
toxicity effects of each drug.

Nifedipine
The side effects of nifedipine are generally due to the vasodilating factors of nifedipine.
The most common side effects are tachycardia, peripheral edema, dizziness, and
headache. When nifedipine is used concomitantly with fentanyl, it can cause severe
hypotension.

Amlodipine
Side effects with the use of amlodipine are generally similar to those of nifedipine, but
the percentage of cases is smaller. Amlodipine used in conjunction with HCT is not
harmful, it can even be more effective.

Verapamil
As with most calcium channel blockers, overdose of verapamil can result in negative
inotropic, chronotropic effects, dilatation of the arterial vasculature, and hypotension.
The most severe complications of verapamil overdose are bradycardia (occurring due
to inhibition of sinoatrial node function) and hypotension. Both of these can lead to
death if not treated immediately. The ability of verapamil to block calcium channels in
pancreatic beta cells can also cause inhibition of insulin release, so that hypoglycemia
can occur. Therefore, we scored the lowest for safety of verapamil.
Diltiazem
Side effects of diltiazem commonly include edema, bradycardia, dizziness, headache,
and fatigue. In rarer cases, diltiazem can cause congestive heart failure, myocardial
infarction, and hepatotoxicity. Diltiazem also has a small peripheral dilating effect.

Nicardipine
Common side effects of nicardipine are flushing, rash, headache, leg swelling, asthenia,
palpitations, dizziness, tachycardia, and dyspepsia. Nicardipine may increase the risk
of or worsen heart failure when used with beta-blocking drugs such as propranolol,
atenolol, and others.

Suitability
Suitability takes into account the convenience of dosage form, dosage schedule, and
route of administration. It also considers the safety features like contraindications and
drug interactions. patients are no longer of productive age, some suitability factors such
as pregnancy and breastfeeding conditions cannot be considering the P-drug score. We
use other factors such as patient compliance.

Nicardipine
Nicardipine is generally given orally although the intravenous route has been used for
the short-term treatment of hypertension. Nicardipine are similar for both hypertension
and angina.

Nifedipine
Nifedipine produced a significant increase of the heart rate which persisted throughout
the study, but it did not influence blood pressure.

Amlodipine
Amlodipine is safe and effective for treatment of high blood pressure, which doctors
refer to as hypertension. Amlodipine can cause hypotension, or low blood pressure, in
some people, particularly those with severe aortic stenosis. Symptoms of hypotension
include feeling faint, tired, and nauseous.

Verapamil
Verapamil is also used to control your heart rate if you have a fast/irregular heartbeat (such as
atrial fibrillation). It helps to lower the heart rate

Diltiazem
Diltiazem is used to treat high blood pressure (hypertension). Lowering high blood
pressure helps prevent strokes, heart attacks, and kidney problems. Diltiazem is called
a calcium channel blocker. It works by relaxing blood vessels in the body and heart so
blood can flow more easily. Diltiazem also lowers your heart rate. These effects help
the heart work less hard and lower blood pressure.

Cost
The cost score on the P-drug table is affected by the price of the stock drugs per
treatment.

Nicardipine
Rp8.066/tablet x 3 = Rp24.200/hari

Nifedipine
Rp240 /tablet x 3 = Rp720/hari

Amlodipine
Rp2.481/tablet x 1 = Rp2.481/hari

Verapamil
Rp651/tablet x 3 = Rp1.953/hari

Diltiazem
 Rp1.476/tablet x 4 = Rp5.904/hari

VI. MIND MAP

 VII. DRUG PRESCRIPTION

Dr. Faris Dary Utama

SIP: 012011133249

Jl. Abcd no 15 surabaya

081259761608

--------------------------------------------------------------------------------------------------------------------------

Surabaya, 8 November 2021

R/ Tab Amplodipine 5 mg No XXX

S 1 dd tab I om pc

-------------------------------------------------------------------------

R/ Tab Hydrochlorothiazide 25 mg No XXX

S 1 dd tab I om pc

--------------------------------------------------------------------------

Pro: Ibu X

Usia: 45 Tahun

Alamat: Jl. Xyz No 123 Surabaya

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Kefarmasian Indonesia, 3(1), 1-9.

de Vries, T. P. G. M., et al. Guide to Good Prescribing A practical manual.

Katzung, B.G., Masters, S.B. dan Trevor, A.J. (2014). Farmakologi Dasar & Klinik, Vol.2,
Edisi 12, Editor Bahasa Indonesia Ricky Soeharsono et al., Penerbit Buku Kedokteran EGC,
Jakarta. Kementerian Kesehatan Republik Indonesia, 282-303.

Manuntung, N. A., & Kep, M. (2019). Terapi perilaku kognitif pada pasien hipertensi. Wineka
Media.

Nguyen, Q., Dominguez, J., Nguyen, L., & Gullapalli, N. (2010). Hypertension management:
an update. American health & drug benefits, 3(1), 47–56.

Ulfa, N. M., Prasetya, R. A., & Adelia, L. (2018). Profil Penurunan Tekanan Darah pada Terapi
Obat Antihipertensi Golongan CCB Dihidropiridin Antara Amlodipin Dibandingkan Nifedipin
Oral Osmotik (Studi Dilakukan di Poli Penyakit Dalam RS Bhayangkara Porong). Journal of
Pharmacy and Science, 3(1), 34-39.

Yonata, A., & Pratama, A. S. P. (2016). Hipertensi sebagai faktor pencetus terjadinya stroke.
Jurnal Majority, 5(3), 17-21.