Ilmu Resep 1

Bagian 3
Muvita Rina Wati, MSc., Apt.
Departemen Farmasetika
Fakultas Farmasi UGM

muvitarinawati@gmail.com/
081.392.101.777
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 Pokok Bahasan

1. Perubahan /interaksi obat karena kondisi

fisiologi dan patofisiologi.
2. Perubahan hasil laboratorium karena
penggunaan obat.
3. Interaksi obat dengan kondisi lingkungan

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 PERUBAHAN /INTERAKSI OBAT KARENA
KONDISI FISIOLOGI DAN PATOFISIOLOGI.

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 Physiology

1. The science which treats of the functions of

living organism and its parts, and of the
physical and chemical factors and processes
involved.
2. The basic processes underlying the
functioning of a species or class of organism,
or any of its parts or processes.

(Dorland’s Medical Dictionary)

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 Pathophysiology

The physiology of disordered function (Dorland’s

Medical Dictionary)

The American Heritage Medical Dictionary:

• The functional changes associated with or
resulting from disease or injury.
• The scientific study of such changes. In both
senses also called physiopathology.

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 Gastro-intestinal Tract

pH
• Gastric pH was highly acidic
(range 1.0-2.5)
• The mean pH in the
proximal small intestine was
6.6
• the mean pH in the terminal
ileum was 7.5
• The left colon with mean pH
value 7.0

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 • The wall of the stomach is lined with millions
of gastric glands, which together secrete
400–800 ml of gastric juice at each meal.
Several kinds of cells are found in the gastric
glands-parietal cells
• chief cells
• mucus-secreting cells
• hormone-secreting (endocrine) cells

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 HCl

Parietal cells contain a H+/K+ ATPase.

This transmembrane protein secretes H+ ions
(protons) by active transport, using the energy
of ATP. The concentration of H+ in the gastric
juice can be as high as 0.15 M, giving gastric
juice a pH somewhat less than 1.

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 Chief cells

• The chief 🡪 pepsinogen, the precursor to the

proteolytic enzyme pepsin.
• Pepsin cleaves peptide bonds, favoring those on
the C-terminal side of tyrosine, phenylalanine,
and tryptophan residues. Its action breaks long
polypeptide chains into shorter lengths.
• Secretion by the gastric glands is stimulated by the
hormone gastrin. Gastrin is released by endocrine
cells in the stomach in response to the arrival of
food.

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 Stomach

• Some water, certain ions, and such drugs as

aspirin and ethanol are absorbed from the
stomach into the blood
• Most of our ingested vitamins and minerals are
absorbed in the first segment (about 10 inches [25
cm] long) of the small intestine.
• Two ducts enter the duodenum:
– one draining the gall bladder and hence the liver
– the other draining the exocrine portion of
the pancreas.

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 Liver

The liver 🡪 bile. Bile contains:

– bile acids. These amphiphilic steroids emulsify
ingested fat.
– bile pigments. These are the products of the
breakdown of hemoglobin removed by the liver
from old red blood cells. The brownish color of the
bile pigments imparts the characteristic brown
color of the feces.

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 Pancreas

• Sodium
bicarbonate (NaHCO3)
• Amylase
• Lipase
• 4 "zymogens“: trypsin,
chymotrypsin, elastase,
carboxypeptidase
• Nuclease

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 • In April 1999, the FDA
approved orlistat as a
treatment for obesity.
Orlistat inactivates
pancreatic lipase. About
one-third of ingested fats
fails to be broken down into
absorbable fatty acids and
monoglycerides and simply
passes out in the feces.

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 Small Intestine

• Aminopeptidases
• Disaccharidases These enzymes convert disaccharides into their
monosaccharide subunits.
– maltase hydrolyzes maltose into glucose.
– sucrase hydrolyzes sucrose (common table sugar)
into glucose and fructose.
– lactase hydrolyzes lactose (milk sugar) into glucose and galactose.
• Fructose simply diffuses into the villi, but both glucose and
galactose are absorbed by active transport.
• fatty acids and monoglycerides. These become resynthesized into
fats as they enter the cells of the villus. The resulting small
droplets of fat are then discharged by exocytosis into the lymph
vessels, called lacteals, draining the villi.

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 Human Physiology

Changes due to:

• Age
• Disease (Liver/ Renal Disease)
• Pregnancy/ breastfeeding
• Environment

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 Age

The pharmacodynamics changes, i.e.:

• changes in the type
• intensity and duration of drug action
• changes in receptor function (e.g. altered receptor number
and affinity, altered second messenger function, altered cell
response)
• changes in the homeostatic mechanisms
• reduced reserve capacity.

These changes can differ greatly among patients, may be responsible

for an increased incidence of adverse drug reactions and therapeutic
failure. They may also mandate a higher dose in some circumstances,
as some organs become less responsive to drug action with age.

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 Physiological changes occur with aging

• The cardiac output decreases,

• Blood pressure increases and arteriosclerosis develops.
• The lungs show impaired gas exchange,
• decrease in vital capacity and slower expiratory flow rates.
• The creatinine clearance decreases with age although the serum
creatinine level remains relatively constant due to a proportionate
age-related decrease in creatinine production.
• altered motility patterns
• atrophic gastritis
• altered hepatic drug metabolism
• progressive elevation of blood glucose
• Osteoporosis

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 Cont’

• The epidermis of the skin atrophies with age and due to changes in
collagen and elastin the skin loses its tone and elasticity.
• Atrophy of muscle cells.
• Degenerative changes occur in many joints and this, combined with the
loss of muscle mass, inhibits elderly patients locomotion.

These changes with age have important practical implications for

• the clinical management of elderly patients: metabolism is altered,
changes
• in response to commonly used drugs make different drug dosages
necessary
• and there is need for rational preventive programs of diet and exercise in
an
• effort to delay or reverse some of these changes.

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 Physiology changes in Pregnancy

• Increased maternal fat and total body water

• Decreased plasma protein concentrations, especially
albumin,
• Increased maternal blood volume, cardiac output, and
blood flow to the kidneys and uteroplacental unit
• And decreased blood pressure
• The maternal blood volume expansion occurs at a larger
proportion than the increase in red blood cell mass, which
results in physiologic anemia and hemodilution
• Other physiologic changes include increased tidal volume,
partially compensated respiratory alkalosis, delayed gastric
emptying and gastrointestinal motility, and altered activity
of hepatic drug metabolizing enzymes

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 Renal Disease

• Creatinine Clearance
• Glomerular filtration rate (GFR)
• Hypoalbuminemia
• Hormones: erythropoietin, calcitriol, renin

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 Liver Disease

• SGOT/ SGPT
• Albumin
• Fat and nutrient absorption

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 PERUBAHAN HASIL LABORATORIUM
KARENA PENGGUNAAN OBAT

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 Serum potassium

Drugs induce hyperkalemia:

• ACEi
• ß-blocker
• ARB
• Immunosupressant (cylosporin, tacrolimus)
• NSAID
• Drospirenone
• Heparin
• Potassium - sparing diuretics
• Potassium suplements
• Succinylcholine
• trimetoprime

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 Hyperkalemia

• The normal potassium level in the blood is

3.5-5.0 milliequivalents per liter (mEq/L)
• Risks: death, cardiac arrest, nausea-vomiting,
muscle weakness,

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 • Alcohol + acetaminophen 🡪 liver
• Drug – induced nephrotoxicity 🡪 renal
insufficiency, glomerular filtration rate (GFR)
less than 60 mL/minute/1.73 m2

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 INTERAKSI OBAT DENGAN KONDISI
LINGKUNGAN

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 THERAPEUTIC DRUG MONITORING

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 Indication

• Drugs with a narrow therapeutic index (where therapeutic drug

levels do not differ greatly from levels associated with serious
toxicity) should be monitored. Example: Lithium, phenytoin,
digoxin.
• Patients who have impaired clearance of a drug with a narrow
therapeutic index are candidates for drug monitoring. The
clearance mechanism of the drug involved must be known.
Example: Patients with renal failure have decreased clearance of
digoxin and therefore are at a higher risk of toxicity.
• Drugs whose toxicity is difficult to distinguish from a patient's
underlying disease may require monitoring. Example: Theophylline
in patients with chronic obstructive pulmonary disease.
• Drugs whose efficacy is difficult to establish clinically may require
monitoring of plasma levels. Example: Phenytoin.

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 TDM is not usefull for..

• Drugs that can be given in extremely high doses before toxicity is

apparent are not candidates for monitoring. Example: Penicillin.
• If there are better means of assessing drug effects, drug level
monitoring may not be appropriate. Example: Warfarin is
monitored by measuring INR, not by serum levels.
• Drug level monitoring to assess compliance is unreliable, since
poor compliance cannot be distinguished from rapid metabolism
without direct inpatient scrutiny of drug administration.
• Drug toxicity is a clinical diagnosis. Drug concentrations within the
usual therapeutic range do not rule out drug toxicity in a given
patient. Example: Digoxin, where other physiologic variables (eg,
hypokalemia) affect drug toxicity.

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