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Part 1

Drug–Nutrient Interactions in Infancy

and Childhood

Kali an
siap ?
Pendahuluan
Nutrition is exceedingly important in
infants, children, and adolescents.
Inadequate nutrition will directly affect growth,
development, and puberty

Chronic medication use can result in a depletion of

certain nutrients which in the growing infant, child,
and adolescent can have long-term consequences.
 1 2 3

• Crushing a tablet, opening a capsule, or

making a liquid preparation from a solid
dosage form may result in changes in drug
efficacy.
• Mixing these forms with food to improve
palatability may lead to a drug–nutrient
interaction.
• Children with chronic illness receive
multiple medications, thus increasing the
likelihood of drug–drug and drug–nutrient
interactions.
• These children receive certain
medications for long periods of time that
can affect growth and development
C hi ld's gr
o wth
and
developm
ent
NUTRITIONAL ASSESSMENT

• Nutritional status is closely related to growth and development

and may be complicated by numerous medical conditions.

• Pediatric patients with complex medical conditions will benefit

from an assessment of nutritional status from a dietitian and

other clinicians who specialize in pediatric nutrition.

• Pediatric conditions which may be high risk for drug–nutrient

or drug–drug interactions include childhood cancers, cystic

fibrosis, congenital heart disease, bronchopulmonary

dysplasia, inflammatory bowel disease, gastrointestinal

disorders, end-organ failure requiring organ transplant, renal

disease, seizure, and other neurologic disorders.

 MEDICATION ADMINISTRATION AND DRUG
ABSORPTION

• Pediatric patients use many of the same

medications as the adult population;
however, the specific method of drug
administration may be different.
• Pediatric patients often cannot swallow a
tablet or a capsule intact
• Since most doses are individualized
based on the child’s weight, a dose that
is appropriate may not be available in a
pre formulated tablet or capsule.
 Effect of Food on Drug Absorption
• Palatability of liquid medications is
another issue that is continually
addressed in the pediatric population.
• To mask the taste of medications, they
are often mixed with a liquid or a soft
food. As a result, the effect of food on
drug absorption must be considered

2
 CONTRADICTORY AND ADDITIVE EFFECTS

Vitamin K-rich foods X Warfarin (anti-koagulan)

• Inconsistent consumption of foods high in vitamin K may decrease
the effectiveness of warfarin and potentially place the patient at risk
for a clot
• Sudden elimination of dietary vitamin K may place a patient at risk
for bleeding episodes

Methamphetamine derivatives and Ephedrine

derivatives (stimulant drugs)
Should not be taken with caffeine as this combination may
result in jitteriness, nervousness, or insomnia

Alcohol (including drug products containing

alcohol)
• Should be avoided when taking medications known to cause
drowsiness, such as antihistamines (e.g., diphenhydramine)
• Pediatric patients often have paradoxical CNS stimulant effects with
antihistamines
NATURAL HEALTH PRODUCTS VITAMIN-DRUG INTERACTION
Part 2

Drug–Nutrient Interactions in
Pregnancy

Kali an
siap ?
 MATERNAL PHYSIOLOGICAL CHANGES IN PREGNANCY ON DRUG
PHARMACOKINETICS AND DISPOSITION

• Symptoms of nausea and vomiting frequent in pregnancy may affect drug

absorptionà Modifying the dosing schedule (drugs are taken when the patient is
least likely to vomit)
• Early on in pregnancy: Increased cardiac output and tidal volume à resulting in
increased pulmonary blood flow and hyperventilationà increase alveolar uptake of
drugs administered by the inhalational route.
• Halothane, isoflurane, and methoxyfl (anesthetics) à reduced dose requirements
in pregnancy
 SPECIAL MATERNAL CONSIDERATIONS: DRUGS AND
DISEASE WHICH AFFECT NUTRIENT STATUS

Antiepileptics and Vitamin K

• Antiepileptic medications, (phenobarbital, phenytoin,
and carbamazepine), have been shown to cross the
placenta and induce hepatic microsomal enzymes in
the fetal liver, potentially inducing the degradation of
vitamin K à neonatal bleeding due to fetal vitamin K
deficiencies

• 24–40% of women with epilepsy receive vitamin K

prophylaxis during the last month of pregnancy

• Antenatal vitamin K can be prescribed on an

individualized basis in certain circumstances, such as
imminent premature delivery however, prophylaxis
is not considered routine practice for all epileptic
pregnant women on AED
 SPECIAL MATERNAL CONSIDERATIONS: DRUGS AND
DISEASE WHICH AFFECT NUTRIENT STATUS

Folic Acid Antagonists

• Aminopterin, methotrexate(antineoplastic, chemotherapy),

sulfasalazine (colitis ulcerative, RA), pyrimethamine
(parasitic diseases toxoplasmosis and cystoisosporiasis) triamterene
1 (potassium-sparing diuretic ), and trimethoprim (antibiotic)
• Dihydrofolate reductase (DHFR) inhibitors
displace folate from the enzymeàblocking the
conversion of folate to its more active reduced
metabolites .

• Carbamazepine, phenytoin, primidone, and

2 phenobarbital (AEDs) à Affect other enzymes of
folate metabolism, impair the absorption of folate,
or increase the degradation of folate.
SPECIAL MATERNAL CONSIDERATIONS: DRUGS AND
DISEASE WHICH AFFECT NUTRIENT STATUS

Hyperemesis Gravidarum

• Persistent vomiting leading to a 5% weight

loss of pre-pregnancy weight along with • Doxylamine/pyridoxine combination
electrolyte imbalance and ketonuria and (Diclectin1), histamine receptor (H1)
occurs in 1% of pregnancies. antagonists (i.e., dimenhydrinate,
diphenhydramine, hydroxyzine)
• Dietary and lifestyle changes (eating small,
frequent meals consisting of bland food), • Metoclopramide is safe in the management of
Alternate remedies (ginger NVP; however, evidence for its efficacy is
supplementation, acupuncture, and limited
acupressure).
Part 3

Drug–Nutrient Interactions in Lactation

Kali an
siap ?
 DRUG DISTRIBUTION INTO HUMAN MILK

• A drug’s lipid solubility, protein binding, acid/base

characteristics, molecular weight, maternal systemic
bioavailability, and its half-life, transport proteins may play
a role in active secretion of drugs into milk.

• Drugs frequently weak acids or bases (slightly more acidic

than human blood) à basic molecules will tend to become
• Almost all drugs will gain access to the milk à transport
ionized, depending on their pKa and become ‘‘ion trapped’’
across the mammary barrier is governed by standard
in the milk
pharmacokinetic and pharmacodynamic principles,
whereby drugs diffuse down the concentration gradient
• Breast milk is relatively high in fat (3–4%)à drugs which
(passive transport)à relates to their inherent
are highly lipid soluble will tend to diffuse into breast milk
physicochemical properties.
to a greater extent.
• Drugs frequently small in molecular weight (< than 100–
• The protein binding of a drug also influences the diffusion
200 Da), à easy diffusion across the lipid bilayers of the
into breast milk since it is only the free fraction of drug
mammary epithelia (alveolar cells) into mature milk.
that is able to diffuse across the lipid bilayerà highly
protein bound drugs are less likely to diffuse into human
milk.
 DRUG DISTRIBUTION INTO
HUMAN MILK

• The mother’s plasma concentration of a drug will

also influence the amount of drug in milk.
• Because the concentrations in milk tend to correlate
with concentrations in maternal plasma (99) and
the two follow similar concentration– time profiles.
• In fact, when sampled over time, the concentration
of drug in milk will display an initial peak followed
by a more gradual decline in concentration. As
maternal plasma concentrations of drug fall, so will
the drug concentrations in breast milk, although
there will be a lag in the breast milk concentrations
to allow for distribution

• Maternal plasma half-life of a drug, therefore, will also influence the

amount of drug in milk.
• Drugs with very short half-lives may be present in the maternal
systemic circulation only for brief periods.
• They may peak rapidly in plasma and dissipate just as rapidly, which
may not allow for significant transfer into milk
 SPECIAL CONSIDERATIONS: DRUGS THAT INFLUENCE MILK PRODUCTION OR
INFANT INTAKE

Drugs that Increase Milk Production

• Human milk production is highly regulated by prolactin

and oxytocin (milk production and milk ejection)
• Disturbed by drugs particularly those which either
stimulate or suppress prolactin release

• Dopamine: acts on the pituitary to decrease prolactinà

decreasing milk production
• Antidopaminergic effect such as domperidone and
metoclopramide can stimulate milk production
(galactogogues)
• Chlorpromazine (antipsychotic) blocks the dopamine
receptorà increase prolactin and subsequently breast
milkà effective, however, its unfavorable side effect profile
(e.g., extrapyramidal effects) would make it less attractive
as a galactogogue
 SPECIAL CONSIDERATIONS: DRUGS THAT INFLUENCE MILK PRODUCTION OR
INFANT INTAKE

Drugs that May Decrease Milk Yield

As part of family planning, many women will need to consider

their contraceptive choices during lactation
• Hormonal contraceptives: modify the normal hormonal
milieu of the woman à lactation and milk production.

• Current recommendations suggest that women should

consider progestin-only agents medroxyprogesterone or
levonorgestrel implants as they do not impair milk volume

• The estrogen–progestin combination contraceptives are

not recommended since they may decrease milk yield

• Alcohol disrupts the hormonal milieu in the lactating

woman and may impair milk ejection

• Infants seem to respond to alcohol-induced flavor changes

by consuming less milk
Infant Issues

• Although drugs may gain access to the milk, if they cannot be absorbed
by the infant to any appreciable degree, they are not likely to pose
significant risks of exposure.
• Many drugs which enter the infant’s gastrointestinal tract become
unstable in the acidic environment of the stomach and are rapidly
inactivated
• Other drugs, due to their physicochemical properties, are simply poorly
absorbed from the gut
• Many drugs undergo significant metabolism in the liver before
reaching the systemic circulation (first-pass effect) à decrease the
likelihood that significant drug concentrations will be found in the
systemic circulation of the infant and hence the likelihood of dose-
related adverse reactions.

• Most drugs will gain access to the breast milk in very low
concentrations, usually less than 10% of the maternal dose on a per kg
basis (maternal weight-adjusted dose) and frequently less than 1%.
• These subclinical concentrations that will be delivered to the infant,
most drugs pose little risk for use in the lactating patient.
• The possibility of local reactions within the gastrointestinal tract
cannot be ruled out
Terima kasih!
?.
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