Professional Documents
Culture Documents
PRESCRIBING PRACTICE
for
SPECIAL GROUPs
ELDERLY /
GERITRIC
PEDIATRIC
SPECIAL Neonate-Infant
GROUPS: & Children.
PREGNANT &
LACTATION
PHARMACOLOGY :
PREGNANCY &
REPRODUCTIVE SYSTEM
3
Objectives of the session
After attending this lecture, med-students
are expected to be able to:
1. Explain the importance of studying drug effects
in pregnant women and breast-feeding period;
2. Explain the pharmacokinetics and
pharmacodynamics process in pregnant women
and breast-feeding period;
3. Explain the impact of medicines in pregnant
women, fetal and during breast-feeding period;
4. Explain how to communicate with mothers
about the risks of medicine use during
pregnancy and breast-feeding period.
4
Introduction
5
REPRODUCTIVE SYSTEM :
FEMALE & MALE
SEX ORGANS
( & URINARY TRACT)
FEMALE ORGANS:
MALE ORGANS :
-Ovariums
-Kidney -Testis
-Tuba falopii
-Ureter -Prostate gland
-Uterus
-Bladder -Seminalis duct
-Portio uteri
-Urethra -Epididymis
-Vagina
-Bladder
-Bladder
-Urethra
-Urethra
-Mammae
6
7
CONGENITAL
TRAUMA
INFEKSI – INFLAMASI
METABOLISME
DEGENERATIVE
MALIGNANCY
TRIMESTER I (0 – 14 weeks)
1ST TRIMESTER
PHARMACO-
2ND TRIMESTER KINETIC (PK)
ANATOMIC ?
PHYSIOLOGIC /
PHARMACO-
FUNCTION ?? 3RD TRIMESTER
DYNAMIC (PD)
PARTURIENT
LACTATION
9
-GASTROINTESTINAL TRACT :
oral cavity
motility
esophagus and stomach
intestine
liver and gallbladder
-KIDNEY and URINARY TRACT
renal dilatation
renal function
bladder
-HEMATOLOGIC SYSTEM
NORMAL blood volume
red blood cells PREGNANCY
WOMAN
iron
white blood cells
platelets
clotting factors
-CARDIOVASCULAR SYSTEM
heart (size, position, rhythms, murmurs)
cardiac output
blood pressure
peripheral resistance
blood flow
-RESPIRATORY SYSTEM
lung volume
lung capacities , etc.
10
MATERNAL PHYSIOLOGICAL CHANGES
DURING PREGNANCY (1)
11
MATERNAL PHYSIOLOGICAL CHANGES
DURING PREGNANCY (2)
12
Principle:
PHARMACOKINETIK (PK) &
PHARMACODYNAMIC (PD)
IN PREGNANCY
13
Trans- Mucosal,
i.v. oral i.m Topical
dermal buccal,
Vag., rectal,
inhalation
ABSORPTION
PRESYSTEMIC METABOLISM
systemic circulation
DISTRIBUTION
CENTRAL
COMPARTEMENT CLEARANCE
ABSORPTION
DRUG
DOSE [ FREE DRUG ]
LIBERATION EXCRETION
PROT.BOUND METABOLIT
ROUTE of
ADMINSTRATION BIOTRANSFORMATION /
METABOLISM
Drug concentration
at site of action
Free Drug
Absorption Drug-protein
metabolites
Excretion
Free Drug
Distribution
Metabolism
17
DRUGS/MEDICINES
PHARMACOKINETIK PHARMACODYNAMIC
A-D-M-E RESPONSE
PREGNANCY
PLACENTA
FOETUS MATERNAL
• THERAPEUTIC EFFECT THERAPEUTIC EFFECT
• TOXIC EFFECT TOXIC EFFECT
• TERATOGENIC EFFECT EFFECT ON PARTURITION
• ABORTION LABOUR EFFECT IN LACTATION
PUERPERIUM
18
PHARMACOKINETIK ( PK )
MOTHER FETUS
CHORION BASAL
LAYER LAYER
20
MATERNAL FETAL
PLACENTAL
21
MOTHER PLACENTA FETUS
BOUND BOUND
METABOLIZED
INGESTED by
the Fetus
EXCRETED
FETAL Intestines
TISSUE
K 1,2 K 2,1
AMNIOTIC FLUID
COMPARTMENT-2 PLACENTA
24
OXYGEN
DRUGS
HORMONES
- diffusion
- influence of Physicochemical properties
- influence of pH Differences
- active transport / fascillitated transportation
- influence of uterine-fetal blood flow
- influence of protein binding
PLACENTAL METABOLISM
26
PLACENTAL ABSORPTION OF MEDICINE
27
Pharmacokinetics:
drug concentrations in plasma over time
Plasma drug concentration
100
Cmax
Minimum Toxic
Concentration
10
AUC
Minimum Effective
Concentration
Tlag Tmax
1 Time
10
12
14
16
18
20
22
24
0
28
Multiple dosing?
• Drugs with narrow therapeutic
60
50 range
40
30
20 • Controlled- release
10
0
0 2 4 6 8 10 12
formulation
• Drugs use in the national
programmes
60
50
40
30
20
10
0
0 2 4 6 8 10 12
29
1000.00
Theophylline 1x daily
Plasma concentration (ug/mL)
15
100.00
10.001
00 24
24 48 48 72 72 96 96 120 120 144 144
Time (Hours)
Suryawati, 1999
30
Approval of copy/generic products
4 .5
7 .5
0
12
15
18
21
24
.5
.5
.5
.5
.5
10
13
16
19
22
Time (hours)
PHARMACOKINETICS :
Most drugs taken in pregnant women can cross the
placenta barrier and will exposed to the developing embryo.
The factors affecting drug transfer across placenta barrier:
1. Lipid solubility, ionization;
2. Molecular size;
3. Protein binding;
4. Metabolism in placenta and fetus.
32
1. Lipid solubility
Drug passage across placenta barriers depend on LIPID SOLUBILITY and
DEGREE of DRUG IONIZATION.
Drug: lipophobic ( low ) ------ difficult to cross the placenta barrier;
lipophilic ( high ) -------- tend to diffuse rapidly.
33
Acids pKa Bases
1 phenazone
Plasma pH 7.4 Plasma pH 1.4
Strong
Lipid
2 Weak
cloxacillin
salicylic acid 3
diazepam
furosemide 4 quinidine
phenylbutazone
warfarin 5
non-ionised [1] non-ionised [1]
6
membran
phenobarbital 7
trimethoprim
sulfadimidine
8
phenytoin
ionised [1000] ionised [0.001]
9 procainamide
nortriptyline
Weak amphetamine
10
sulfanilamide
11
pentamidine
12 Strong
34
2. Molecular size
3. Protein binding.
Leakage
36
PHARMACOKINETIK VARIABLES :
1. ABSORPTION
2. CLEARANCE
3. VOLUME DISTRIBUTTION
4. HALF-LIFE
PHARMACODYNAMIC VARIABLES :
1. MAXIMUM EFFECT
2. SENSITIVITY
37
CLEARENCE
( CL – L/hour or mL/minute )
38
CLEARENCE
DR dose (mg)
CL = or CL (L/hour) =
Css AUC ( mg.hour/L )
40
VOLUME of DISTRIBUTION
( Vd Litre )
42
HALF-LIFE
( t ½ - hours )
t½ = 0.693 x V
CL
43
ABSORPTION PROCESSES IN PLACENTA:
Passive diffusion down a concentration gradient
- most drugs
Cell membrane and fat-solubility of drugs
- most drugs
Active transport - few drugs
PLACENTA ;
FETAL PROTECTION
FETAL FEEDING
ENDOCRINE SECRETION
44
Pharmacodynamics
1. Drug action in maternal body system.
Drug effects in pregnant women:
- Reproductive tissues, e.g. breast, uterus, etc., are
altered the change of endocrine system according
to the stage of pregnancy;
- Other maternal organs (heart, lung, kidneys, CNS,
intestine, etc.) not changed, same as the effect in
non pregnant condition.
46
New born
normal
Gametes
Blastocyst Embryo Fetus
Functional
Abnormalities
Major
Death structural
Death abnormalities
Death
Sterility
42
TIME LINE I I I I I I I II I I I
DAY 0 7 15 I 60 90 120 150 1-6 weeks
of life
O
6-12 week 4-9 mo.
ORGANOGENESIS
49
COMPLETE (generally)
A
B
5 CATAGORIES
DRUG USE IN C
PREGNANCY
X
( detail >> modul TERATOGEN )
(US-FDA; TGA-Australia)
50
CATEGORY A
Adequate and well-controlled studies have failed to
demonstrate a risk to the fetus in the first trimester
of pregnancy (and there is no evidence of risk in later
trimesters)
CATEGORY B
Animal reproduction studies have failed to
demonstrate a risk to the fetus and there are
no adequate and well-controlled studies
in pregnant women.
52
CATEGORY D:
53
CATEGORY X
(contraindicated in pregnancy)
•ACE inhibitors
•Griseofulvin
•Alcohol
•Isotretinoin •Thalidomide
•A-II antagonist
•Lithium •Tabacco smoking
•Androgens
•Methotrexate •Trimethoprim (3rd
•Anticonvulsants
•Misoprostol trmstr)
•(fenitoin; valproic acid;
•NSAIDs (3rd trimester) •Warfarin & other
carbamazepine)
•Opioids (prolonged coumarin anticoagulants
•Benzodiazepins
use)
•Carbasone (amebecide)
•Progestins -----------------
•Chloramphenicol (3rd
•Radioiodine Note:
trimester)
(antithyroid) ACE= angiotensin
•Cyclophosfamide
•Reserpine converting enzyme;
•Diazoside
•Ribavin SSRIs = selective
•Diethylstilbestrol
•Sulfonamide (3rd trimst) serotonin reuptake
•Disulfiram
•SSRIs inhibitors
•Ergotamine
•Tetracyclin (3rd trimest)
•Estrogens
(Rogers,VL; Cox,S.,CMDT,2011) 55
MEDICINE in LABOR / PARTUS
56
NORMAL LABOR : 1ST STAGE : begin onset labor until
cervix dilatation (10 cm).
Duration : 6-8 hr multipara
8-12 hr primipara.
depends: parity; frequency-intensity-
duration uterine contraction;
the ability of the cervix;
feto-pelvic diameter;
presentation-position of the
fetus.
2ND STAGE : full dilatation of the cervix
to the birth
Duration menutes – 2 hours
(± 20 – 50 mnt), depend : fetal & mother.
3RD STAGE : from the birth of the infant
to delivery of the placenta.
Warning : bleeding post partum !
57
MEDICINE-USE in LABOR:
analgetics ( if needed ) :
meperidine; butorphanol;
anesthesia (epidural)
fluids (Ringer laktat; dextrose 5%);
(1ST STAGE)
59
LACTATION /
MEDICINE in
BREAST FEEDING 60
DRUG USE DURING
BREAST-FEEDING / LACTATION
MOTHER LACTATION TAKE MEDICINE :
61
DRUG USE DURING BREAST-FEEDING
Most drugs administered to lactating women are
detectable in breast milk. The mechanism of drug
transferring the breast milk is not different as
crossing the placenta.
62
TISSUE
MOTHER/
MATERNAL
BLOOD
BREAST MILK
ELIMINATION
ELIMINATION
64
BEBERAPA CONTOH :
OBAT YANG DAPAT DISEKRESSI MELALUI ASI.
67
DOSAGE FORMULA
FOR INFANT / CHILDREN :
Age ( years)
by AGE ( Young’s rule ) : Dose = adult dose x
Age + 12
68
TABLE BASED :
BODY SURFACE AREA
Weight
Approximate Surface Percent ( % ) of
(kg) (lb Age Area (m²) Adult Dose
10 22 1 yr 0.45 28
20 44 5.5 yr 0.8 48
30 66 9 yr 1 60
40 88 12 yr 1.3 78
70
CONCLUSION
1. After the thalidomide disaster, studying drugs
effects in pregnancy and during breast-feeding
become important
2. Changing anatomic and physiologic in
pregnancy change the pharmacokinetic and
pharmacodynamic process
3. The impact of drug use in pregnancy can
terminate the gestation, causing fetal
abnormality and harmful breast-feeding
4. The impact and the risks taking the medicine
during pregnancy and breast-feeding should be
discuss with the pregnant patient
71
MEDICINE