Good summary tool for health students.

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MENSTRAL CYCLE
DISORDERS,
MENOPAUSE, AND
DRUGS IN
PREGNANCY AND
LACTATION
Prepared by:
Sittie Shairah M. Sampal

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MENSTRUAL CYCLE DISORDERS
Menstruation is an event that occurs relatively late in puberty and 95% of girls
reach the menarche between the ages of 11 and 15 years. Menses is the blood and
other materials discharged from the uterus at menstruation. Menstrual cycle is the
periodic sequence of events in sexually mature nonpregnant women by which an egg
cell (ovum) is released from the ovary at four-week intervals until menopause.
Nitric Oxide is involved in the inhibition and maintenance of menstrual bleeding
by promoting vasodilation and inhibiting platelet aggregation. Myometrium is the
muscular layers of the uterus that contract spontaneously throughout the menstrual
cycle and is also more active during menstruation. The average loss per period is
between 30 to 40 ml.
PREMENSTRUAL SYNDROME (PMS)
PMS encompasses both mood changes and physical symptoms. Symptoms may
start up to 14 days before menstruation, although more usually they begin just a few
days before and disappear at the onset of, or shortly after, menstruation. However, for
some women, the beginning of menstruation may not signal the complete resolution of
symptoms. Severity varies from cycle to cycle and may be influenced by other life
factors such stress and tiredness. The most severe form of PMS may be referred to be
as premenstrual dysphoric disorder (PMDD).
Diagnostic criteria for premenstrual dysphoric disorder (PMDD):
One year duration of symptoms which are present for the majority of cycles
(occur luteal/remit follicular).
Five of the following symptoms (with at least one of these*) must occur during the
week before menses and remit within days of menses.
 Irritability*
 Depressed mood or hopelessness*
 Affective lability* (suddenly mood swings)
 Tension or anxiety*
 Decreased interest in activities
 Change in sleep patterns
 Difficulty concentrating
 Feeling out of control or overwhelmed
 Lack of energy
 Other physical symptoms, for example, breast tenderness bloating
 Change in appetite, for example, food cravings
Seriously interferes with work, social activities, relationships. Not an exacerbation of
another disorder. Confirmed by prospective daily ratings during at least consecutive
symptomatic cycles.

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Diagnostic criteria for premenstrual syndrome (PMS):
Patient reports ≥ 1of the following affective and somatic symptoms during the 5
days before menses in each of three prior menstrual cycles:
AFFECTIVE SOMATIC
Depression Breast tenderness
Angry outburns Abdominal bleeding
Irritability Headache
Anxiety Swelling of extremities
Confusion
Social withdrawal
Symptoms relieved within 4 days of menses onset without recurrence until at
least cycle day 13. Symptoms present in absence of any pharmacological therapy,
hormone ingestion, or drug or alcohol abuse. Symptoms occur reproducibly during two
cycles of prospective recording. Patient suffers from indentifiable dysfunction in social or
economic performance.
Hormones that contibutes symptoms for PMS:
1. Prolactin
- is secreted from the decidual cells at the end of luteal phase of the
menstrual cycle as well as from the anterior pituitary. This hormone has a
direct effect upon breast tissue and hence may be associated with breast
tenderness. It is also associated with stress and has an indirect
relationship with dopamine metabolism and release in the CNS. It
promotes sodium, potassium, and water retention.
2. Estradiol
- is increases neuronal excitability possibly via increasing the activity of
glutamate (an important excitatory neurotransmitter).
3. Mineralcorticoid, Aldosterone
- is associated with the increase in fluid retention as serum levels of this
hormone are elevated in the luteal phase.
Vitamins and Minerals that reduce symptoms for PMS:
1. Pyridoxine phosphate
- is a co-factor in a number of enzyme reactions, particularly those leading
to production of dopamine and serotonin. Decrease dopamine levels
would tend to increase serum prolactin and decreases serotonin levels
could be a factor in emotional disturbances, particularly depression.
2. Vitamin D
- high total vitamin D intake lowered risk of PMS by almost a third.
3. Vitamin C
- is also help to reduce the PMS in women.
Management:Non-Pharmacological Strategies:
 Dietary modififcations that may be helpful include restricting caffeine and alcohol
intake. (Smoking can exacerbate symptoms)
 Exercise may help as may learning simple relaxation techniques.

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 Increasing the intake of natural diuretics such as prunes, figs, celery, cucumber,
parsley, and foods high in potassium such ad bananas, oranges, dried fruits,
nuts, soya beans and tomatoes may all be useful.
 A typical dosage regimen would be 50 mg twice daily after meals or 100 mg after
breakfast. The dose should not exceed at doses greater than 200 mg. High
doses over long periods have also been associated with peripheral neuropathies.
Pyridoxine should be recommended 3 days before symptom onset and continued
for 2 days after menstruation has started.
 Calcium supplementation may also reduce the emotional, behavioural and
physical symptoms.
Pharmacological Management:
1. Progesterone
- synthetic progesterones in preparations such as Cyclogest® and
Duphaston® used in the past. Because of the lack of convincing trial
evidence and the risk of side effects, the use of progestogens is no longer
recommended.
Possible side effects:
 Weight gain
 Nausea
 Breast discomfort
 Breakthrough bleeding
 Changes in cycle length
2. Combined Oral Contraceptives (COC)
- some women are helped by the COC pill because it prevents
ovulation from taking place. However, the use of exogenous oestrogen
may be contraindicated because it can increase the risk of venous
thromboemblosim. It diminishes the efficacy with which activated protein C
down regulates in vitro thrombin formation. A genetic factor known s factor
V Leiden mutation is the most common inherited cause of thrombophilia,
and this mutation results in resistence to the effects of activated protein C.
- combination of ethinylestradiol with drospirenone is also available
as an oral contraceptive and appears to be useful in the management of
PMS.
3. Bromocriptine
- stimulates central dopamine receptors and thus inhibits the
release of prolactin. It useful for breast tenderness and occasionally has
beneficial effects upon fluid retention and mood changes. The dose can
be slowly increased to 2.5 mg twice a day if required.
4. Danazol
- is a synthetic steroid derived from ethisterone. It interacts with
androgen receptors, but it also has some affinity for the progesterone
receptor. Side effects can be minimized by using low doses of 200 mg a
day of Danazol.
Possible side effects:
 Nausea
 Giddiness
 Muscular pain
 Weight gain
 Acne

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 Virilisation
5. Gonadotrophin-releasing hormone analogues
- sometimes referred to as gonadorelin analogues, are useful for
managing the physical symptoms, but are less effective with respect to
emotional symptoms. It can be used for short periods of time, no more
than 6 months because it induce a hypo-oestrogenic state and therefore
bone loss becomes significant after 6 months treatment.
6. Prostaglandin synthesis inhibitors
- improvements in tension, irritability, depression, headache, and
general aches and pains can be seen in some women who take
prostaglandin synthesis inhibitors.
- use of Mefenamic acid at dose of 250 mg three times a day 12
days before a period is due, increasing to 500 mg three times a day 9
days before the period and continuing until the third day of menstruation.
7. Antidepressants
- selective serotonin reuptake inhibitors (SSIs) are more popular in
the treatment of PMS-related depression because they are effective and
well tolerated.
Common side effects:
 Headache
 Nervousness
 Drowsiness and Fatigue
 Sexual dysfunction
 Gastrointestinal disturbances
DYSMENORRHOEA
Dysmenorrhoea is usually subdivided into primary and secondary
dysmenorrhea.
1. Primary Dysmenorrhea
- it also referred as spasmodic dysmenorrhea, which is a uterine
problem and is predominantly a complaint of young women. The incidence
of primary dysmenorrhea peaks in women in their late teens and early
20s, the pain coinciding with establishment of ovulatory cycles.
Sites of Pain:
 Lower abdominal (cramping), which radiate into
thighs, and backache
 Gastrointestinal (nausea, vomiting diarrhea)
 Headache and Faintnes
- symptoms are intense on the first day of menses but rarely
continue beyond day 1 or 2 of the cycle.
Factors appear to increase the severity include young age at menarche:
 extended duration of menstrual flow (pain can be
most severe when the flow is higher)
 smoking and parity (prevalence and severity of
dysmenorrhea is decreased in parous women)

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2. Secondary dysmenorrhea
-it occurs secondary to some underlying pelvic pathology such as
endometriosis or pelvic inflammatory disease (PID). It tends to afflict
women in their 30s and 40s, and usually occurs as consequence of some
other pelvic pathology such as endometriosis or pelvic inflammation.
-symptoms starts before menstruation begins, continue for the duration of
menses and be associated with abdominal bloating, backache and
general feeling of heaviness in the pelvic area.
-intrauterine contraceptive device may exacerbate menstrual pain causes
localized inflammation that triggers the release of prostaglandins.
Treatment for Dysmenorrhoea:
DRUG SIDE EFFECTS
NSAIDs Gastric irritation, which can be minimized
by taking with or after food or selecting an
agent with less gastrotoxicity, for example,
ibuprofen.
Hypersensitivity reactions, particularly
bronchospasm.
Headache, dizziness, vertigo, hearing
problems (tinnitus) and haematuria
NSAIDs may adversely affect renal
function and provoke acute renal failure.
Combined Oral Contraceptives Thromboembolism is the most serious
potential adverse effect, due to a decrease
in circulating levels of antithrombin III while
increasing serum levels of some clotting
factors.
Progesterone-only Preparations Use of these agents may cause menstrual
disturbances, for example, breakthrough
bleeding. Other adverse effects relate to
the selectivity of the synthetic hormone, for
example, norethisterone. This should be
advantageous as it’s the androgenicity of
the compounds that contains with the
decrease in high-density lipoproteins.
MENORRHAGIA
Menorrhagia is by the woman’s subjective assessment of blood loss. Blood
Loss is considered to be excessive if it exceeds 80 ml per period, although both women
themselves and clinicians find it difficult objectively quantify blood loss. Physically
excessive blood loss will precipitate iron deficiency anaemia (haemoglobin <12 g/dL)
which. If left undiagnosed and untreated, will compound the problems outlines earlier.
Causes of Menorrhagia:
Dysfunctional uterine bleeding (60%), that is cause is unknown.
Other gynaecological causes (30%):
 Uterine or ovarian tumours
 Endometriosis
 Pelvic inflammatory disease
 Intrauterine contraceptive devices
 Early pregnancy complications

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Endocrine and haematological causes (>5%):
 Thyroid disorders, for example hypothyroidism
 Platelet problems and clotting abnormalities
Symptoms of underlying pelvic pathology:
 Irregular bleeding
 Sudden change in blood loss
 International bleeding
 Postcoital bleeding
 Dyspareunia
 Pelvic pain
 Premenstrual pain
Drug Treatment for Menorrhagia:
DRUG COMMENTS
Combined oral contraceptives Preparations are taken for 21 days with a
7-day pill free
Progestrogen-only preparations 5 mg three times daily or 10 mg twice daily
for the latter half of the cycle. Ten days of
therapy should be sufficient from day 15 of
the cycle in ovulatory cycle.
Intrauterineprogestogen-only
Contraceptive
This device typically releases 20µcg of
levonorgestrel/24h. It reduce menstrual
blood loss by up to 90% after 12 months of
use.
Danazol Suppress the pituitary-ovarian axis. Side
effects include arnenorrhoea, hot flushes,
sweating, changes in libido, vaginitis and
emotional lability. Also causes androgenic
side effects such as acne, oily skin and
hair, hirsutism, oedema, weight gain, voice
deeping and decresing breast size. It is to
be taken daily.
GnRH analogues (gonadorelin) These should only be used for 6 months
because they may decrease trabecular
bone density.
NSAIDs These agents only need to be taken for the
first 3-4 days of menses
Tranexamic acid This compound is usually only taken for
the first 3 days of menses.
ENDOMETRIOSIS
It is a condition in which endometrial tissue is found outside the uterus. These so-
called ectopic endometrial foci found outside the reproductive tract in the
gastrointestinal tract, the urinary tract and even the lungs. Women who have frequent
and heavier periods also seem to be more likely to suffer from endometriosis.
Although not all women with endometriosis, the pelvis is the most commonly
affected site. Symptoms take the form of dysmenorrhea and pelvic pain.

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Drug Treatment for Endometriosis:
 GnRH (buserelin, goserelin, leuprorelin and nafarelin)
-initially stimulate the hypothalamic-pituitary-ovarian axis but thereafter
induce a hypoestrogenic state by paradoxically inhibiting follicle-
stimulating hormone (FSH) and LH release.
 Low-dose COC (20-30µcg of ethinylestradiol) monophasic preparations
 Compounds with androgenic activity such as danazol
 Progestogens such as dydrogesterone. Medroxyprogesterone acetate and
norethisterone

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MENOPAUSE
Menopause is signaled by the last menstrual periods; this cessation of
menstruation results from a loss of ovarian follicular activity. It is a natural event in the
anatomical, physiological and psychological changes which form the female climacteric.
The problem associated with menopause result from the ensuing loss of the female sex
steroid oestrogen.
Symptoms associated with oestrogen lack, whether in the peri-menopausal or post-
menopausal phase, which include:
 Vasomotor symptoms (hot flushes, night sweats and palpitations)
 Localized atrophy of urogenital tissues
-ovarian function includes two major roles: the production of eggs
(gametogenesis) and the synthesis and secretion of hormones
(hormonogenesis) Both of these functions undergo subtle changes
with ageing so that fewer ova are produced and they are less
readily fertilized and the hormone levels become irregular.
 Osteoporosis
- is a systematic skeletal disease characterized by low bone mass
and microarchitectural deterioration of bone tissue leading to
enhances bone fragility and a consequent increase in fracture risk.
The most common cites for fractures are the hip, vertebrae and
wrist. Typical morbidities after a vertebral fracture include:
 Back pain
 Loss of height
 Deformity (kyphosis, protuberant abdomen)
 Reduced pulmonary function
 Diminished quality of life: Loss of self-esteem, distorted body
image, dependence on narcotic analgesics, sleep disorder,
depression, loss of independence.
 Psychological problems
-older age at menarche and younger age at menopause are
associated with poorer cognitive functioning during ageing.
Depression is twice as common in women as in men and may
increase during times of changing hormonal levels such as at
menopause.
 Coronary heart disease or CHD
-significant loss of calcium from the bones, which may give rise to
frequent fractures, and there is a change in the blood lipid profile,
which is associated with a rise in coronary heart disease.
Management for Menopausal Women:
1. Hormone replacement therapy
-is effective for symptomatic relief of menopausal symptoms, and its use is
justified when symptoms adversely affect quality of life.
Contraindications:
 undiagnosed vaginal bleeding in post-menopausal women
 presence of an oestrogen-dependent tumour
 liver disease (where liver function tests have failed to return to
normal)
 active thrombophlebitis
 active or recent arterial thromboembolic disease (angina or
myocardial infarction)
 Dubin-Johnson and Rotor syndromes

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2. Oestrogen therapy
-symptoms and long-term effects of menopause are due to oestrogen
deprivation, mainstay of HRT is oestrogen. This may be administered
orally or parentally but, in either case, the oestrogens used are naturally
occurring and include:
 Estradiol
 Estriol
 Estrone
 Estropipate
 Conjugated equine oestrogen (estrone sulphate 40%)
 Estradiol valerate
-the use of natural oestrogens reduces the risk of the potentially
dangerous oestrogenic effects such as raised blood pressure, alteration in
coagulation factors and an undersirable lipid profile, which sometimes
occur with the more potent synthetic oestrogens used in the oral
contraceptive agents.
There are four main routs of administration for oestrogen in HRT:
 Oral
 Transdermal (patches/gels/cream)
 Subcutaneous (implants)
 Vaginal (creams and medicated rings)
Effect of HRT administration route on lipid profile:
ORAL TRANSDERMAL
Decrease low-density lipoprotein Decrease low-density lipoprotein
Decrease total cholesterol Decrease total cholesterol
Increase high-density lipoprotein Decrease/Increase high density lipoprotein
Increase triglycerides Decrease triglycerides
Increase bile cholesterol Decrease/Increase bile cholesterol
3. Progesterone Therapy
-is the only progestogen to act solely on the progesterone receptor.
It may be administered at night in the form of pessary or suppository or by
injection in the form of a long-lasting subdermal implant. It is the most
common administered orally or transdermally and usually one of the
synthetic progestogens is used.
4. Tibolone
-is a synthetic that has oestrogenic, progestogenic and androgenic
effects that alleviate menopausal symptoms without a monthly bleed.
5. Raloxifene
- is a non-steroidal benzothiophene that binds to some oestrogen
receptors and belongs to a class of drugs referred to as selective
oestrogen receptor modulators (SERMs). It is licensed for the prevention
and treatment of osteoporosis as an alternative to HRT
Signs and Symptoms which advised women immediately stop taking HRT and these
include:
 Sudden severe chest pain
 Sudden breathlessness or cough with blood-stained sputum
 Unexplained severe pain in calf of one leg
 Severe stomach pain

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 Serious stomach pain
 Serious neurological effects
 Hepatitis, jaundice, liver enlargement
 Blood pressure above systolic 160 mm Hg and diastolic 100 mmHg.
 Detection of a risk factor, for example, prolonged immobility after surgery or leg
injury
Psychological symptoms of HRT:
 Depression
 Mood changes and irritability, which may also be associated with other life
changes occurring at this time
 Exhaustion
 Poor concentration and memory
 Panic attacks
 Lowered libido, which may be exacerbated by the above symptoms together with
dyspareunia linked to lack of oestrogen and falling androgen levels.

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DRUGS IN PREGNANCY AND LACTATION
Drugs in Pregnancy
 Assess risk/benefit ratio for the mother-fetus pair.
 Avoid non-essential drugs.
 Where drug treatment is clinically indicated, select an effective agent with the
best safety profile.
 Use the lowest effective dose for the shortest possible time.
 Provide timely and accurate counselling to help avoid unfounded maternal fears
about drug safety that may otherwise result in non-adherence with drug therapy
or unnecessary pregnancy termination.
 Use the statement ‘avoid all drugs in the first trimester where possible cautiously
as drug exposure in the second and third trimesters may still result in fetal harm,
 Remember that the harmful effects of a drug on the fetus may differ depending
on the trimester of exposure.
Drugs in Lactation
 Avoid unnecessary use of drugs
 Maternal therapy only rarely constitutes a reason to avoid breastfeeding.
 Assess the risk/benefit ration of both mother and infant.
 Monitor the infant for unusual signs and symptoms.
 Avoid use of new drugs if there is a therapeutic equivalent for which data use of
in lactation are available.
DRUGS AS PREGNANCY
Teratogens is defined as any agent that results in structural or functional
abnormalities in the fetus, or in the child after birth, as a consequence of maternal
exposure during pregnancy.
Examples of drugs considered to be human teratogens:
 ACE inhibitors
 Androgens
 Carbamazepine
 Carbimazole
 Cytotoxics (some)
 Danazol
 Diethylstilboestrol
 Ethanol
 Lithium
 Misoprostol
 Penicillamine
 Phenytoin
 Tetracylines
 Thalidomide
 Valproic acid
 Vitamin A and derivatives (isotretinoin)
 Warfarin
Critical Periods in Human Fetal Development:
1. Pre-embryonic stage (weeks 0-2 post-conception)
-teratogenic exposure during the pre-embryonic stage is thought to elicit
an ‘’all-or-nothing’’ response, leading either to death of the embryo or
complete recovery and normal development of the fetus.

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2. Embryonic stage (week 3-8 post-conception)
-exposure to drugs during this critical period therefore represents the
greatest risk major birth defects. For this reason, women are often advised to avoid or
minimize all drug use in the first trimester whenever possible.
3. Fetal stage (week 9-28 post-conception)
-during the fetal stage, the fetus continues to develop, grow and mature
and, importantly, remains susceptible to some drug effects. The central nervous system,
which can be damaged by exposure to certain drugs, for example, ethanol, at any stage
of pregnancy.
Principles of Teratogenics:
 Timing of exposure
- the stage of pregnancy at which a drug exposure occurs is key to
determining the likelihood, severity or nature of any adverse effect on the
fetus. For example, one drug for which this period is thalidomide, where
exposure between days 20 and 36 post-conception is associated with a
high risk of congenital malformation.
 Drug dose
- a threshold dose above which drug induced malformations are more
likely to occur for certain teratogenic compounds, although for most a ‘safe
dose’ has not been conclusively determined. For this reason, more
frequent monitoring of drug levels may be recommended for certain drugs
pregnancy.
 Species
- teratogenicity of a drug may be species dependent.
 Genotype and environmental interaction
-it remains undetermined as to whether this variable susceptibility to
teratogenic drugs is a result of genetic differences in the exposed
mothers, the fetal genotype, modifying environmental factors or a
combination of all three.
Examples of drugs with pharmacological effects on the fetus or neonate:
DRUG POSSIBLE ADVERSE PHARMACOLOGICAL
EFFECT
ACE inhibitors Fetal and neonatal hypoxia, hypotensin, renal
dysfunction, obliogohydramnios and intra-uterine
growth retardation
ᵦ-Blockers (atenolol, etc.) Neonatal bradycardia, hypotension and
hyperglycemia
Benzodiazepines Floppy infant syndrome, Withdrawal reactions
Corticosteroids (high dose) Fetal adrenal suppression
NSAID Premature closure of the ductus arteriosus
(affecting fetal circulation) and fetal renal
impairment (decreased urine output)
Opioids Neonatal withdrawal
Respiratory depression
Phenothiazines Neonatal withdrawal and transient extrapyramidal
symptoms
Tricyclic and SSRI
antidepressants
Neonatal withdrawal symptoms

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Pharmacokinetics changes during pregnancy:
ABSORPTION CHANGE DURING PREGNANCY
 Gastro-intestinal motility
 Lung function
 Skin blood circulation
Decrease
Increase
Increase
DISTRIBUTION
 Plasma volume
 Body water
 Plasma protein
 Fat deposition
Increase
Increase
Decrease
Increase
METABOLISM
 Liver activity Increase/Decrease (vice versa)
Excretion
 Glomerular filtration Increase
DRUGS IN LACTATION
Breast feeding is the best form of nutrition for young infants. It provides all the
energy and nutrients required for the first 6 months of life. It also strengthens the
mother-infant bond.
Benefits in Young infants:
 Protection of the infant against gastric, respiratory and urinary tract
infections
 Reduction in rates of obesity
 Juvenile-onset diabetes
 Atopic disease
Benefits in Adults:
 Lower blood pressure
 Lower cholesterol level
Maternal benefits:
 Reduced risk of developing pre-menopausal breast cancer
 Delayed resumption of menstrual cycle
Adverse Reactions in Breastfed Infants:
Atenolol Bradycardia, cyanosis, hypotension
Ciprofloxacin Pseudomembranous colitis
Codeine Death
Dapsone Haemolytic anaemia
Diazepam Lethargy, sedation, poor suckling
Doxepin Sedation and respiratory arrest
Erythromycin Pyloric stenosis
Fluoxetine Colic, irritability, sedation
Indometacin Seizures
Lithium T-wave abnormalities
Naproxen Prolonged bleeding, haemorrhage,
anaemia
Phenytoin Methaemoglobinaemia
Calculating the infant ‘dose’ ingested via milk:
Dinf = Cpmat x M/P x Vmilk
Where Dinf is infant dose

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Cpmat is the average maternal plasma concentration
M/P is used in preference to a ratio based on paired concentrations when
available.
Vmilk is milk ingested
The above equation simplifies if the actual milk concentration data are available:
Dinf = Cmilk x Vmilk
In the absence of a clearly define d range of infant doses, the weight adjusted
maternal dose expressed as percentage is widely used to indicate infant drug expose.
Relative infant dose (RID) = Dose in infant via milk [Dinf (mg/kg/day) x 100
Dose in mother [Dmat (mg/kg/day)
Factors affecting infant risk from maternal therapy:
 Drug adverse reaction profile
 Relative infant dose (RID)
 Oral biavailability
 Active metabolites
 Half-life
 Gestational age of the infant
 Full maternal drug regimen
 Pharmacogenetic factors
Measures to ensure the safety of the breastfed infant:
 Avoid unnecessary maternal drug use
 Seek professional advice on the suitability of over-the-counter products
 Avoid herbal products because of lack of data to support safe use
 Use the minimum clinically effective dose for the shortest possible time
 Review maternal therapy towards the end of pregnancy
 Choose a drug regimen and route of administration which presents the minimum
of drug to the infant via breast milk
 Avoid drugs known to cause serious toxicity in adults or children
 Monitor the infant for unusual signs or symptoms
 Avoid new drugs if there is a therapeutic equivalent with data to support safe use
in lactation
 Recognize risk factors, for example, prematurity, infant morbidity, multiple
maternal medications
Commonly Used Drugs thought to be Safe for Use in Breastfeeding Mothers of Full-
term Healthy Infants:
DRUG GROUPS INDIVIDUAL DRUGS
Antacids
Bulk laxatives
Cephalosporins
Inhaled medications, for
example, salbutamol
Penicillins
Progestogens
Vaccines (except smallpox)
Vitamines (except high-dose A and D)
Cetirizine
Clotrimazole
Cromoglycate
Diclofenac
Heparin
Ibuprofen
Insulin
Iron supplements
Lactulose
Levothyroxine
Loratadine
Nystatin
Paracetamol
Warfarin

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