METHOTREXATE

Therapeutic Group : Cytotoxic agent- Anti metabolite

Mode of Action :
Folate
METHOTREXATE
Dihydrofolate
dihydrofolate reductase
Tetrahydrofolate

Role in purine synthesis and thymidylic acid synthesis

Required for DNA synthesis

 INDICATIONS
• Choriocarcinoma
As single agent
5mg x five times a day x 5 days
repeated at 10 – 20 days interval till regression occurs
In combination therapy
(with drugs like actinomycin D, Cyclophosphamide and Etoposide)

• For prophylaxis following Molar Pregnancy

5mg x five times a day x 5 days
3 courses repeated at 7-10 days

• Medical management of Ectopic Pregnancy

– IM 1mg/kg body wt. OR
– Inj 25-50 mg into gestational sac under USG or laparoscopic guidance
 OTHER INDICATIONS
AS CYTOTOXIC AGENT AS IMMUNOSUPPRESSANT

• Acute lymphocytic • Systemic Lupus

leukemia Erythematosus
• Non Hodgkin’s • Rheumatoid Arthritis
Lymphoma • Crohn’s Disease
• Tumors of Breast, Lung, • Psoriasis
Testis, Bladder • Following organ
transplantation
Route of administration : oral, IV, IM, SC,
intrathecal
 ADVERSE EFFECTS
• Anemia
• Leucopenia Leucovorin ( Folinic
• Agranulocytosis Acid) Rescue Therapy :
• Liver : Hepatoxicity
• Renal : Nephrotoxicity 0.1 mg/kg IM given
• alternating with methotrexate
GI : Nausea and vomiting
i.e
( most common),
If methotrexate given at 1, 3,
Mucositis, Gastric
5, 7th days
hemorrhage
Give folinic acid at 2, 4, 6, 8th
• Alopecia days
• Pneumonitis
 CONTRAINDICATIONS
• Pregnancy ( Category X)
• Breastfeeding
• Serum creatinine level > 1.3 mg%
• Deranged Liver Function Test ( SGOT, SGPT > 50
IU/L)
• Pre-existing blood dyscrasias
• Acute pulmonary disease
• Immunodeficiency disease
• Peptic Ulcer
 ONDANSETRON (Cat-B)
Therapeutic Group: Anti emetic - Selective Serotonin
Antagonist

Mode of Action :

Blocks action of serotonin on serotonin receptor( 5HT3 type)

located on vagal afferents, NTS and CTZ

Blockage of emetogenic impulses both centrally and peripherally

Anti emetic action

 INDICATIONS
• Post operative nausea and vomiting
• Vomiting due to cancer chemotherapeutic agents
• Vomiting due to drug overdosage, GI disorders,
uremia, or neurological injuries

Not effective in cases of motion sickness

Is a category B drug. Although it is not FDA
approved for use in pregnancy, it is widely used.
Route of Use : IV, oral
 ADVERSE EFFECTS
Generally well tolerated.
• Headache
• Dizziness
• Constipation
• Abdominal discomfort
• Iv inj. – Hypotension, bradycardia, chest pain
and allergic reactions rarely
 Drugs that can be used in Hyperemesis
Gravidarum
• Promethazine
• Prochlorperazine
• Metoclopramide
 OMEPRAZOLE
• MOA- proton pump inhibitor by inhibiting
H+K+ATPase to the apical membrane of
parietal cell
• No effect on pepsin, intrinsic factor, juice
volume or gastric motility
• Active only at pH less than 5
• Bioavailability decreases by food; should be
taken empty stomach
• 20 mg tablets available
• Uses
– Peptic ulcer
– Stress ulcer
– Gastroesophageal reflux disease
– Zollingger-Ellison syndrome
• Adverse effect
- Nausea, Loose stool
- Headache, Joint pain,
- Rashes
 Promethazine
• Phenergan
• First generation Antihistaminic drug
• MOA- By blocking H1-receptor and
anticholinergic action
• Uses
– Morning sickness
– Motion sickness
– Post operative vomiting
• Adverse effects
– Category C drug
– Has sedative, anticholinergic, anti histaminic and weak
antidopaminergic properties
• Sedation
• Dryness of mouth
• Constipation
• Tardive diskinesia
• Respiratory depression

Promethazine- im 25mg TDS

 Clomiphene Citrate (Category X)
• Nonsteroidal anti oestrogenic drug: antagonize oestrogen at
receptor level
• Ovulation Inducing drug
• It is a mixture of two isomers, cis (know as zuclomiphene) and
trans (know as enclomiphene citrate). Cis fraction is
responsible for inducing ovulation.
• Half life of 5 days
• It is metabolized in liver and secreted in bile and faeces.
Mechanism of action
It binds to Estrogen receptors in
Hypothalamus

Prevents -ve feedback of endogenous

estrogen

Increased pulsatile GnRH secretion

Increased lH and FSH secretion

Ovary enlarges and ovulates

• Clomiphene citrate also exerts its antiestrogen effects in the
cervix and the endometrium
• It causes the cervical mucus to be thick and viscid, thereby
hindering sperm penetration.
 Indications
• Anovulatory Infertility (Chief Use)
• Assisted reproductive techniques(ART) : as
an aid in in-vitro fertilization. Causes
maturation of several ova—improves
harvesting for in vitro fertilization .
• PCOS associated with infertility:
dexamethasone(0.5mg) at bedtime reduces
androgen production and is used in some
women with clomiphene if DHEA is raised
above 5ng/ml.
• Oligo-zoospermia in male: 25mg orally for 25 days each
month for 3 to 6 months to stimulate spermatogenesis by
increasing gonadotropin secretion.
 Dose
• In women suffering from amenorrhoea it can be started at
any day.
• In normal cycle: drug is started on second day of period in
a dose of 50 mg daily for 5 days
• Monitoring is done by serial ultrasound from 10th day
onward until the sign of ovulation are observed.
• When the dominant follicle reaches 20mm , hCG 5000 IU is
injected intramuscularly .
• About 36 to 40 hr after hCG is injected , ovulation occur –
so the couple is advised intercourse around this time
• As hCG injection indicate precise time of ovulation and also
compensate for corpus luteal phase defect caused by
clomiphene its used is justified.
Withheld in a cycle if more than 20 follicle are seen
on ultrasound , in PCOS and E2 level rises to 3000pg/ml due
to high risk of ovarian hyperstimulation syndrome.
• Cyclical therapy is recommended for 6 mths
after which a break is given for 2 to 3 mths. If
ovulation is not induced and follicular size
does not attain 20mm : Increased by 50 mg
each cycle to maximum dose of 150mg
 Signs of Ovulation
• Rise in the Basal Body Temperature
• Cervical Mucus Study (Clear, Watery, Stretchable Type)
• Folliculometry (USG evidence of growing follicles)
• Serial estimation of plasma E2
 Couple Instruction
Couple are advised to have sexual intercourse as per following
guidelines:

• Number of times over 36 to 40 hour following hCG

administration.
• Several time for 24 to 48 hr after the colour changein urine
tested for LH kit.
• Daily or on alternate days beginning 5-7 days after last dose of
clomiphene therapy.
 Adjuvant Therapy Required During
Clomiphene Citrate Therapy
• PCOS: Obesity (weight reduction; Insulin sensitizers
like Metformin)
• Elevated Prolactin level causes abnormal GnRH
secretion leading to ovulatory dysfunction :
Dopamine agonists like Bromocriptine and
Carbegoline to increase the ovarian responsiveness
to Clomiphene
• To counteract its antiestrogen effect on the cervix :
Conjugated estrogen 1.25 mg given daily for 10 days
starting on first day of the cycle.
 Adverse Drug Reactions
• Hyperstimulation syndrome– potentially life threatening
condition characterized by ovarian enlargement ,pleural
effusion ,peritoneal effusion oliguria, liver damage and
thromboembolism.
• Corpus luteal phase defect(CLPD)
• Abortion rate 25 to 40% due to corpus luteal phase defect
• Multiple pregnancy due to multiple ovulation in 10%
• Ovarian enlargement in 10%
• Visual disturbance and headache
• Hot flushes
• Breast tenderness
• Abdominal discomfort
• Loss of hair
• Rashes
• Increased risk of ovarian tumor
 Contraindications
• Ovarian cyst –the cyst can increase in size
• Chronic liver disease –because it is metabolized in liver
 Results
On clomiphene administration
• Successful ovulation : 80%
• Pregnancy rate: 50%
Due to Antiestrogenic effect of clomiphene on cervical
mucus, CLPD on endometrium.
• Multiple pregnancy: 10%
 Tranexamic Acid
• An antifibrinolytic drug
• Category B
MECHANISM OF ACTION
Reversibly bind to lysine binding sites of plasmin

Prevent binding of fibrin to plasmin

Fibrin isn’t broken down within endometrial

vessels

Bleeding is prevented.
 Indications
• Abnormal uterine bleeding
• IUCD induced menorrhagia
 DOSES
The recommended dose
• Two 650-mg (1300mg) tablets orally tds for a
maximum
of 5 days during menstruation
 Side effect
Common side effects:

Headache

Backaches

Abdominal pain

Diarrhea

Fatigue
• Rare side effects:
Pulmonary embolism
Deep vein thrombosis
Anaphylaxis
 Contraindications
• History of thromboembolism

Strong caution:
concurrently prescribing hormonal
contraceptives that also increase
thromboembolic risk

• However it has no effect on other

blood coagulation parameters such
as platelet count,aPTT and PT
 Mephenamic Acid (Category C)
• Analgesic, antipyretic and weak
antiinflammatory drug
• Is a Nonselective COX inhibitors
• Acts by inhibiting Prostaglandin synthesis
• Plasma half life of 2-4 hours
 Uses
• Spasmodic pain during dysmenorrhea is
attributed to myometrial contraction due to
increase PGF2 alpha secreted under
progesterone effect
So used in dysmenorrhea
• Also can be used in
Rheumatoid arthritis
Osteoarthritis
 Dose
• Mephenamic acid 500 mg tds
• Starting from D1-D3 of menstrual cycle
 Adverse Effects
• Diarrhea (Most common)
• Epigastric distress
• Skin rashes, dizziness rare
• Hemolytic anemia (Rare but serious)
 Contraindication
• Hypersensitivity
• late pregnancy
• Lactation
• Other: GI tract ulcer, renal disease
Glucocorticoids
• Category C
Glucocorticoids
• Dexamethasone and Betamethasone

• Mechanism of action
Acts on type II pneumocytes

Stimulate Phospholipid synthesis

(Surfactant)
Uses and Benefits
• Pregnancy less than 34 weeks of gestation

• Benefits
 Fetal lung maturation
 Decrease incidence of
• Respiratory distress syndrome (RDS)
• Necrotizing Enterocolitis (NEC)
• Intraventricular hemorrhage (IVH)
 Doses
1. Betamethasone 12 mg IM 2 doses 24 hours apart
2 doses
OR
2. Dexamethasone 6 mg IM 4 doses every 12 hours
apart 4 doses
Betamethasone is the steroid of choice.

• Benefit is seen after 24 hours of therapy.

• Action continues for 7 days.
Risk of Antenatal Steroid
• PROM especially with the evidence of
infection
• Insulin dependent Diabetes Mellitus
• Transient reduction of fetal breathing and
body movements
Analgesics In Labor
Pethidine
Tramadol
Pethidine

• Category C
• synthetic opioid analgesic of
phenylpiperidine class
• Strong sedative & spasmolytic but less analgesic
efficacy
• Used in 1st stage of labor
Uses
• Preoperative management of musculoskeletal and
visceral pain.
• Premedication prior to general anaesthesia.
• An adjunct to inhalational and other anaesthetic
agents during major surgical interventions.
• Postoperative and obstetric analgesia.
• In combination with diazepam, and in the absence
of other agents, for reduction of fractures and
other minor interventions.
Mechanism of Action
• Acts on µ-receptors
• Inhibits neurotransmitter release hence the pain
pathway,increase pain threshold and alters pain perception
• Chemically related to
atropine(not morphine)
so antimuscarinic effects
seen
• Actions blocked by N-type
Naloxone

K+
 Dosage & Preparations
• Pethidine Hydrochloride
• Injection: 50 mg (hydrochloride) in 1-ml
ampoule(iv, im, sc)
Tablet: 50 mg (hydrochloride)
• Dose: 1mg/kg (1.5mg/kg) repeated 4 hourly
i.e. 50-100mg IM tds
• Should not be used iv within 2hrs and im
within 3 hrs of delivery for fear of birth
asphyxia
 Side Effects
• Maternal
-Nausea, vomitting
•Fetal
-headache -Respiratory depression
-sedation
-delayed gastric emptying
& Birth asphyxia
-drowsiness -less than morphine
-dizziness -highest conc. – 2-3 hrs
-confusion
-tremors, mydriasis after administration
hypereflexia,
convulsions
(norpethidine)
- tachycardia (atropine)
Contraindications
•Preterm

• Bronchial asthma, emphysema or heart failure secondary to

chronic lung disease.
• Increased intracranial pressure, head injury or brain tumour.
• Severe hepatic impairment, adrenocortical insufficiency,
hypothyroidism.
• Convulsive disorders, acute alcoholism, delirium tremens.
• Use of monoamine oxidase inhibitors within the previous 14
days.
Tramadol
• Category C
• Centrally acting analgesic
• Atypical Opioid releives pain by opioid +
additional mechanism
Mechanism of Action
• Low affinity for µ-receptor
• Inhibits reuptake of NA& 5-HT
• Increases 5-HT release
• Activates monoaminergic spinal inhibition of
pain
• Onset- 1/2 hr ; lasts for 10-12 hrs
• Actions only partially reversed by Naloxone
Dose & Preparations
• 50 mg iv bolus

• Preparations:
oral - 50mg capsule
-100mg controlled release tab
injection – 50mg/ml
Uses
• Mild-moderate short lasting pain d/t:
-diagnostic procedures
-surgery
-injury
• Chronic pain – cancer
• NOT effective in severe pain
Side effects
• Well tolerated
• Dizziness
• Nausea
• Sleepiness
• Dry mouth
• Lowering of seizure threshold
Contraindications
• Patients using SSRI  SEROTONIN SYNDROME
• In patient receiving warfarin because it
prolongs  (INR) and prothrombin time and
extensive ecchymoses.
Narcotic antagonists
• Naloxone
• Reverse respiratory depression by opioids
• O.4mg iv in labour(may be repeated)
• Newborn 10µg/kg im/iv
• Repeated if born with narcotic depression
THANK YOU !!!