Drugs in Gynaecology😍

Drugs in Gynaecology

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Summary

  • PPH + AMTSL + IOL → Oxytocin, Misoprost
  • PPH + AMTSL → Methergine
  • PPH only → Carboprost
  • AMTSL only → Syntometrine (methergine 0.5 mg + Oxytocin 5u)
  • IOL only →
    • Carbitosine
    • Dinoprost
  • Mnemonic:
    • words with “M” for AMTSL
    • Induction of Labor
      • “IO” → IOL except Syntometrine
    • PPH:
      • Miss (misoprost) → mother (methergine) → carbon (carboprost) and oxygen (oxytocin)
    • Prostins
      • Miss → single/mono → PGE1
      • Dino → di → PGE2
      • Carbo → Fuck in Car with 2 α → PGF2α

Uterotonics

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  • Recommended by WHO:
    • Oxytocin:
      • t 1/2 = 3 mins
      • DOC for AMTSL
      • DOC for PPH
      • No IV Bolus
        • Hypotension on IV bolus
      • S/E:
        • Water Intoxication
          • ADH like action
  • If Oxytocin is unavailable, the following can be given:
    • Methylergometrine (Methergine):
      • 0.2 mg IM
        • Never given IV (can lead to hypertension)
      • Used in AMTSL, PPH
        • NOT IOL
      • Avoid in
        • Cardiac and hypertensive patients,
        • Twins, Rh negative, HIV positive mother on PIs, PVD
        • NOTE: After delivery of 1st twinMethergine can be given
          • Mnemonic: Methyl kidathath are? → Rich people, tension people, cardiac patients, twins ne
    • For IOL
        • Misoprost (PGE 1):
          • Can be given in asthma
            • Uses
              Doses
              MTP T1
              800 mcg
              MTP T2
              400 mcg every 3 - 4 hrly (max: 6 doses)
              IOL
              Tab. 25 mcg Q4H P/V (max: 6 doses)
              Not given in Prev CS for IOL
              AMTSL
              600 mcg Oral
              PPH
              800 - 1000 SL or PR
          • Misoprost
            • Baby miss (Abortion) avumbo misoprost
            • Baby Miss avumbo Fever and hypotension
          • WHO recommends misoprostol distribution to pregnant females
            • To prevent PPH.
          • S/E: Fever with chills
        • Dinoprostone (PGE2):
          • Only for IOL
          • Time gap with Oxytocin = 6 hrs
          • Maximum does: 3
          • Cerviprime: Gel 0.5 mg Q6H (max: 4 doses).
          • Cervidil: 10mg dinoprostone placed in posterior vaginal fornix (Slow release).
          • NOTE: Dinoprost (Carboprost/ Hemabate): PGF2α
          • S/E: Hyperstimulation
          • Only as gel
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    • Syntometrine:
      • Fixed dose combination of
        • 5 IU oxytocin and 0.5 mg methyl ergometrine
        • NOT GIVEN FOR PPH
    • Carbetocin:
      • Synthetic oxytocin with longer T½
        • 100 mcg slow IV
        • NOT GIVEN FOR PPH
      • C/I: Asthma
  • Note: 
    • Dinoprost/Carboprost/ Hemabate
      • PGF2α is used for management of PPH
      • Not for AMTSL
      • C/I: Asthma
      • S/E: Diarrhea
    • MgSO4
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    Classification by Progesterone

    • 1st Generation: Norethindrone
    • 2nd Generation: LNG

    Third Generation/Artificial Progesterone

    • As generation increases: Androgenic side effects decrease.
    • Third generation:
      • Desogestrel
      • Norgestimate
      • Gestodene
      • Mnemonic: Just (Gestodene) 10 um (desogestrel) 100 um (Norgestimate)
    • Least androgenic side effect: Gestodene.

    4th generation:

    • Cyproterone acetate
    • Drospirenone
      • Antiandrogenic
      • Antimineralocorticoid ⟹ weight loss
      • Increases K+

    Drugs for Endometriosis/Dysmenorrhea

    • Hyperestrogenic condition:
      • Rx aims to decrease estrogen
    • Minimal–mild:
      • 1st line: NSAIDs/OCPs.
      • 2nd line: Progesterone (downregulates estrogen receptor).
      • 3rd line: GnRH continuous.
      • If no relief: Laparoscopic management.
    • Moderate–Severe:
      • 1st line: Continuous GnRH.
      • If no relief: Laparoscopic management.

    Estrogen

    • Synthetic
      • EE
      • CEE
    • Physiological
      • E1, E2, E3

    Potency

    • Ethinyl Estradiol (EE) >
    • Conjugated Equine Estrogen (CEE) >
    • Estradiol (E2) >
    • Estrone (E1) >
    • Estriol (E3)

    Common Estrogen Types

    Condition
    Estrogen Most Common/Specific
    Most common synthetic Estrogen in OCP
    EE
    Most common synthetic Estrogen in HRT
    17-beta estradiol
    Most common in reproductive age female
    E2 (Estradiol)
    Most common in pregnancy
    E2
    Most specific in pregnancy,
    Synthesised
    by Placenta
    [From DHEA from fetal adrenal gland]
    E3
    Most common in menopausal female, PCOS
    E1 (Estrone)

    Low Estrogen

    • POI
    • Menopause
    • Gonadal dysgenesis
    • Sheehan’s Syndrome
    • Kallman’s syndrome

    Progesterone challenge test is Negative

    • If Low Estrogen
      • Progesterone can only act on Estrogen primed endometrium
    • Normal Estrogen
      • Ascherman syndrome
        • d/t no endometrium
    • [Positive in PCOS]

    NOTE

    • Tocolytics
      • Nifedipine
      • Indomethacin if < 32 weeks
        • ≥ 32 weeks → PDA closure
      • Atosiban
        • Oxytocin Receptor antagonist
        • Preferred with heart diseases
      • Ritodrine
        • β₂ agonist (tocolytic drug)
        • → Inhibits uterine contractions
        • Avoided in Diabetic Pregnancy
          • they cause hyperglycemia, hypokalemia
      • Terbutaline
        • Only 1 dose
        • Preferred for ECV
    • C/I for Tocolysis
      • Preferred method is Vaginal delivery
      • Abruption
      • Eclampsia
      • Chorioamnionitis

    Hirsutism

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    • Hair growth in male pattern + Alopecia + Acne.
    • Excessive hair growth in androgen-dependent areas in females.
    • Conversion of vellus hair to terminal hair (opposite of AGA).
    • Seen in: Increased Androgen.
      • PCOS
      • Congenital adrenal hyperplasias
      • Virilizing tumors
      • SAHA syndrome
      • Idiopathic
    • Androgens in Females
      • Mild increase: Hirsutism.
      • Excessive increase: Virilisation.
    • Score: Ferriman-Gallwey scoring. ( ≥8 ).
    • Rule out hyperandrogenism
    • 1st line: 
      • OCP: DOC.
        • leading to ↓↓ Androgen,
        • Use for 6 months
      • If not relieved →
        • Anti-androgens 
          • Add Spironolactone + OCPs
        • spironolactone is antiandrogenic → can affect external genitalia of a male fetus in case of conception → Hence OCPs are added in reproductive age group.
    • Alternative:
      • Flutamide.
      • Finasteride.
      • Ketoconazole.
      • Cyproterone acetate.
    • TopicalEflornithine.
    • Last resortContinuous GnRH (decreased LH & FSH).
    • Most important: 
      • Laser hair reduction.
      • Lasers:
        • Diode
        • long pulsed Nd:YAG laser.
    • Mnemonic: Ocinu Ferriyil (Ferriman gellaway score) keetti → Spiral (Spironolactone) shape il odich → Flooril (Eflornithine) kidathi → Fine (Finasteride) Flute (Flutamide) keetti → Last continuous (Continuous GnRH) cheythu

    Note

    • Drug not used for hirsutism: Danazol (Causes hirsutism).

    Female with Hirsutism:

    • Check testosterone levels (Next step)
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        1. Normal: Idiopathic.
        1. 70 - 200:
            • PCOS.
            • Late onset CAH.
        1. 200:
            • CAH.
            • Androgen secreting tumour in ovaries.
    • M/C cause of hirsutism in young:
      • PCOS.
    • M/C cause of rapid onset hirsutism in young females:
      • Androgen secreting tumour of ovaries.

    Virilization

    All 5 present
    1. Clitoromegaly.
    1. Breast atrophy.
    1. Deepening of voice.
    1. Muscle mass increase.
    1. Hirsutism.
    Mnemonic:
    • Ferriman (Ferriman score) hersuitism () ulla pennine () ossinu (OCP) ferriyil keetti → Boat spiral (Spironolactone) shape il odichitt flooril (Eflornithine) kidathi → Fine (Finasteride) flute (FLutamide) keetti (Ketoconazole) → Last (Last resort) ayapo continuous (Continuous GnRh) cheyth

    SERM (Selective Estrogen Receptor Modulator)

    Clomiphene

    • Uses: Ovulation induction (if HPO axis intact i.e. FSH increase).
    • Most common side effect: Hot flushes.
    • 2nd most common side effect: Formation of ovarian cyst.
    • Common S/E: Vaginal dryness.
    • Chances of multiple pregnancy: 7–10%.
    • Stopped immediately:
      • Visual disturbances.

    Raloxifene

    • Use: Osteoporosis.
    • Side effect: Hot flushes, vaginal dryness.

    Tamoxifene

    • Use: Breast cancer.
    • Side effect: Hot flushes, vaginal dryness.
    • Leads to: Endometrial Ca.
    • Minimum time gap between tamoxifen & pregnancy:
      • 2 months.
      • Ideal gap: 3 months.
    • Teratogenic.
    • Mnemonic: Tamoxifene → Tame → Breast (use), endometrium (E/E) → 2-3 month () → kunju avum (teratogenic) → ends with endometrial carcinoma ()

    Ospemifene

    • Mx of vaginal dryness.

    Ormiloxifene

    • SERM
    • Component of centchroman (Chhaya).
    • Mnemonic:
      • Oormila (Ormilofene) somanu (Centrochroman) chayya () koduthu

    Drugs for Subserous/Intramural Fibroid

    • 1st line D's which decrease bleeding but NOT size of fibroid:
        1. Tranexamic acid.
        1. OCPCause anovulatory cycles → So ↓↓ estrogen
        1. Progesterone.
      • Size of fibroid is dependent on both estrogen and progesterone
        • So size of fibroid doesn't ↓↓
    • 2nd line D's which decrease size of fibroid & bleeding:
      • Drugs Decrease Estrogen
          1. Letrozole (Androgen to Estrogen).
          1. Danazole (S/E: Hirsutism).
          1. GnRH analogues (Continuous).
          1. GnRH antagonist.
      • Drugs Decrease Progesterone
          1. SPRM: Selective Progesterone Re-uptake modulator.
              • Ulipristal
              • Most effective hormonal emergency contraception
                • Order: CuT > Ulipristal
              • 30mg SD upto 5 days
          1. Progesterone antagonist:
              • Mifepristone (RU 486: medical abortion).
      • Mnemonic: Fibroid → bleeding olla female → Let (Letrozole) the girl (GnRh continuous, antagonist) dance (Danazole) Pristine (Ullipristal, Mifepristone)

    GnRH

    Analogue

    • Synthetic Analogue: Leuprolide, Goserelin.
    • Route:
      • S/c injections.
      • Intranasal spray (Orally inactive).
    • Mnemonic: Girl: Le (Leuprolide) Serine (Goserilin)
    • Uses
      • Pulsatile = Increased E, LH, FSH:
          1. Delayed puberty.
          1. Kallmann syndrome.
          1. Anovulation.
      • Continuous GnRH =
          1. Decreased E
          1. decreased androgen
          1. decreased LH
          1. decreased FSH
        • Rx: Hyperestrogenic conditions.
            1. Fibroid.
            1. Endometriosis.
            1. Precocious puberty.
            1. Hirsutism.
            1. ER +ve breast cancer.
            1. Prostate cancer.

    GnRH antagonist.

    • Elagolix
    • Cetrorelix
    • Mnemonic: 2nd girl → Elsy (Elagolix, Cetrorelix)
    • Usually active but expensive.
    • Used same as continuous GnRH.