• Dental prophylaxis - professional teeth cleaning to prevent cavities and gum disease
• Pre-exposure prophylaxis (PrEP) - taking medication before potential HIV exposure to prevent infection
• Antibiotic prophylaxis - giving antibiotics before surgery to prevent post-operative infection
• Malaria prophylaxis - taking antimalarial drugs before traveling to a high-risk area

Monoclonal Antibody

Breaking Down the Term

How They Are Made

1. A mouse (or other animal) is injected with a specific antigen
2. Its immune system produces B-cells that make antibodies
3. One B-cell is fused with a cancer cell to create a hybridoma (which can multiply indefinitely)
4. This hybridoma produces large quantities of identical antibodies - all targeting the same antigen

Why They Matter

• Target cancer cells without harming normal cells (e.g., trastuzumab for breast cancer)
• Block inflammation (e.g., adalimumab for rheumatoid arthritis)
• Prevent infections (e.g., nirsevimab for RSV prevention)
• Diagnose diseases in lab tests

Naming Clue

• rituximab, pembrolizumab, bevacizumab, etc.

Triptans in Migraine - Role of Action (RODA)

What Are Triptans?

• Sumatriptan (prototype, first available)
• Almotriptan, Eletriptan, Frovatriptan, Naratriptan, Rizatriptan, Zolmitriptan

Mechanism of Action

1. Vasoconstriction - Activation of 5-HT1B receptors causes constriction of dilated intracranial blood vessels and arteriovenous anastomoses, reversing the abnormal blood flow that causes migraine pain.
2. Neuronal inhibition - Activation of 5-HT1D presynaptic autoreceptors inhibits the release of pro-inflammatory neuropeptides (substance P, neurokinin A, CGRP) from trigeminal nerve terminals in the perivascular space.

Clinical Use

Routes of Administration

Adverse Effects

• Pain, pressure, or tightness in chest, neck, throat, jaw (vasospastic)
• Dizziness and malaise
• Injection site irritation (SC route)
• Headache recurrence within 24-48 hours after a single dose - a second dose is usually effective

Contraindications

• Coronary artery disease or significant cardiac risk factors (due to vasoconstrictor effect)
• Do not combine with ergot derivatives or another triptan (wait at least 24 hours between)
• Caution with SSRIs (risk of serotonin syndrome)

Where Triptans Fit in Migraine Treatment

Acute Migraine Attack
       |
       +-- Mild-Moderate → NSAIDs, antiemetics
       |
       +-- Moderate-Severe → TRIPTANS (first-line, migraine-specific)
                              + NSAID (e.g., sumatriptan + naproxen combo)
                              + Antiemetic (e.g., metoclopramide, prochlorperazine)

Choice of Route of Administration (ROA) for Triptans in Migraine

Available Routes and Their Characteristics

Decision Guide - Which Route to Choose?

Patient has acute migraine attack
              |
              +── Can the patient swallow tablets?
              |          |
              |         YES → Is nausea/vomiting present?
              |                     |
              |                    NO  → ORAL tablet (most convenient)
              |                    YES → INTRANASAL or SC injection
              |
              +── Severe attack, needs fastest relief?
                           |
                          YES → SUBCUTANEOUS (sumatriptan SC, fastest)

Key Clinical Points

1. Oral route - first choice for most patients; most convenient but slowest onset (1-2 hrs). May be impractical when nausea and vomiting are present.
2. Subcutaneous route - gives the fastest and most reliable absorption (~20 min onset). Approximately 70% of patients get significant relief from sumatriptan 6 mg SC. The dose can be repeated once within 24 hours if the first dose fails.
3. Intranasal route - a good middle ground; faster than oral, avoids the GI tract, useful when vomiting is present but the patient wants to avoid injections.
4. If one route fails, try another - if a triptan is ineffective by one route, switching to another drug or an alternative route of administration may succeed.

Important Practical Rules

• Start treatment early - as soon as the migraine begins (during aura or at very first headache onset). Earlier treatment = better response.
• Do not repeat within 2 hours for most triptans (24 hours for SC sumatriptan second dose).
• No triptan + ergot within 24 hours of each other (risk of vasospasm).
• If oral triptans are used alongside naproxen (sumatriptan/naproxen combo), efficacy is improved.

Choice of Route of Administration (ROA) for Ergotamine in Migraine

Ergotamine Tartrate - Available Routes

Caffeine combination: Ergotamine is often combined with 100 mg caffeine per 1 mg ergotamine tartrate specifically to facilitate and improve absorption of the ergot alkaloid.

Dihydroergotamine (DHE) - Available Routes

DHE has efficacy similar to sumatriptan and is specifically reserved for severe or intractable migraine cases.

Decision Guide - Which Route to Choose?

Ergot therapy needed for migraine
              |
    ┌─────────┴──────────┐
ERGOTAMINE             DHE
    |                    |
Early attack?        Severe/intractable?
    |                    |
YES → Sublingual    YES → IV or IM (0.5-1 mg)
    |                    |
Nausea/vomiting?    Moderate, no injection?
    |                    |
YES → Rectal        YES → Intranasal
suppository
    |
No nausea?
→ Oral tablet
  (+ caffeine)

Dosage Limits (Important - Ergotamine)

Key Practical Rules

1. Give early - ergotamine becomes progressively less effective if delayed; must be given during the prodrome or at onset
2. Never combine ergot + triptan within 24 hours - risk of severe coronary vasospasm and ischemia
3. Avoid with CYP3A4 inhibitors (e.g., macrolide antibiotics, azole antifungals) - risk of life-threatening peripheral ischemia
4. Contraindicated in angina, peripheral vascular disease, pregnancy, hypertension

Why Triptans Remain the Drug of Choice Over Lasmiditan

Head-to-Head Comparison

The 4 Core Reasons Triptans Stay First-Line

• Significant sedation and CNS depression
• Dizziness, fatigue, paraesthesia
• Patients cannot drive or operate machinery for 8 hours after taking it Triptans do not carry this burden.

So When IS Lasmiditan Used?

• Contraindicated (CAD, uncontrolled hypertension, stroke, peripheral vascular disease)
• Not tolerated (intolerable side effects)

Acute Migraine
      |
      +--> No cardiac/vascular risk? → TRIPTAN (first-line)
      |
      +--> Cardiac contraindication to triptans? → LASMIDITAN or GEPANTS
                                                    (but warn about sedation/driving)

Bottom Line

General Side Effects of Prostaglandins

1. Gastrointestinal (Most Common)

These occur even at low doses and are consistent with prostaglandins acting on GI serotonin receptors and smooth muscle. (Katzung's Basic and Clinical Pharmacology, 16th Edition)

2. Pain and Hyperalgesia

• They sensitize nociceptors (pain receptors) to other stimuli like bradykinin and histamine
• This results in hyperalgesia (exaggerated pain response) and allodynia (pain from normally non-painful stimuli)
• PGE2 mediates both peripheral and central pain sensitization

3. Fever (Pyrexia)

• PGE2 acts on the hypothalamic thermoregulatory centre to raise the body temperature set point
• This is why NSAIDs (which block prostaglandin synthesis) are effective antipyretics
• Exogenous prostaglandins given as drugs can cause pyrexia and chills

4. Cardiovascular

5. Respiratory

6. Uterine / Reproductive

• Uterine contractions - all prostaglandins (especially PGE and PGF series) stimulate myometrial smooth muscle
• Can cause uterine cramping, pain, and hyperstimulation when used as uterotonics/abortifacients
• Cervical ripening effects may be uncomfortable

7. Ocular (with Topical Prostaglandins)

• Iris pigmentation changes (darkening of eye colour - permanent)
• Eyelash growth (hypertrichosis)
• Conjunctival hyperaemia (red eye)
• Periorbital fat atrophy (sunken appearance)

Quick Summary Table

Key Clinical Point

Patent Ductus Arteriosus (PDA)

What is the Ductus Arteriosus?

What Happens Normally at Birth?

1. Lungs expand → blood PO2 rises sharply (from ~15-20 mmHg in fetal life to ~100 mmHg)
2. High oxygen causes contraction of the smooth muscle in the ductus wall
3. Prostaglandin E2 (PGE2) - which kept the ductus open during fetal life - is now cleared
4. Functional closure occurs within hours of birth
5. Over weeks to months, anatomic closure follows (fibrosis), forming the ligamentum arteriosum

In fetal life, PGE2 and prostacyclin (PGI2) actively keep the ductus open. After birth, rising oxygen levels suppress PGE2 and trigger constriction.

What is Patent Ductus Arteriosus?

NORMAL (after birth):          PDA:
Aorta ←X→ Ductus              Aorta ──────→ Pulmonary Artery
           (closed)                  (ductus stays open)
                                      ↓
                              Left-to-right shunt

Epidemiology & Risk Factors

Pathophysiology - What Goes Wrong?

• Blood flows left-to-right (aorta → pulmonary artery) continuously, throughout systole AND diastole
• This extra blood volume returns to the left heart → left atrium and left ventricle dilate
• Over time, pulmonary blood flow increases → pulmonary hypertension develops
• Eventually, if uncorrected, pressures equalize and shunt reverses (right-to-left) = Eisenmenger syndrome (5% of cases)

Clinical Features

Treatment

The Prostaglandin Connection (Key Pharmacology Link)

• PGE2 keeps ductus open → NSAIDs (indomethacin, ibuprofen) close PDA by blocking PGE2
• NSAIDs in pregnancy (3rd trimester) are contraindicated because they can cause premature closure of the ductus arteriosus in the fetus
• Alprostadil (PGE1 analogue) is used to deliberately keep the ductus open in cyanotic congenital heart defects where the ductus is life-sustaining

Cervical Ripening in Labour

Definition

Normal Cervical Ripening - What Happens Biologically?

Unripe Cervix                     Ripe Cervix
--------------                    ------------
Firm, closed, long,               Soft, dilating, short,
organised collagen                disorganised collagen
                    ↓↓↓
         Ripening Process

Reduced endocervical expression of 17β-HSD-2 enzyme and changes in progesterone receptor (PR) isoforms shift the balance from progesterone to oestrogen dominance locally - this drives ripening even though circulating progesterone levels do not actually fall until after birth.

Role of Prostaglandins in Cervical Ripening

• Promote collagen solubility and breakdown
• Alter extracellular matrix composition
• Stimulate uterine contractions
• Expression of PGHS-2 (COX-2) is upregulated in the endocervical epithelium during labour

Assessment - The Bishop Score

Pharmacological Agents Used for Cervical Ripening

1. Dinoprostone (PGE2 analogue) - FDA Approved

• What it is: Synthetic PGE2 analogue
• Mechanism: Relaxes cervical smooth muscle + induces uterine contractions
• Routes:
  • Intracervical gel (Prepidil): 0.5 mg via syringe - max 3 doses in 24 hours
  • Vaginal insert/pessary (Cervidil): 10 mg, releases 0.3 mg/hour over 12 hours - removed at onset of labour or after 12 hours
• Advantage of insert: Can be removed immediately if uterine hyperstimulation occurs
• Contraindications: Asthma, glaucoma, myocardial infarction
• Main adverse effect: Uterine hyperstimulation

2. Misoprostol (PGE1 analogue) - Off-Label but Widely Used

• What it is: Synthetic PGE1 analogue (primarily a gastric cytoprotective drug)
• Mechanism: Acts on prostaglandin receptors in uterus → contractions; also promotes cervical ripening
• Routes:
  • Oral: 100 µg
  • Vaginal: 25 µg
• Advantages: Very cheap, stable at room temperature, widely available
• Evidence: Meta-analyses show misoprostol is more effective in cervical ripening and labour induction than intravaginal/intracervical PGE2 (dinoprostone)
• Key rule: Discontinue misoprostol at least 3 hours before starting oxytocin
• Adverse effects: Uterine hyperstimulation, rarely uterine rupture, diarrhoea, abdominal pain
• Contraindicated in pregnancy (can induce abortion) unless intentionally used for induction

3. Oxytocin - Drug of Choice for Labour Induction (NOT ripening)

• Used after cervical ripening for labour induction
• Given as IV infusion starting at 6 mIU/min, increased up to 40 mIU/min
• Short half-life (12-15 min) - easy to reverse hyperstimulation by stopping infusion

Sequence: Ripening → Induction

Unripe cervix (low Bishop score)
           ↓
  CERVICAL RIPENING
  (Dinoprostone or Misoprostol)
           ↓
  Cervix softened & effaced
           ↓
  LABOUR INDUCTION
  (Oxytocin IV infusion)
           ↓
  Active labour / delivery

Key Adverse Effect to Remember - Uterine Hyperstimulation

• Remove vaginal insert (dinoprostone pessary)
• Stop misoprostol
• Consider tocolytics if severe

Postpartum Haemorrhage (PPH)

Definition

Note: Pregnancy increases plasma volume by 40% and red cell volume by 25% - this masks blood loss. Blood pressure may not drop until 30% of total blood volume is lost. First sign is often only a mild rise in pulse rate.

Types of PPH

Causes - The "4 T's"

         4 T's of PPH
         ─────────────
TONE     →  Uterine ATONY (70% of all PPH - most common)
TISSUE   →  Retained placental fragments / placenta accreta (10%)
TRAUMA   →  Cervical, vaginal, perineal lacerations (20%)
            Uterine rupture, uterine inversion
THROMBIN →  Coagulopathy (DIC, haemophilia) - uncommon

Uterine atony = failure of the uterus to contract after delivery. The uterus remains boggy/soft instead of firm, and the open blood vessels at the placental site keep bleeding.

Risk Factors for Uterine Atony (Most Common Cause)

• Prolonged labour
• Multiparity (multiple previous pregnancies)
• Overdistended uterus (twins, macrosomia, polyhydramnios)
• Retained placenta
• Uterine infection (chorioamnionitis)
• Preeclampsia
• Prolonged use of uterotonics or tocolytics

Management - Step-by-Step

Immediate Resuscitation

• Monitor vital signs
• Establish IV access (wide bore)
• Fluid resuscitation (Lactated Ringer's)
• Prepare for blood transfusion

Identify the Source

• Uterine atony? Laceration? Retained placenta? Coagulopathy?
• Ultrasound to identify retained placental tissue/blood clots

Pharmacological (Uterotonic) Therapy - Escalating Steps

Role of Carboprost in PPH

• Causes powerful, sustained uterine contraction
• Used specifically when oxytocin infusion has failed
• Dose: 250 µg IM, repeated if needed
• Contraindicated in asthma - PGF2α causes bronchoconstriction (life-threatening in asthmatic patients)
• Also contraindicated in cardiovascular disease

Non-Pharmacological / Surgical Management (if drugs fail)

Summary Flow

Delivery → Excessive bleeding
                ↓
         Identify cause (4 T's)
                ↓
    TONE (most likely) → Uterine massage
                ↓
         Oxytocin IV
                ↓ (if fails)
    Methylergonovine IM
                ↓ (if fails)
    CARBOPROST IM (PGF2α)  ← Contraindicated in asthma
                ↓ (if fails)
    Misoprostol rectal
                ↓ (if all fail)
    Surgical/interventional procedures