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🧠 ANS Pharmacology — Complete MBBS Guide

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PART 1 — ANATOMY & PHYSIOLOGY REVIEW

Organization of the ANS

• Preganglionic neuron → cell body in CNS → exits to a ganglion
• Postganglionic neuron → cell body in ganglion → innervates effector organ

Adrenal medulla = modified sympathetic ganglion. Receives preganglionic cholinergic fibers → secretes 80% epinephrine + 20% NE directly into blood.

Functional Effects (Fight-or-Flight vs Rest-and-Digest)

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PART 2 — NEUROTRANSMITTER PHYSIOLOGY

Cholinergic Transmission (6 Steps)

1. Synthesis: Choline + Acetyl-CoA → ACh (enzyme: choline acetyltransferase)
2. Storage: Packaged into vesicles by VAChT (vesicular ACh transporter)
3. Release: Action potential → Ca²⁺ influx → exocytosis
4. Receptor binding: ACh binds muscarinic or nicotinic receptors
5. Degradation: Acetylcholinesterase (AChE) cleaves ACh → choline + acetate in synaptic cleft
6. Recycling: Choline taken back up into neuron by choline transporter

Key drug target: AChE inhibitors block step 5 → prolong ACh action

Adrenergic Transmission (4 Steps)

1. Synthesis: Tyrosine → DOPA (rate-limiting step: tyrosine hydroxylase) → Dopamine → NE
2. Storage: Dopamine transported into vesicles by VMAT (vesicular monoamine transporter) — blocked by reserpine
3. Release: Action potential → Ca²⁺ influx → exocytosis
4. Termination:
   • Reuptake (Uptake-1) into neuron — major mechanism — blocked by cocaine, TCAs
   • MAO (intraneuronal) — degrades NE
   • COMT (extraneuronal/synaptic cleft) — methylates catecholamines
   • Final metabolite: VMA (vanillylmandelic acid) — excreted in urine (useful in diagnosing pheochromocytoma)

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PART 3 — RECEPTORS

Cholinergic Receptors

Mnemonic: M1 = CNS/stomach; M2 = heart ("2 = two-pump organ"); M3 = smooth muscle/glands ("3 = three systems")

Adrenergic Receptors (Adrenoceptors)

• α receptors: Epi ≥ NE >> Isoproterenol
• β receptors: Isoproterenol > Epi > NE

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PART 4 — CHOLINERGIC DRUGS

A. Direct-Acting Cholinergic Agonists

Choline Esters

Bethanechol key fact: Selective M agonist, resistant to AChE → preferred for GI/urinary use. CI in asthma, peptic ulcer, obstruction.

Alkaloids

B. Indirect-Acting Cholinergic Agonists (AChE Inhibitors)

Reversible AChE Inhibitors

Irreversible AChE Inhibitors (Organophosphates)

• Salivation, Lacrimation, Urination, Defecation, GI distress, Emesis
• Diaphoresis, Urination, Miosis, Bradycardia, Bronchospasm/bronchorrhea, Emesis, Lacrimation, Salivation
• Muscle fasciculations → weakness → paralysis (NMJ overactivation)
• CNS: anxiety, seizures, coma

1. Atropine — blocks muscarinic effects (high doses needed) — endpoint is drying of secretions
2. Pralidoxime (2-PAM) — reactivates AChE before aging occurs (within ~24–48 hours); does NOT reverse CNS effects (quaternary, can't cross BBB)
3. Benzodiazepines — for seizures

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PART 5 — ANTICHOLINERGIC DRUGS (Muscarinic Antagonists)

Antimuscarinic Agents — Overview

"Hot as a hare, Dry as a bone, Red as a beet, Blind as a bat, Mad as a hatter, Full as a flask"

Key Antimuscarinics

CI for antimuscarinics: Angle-closure glaucoma, BPH, myasthenia gravis, paralytic ileus

Ganglionic Blockers

• Mecamylamine, Trimethaphan — Block NN receptors at ganglia
• Rarely used clinically; historically for hypertensive emergencies
• Block BOTH sympathetic and parasympathetic ganglia → unpredictable effects

Neuromuscular Blocking Agents (NMJ Blockers)

Succinylcholine contraindications: Burns, crush injury, hyperkalemia risk, pseudocholinesterase deficiency (prolonged apnea), malignant hyperthermia (with volatile anesthetics)

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PART 6 — ADRENERGIC DRUGS

A. Adrenergic Agonists (Sympathomimetics)

1. Direct-acting — bind adrenoceptors directly
2. Indirect-acting — stimulate NE release or block reuptake
3. Mixed-acting — both direct and indirect (e.g., ephedrine)

Catecholamines (direct-acting)

Cannot cross BBB (polar); not orally active (metabolized by MAO/COMT); short duration

Non-catecholamine Sympathomimetics

• Low (1–5 mcg/kg/min): D1 → renal & mesenteric vasodilation
• Moderate (5–10 mcg/kg/min): β1 → ↑cardiac output
• High (>10 mcg/kg/min): α1 → vasoconstriction

B. Adrenergic Antagonists (Sympatholytics)

α-Blockers

β-Blockers

• Bradycardia, AV block, ↓cardiac output
• Bronchoconstriction (β2 block) — CI in asthma/COPD (use cardioselective if must)
• Masking hypoglycemia symptoms (CI in brittle diabetics)
• Fatigue, cold extremities, sexual dysfunction
• Abrupt withdrawal → rebound tachycardia, angina, MI — always taper
• Metabolic: ↑triglycerides, ↑LDL (except carvedilol)

• Asthma / reactive airways (relative)
• Decompensated heart failure (acute)
• Bradycardia/AV block (2nd/3rd degree)
• Cocaine-induced chest pain (β-block leaves α vasospasm unopposed → use phentolamine instead)

Mixed α/β Blockers

• Labetalol — IV for hypertensive emergencies, hypertension in pregnancy
• Carvedilol — Chronic heart failure, post-MI LV dysfunction

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PART 7 — HIGH-YIELD COMPARISONS & EXAM PEARLS

Effect of Key Drugs on Heart Rate

Drug of Choice Summary

Receptor Summary for Catecholamines

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PART 8 — CLINICAL SCENARIOS (Exam-Focused)

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PART 9 — MEMORY AIDS

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🧒 Components of Pediatric Clerking — Complete MBBS Guide

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What is Pediatric Clerking?

• The historian is usually a parent/caregiver, not the patient (especially <8 years)
• Developmental history is a mandatory component
• Birth history and antenatal history are unique to pediatrics
• Physical examination approach is age-dependent and must be child-friendly
• Growth and nutritional assessment are core parts
• Immunization history is always reviewed
• Normal values (HR, BP, RR, weight) are age-specific

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STRUCTURE OF PEDIATRIC CLERKING

1. Biodata
2. Presenting Complaint(s)
3. History of Presenting Complaint
4. Antenatal & Birth History
5. Neonatal History
6. Feeding & Nutritional History
7. Developmental History
8. Immunization History
9. Past Medical & Surgical History
10. Drug & Allergy History
11. Family History
12. Social & Environmental History
13. Systems Review
14. Physical Examination
15. Summary, Differential Diagnosis & Problem List
16. Investigations
17. Management Plan

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SECTION 1 — BIODATA

Age in months is critical — many drug doses, milestones, and normal values depend on exact age in months.

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SECTION 2 — PRESENTING COMPLAINT(S)

• List in the patient's/informant's own words, e.g., "fever and inability to walk for 3 days"
• Record duration alongside each complaint
• List in chronological or priority order (most serious first)

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SECTION 3 — HISTORY OF PRESENTING COMPLAINT (HPC)

• Onset — sudden or gradual? When exactly did it start?
• Duration — how long has it lasted?
• Character — describe the symptom (e.g., type of cough, nature of fever)
• Severity — how has it affected the child? Activity level? Feeding?
• Progression — getting better, worse, or fluctuating?
• Associated symptoms — ask about related systems
• Aggravating / Relieving factors
• Previous similar episodes
• Treatment already given — home remedies, medications, herbal preparations

Pediatric-Specific Symptom Probes

• Onset, duration, pattern (continuous, intermittent, remittent)
• Highest temperature measured? How measured?
• Associated rigors, night sweats, rash, seizures?
• Contact with ill persons? Travel history? Mosquito exposure?
• Response to antipyretics?

• Duration (>2 weeks = chronic), nature (dry/productive), timing (nocturnal = asthma/pertussis)
• Associated wheeze, stridor, difficulty breathing, cyanosis?
• Foreign body aspiration history?

• Frequency per day, consistency, blood or mucus in stool, offensive odor
• Associated fever, pain, tenesmus
• Signs of dehydration — last urine output, sunken eyes, dry mouth, lethargy
• Recent food intake, other family members affected

• Febrile or afebrile?
• Type — focal or generalized (tonic, clonic, tonic-clonic, absence, myoclonic)
• Duration, post-ictal state, frequency
• Family history of seizures/epilepsy
• Prior similar episodes, developmental status before seizures

• Work of breathing — grunting, nasal flaring, subcostal/intercostal recession?
• Feeding difficulty (can't finish feeds = significant respiratory distress)
• Stridor (inspiratory = upper airway; expiratory = lower airway)
• Cyanosis?

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SECTION 4 — ANTENATAL HISTORY

TORCH infections: Toxoplasma, Other (syphilis, HIV, VZV), Rubella, CMV, Herpes — all associated with congenital abnormalities and IUGR.

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SECTION 5 — BIRTH HISTORY (PERINATAL HISTORY)

A birth weight should be compared with gestational age: SGA (small for gestational age), AGA, or LGA (large = macrosomia, suggests maternal diabetes).

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SECTION 6 — NEONATAL HISTORY

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SECTION 7 — FEEDING & NUTRITIONAL HISTORY

For Infants:

For Older Children:

• Appetite — good, poor, or selective?
• Dietary diversity — fruits, vegetables, proteins, carbohydrates
• Pica (eating non-food substances — suggests iron deficiency or lead poisoning)
• Food security — can the family afford adequate nutrition?
• Recent weight loss or failure to thrive?

Assess Nutritional Status (WHO criteria):

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SECTION 8 — DEVELOPMENTAL HISTORY

Ask the parent:

• "At what age did the child first sit without support?"
• "When did the child walk independently?"
• "When did the child say their first meaningful word? First sentences?"
• "Does the child play with other children? Make eye contact?"
• "Is the child toilet-trained?"
• "Have you noticed any regression — losing skills they previously had?"

Key Developmental Milestones (from Harriet Lane):

Developmental Red Flags (alarm signs — refer immediately):

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SECTION 9 — IMMUNIZATION HISTORY

1. Is the child up-to-date on vaccinations?
2. Where is the vaccination card? (request it)
3. Any adverse reactions to previous vaccines?
4. Any reasons why vaccines may have been missed (illness, travel, refusal)?

WHO Expanded Programme on Immunization (EPI) — Standard Schedule:

Countries vary in schedules — always compare with your national EPI schedule.

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SECTION 10 — PAST MEDICAL & SURGICAL HISTORY (PMH/PSH)

• Previous illnesses (hospitalization, serious infections)
• Previous surgeries — what, when, complications?
• Chronic illnesses: asthma, sickle cell disease, epilepsy, diabetes, congenital heart disease
• Recurrent infections (otitis media, pneumonia, UTI — may suggest immunodeficiency)
• Previous blood transfusions

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SECTION 11 — DRUG & ALLERGY HISTORY

• Current medications — name, dose, route, frequency, duration
• Herbal/traditional preparations (very common — must ask specifically)
• Over-the-counter medications
• Vitamins and supplements

• Drug allergies — specify drug, reaction type (rash, anaphylaxis, GI intolerance)
• Food allergies — peanuts, eggs, milk protein
• Environmental allergies — dust, pollen, animals

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SECTION 12 — FAMILY HISTORY

• Parents' health — chronic illnesses, similar symptoms
• Siblings — number, ages, health status; any siblings died young (sudden death, unknown illness)?
• Consanguinity — are parents related? (risk of autosomal recessive conditions)
• Specific family diseases:
  • Sickle cell disease / trait
  • Tuberculosis (household contact)
  • Epilepsy / febrile seizures
  • Congenital heart disease
  • Genetic conditions (metabolic disorders, chromosomal)
  • Mental health conditions
  • Hypertension, diabetes, asthma

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SECTION 13 — SOCIAL & ENVIRONMENTAL HISTORY

HEEADSSS Assessment (Adolescents — from Harriet Lane):

• H — Home: household dynamics, stability, changes
• E — Education/Employment: school performance, truancy, future plans
• E — Eating: body image, dieting, eating disorders, food security
• A — Activities: physical activity, hobbies, sleep, screen time, social media
• D — Drugs: tobacco, alcohol, illicit substances, prescription misuse
• S — Sexuality: sexual identity, activity, contraception, STI risk
• S — Suicide/Depression: mood, self-harm, suicidal ideation, mental health
• S — Safety: seatbelt, helmet use, violence exposure, abuse

Adolescent consultations should include one-on-one time (without the parent present) to allow confidential disclosure. Begin integrating this from age 11 years.

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SECTION 14 — SYSTEMS REVIEW

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SECTION 15 — PHYSICAL EXAMINATION

General Approach:

• Make the child comfortable — examine on parent's lap when possible for young children
• Start with least distressing examination first (observe, auscultate before palpating/percussing)
• Examine the ears and throat last (most distressing)
• Adapt examination to age and cooperation
• Observe the parent-child interaction

A. General Examination

B. Vital Signs (Age-Specific Normal Values)

Temperature: Normal axillary = 36.5–37.2°C. Fever = ≥38°C. Rectal temperature is 0.5°C higher than axillary.

C. Anthropometry & Growth

• Weight (kg) — use calibrated scale; infant naked or in minimal clothing
• Length/Height — length lying (< 2 years); standing height (≥ 2 years)
• Head circumference (OFC) — measure until age 3 years (frontal-occipital circumference)
• MUAC (mid-upper arm circumference) — screen for acute malnutrition in 6–59 months
• BMI — in older children and adolescents

D. Systemic Examination

• Precordial inspection (heaves, deformity), palpation (apex beat, thrills), auscultation (S1, S2, murmurs)
• Peripheral pulses (rate, rhythm, character, volume), capillary refill time (normal <2 sec)
• Jugular venous pressure (JVP) in older children
• Four-limb BP difference (coarctation of aorta)
• Murmur grading (I–VI; thrill from grade IV onward)

• Inspection: shape of chest, recession, use of accessory muscles, symmetry
• Palpation: tracheal position, chest expansion, vocal fremitus
• Percussion: resonance, dullness, hyperresonance
• Auscultation: breath sounds (vesicular, bronchial), adventitia (crackles, wheeze, pleural rub)

• Inspect: shape (scaphoid = malnutrition; distended = masses/organomegaly/ascites), umbilicus, hernias, dilated veins
• Auscultate first (bowel sounds)
• Palpate: light then deep; liver (starts from RIF moving up), spleen (starts from RIF moving to LUQ), kidneys (ballottement), bladder
• Percuss: liver span, spleen, shifting dullness for ascites
• Normal liver edge: palpable 1–2 cm below RCM in infants (normal variant)

• Level of consciousness — AVPU (Alert, Voice, Pain, Unresponsive) or GCS (modified for children)
• Anterior fontanelle — bulging (raised ICP) or sunken (dehydration)
• Tone, power, reflexes (DTRs, plantar response)
• Cranial nerves (test age-appropriate)
• Cerebellar signs (older children)
• Developmental assessment during examination

• Limb deformities (genu varum/valgum, club foot, rickets)
• Joint swelling, warmth, tenderness
• Gait (observe child walk/run)

• Eyes: conjunctival pallor, jaundice, red reflex (every newborn), strabismus, corneal clouding
• Ears: otoscopy (TM appearance, discharge)
• Nose: nasal flaring, discharge, deviated septum
• Throat/mouth: tonsils (size, exudate), teeth, dental caries, oral thrush, cleft palate
• Lymph nodes: cervical, tonsillar, preauricular

• Males: undescended testes, hydrocele, hypospadias, phimosis
• Females: labial adhesions, ambiguous genitalia
• Anus: anal fissures, perianal excoriation (pinworm), rectal prolapse
• Always done with a chaperone present and explain to child/parent beforehand

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SECTION 16 — SUMMARY & PROBLEM LIST

• Age, sex, presenting complaint
• Key positives in history
• Key positives on examination
• Relevant negatives

1. Problem 1 (e.g., "Severe acute malnutrition with oedema")
2. Problem 2 (e.g., "Febrile illness — possible malaria")
3. Problem 3 (e.g., "Global developmental delay")

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SECTION 17 — DIFFERENTIAL DIAGNOSIS

1. Cerebral malaria — fever + seizures + altered consciousness in malaria-endemic area
2. Bacterial meningitis — fever + neck stiffness + bulging fontanelle
3. Febrile seizure — age 6 months–5 years, simple first seizure with fever

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SECTION 18 — INVESTIGATIONS

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SECTION 19 — MANAGEMENT PLAN

1. Resuscitation / immediate stabilisation (if sick child — ABC, fluids, glucose)
2. Definitive treatment (antimicrobials, specific drugs, nutrition rehabilitation, surgery)
3. Supportive care (antipyretics, hydration, nutritional support, pain relief)
4. Preventive measures / anticipatory guidance (vaccines, insecticide-treated nets, hand washing, deworming)
5. Follow-up plan (when to review, what to watch for, when to return urgently)
6. Counselling (explain diagnosis and treatment to parent in understandable terms)

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QUICK REFERENCE: Pediatric Clerking vs Adult Clerking

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