1. Drugs acting on uterus
   • Oxytocics
   • Tocolytics
2. Gastrointestinal system (GIS)
   • Anti-peptic ulcer drugs
   • Drugs for GERD
   • Antidiarrhoeals
   • Antiemetics
   • Drugs for constipation
   • Oral rehydration solution (ORS)
   • Drugs for IBS and IBD
3. Respiratory system
   • Anti-asthmatic drugs
   • Cough suppressants
   • Mucolytics
4. Immunosuppressants and immunostimulants

• Drugs acting on uterus
• Peptic ulcer and GERD
• Antidiarrhoeals, laxatives and ORS
• Antiemetics
• IBS and IBD drugs
• Anti-asthmatic drugs
• Cough suppressants and mucolytics
• Immunosuppressants and immunostimulants

1. Drugs acting on uterus
   • Oxytocics
   • Tocolytics
2. Gastrointestinal system
   • Anti-peptic ulcer drugs
   • GERD drugs
   • Antidiarrhoeals
   • Antiemetics
   • Drugs for constipation
   • ORS
   • IBS and IBD drugs
3. Respiratory system
   • Anti-asthmatic drugs
   • Cough suppressants
   • Mucolytics
4. Immunosuppressants and immunostimulants

1. Drugs Acting on the Uterus

1. Uterotonics / oxytocics: increase uterine contraction
2. Tocolytics: relax the uterus and suppress premature labour

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A. Uterotonics (Oxytocics)

Definition

Classification

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1. Oxytocin

Mechanism of action

Effect on uterine contraction

Uses

1. Induction of labour
   • When continuation of pregnancy is unsafe, for example post-term pregnancy, certain maternal or fetal indications.
   • Cervix should be favourable or first ripened using a prostaglandin.
2. Augmentation of labour
   • When uterine contractions are weak or inadequate.
3. Active management of third stage of labour
   • Helps prevent PPH by ensuring firm uterine contraction after delivery.
4. Treatment of atonic PPH
   • Uterine atony means failure of the uterus to contract after childbirth, producing severe bleeding.
5. Milk let-down
   • Oxytocin nasal preparations were historically used, but this is not a routine current use.

Adverse effects

• Uterine hyperstimulation or tetany
• Fetal hypoxia, fetal bradycardia, fetal distress
• Uterine rupture, particularly if there is scarred uterus or obstruction
• Hypotension and reflex tachycardia if given as a rapid IV bolus
• Water intoxication and hyponatraemia with prolonged high-dose infusion, because oxytocin has weak ADH-like action

Contraindications or major precautions

• Cephalopelvic disproportion
• Malpresentation, for example transverse lie
• Placenta previa
• Cord prolapse
• Previous classical caesarean scar or high risk of uterine rupture
• Fetal distress requiring immediate delivery
• Hypertonic uterine contractions

Important exam point

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2. Carbetocin

Uses

• Prevention of PPH, especially after caesarean delivery in some settings.
• It produces sustained uterine contraction with a single dose.

Adverse effects

• Hypotension
• Tachycardia
• Nausea, vomiting
• Headache
• Uterine hyperstimulation if used inappropriately

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3. Ergot Alkaloids

Drugs

• Ergometrine
• Methylergometrine

Mechanism

• α-adrenergic receptors
• 5-HT₂ receptors
• Some dopamine receptors

Effect on uterus

Uses

• Prevention and treatment of atonic postpartum haemorrhage
• After delivery of placenta, when firm uterine contraction is required

Adverse effects

• Nausea and vomiting
• Headache
• Rise in blood pressure
• Vasoconstriction
• Angina, myocardial ischemia, peripheral ischemia in susceptible patients
• Rarely seizures

Contraindications

• Hypertension
• Pre-eclampsia or eclampsia
• Ischaemic heart disease
• Peripheral vascular disease
• Severe liver or kidney disease

Oxytocin vs Ergometrine

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4. Prostaglandins

A. Dinoprostone

• A PGE₂ analogue.
• Used vaginally or intracervically for cervical ripening and induction of labour.

Uses

• Cervical ripening before induction
• Induction of labour when the cervix is unfavourable
• Evacuation in missed abortion or intrauterine fetal death in selected cases

Adverse effects

• Uterine hyperstimulation
• Nausea, vomiting, diarrhoea
• Fever
• Fetal distress due to excessive uterine activity

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B. Misoprostol

• A PGE₁ analogue
• Stable, inexpensive and can be given orally, sublingually, buccally, vaginally or rectally.

Uses

1. Medical termination of pregnancy, together with mifepristone
2. Cervical ripening
3. Induction of labour in selected cases
4. Management of incomplete abortion or missed abortion
5. Prevention or treatment of PPH where appropriate, especially when injectable uterotonics are not available
6. Prevention of NSAID-induced peptic ulcer, which is its non-obstetric use

Adverse effects

• Diarrhoea, abdominal cramps
• Nausea and vomiting
• Fever, chills, shivering
• Uterine tachysystole or hyperstimulation
• Fetal distress
• Uterine rupture, especially with a uterine scar or inappropriate dosing

Important caution

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C. Carboprost

• A PGF₂α analogue
• Strong uterotonic.

Main use

• Refractory atonic PPH, especially when oxytocin and other initial measures are inadequate.

Adverse effects

• Severe diarrhoea
• Vomiting
• Fever
• Hypertension
• Bronchospasm

Contraindication

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5. Mifepristone

Mechanism

• Decidual breakdown occurs
• The cervix softens
• Uterus becomes more sensitive to prostaglandins
• Pregnancy is expelled when followed by misoprostol

Use

• Medical abortion in combination with misoprostol
• It is not used alone for complete medical abortion.

Adverse effects

• Vaginal bleeding
• Cramping abdominal pain
• Nausea, vomiting, diarrhoea
• Incomplete abortion
• Rare severe bleeding or infection

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B. Tocolytics

Definition

Main aim

• Administration of antenatal corticosteroids for fetal lung maturation
• Maternal transfer to a facility with neonatal intensive care
• Administration of magnesium sulfate for fetal neuroprotection when indicated

Classification

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1. Nifedipine

Mechanism

Uses

• Commonly used first-line tocolytic in many clinical settings for threatened preterm labour, if no contraindication exists.

Adverse effects

• Headache
• Flushing
• Dizziness
• Hypotension
• Palpitations, tachycardia
• Nausea

Caution

• Maternal hypotension
• Significant cardiac disease
• Concomitant drugs causing major hypotension

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2. Beta-2 Adrenergic Agonists

Drugs

• Terbutaline
• Ritodrine
• Salbutamol

Mechanism

Adverse effects

• Tachycardia and palpitations
• Tremor
• Anxiety
• Hyperglycaemia
• Hypokalaemia
• Hypotension
• Pulmonary oedema
• Arrhythmias

• Fetal tachycardia
• Neonatal hypoglycaemia after delivery

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3. Atosiban

Mechanism

Advantages

• More selective action
• Fewer cardiovascular adverse effects than beta-2 agonists

Limitations

• Costly
• Availability may be limited
• Not routinely available in all regions

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4. Indomethacin

Mechanism

Use

• Short-term tocolysis, particularly at earlier gestations.

Major fetal adverse effects

• Premature closure or constriction of ductus arteriosus
• Oligohydramnios due to decreased fetal urine output
• Possible neonatal complications if prolonged use occurs

Key point

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5. Magnesium Sulfate

Mechanism

Current clinical importance

• Prevention and treatment of eclamptic seizures
• Fetal neuroprotection in imminent very preterm birth

Toxicity

• Loss of deep tendon reflexes
• Respiratory depression
• Hypotension
• Cardiac arrest in severe toxicity

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When Tocolysis Should Not Be Used

• Chorioamnionitis
• Severe pre-eclampsia or eclampsia
• Severe antepartum haemorrhage
• Placental abruption with maternal or fetal compromise
• Fetal death
• Fetal distress requiring delivery
• Advanced labour where delivery is unavoidable

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Rapid Revision

Best drugs to remember

• Oxytocin: induction/augmentation of labour, first-line PPH prevention and treatment
• Ergometrine: PPH, but avoid in hypertension/pre-eclampsia
• Misoprostol: abortion, cervical ripening, PPH
• Carboprost: refractory PPH, avoid in asthma
• Mifepristone + misoprostol: medical abortion
• Nifedipine: common tocolytic
• Indomethacin: short-term tocolytic, avoid late pregnancy
• Atosiban: oxytocin antagonist tocolytic
• Magnesium sulfate: chiefly eclampsia and fetal neuroprotection

One-line difference

• Oxytocics contract the uterus.
• Tocolytics relax the uterus temporarily.

2. Gastrointestinal System: Anti-Peptic Ulcer Drugs

Peptic ulcer disease: basic idea

1. Helicobacter pylori infection
2. NSAID use, for example aspirin, ibuprofen, diclofenac

• Reduce gastric acid secretion
• Neutralize acid already present
• Improve mucosal defence
• Eradicate H. pylori
• Prevent NSAID-induced ulcers and ulcer recurrence

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Classification of anti-ulcer drugs

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A. Antacids

Definition

Mechanism

Types

1. Systemic or absorbable antacid

• Rapid onset
• Useful for immediate, short-term relief

• Metabolic alkalosis
• Sodium overload, oedema, hypertension
• Belching and gastric distension due to CO₂ formation
• Acid rebound may occur

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2. Non-systemic or non-absorbable antacids

Magnesium hydroxide

• Fast onset
• Can cause diarrhoea
• Hypermagnesaemia may occur in renal failure

Aluminium hydroxide

• Slow onset and longer action
• Can cause constipation
• May cause hypophosphataemia with prolonged use
• Avoid prolonged use in renal failure because aluminium accumulation can occur

Magnesium + aluminium combinations

Calcium carbonate

• Potent and rapidly acting
• May cause constipation, hypercalcaemia, renal stones and acid rebound
• Excessive intake can cause milk-alkali syndrome

Drug interactions with antacids

• Tetracyclines
• Fluoroquinolones
• Iron preparations
• Isoniazid
• Ketoconazole
• Levothyroxine

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B. H2-Receptor Blockers

Drugs

• Famotidine
• Cimetidine
• Nizatidine
• Ranitidine is no longer routinely used in many countries because of NDMA impurity concerns.

Mechanism

Uses

• Duodenal ulcer
• Benign gastric ulcer
• Mild or intermittent GERD
• Dyspepsia
• Stress-ulcer prophylaxis in selected hospitalised patients

Adverse effects

• Headache
• Dizziness
• Diarrhoea or constipation
• Confusion, especially in elderly patients or in renal impairment

Cimetidine: important adverse effects and interactions

• Gynecomastia
• Decreased libido
• Erectile dysfunction
• Galactorrhoea, rarely
• Confusion in elderly persons
• Increased serum creatinine due to reduced tubular secretion, without necessarily reducing GFR

Drug interactions

• Warfarin
• Phenytoin
• Theophylline
• Diazepam
• Some beta blockers

Famotidine

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C. Proton-Pump Inhibitors (PPIs)

Drugs

• Omeprazole
• Esomeprazole
• Pantoprazole
• Rabeprazole
• Lansoprazole
• Dexlansoprazole

Mechanism of action

How to take PPIs

Uses

1. Peptic ulcer disease
2. GERD, especially erosive oesophagitis
3. H. pylori eradication regimens
4. NSAID-induced ulcer treatment and prophylaxis in high-risk patients
5. Zollinger-Ellison syndrome and other hypersecretory states
6. Upper GI bleed due to peptic ulcer, usually high-dose IV PPI after appropriate assessment/endoscopic treatment
7. Stress-ulcer prophylaxis in selected critically ill patients

Adverse effects

Common

• Headache
• Nausea
• Abdominal discomfort
• Diarrhoea or constipation

Long-term or important risks

• Rebound acid hypersecretion after abrupt discontinuation
• Hypomagnesaemia
• Vitamin B12 deficiency with prolonged use
• Reduced absorption of iron in susceptible patients
• Increased risk of enteric infections, including Clostridioides difficile
• Possible increased fracture risk with long-term high-dose use, particularly in high-risk patients
• Acute interstitial nephritis, rarely
• Possible association with chronic kidney disease, though causality is less certain

Drug interactions

• Omeprazole and esomeprazole can inhibit CYP2C19.
• This may reduce activation of clopidogrel. Pantoprazole is often preferred when a PPI is required in a patient receiving clopidogrel.

PPIs versus H2 blockers

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D. Potassium-Competitive Acid Blocker

Vonoprazan

Features

• Produces rapid and potent acid suppression
• Does not require activation in an acidic environment as PPIs do
• Used in some H. pylori eradication regimens and acid-related disorders

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E. Antimuscarinic Drugs

Drugs

• Pirenzepine
• Telenzepine
• Propantheline

Mechanism

Why rarely used now?

• Dry mouth
• Blurred vision
• Constipation
• Urinary retention
• Tachycardia

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F. Prostaglandin Analogue: Misoprostol

Mechanism

• Decreases gastric acid secretion
• Increases mucus secretion
• Increases bicarbonate secretion
• Improves mucosal blood flow

Main use

Adverse effects

• Diarrhoea, very common
• Abdominal cramps
• Nausea
• Uterine contractions and vaginal bleeding

Contraindication

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G. Sucralfate

Mechanism

• Binds pepsin
• Binds bile salts
• Increases local prostaglandin and bicarbonate production

Uses

• Duodenal ulcer
• Stress-related mucosal injury in selected circumstances
• Sometimes used where acid suppression needs to be avoided or reduced

Adverse effects

• Constipation
• Aluminium accumulation in severe renal impairment
• Reduced absorption of other medicines, such as fluoroquinolones, tetracyclines, phenytoin and digoxin

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H. Bismuth Compounds

Examples

• Bismuth subsalicylate
• Colloidal bismuth subcitrate

Actions

• Coats ulcers and erosions
• Increases mucus and bicarbonate secretion
• Has some activity against H. pylori
• Used as part of bismuth quadruple therapy for H. pylori

Adverse effects

• Black discoloration of stool
• Black tongue
• Constipation
• Salicylate toxicity can occur with bismuth subsalicylate in excessive use

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I. Helicobacter pylori Eradication

Why eradicate it?

• Heals the ulcer
• Greatly reduces recurrence
• Reduces ulcer bleeding recurrence
• Is important for long-term risk reduction in relevant gastric disease

Regimens

Bismuth quadruple therapy

• PPI
• Bismuth
• Tetracycline
• Metronidazole

Important follow-up

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Treatment Approach for Common Situations

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Rapid Revision Points

• Antacids: neutralize existing acid, rapid symptom relief.
• H2 blockers: reduce histamine-mediated acid secretion, especially nocturnal secretion.
• Cimetidine: gynecomastia and CYP450 inhibition.
• PPIs: irreversible H⁺/K⁺ ATPase inhibitors and most potent acid-suppressant drugs.
• Misoprostol: prevents NSAID ulcers but causes diarrhoea and is contraindicated for GI use during pregnancy.
• Sucralfate: coats the ulcer; may cause constipation and drug interactions.
• Bismuth: black stool/black tongue and part of H. pylori quadruple therapy.
• H. pylori ulcer: needs eradication therapy, not PPI alone.

3. Drugs Used in GERD

What is GERD?

Main symptoms

• Heartburn, especially after meals or on lying down
• Acid regurgitation
• Sour taste in mouth
• Retrosternal burning pain
• Night cough, hoarseness or sore throat in some patients

---

Goals of treatment

1. Reduce acidity of refluxed gastric contents
2. Reduce frequency/volume of reflux
3. Improve oesophageal clearance and gastric emptying in selected cases
4. Heal reflux oesophagitis
5. Prevent complications such as stricture and Barrett oesophagus

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Classification of drugs used in GERD

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A. Non-drug measures

• Weight reduction if overweight
• Avoid lying down for 2-3 hours after meals
• Elevate the head end of bed for night symptoms
• Take smaller meals
• Avoid personal trigger foods, commonly fatty meals, chocolate, caffeine, alcohol and smoking
• Avoid tight clothing around the abdomen
• Review drugs that can aggravate reflux, for example nitrates, anticholinergics, calcium-channel blockers and theophylline

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B. Antacids

Examples

• Aluminium hydroxide
• Magnesium hydroxide
• Calcium carbonate
• Sodium bicarbonate

Mechanism

Role in GERD

• Give quick relief of occasional heartburn
• Do not heal significant erosive oesophagitis
• Often used as self-medication or as add-on treatment

Adverse effects

Important interaction

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C. Alginates

Example

• Sodium alginate, commonly combined with antacid

Mechanism

Uses

• Post-meal heartburn
• Regurgitation
• Mild GERD
• Often useful in pregnancy because systemic absorption is minimal

Limitation

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D. H2-Receptor Blockers

Drugs

• Famotidine
• Cimetidine
• Nizatidine

Mechanism

Uses in GERD

• Mild, infrequent symptoms
• Night-time symptoms
• Intermittent or on-demand treatment in selected patients
• Add-on at bedtime in some patients with nocturnal acid breakthrough

Limitations

• Less effective than PPIs for healing reflux oesophagitis
• Tolerance can develop with continued use

Adverse effects

• Headache
• Dizziness
• Diarrhoea or constipation
• Confusion in elderly people, especially with renal impairment

Cimetidine: high-yield points

• Gynecomastia
• Decreased libido and erectile dysfunction
• Inhibits CYP450 enzymes
• Increases levels of drugs such as warfarin, phenytoin, diazepam and theophylline

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E. Proton-Pump Inhibitors (PPIs)

Drugs

• Omeprazole
• Esomeprazole
• Pantoprazole
• Rabeprazole
• Lansoprazole
• Dexlansoprazole

Mechanism of action

Why PPIs are preferred

• Healing erosive oesophagitis
• Controlling frequent heartburn
• Maintaining healing in severe oesophagitis

How to administer

Uses

• Frequent typical GERD symptoms
• Erosive reflux oesophagitis
• Barrett oesophagus when acid suppression is indicated
• Peptic stricture, alongside endoscopic management
• Severe GERD not responding to H2 blockers
• GERD with troublesome night-time symptoms

Adverse effects

Common

• Headache
• Abdominal pain
• Nausea
• Diarrhoea or constipation

Important long-term concerns

• Hypomagnesaemia
• Vitamin B12 deficiency in prolonged treatment
• Enteric infection risk, including C. difficile
• Rare acute interstitial nephritis
• Possible association with bone fracture and chronic kidney disease in high-risk long-term users

Important interaction

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F. Prokinetic Drugs

1. Metoclopramide

Mechanism

• D2 receptor antagonist
• 5-HT4 agonist action at higher doses
• Enhances acetylcholine release in the gut

• Increases lower oesophageal sphincter tone
• Enhances oesophageal clearance
• Speeds gastric emptying
• Also has antiemetic action by blocking D2 receptors in the chemoreceptor trigger zone

Adverse effects

• Drowsiness
• Restlessness
• Extrapyramidal reactions: dystonia, parkinsonism, akathisia
• Tardive dyskinesia with prolonged use
• Hyperprolactinaemia

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2. Domperidone

Mechanism

Difference from metoclopramide

Adverse effects and caution

• Hyperprolactinaemia
• QT prolongation
• Serious ventricular arrhythmias in susceptible patients

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3. Levosulpiride

• Hyperprolactinaemia
• Galactorrhoea
• Menstrual irregularities
• Extrapyramidal effects

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G. Sucralfate

Mechanism

Role in GERD

• Limited role in routine adult GERD
• May sometimes be considered in pregnancy because it has negligible systemic absorption
• Does not suppress acid as effectively as PPIs

Adverse effects

• Constipation
• Decreased absorption of medicines such as tetracyclines, fluoroquinolones, phenytoin and digoxin
• Aluminium accumulation in severe renal impairment

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H. Potassium-Competitive Acid Blocker

Vonoprazan

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Stepwise Drug Treatment of GERD

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GERD Alarm Features

• Dysphagia or painful swallowing
• GI bleeding, black stool or vomiting blood
• Unexplained weight loss
• Persistent vomiting
• Anaemia
• New symptoms at older age
• Recurrent symptoms despite adequate PPI treatment

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High-yield KDT Revision

• Antacids neutralize existing acid and give rapid temporary relief.
• Alginates form a physical anti-reflux barrier.
• H2 blockers reduce predominantly nocturnal acid secretion.
• Cimetidine causes CYP450 inhibition, gynecomastia and impotence.
• PPIs irreversibly inhibit H⁺/K⁺ ATPase and are the most effective anti-reflux drugs.
• Take PPIs 30-60 minutes before meals.
• Metoclopramide increases LES tone and gastric emptying but can cause extrapyramidal effects.
• Domperidone has fewer CNS effects but can prolong QT interval.
• Sucralfate protects mucosa but does not strongly suppress acid.

5. Immunosuppressants and Immunostimulants

Immunosuppressants

• Glucocorticoids
• Calcineurin inhibitors: cyclosporine, tacrolimus
• mTOR inhibitors: sirolimus, everolimus
• Antimetabolites: azathioprine, mycophenolate mofetil, methotrexate
• Cytotoxic drugs: cyclophosphamide
• Biological agents: monoclonal antibodies, TNF-α inhibitors, rituximab, etc.
• Uses in organ transplantation and autoimmune diseases
• Adverse effects, drug interactions and therapeutic uses

Immunostimulants

• Vaccines
• Interferons
• Interleukins
• Colony-stimulating factors: G-CSF, GM-CSF
• Immunoglobulins
• BCG and other immunomodulators

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8. Miscellaneous

A. Drugs used in Dermatology

• Topical corticosteroids
• Drugs for acne: benzoyl peroxide, retinoids, antibiotics
• Antifungals
• Antiscabies and pediculicides
• Drugs for psoriasis
• Drugs for leprosy and vitiligo
• Sunscreens and topical preparations

B. Drugs used in Ophthalmology

• Antiglaucoma drugs
• Mydriatics and miotics
• Topical ocular antimicrobials
• Topical corticosteroids and NSAIDs
• Local anaesthetics
• Artificial tears and lubricants

C. Antiseptics and Disinfectants

• Alcohols
• Halogens: iodine, chlorine compounds
• Oxidizing agents: hydrogen peroxide, potassium permanganate
• Phenols and cresols
• Chlorhexidine
• Aldehydes: formaldehyde, glutaraldehyde
• Quaternary ammonium compounds
• Uses, spectrum, advantages and limitations

D. Vitamins and Enzymes

• Fat-soluble vitamins: A, D, E, K
• Water-soluble vitamins: B-complex and C
• Vitamin deficiency states and therapeutic uses
• Enzyme preparations: streptokinase, urokinase, asparaginase, hyaluronidase, digestive enzymes

E. Vaccines and Sera

• Types of vaccines: live attenuated, killed/inactivated, toxoid, subunit/recombinant, conjugate
• National immunization schedule
• Passive immunization: antisera and immunoglobulins
• Adverse effects, contraindications and cold-chain principles

Topic 5: Immunosuppressants and immune stimulants

1. Basic immune response and sites of drug action
2. Corticosteroids
3. Calcineurin inhibitors: cyclosporine, tacrolimus
4. Antimetabolites: azathioprine, mycophenolate
5. mTOR inhibitors: sirolimus, everolimus
6. Cytotoxic drugs: cyclophosphamide, methotrexate
7. Biologics and monoclonal antibodies
8. Transplant rejection regimens and autoimmune uses
9. Immunostimulants: interferons, interleukins, colony-stimulating factors, BCG, immunoglobulins

Topic 8: Miscellaneous

1. Dermatology drugs
2. Ophthalmology drugs
3. Antiseptics and disinfectants
4. Vitamins
5. Enzymes
6. Vaccines and sera

5. Immunosuppressants and Immunostimulants

Introduction

• Organ transplantation: recipient immune cells reject the graft.
• Autoimmune diseases: immune system attacks self tissues, for example rheumatoid arthritis, SLE, psoriasis, inflammatory bowel disease.
• Allergic/inflammatory diseases: excessive immune activation causes tissue injury.

• Immunosuppressants decrease immune reactions.
• Immunostimulants enhance selected immune functions, especially haematopoiesis or host defence.

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A. Immunosuppressants

Basic concept: T-cell activation

1. Signal 1: antigen presented by antigen-presenting cell to T-cell receptor.
2. Signal 2: co-stimulatory signal, mainly CD80/86 on APC binding CD28 on T cell.
3. Cytokine signal: especially IL-2, which promotes T-cell proliferation.

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Classification of immunosuppressants

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1. Glucocorticoids

Drugs

• Prednisolone
• Methylprednisolone
• Hydrocortisone
• Dexamethasone

Mechanism of immunosuppression

• Decrease production of inflammatory cytokines such as IL-1, IL-2, IL-6, TNF-α and interferon-γ.
• Reduce activation and proliferation of T cells.
• Reduce macrophage function and antigen presentation.
• Reduce migration of leukocytes to inflammatory sites.
• Decrease prostaglandin and leukotriene formation by inducing lipocortin and inhibiting phospholipase A₂.

Uses

• Prevention and treatment of transplant rejection
• Acute rejection episodes, often high-dose IV methylprednisolone
• Rheumatoid arthritis
• SLE
• Vasculitis
• Inflammatory bowel disease
• Nephrotic syndrome
• Severe asthma and allergic disorders
• Autoimmune haemolytic anaemia, immune thrombocytopenia

Adverse effects

• Increased susceptibility to infection
• Hyperglycaemia and steroid-induced diabetes
• Hypertension
• Osteoporosis
• Muscle wasting
• Peptic ulcer risk
• Cataract and glaucoma
• Mood changes, psychosis
• Cushingoid appearance
• Growth retardation in children
• Adrenal suppression after prolonged therapy

Important exam point

---

2. Calcineurin Inhibitors

Drugs

• Cyclosporine
• Tacrolimus

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A. Cyclosporine

Mechanism

Uses

• Kidney, liver, heart and other organ transplantation
• Prevention and treatment of graft rejection
• Severe rheumatoid arthritis
• Severe psoriasis
• Atopic dermatitis
• Uveitis
• Nephrotic syndrome in selected patients

Adverse effects

1. Nephrotoxicity: most important dose-limiting toxicity
2. Hypertension
3. Tremor, headache, seizures at high levels
4. Hyperlipidaemia
5. Hyperuricaemia and gout
6. Hyperkalaemia
7. Gingival hyperplasia
8. Hirsutism
9. Increased risk of infections and lymphoma

Drug interactions

• Macrolides such as erythromycin and clarithromycin
• Azole antifungals
• Diltiazem and verapamil
• Grapefruit juice

• Rifampicin
• Phenytoin
• Carbamazepine
• St John's wort

Monitoring

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B. Tacrolimus

Mechanism

Uses

• Prevention of rejection after kidney, liver and heart transplantation
• Topical tacrolimus for atopic dermatitis
• Selected autoimmune diseases

Adverse effects

• Nephrotoxicity
• Neurotoxicity: tremor, headache, seizures
• Hyperkalaemia
• Hypertension
• Increased risk of infection and malignancy
• Diabetes mellitus is more common than with cyclosporine
• Alopecia may occur

Cyclosporine versus Tacrolimus

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3. Antimetabolites / Antiproliferative Drugs

---

A. Azathioprine

Mechanism

• Reduced proliferation of T and B lymphocytes
• Reduced antibody formation

Uses

• Kidney transplantation
• Rheumatoid arthritis
• SLE
• Inflammatory bowel disease, especially Crohn disease and ulcerative colitis
• Autoimmune hepatitis
• Steroid-sparing agent in chronic autoimmune disease

Adverse effects

• Bone marrow suppression: leucopenia, thrombocytopenia, anaemia
• Nausea, vomiting
• Hepatotoxicity
• Pancreatitis
• Increased infection risk
• Increased risk of malignancy with prolonged use

Important interaction

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B. Mycophenolate Mofetil (MMF)

Mechanism

Uses

• Prevention of organ transplant rejection
• Usually combined with tacrolimus or cyclosporine and corticosteroids
• Lupus nephritis
• Some autoimmune disorders

Adverse effects

• Diarrhoea
• Nausea and abdominal pain
• Bone marrow suppression
• Infections
• Increased malignancy risk
• Teratogenicity: avoid in pregnancy

Key comparison

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C. Methotrexate

Mechanism

Uses

• First-line disease-modifying drug for rheumatoid arthritis
• Psoriasis and psoriatic arthritis
• Some inflammatory bowel disorders
• Ectopic pregnancy and malignancy at different regimens

Adverse effects

• Stomatitis and mucositis
• Bone marrow suppression
• Hepatotoxicity
• Pneumonitis
• Teratogenicity
• Alopecia

Important points

• Folic acid reduces some adverse effects.
• Avoid in pregnancy.
• Avoid or use carefully in significant liver disease, renal dysfunction and heavy alcohol use.

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4. mTOR Inhibitors

Drugs

• Sirolimus or rapamycin
• Everolimus

Mechanism

Difference from tacrolimus

• Tacrolimus blocks IL-2 production.
• Sirolimus blocks response to IL-2.

Uses

• Kidney transplant maintenance therapy
• Used with or as an alternative to calcineurin inhibitor regimens in selected recipients
• Drug-eluting coronary stents
• Lymphangioleiomyomatosis
• Everolimus is used in selected cancers and transplantation settings

Adverse effects

• Hyperlipidaemia
• Thrombocytopenia and leucopenia
• Delayed wound healing
• Mouth ulcers
• Proteinuria
• Pneumonitis
• Increased infection risk

Key point

---

5. Cytotoxic Drugs

A. Cyclophosphamide

Mechanism

• Cell-mediated immunity
• Humoral immunity

Uses

• Severe SLE, especially lupus nephritis
• Severe vasculitis, for example granulomatosis with polyangiitis
• Severe rheumatoid arthritis in rare cases
• Some cancers
• Conditioning before bone marrow transplantation

Adverse effects

• Bone marrow suppression
• Haemorrhagic cystitis due to acrolein metabolite
• Infertility
• Alopecia
• Nausea and vomiting
• Secondary malignancy, especially bladder cancer
• Serious infections

Prevention of haemorrhagic cystitis

• Adequate hydration
• Mesna, which binds toxic acrolein in urine

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B. Chlorambucil

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6. Biological Agents and Monoclonal Antibodies

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A. Antilymphocyte Antibodies

1. Antithymocyte globulin, ATG

• Induction immunosuppression in transplantation
• Treatment of acute steroid-resistant transplant rejection
• Aplastic anaemia in selected cases

• Cytokine-release reaction: fever, chills, hypotension
• Leucopenia and thrombocytopenia
• Infection
• Serum sickness
• Anaphylaxis, rarely

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2. Basiliximab

---

B. Anti-CD20 Antibody: Rituximab

Mechanism

Uses

• Non-Hodgkin lymphoma
• Rheumatoid arthritis
• ANCA-associated vasculitis
• Some cases of SLE and autoimmune haemolytic anaemia
• Antibody-mediated transplant rejection in selected protocols

Adverse effects

• Infusion reaction
• Serious infections
• Reactivation of hepatitis B
• Rare progressive multifocal leukoencephalopathy, PML

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C. TNF-α Inhibitors

Drugs

• Infliximab
• Adalimumab
• Etanercept
• Golimumab
• Certolizumab

Mechanism

Uses

• Rheumatoid arthritis
• Ankylosing spondylitis
• Psoriasis and psoriatic arthritis
• Crohn disease
• Ulcerative colitis

Adverse effects

• Serious bacterial, fungal and viral infections
• Reactivation of tuberculosis
• Hepatitis B reactivation
• Infusion or injection-site reaction
• Rare demyelinating disorders
• May worsen heart failure

Important exam point

• Tuberculosis
• Hepatitis B
• Current serious infection

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D. Other Important Cytokine-targeted Biologicals

---

E. Co-stimulation Blockers

Abatacept and Belatacept

• Abatacept: rheumatoid arthritis and selected autoimmune diseases.
• Belatacept: maintenance immunosuppression after kidney transplantation.

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F. JAK Inhibitors

Drugs

• Tofacitinib
• Baricitinib
• Upadacitinib

Mechanism

Uses

• Rheumatoid arthritis
• Psoriatic arthritis
• Ulcerative colitis
• Atopic dermatitis, depending on drug and indication

Adverse effects

• Serious infections, including herpes zoster
• Cytopenia
• Hyperlipidaemia
• Thromboembolic and cardiovascular risk in certain high-risk patients

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Clinical Uses of Immunosuppressants

1. Organ transplantation

Induction therapy

• Basiliximab
• Antithymocyte globulin
• High-dose corticosteroids

Maintenance therapy

• Tacrolimus or cyclosporine
• Mycophenolate mofetil
• Prednisolone, depending on protocol

Treatment of acute rejection

• High-dose corticosteroids
• Antithymocyte globulin if steroid-resistant or severe
• Adjustment of baseline regimen

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2. Autoimmune and inflammatory diseases

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General Adverse Effects of Immunosuppressants

1. Infections
   • Bacterial, viral, fungal and opportunistic infections
   • Latent TB or hepatitis B may reactivate with certain biological agents.
2. Malignancy
   • Lymphoma
   • Skin cancers
   • Virus-related cancers due to weakened immune surveillance
3. Bone marrow suppression
   • Leucopenia
   • Anaemia
   • Thrombocytopenia
4. Drug-specific organ toxicity
   • Nephrotoxicity: cyclosporine, tacrolimus
   • Hepatotoxicity: methotrexate, azathioprine
   • Haemorrhagic cystitis: cyclophosphamide
   • Hyperlipidaemia: sirolimus
   • Diabetes: corticosteroids and tacrolimus

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B. Immunostimulants

Classification

---

1. Interferons

Types and actions

Mechanism

• Inhibit viral replication
• Increase MHC expression
• Enhance natural killer cell and macrophage activity
• Modify immune responses

Uses

IFN-α

• Some viral hepatitis regimens historically
• Hairy-cell leukaemia
• Kaposi sarcoma
• Some myeloproliferative disorders

IFN-β

• Relapsing forms of multiple sclerosis

IFN-γ

• Chronic granulomatous disease
• Severe congenital osteopetrosis in selected settings

Adverse effects

• Flu-like symptoms: fever, myalgia, fatigue
• Depression and neuropsychiatric effects
• Bone marrow suppression
• Thyroid dysfunction
• Hepatotoxicity
• Autoimmune phenomena

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2. Interleukin-2: Aldesleukin

Actions

• Stimulates proliferation and activation of T lymphocytes
• Activates NK cells
• Enhances cytotoxic immune activity

Uses

• Metastatic renal cell carcinoma
• Metastatic melanoma, in specialized settings

Adverse effects

• Capillary-leak syndrome
• Hypotension
• Oedema
• Renal dysfunction
• Arrhythmias
• Fever and flu-like symptoms

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3. Colony-Stimulating Factors

A. G-CSF

Drugs

• Filgrastim
• Pegfilgrastim

Action

Uses

• Chemotherapy-induced neutropenia
• After bone marrow transplantation
• Mobilisation of peripheral blood stem cells
• Severe chronic neutropenia

Adverse effects

• Bone pain
• Leucocytosis
• Splenic enlargement, rarely rupture
• Rare acute respiratory distress syndrome

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B. GM-CSF

Drug

• Sargramostim

Action

Uses

• Bone marrow recovery after chemotherapy or transplantation
• Selected cases of marrow suppression

Adverse effects

• Fever
• Myalgia
• Bone pain
• Capillary leak and oedema
• Hypotension

G-CSF versus GM-CSF

---

4. BCG

Uses

1. Vaccine for tuberculosis in national immunisation programmes.
2. Intravesical BCG for superficial urinary bladder carcinoma.

Mechanism in bladder cancer

Adverse effects

• Cystitis symptoms
• Fever
• Haematuria
• Rare disseminated BCG infection

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5. Immunoglobulins

A. Normal human immunoglobulin

Preparations

• Intravenous immunoglobulin, IVIG
• Subcutaneous immunoglobulin, SCIG

Uses

• Primary immunodeficiency states
• Immune thrombocytopenia
• Kawasaki disease
• Guillain-Barré syndrome
• Certain autoimmune neurological diseases

Mechanisms

• Replace missing antibodies
• Neutralize toxins or pathogens
• Modulate Fc receptors
• Reduce harmful autoantibody activity
• Alter complement activation

Adverse effects

• Headache, fever, chills
• Thrombosis
• Haemolysis
• Acute renal injury, rarely
• Anaphylaxis, particularly in some IgA-deficient patients

B. Specific immunoglobulins / antisera

• Rabies immunoglobulin
• Tetanus immunoglobulin
• Hepatitis B immunoglobulin
• Anti-D immunoglobulin
• Snake antivenom

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High-yield Exam Table

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Very Important One-liners for Viva

1. Cyclosporine and tacrolimus inhibit calcineurin and decrease IL-2 production.
2. Cyclosporine binds cyclophilin; tacrolimus binds FKBP.
3. Tacrolimus causes diabetes more frequently; cyclosporine causes hirsutism and gingival hyperplasia.
4. Mycophenolate inhibits IMPDH and blocks de novo guanine synthesis.
5. Sirolimus inhibits mTOR and blocks T-cell response to IL-2.
6. Azathioprine toxicity increases with allopurinol.
7. Cyclophosphamide can cause haemorrhagic cystitis, prevented by mesna.
8. Anti-TNF drugs can reactivate latent tuberculosis.
9. Rituximab is anti-CD20 and depletes B cells.
10. Filgrastim is G-CSF and is used for chemotherapy-induced neutropenia.

8. Miscellaneous: KDT Paper 2 Topics

1. Drugs used in dermatology
   • Topical corticosteroids
   • Acne drugs
   • Psoriasis drugs
   • Antifungals
   • Antiscabies and pediculicides
   • Drugs for vitiligo and alopecia
2. Drugs used in ophthalmology
   • Mydriatics and cycloplegics
   • Miotics
   • Antiglaucoma drugs
   • Ocular local anaesthetics
   • Ocular antimicrobials and corticosteroids
3. Antiseptics and disinfectants
   • Alcohols
   • Iodine and chlorine compounds
   • Chlorhexidine
   • Oxidizing agents
   • Phenols
   • Aldehydes
   • Cationic detergents
4. Vitamins
   • Fat-soluble: A, D, E, K
   • Water-soluble: B-complex and C
   • Deficiency states, therapeutic uses and toxicity
5. Enzymes
   • Digestive enzymes
   • Thrombolytics: streptokinase, urokinase, alteplase
   • L-asparaginase
   • Hyaluronidase
   • Enzyme replacement therapy
6. Vaccines and sera
   • Active versus passive immunization
   • Types of vaccines
   • Immunoglobulins and antisera
   • Adverse effects, contraindications and storage

1. Drugs acting on uterus
   • Oxytocics
   • Tocolytics
2. Gastrointestinal system (GIS)
   • Anti-peptic ulcer drugs
   • Drugs for GERD
   • Antidiarrhoeals
   • Antiemetics
   • Drugs for constipation
   • Oral rehydration solution (ORS)
   • Drugs for IBS and IBD
3. Respiratory system
   • Anti-asthmatic drugs
   • Cough suppressants
   • Mucolytics
4. Immunosuppressants and immunostimulants

• Drugs acting on uterus
• Peptic ulcer and GERD
• Antidiarrhoeals, laxatives and ORS
• Antiemetics
• IBS and IBD drugs
• Anti-asthmatic drugs
• Cough suppressants and mucolytics
• Immunosuppressants and immunostimulants

1. Drugs acting on uterus
   • Oxytocics
   • Tocolytics
2. Gastrointestinal system
   • Anti-peptic ulcer drugs
   • GERD drugs
   • Antidiarrhoeals
   • Antiemetics
   • Drugs for constipation
   • ORS
   • IBS and IBD drugs
3. Respiratory system
   • Anti-asthmatic drugs
   • Cough suppressants
   • Mucolytics
4. Immunosuppressants and immunostimulants

1. Uterotonics / oxytocics: increase uterine contraction
2. Tocolytics: relax the uterus and suppress premature labour

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A. Uterotonics (Oxytocics)

Definition

Classification

---

1. Oxytocin

Mechanism of action

Effect on uterine contraction

Uses

1. Induction of labour
   • When continuation of pregnancy is unsafe, for example post-term pregnancy, certain maternal or fetal indications.
   • Cervix should be favourable or first ripened using a prostaglandin.
2. Augmentation of labour
   • When uterine contractions are weak or inadequate.
3. Active management of third stage of labour
   • Helps prevent PPH by ensuring firm uterine contraction after delivery.
4. Treatment of atonic PPH
   • Uterine atony means failure of the uterus to contract after childbirth, producing severe bleeding.
5. Milk let-down
   • Oxytocin nasal preparations were historically used, but this is not a routine current use.

Adverse effects

• Uterine hyperstimulation or tetany
• Fetal hypoxia, fetal bradycardia, fetal distress
• Uterine rupture, particularly if there is scarred uterus or obstruction
• Hypotension and reflex tachycardia if given as a rapid IV bolus
• Water intoxication and hyponatraemia with prolonged high-dose infusion, because oxytocin has weak ADH-like action

Contraindications or major precautions

• Cephalopelvic disproportion
• Malpresentation, for example transverse lie
• Placenta previa
• Cord prolapse
• Previous classical caesarean scar or high risk of uterine rupture
• Fetal distress requiring immediate delivery
• Hypertonic uterine contractions

Important exam point

---

2. Carbetocin

Uses

• Prevention of PPH, especially after caesarean delivery in some settings.
• It produces sustained uterine contraction with a single dose.

Adverse effects

• Hypotension
• Tachycardia
• Nausea, vomiting
• Headache
• Uterine hyperstimulation if used inappropriately

---

3. Ergot Alkaloids

Drugs

• Ergometrine
• Methylergometrine

Mechanism

• α-adrenergic receptors
• 5-HT₂ receptors
• Some dopamine receptors

Effect on uterus

Uses

• Prevention and treatment of atonic postpartum haemorrhage
• After delivery of placenta, when firm uterine contraction is required

Adverse effects

• Nausea and vomiting
• Headache
• Rise in blood pressure
• Vasoconstriction
• Angina, myocardial ischemia, peripheral ischemia in susceptible patients
• Rarely seizures

Contraindications

• Hypertension
• Pre-eclampsia or eclampsia
• Ischaemic heart disease
• Peripheral vascular disease
• Severe liver or kidney disease

Oxytocin vs Ergometrine

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4. Prostaglandins

A. Dinoprostone

• A PGE₂ analogue.
• Used vaginally or intracervically for cervical ripening and induction of labour.

Uses

• Cervical ripening before induction
• Induction of labour when the cervix is unfavourable
• Evacuation in missed abortion or intrauterine fetal death in selected cases

Adverse effects

• Uterine hyperstimulation
• Nausea, vomiting, diarrhoea
• Fever
• Fetal distress due to excessive uterine activity

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B. Misoprostol

• A PGE₁ analogue
• Stable, inexpensive and can be given orally, sublingually, buccally, vaginally or rectally.

Uses

1. Medical termination of pregnancy, together with mifepristone
2. Cervical ripening
3. Induction of labour in selected cases
4. Management of incomplete abortion or missed abortion
5. Prevention or treatment of PPH where appropriate, especially when injectable uterotonics are not available
6. Prevention of NSAID-induced peptic ulcer, which is its non-obstetric use

Adverse effects

• Diarrhoea, abdominal cramps
• Nausea and vomiting
• Fever, chills, shivering
• Uterine tachysystole or hyperstimulation
• Fetal distress
• Uterine rupture, especially with a uterine scar or inappropriate dosing

Important caution

---

C. Carboprost

• A PGF₂α analogue
• Strong uterotonic.

Main use

• Refractory atonic PPH, especially when oxytocin and other initial measures are inadequate.

Adverse effects

• Severe diarrhoea
• Vomiting
• Fever
• Hypertension
• Bronchospasm

Contraindication

---

5. Mifepristone

Mechanism

• Decidual breakdown occurs
• The cervix softens
• Uterus becomes more sensitive to prostaglandins
• Pregnancy is expelled when followed by misoprostol

Use

• Medical abortion in combination with misoprostol
• It is not used alone for complete medical abortion.

Adverse effects

• Vaginal bleeding
• Cramping abdominal pain
• Nausea, vomiting, diarrhoea
• Incomplete abortion
• Rare severe bleeding or infection

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B. Tocolytics

Definition

Main aim

• Administration of antenatal corticosteroids for fetal lung maturation
• Maternal transfer to a facility with neonatal intensive care
• Administration of magnesium sulfate for fetal neuroprotection when indicated

Classification

---

1. Nifedipine

Mechanism

Uses

• Commonly used first-line tocolytic in many clinical settings for threatened preterm labour, if no contraindication exists.

Adverse effects

• Headache
• Flushing
• Dizziness
• Hypotension
• Palpitations, tachycardia
• Nausea

Caution

• Maternal hypotension
• Significant cardiac disease
• Concomitant drugs causing major hypotension

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2. Beta-2 Adrenergic Agonists

Drugs

• Terbutaline
• Ritodrine
• Salbutamol

Mechanism

Adverse effects

• Tachycardia and palpitations
• Tremor
• Anxiety
• Hyperglycaemia
• Hypokalaemia
• Hypotension
• Pulmonary oedema
• Arrhythmias

• Fetal tachycardia
• Neonatal hypoglycaemia after delivery

---

3. Atosiban

Mechanism

Advantages

• More selective action
• Fewer cardiovascular adverse effects than beta-2 agonists

Limitations

• Costly
• Availability may be limited
• Not routinely available in all regions

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4. Indomethacin

Mechanism

Use

• Short-term tocolysis, particularly at earlier gestations.

Major fetal adverse effects

• Premature closure or constriction of ductus arteriosus
• Oligohydramnios due to decreased fetal urine output
• Possible neonatal complications if prolonged use occurs

Key point

---

5. Magnesium Sulfate

Mechanism

Current clinical importance

• Prevention and treatment of eclamptic seizures
• Fetal neuroprotection in imminent very preterm birth

Toxicity

• Loss of deep tendon reflexes
• Respiratory depression
• Hypotension
• Cardiac arrest in severe toxicity

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When Tocolysis Should Not Be Used

• Chorioamnionitis
• Severe pre-eclampsia or eclampsia
• Severe antepartum haemorrhage
• Placental abruption with maternal or fetal compromise
• Fetal death
• Fetal distress requiring delivery
• Advanced labour where delivery is unavoidable

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Rapid Revision

Best drugs to remember

• Oxytocin: induction/augmentation of labour, first-line PPH prevention and treatment
• Ergometrine: PPH, but avoid in hypertension/pre-eclampsia
• Misoprostol: abortion, cervical ripening, PPH
• Carboprost: refractory PPH, avoid in asthma
• Mifepristone + misoprostol: medical abortion
• Nifedipine: common tocolytic
• Indomethacin: short-term tocolytic, avoid late pregnancy
• Atosiban: oxytocin antagonist tocolytic
• Magnesium sulfate: chiefly eclampsia and fetal neuroprotection

One-line difference

• Oxytocics contract the uterus.
• Tocolytics relax the uterus temporarily.# 2. Gastrointestinal System: Anti-Peptic Ulcer Drugs

Peptic ulcer disease: basic idea

1. Helicobacter pylori infection
2. NSAID use, for example aspirin, ibuprofen, diclofenac

• Reduce gastric acid secretion
• Neutralize acid already present
• Improve mucosal defence
• Eradicate H. pylori
• Prevent NSAID-induced ulcers and ulcer recurrence

---

Classification of anti-ulcer drugs

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A. Antacids

Definition

Mechanism

Types

1. Systemic or absorbable antacid

• Rapid onset
• Useful for immediate, short-term relief

• Metabolic alkalosis
• Sodium overload, oedema, hypertension
• Belching and gastric distension due to CO₂ formation
• Acid rebound may occur

---

2. Non-systemic or non-absorbable antacids

Magnesium hydroxide

• Fast onset
• Can cause diarrhoea
• Hypermagnesaemia may occur in renal failure

Aluminium hydroxide

• Slow onset and longer action
• Can cause constipation
• May cause hypophosphataemia with prolonged use
• Avoid prolonged use in renal failure because aluminium accumulation can occur

Magnesium + aluminium combinations

Calcium carbonate

• Potent and rapidly acting
• May cause constipation, hypercalcaemia, renal stones and acid rebound
• Excessive intake can cause milk-alkali syndrome

Drug interactions with antacids

• Tetracyclines
• Fluoroquinolones
• Iron preparations
• Isoniazid
• Ketoconazole
• Levothyroxine

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B. H2-Receptor Blockers

Drugs

• Famotidine
• Cimetidine
• Nizatidine
• Ranitidine is no longer routinely used in many countries because of NDMA impurity concerns.

Mechanism

Uses

• Duodenal ulcer
• Benign gastric ulcer
• Mild or intermittent GERD
• Dyspepsia
• Stress-ulcer prophylaxis in selected hospitalised patients

Adverse effects

• Headache
• Dizziness
• Diarrhoea or constipation
• Confusion, especially in elderly patients or in renal impairment

Cimetidine: important adverse effects and interactions

• Gynecomastia
• Decreased libido
• Erectile dysfunction
• Galactorrhoea, rarely
• Confusion in elderly persons
• Increased serum creatinine due to reduced tubular secretion, without necessarily reducing GFR

Drug interactions

• Warfarin
• Phenytoin
• Theophylline
• Diazepam
• Some beta blockers

Famotidine

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C. Proton-Pump Inhibitors (PPIs)

Drugs

• Omeprazole
• Esomeprazole
• Pantoprazole
• Rabeprazole
• Lansoprazole
• Dexlansoprazole

Mechanism of action

How to take PPIs

Uses

1. Peptic ulcer disease
2. GERD, especially erosive oesophagitis
3. H. pylori eradication regimens
4. NSAID-induced ulcer treatment and prophylaxis in high-risk patients
5. Zollinger-Ellison syndrome and other hypersecretory states
6. Upper GI bleed due to peptic ulcer, usually high-dose IV PPI after appropriate assessment/endoscopic treatment
7. Stress-ulcer prophylaxis in selected critically ill patients

Adverse effects

Common

• Headache
• Nausea
• Abdominal discomfort
• Diarrhoea or constipation

Long-term or important risks

• Rebound acid hypersecretion after abrupt discontinuation
• Hypomagnesaemia
• Vitamin B12 deficiency with prolonged use
• Reduced absorption of iron in susceptible patients
• Increased risk of enteric infections, including Clostridioides difficile
• Possible increased fracture risk with long-term high-dose use, particularly in high-risk patients
• Acute interstitial nephritis, rarely
• Possible association with chronic kidney disease, though causality is less certain

Drug interactions

• Omeprazole and esomeprazole can inhibit CYP2C19.
• This may reduce activation of clopidogrel. Pantoprazole is often preferred when a PPI is required in a patient receiving clopidogrel.

PPIs versus H2 blockers

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D. Potassium-Competitive Acid Blocker

Vonoprazan

Features

• Produces rapid and potent acid suppression
• Does not require activation in an acidic environment as PPIs do
• Used in some H. pylori eradication regimens and acid-related disorders

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E. Antimuscarinic Drugs

Drugs

• Pirenzepine
• Telenzepine
• Propantheline

Mechanism

Why rarely used now?

• Dry mouth
• Blurred vision
• Constipation
• Urinary retention
• Tachycardia

---

F. Prostaglandin Analogue: Misoprostol

Mechanism

• Decreases gastric acid secretion
• Increases mucus secretion
• Increases bicarbonate secretion
• Improves mucosal blood flow

Main use

Adverse effects

• Diarrhoea, very common
• Abdominal cramps
• Nausea
• Uterine contractions and vaginal bleeding

Contraindication

---

G. Sucralfate

Mechanism

• Binds pepsin
• Binds bile salts
• Increases local prostaglandin and bicarbonate production

Uses

• Duodenal ulcer
• Stress-related mucosal injury in selected circumstances
• Sometimes used where acid suppression needs to be avoided or reduced

Adverse effects

• Constipation
• Aluminium accumulation in severe renal impairment
• Reduced absorption of other medicines, such as fluoroquinolones, tetracyclines, phenytoin and digoxin

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H. Bismuth Compounds

Examples

• Bismuth subsalicylate
• Colloidal bismuth subcitrate

Actions

• Coats ulcers and erosions
• Increases mucus and bicarbonate secretion
• Has some activity against H. pylori
• Used as part of bismuth quadruple therapy for H. pylori

Adverse effects

• Black discoloration of stool
• Black tongue
• Constipation
• Salicylate toxicity can occur with bismuth subsalicylate in excessive use

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I. Helicobacter pylori Eradication

Why eradicate it?

• Heals the ulcer
• Greatly reduces recurrence
• Reduces ulcer bleeding recurrence
• Is important for long-term risk reduction in relevant gastric disease

Regimens

Bismuth quadruple therapy

• PPI
• Bismuth
• Tetracycline
• Metronidazole

Important follow-up

---

Treatment Approach for Common Situations

---

Rapid Revision Points

• Antacids: neutralize existing acid, rapid symptom relief.
• H2 blockers: reduce histamine-mediated acid secretion, especially nocturnal secretion.
• Cimetidine: gynecomastia and CYP450 inhibition.
• PPIs: irreversible H⁺/K⁺ ATPase inhibitors and most potent acid-suppressant drugs.
• Misoprostol: prevents NSAID ulcers but causes diarrhoea and is contraindicated for GI use during pregnancy.
• Sucralfate: coats the ulcer; may cause constipation and drug interactions.
• Bismuth: black stool/black tongue and part of H. pylori quadruple therapy.
• H. pylori ulcer: needs eradication therapy, not PPI alone.

What is GERD?

Main symptoms

• Heartburn, especially after meals or on lying down
• Acid regurgitation
• Sour taste in mouth
• Retrosternal burning pain
• Night cough, hoarseness or sore throat in some patients

---

Goals of treatment

1. Reduce acidity of refluxed gastric contents
2. Reduce frequency/volume of reflux
3. Improve oesophageal clearance and gastric emptying in selected cases
4. Heal reflux oesophagitis
5. Prevent complications such as stricture and Barrett oesophagus

---

Classification of drugs used in GERD

---

A. Non-drug measures

• Weight reduction if overweight
• Avoid lying down for 2-3 hours after meals
• Elevate the head end of bed for night symptoms
• Take smaller meals
• Avoid personal trigger foods, commonly fatty meals, chocolate, caffeine, alcohol and smoking
• Avoid tight clothing around the abdomen
• Review drugs that can aggravate reflux, for example nitrates, anticholinergics, calcium-channel blockers and theophylline

---

B. Antacids

Examples

• Aluminium hydroxide
• Magnesium hydroxide
• Calcium carbonate
• Sodium bicarbonate

Mechanism

Role in GERD

• Give quick relief of occasional heartburn
• Do not heal significant erosive oesophagitis
• Often used as self-medication or as add-on treatment

Adverse effects

Important interaction

---

C. Alginates

Example

• Sodium alginate, commonly combined with antacid

Mechanism

Uses

• Post-meal heartburn
• Regurgitation
• Mild GERD
• Often useful in pregnancy because systemic absorption is minimal

Limitation

---

D. H2-Receptor Blockers

Drugs

• Famotidine
• Cimetidine
• Nizatidine

Mechanism

Uses in GERD

• Mild, infrequent symptoms
• Night-time symptoms
• Intermittent or on-demand treatment in selected patients
• Add-on at bedtime in some patients with nocturnal acid breakthrough

Limitations

• Less effective than PPIs for healing reflux oesophagitis
• Tolerance can develop with continued use

Adverse effects

• Headache
• Dizziness
• Diarrhoea or constipation
• Confusion in elderly people, especially with renal impairment

Cimetidine: high-yield points

• Gynecomastia
• Decreased libido and erectile dysfunction
• Inhibits CYP450 enzymes
• Increases levels of drugs such as warfarin, phenytoin, diazepam and theophylline

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E. Proton-Pump Inhibitors (PPIs)

Drugs

• Omeprazole
• Esomeprazole
• Pantoprazole
• Rabeprazole
• Lansoprazole
• Dexlansoprazole

Mechanism of action

Why PPIs are preferred

• Healing erosive oesophagitis
• Controlling frequent heartburn
• Maintaining healing in severe oesophagitis

How to administer

Uses

• Frequent typical GERD symptoms
• Erosive reflux oesophagitis
• Barrett oesophagus when acid suppression is indicated
• Peptic stricture, alongside endoscopic management
• Severe GERD not responding to H2 blockers
• GERD with troublesome night-time symptoms

Adverse effects

Common

• Headache
• Abdominal pain
• Nausea
• Diarrhoea or constipation

Important long-term concerns

• Hypomagnesaemia
• Vitamin B12 deficiency in prolonged treatment
• Enteric infection risk, including C. difficile
• Rare acute interstitial nephritis
• Possible association with bone fracture and chronic kidney disease in high-risk long-term users

Important interaction

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F. Prokinetic Drugs

1. Metoclopramide

Mechanism

• D2 receptor antagonist
• 5-HT4 agonist action at higher doses
• Enhances acetylcholine release in the gut

• Increases lower oesophageal sphincter tone
• Enhances oesophageal clearance
• Speeds gastric emptying
• Also has antiemetic action by blocking D2 receptors in the chemoreceptor trigger zone

Adverse effects

• Drowsiness
• Restlessness
• Extrapyramidal reactions: dystonia, parkinsonism, akathisia
• Tardive dyskinesia with prolonged use
• Hyperprolactinaemia

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2. Domperidone

Mechanism

Difference from metoclopramide

Adverse effects and caution

• Hyperprolactinaemia
• QT prolongation
• Serious ventricular arrhythmias in susceptible patients

---

3. Levosulpiride

• Hyperprolactinaemia
• Galactorrhoea
• Menstrual irregularities
• Extrapyramidal effects

---

G. Sucralfate

Mechanism

Role in GERD

• Limited role in routine adult GERD
• May sometimes be considered in pregnancy because it has negligible systemic absorption
• Does not suppress acid as effectively as PPIs

Adverse effects

• Constipation
• Decreased absorption of medicines such as tetracyclines, fluoroquinolones, phenytoin and digoxin
• Aluminium accumulation in severe renal impairment

---

H. Potassium-Competitive Acid Blocker

Vonoprazan

---

Stepwise Drug Treatment of GERD

---

GERD Alarm Features

• Dysphagia or painful swallowing
• GI bleeding, black stool or vomiting blood
• Unexplained weight loss
• Persistent vomiting
• Anaemia
• New symptoms at older age
• Recurrent symptoms despite adequate PPI treatment

---

High-yield KDT Revision

• Antacids neutralize existing acid and give rapid temporary relief.
• Alginates form a physical anti-reflux barrier.
• H2 blockers reduce predominantly nocturnal acid secretion.
• Cimetidine causes CYP450 inhibition, gynecomastia and impotence.
• PPIs irreversibly inhibit H⁺/K⁺ ATPase and are the most effective anti-reflux drugs.
• Take PPIs 30-60 minutes before meals.
• Metoclopramide increases LES tone and gastric emptying but can cause extrapyramidal effects.
• Domperidone has fewer CNS effects but can prolong QT interval.
• Sucralfate protects mucosa but does not strongly suppress acid.Your credits are exhausted. You can purchase a top-up or subscribe to a plan to continue using Orris. If you're already subscribed, your daily credits will reset tomorrow.## 5. Immunosuppressants and Immunostimulants

Immunosuppressants

• Glucocorticoids
• Calcineurin inhibitors: cyclosporine, tacrolimus
• mTOR inhibitors: sirolimus, everolimus
• Antimetabolites: azathioprine, mycophenolate mofetil, methotrexate
• Cytotoxic drugs: cyclophosphamide
• Biological agents: monoclonal antibodies, TNF-α inhibitors, rituximab, etc.
• Uses in organ transplantation and autoimmune diseases
• Adverse effects, drug interactions and therapeutic uses

Immunostimulants

• Vaccines
• Interferons
• Interleukins
• Colony-stimulating factors: G-CSF, GM-CSF
• Immunoglobulins
• BCG and other immunomodulators

---

8. Miscellaneous

A. Drugs used in Dermatology

• Topical corticosteroids
• Drugs for acne: benzoyl peroxide, retinoids, antibiotics
• Antifungals
• Antiscabies and pediculicides
• Drugs for psoriasis
• Drugs for leprosy and vitiligo
• Sunscreens and topical preparations

B. Drugs used in Ophthalmology

• Antiglaucoma drugs
• Mydriatics and miotics
• Topical ocular antimicrobials
• Topical corticosteroids and NSAIDs
• Local anaesthetics
• Artificial tears and lubricants

C. Antiseptics and Disinfectants

• Alcohols
• Halogens: iodine, chlorine compounds
• Oxidizing agents: hydrogen peroxide, potassium permanganate
• Phenols and cresols
• Chlorhexidine
• Aldehydes: formaldehyde, glutaraldehyde
• Quaternary ammonium compounds
• Uses, spectrum, advantages and limitations

D. Vitamins and Enzymes

• Fat-soluble vitamins: A, D, E, K
• Water-soluble vitamins: B-complex and C
• Vitamin deficiency states and therapeutic uses
• Enzyme preparations: streptokinase, urokinase, asparaginase, hyaluronidase, digestive enzymes

E. Vaccines and Sera

• Types of vaccines: live attenuated, killed/inactivated, toxoid, subunit/recombinant, conjugate
• National immunization schedule
• Passive immunization: antisera and immunoglobulins
• Adverse effects, contraindications and cold-chain principlesTopics 5 and 8 together are very large. We’ll do them in exam-ready KDT format, one section at a time.

Topic 5: Immunosuppressants and immune stimulants

1. Basic immune response and sites of drug action
2. Corticosteroids
3. Calcineurin inhibitors: cyclosporine, tacrolimus
4. Antimetabolites: azathioprine, mycophenolate
5. mTOR inhibitors: sirolimus, everolimus
6. Cytotoxic drugs: cyclophosphamide, methotrexate
7. Biologics and monoclonal antibodies
8. Transplant rejection regimens and autoimmune uses
9. Immunostimulants: interferons, interleukins, colony-stimulating factors, BCG, immunoglobulins

Topic 8: Miscellaneous

1. Dermatology drugs
2. Ophthalmology drugs
3. Antiseptics and disinfectants
4. Vitamins
5. Enzymes
6. Vaccines and sera

Introduction

• Organ transplantation: recipient immune cells reject the graft.
• Autoimmune diseases: immune system attacks self tissues, for example rheumatoid arthritis, SLE, psoriasis, inflammatory bowel disease.
• Allergic/inflammatory diseases: excessive immune activation causes tissue injury.

• Immunosuppressants decrease immune reactions.
• Immunostimulants enhance selected immune functions, especially haematopoiesis or host defence.

---

A. Immunosuppressants

Basic concept: T-cell activation

1. Signal 1: antigen presented by antigen-presenting cell to T-cell receptor.
2. Signal 2: co-stimulatory signal, mainly CD80/86 on APC binding CD28 on T cell.
3. Cytokine signal: especially IL-2, which promotes T-cell proliferation.

---

Classification of immunosuppressants

---

1. Glucocorticoids

Drugs

• Prednisolone
• Methylprednisolone
• Hydrocortisone
• Dexamethasone

Mechanism of immunosuppression

• Decrease production of inflammatory cytokines such as IL-1, IL-2, IL-6, TNF-α and interferon-γ.
• Reduce activation and proliferation of T cells.
• Reduce macrophage function and antigen presentation.
• Reduce migration of leukocytes to inflammatory sites.
• Decrease prostaglandin and leukotriene formation by inducing lipocortin and inhibiting phospholipase A₂.

Uses

• Prevention and treatment of transplant rejection
• Acute rejection episodes, often high-dose IV methylprednisolone
• Rheumatoid arthritis
• SLE
• Vasculitis
• Inflammatory bowel disease
• Nephrotic syndrome
• Severe asthma and allergic disorders
• Autoimmune haemolytic anaemia, immune thrombocytopenia

Adverse effects

• Increased susceptibility to infection
• Hyperglycaemia and steroid-induced diabetes
• Hypertension
• Osteoporosis
• Muscle wasting
• Peptic ulcer risk
• Cataract and glaucoma
• Mood changes, psychosis
• Cushingoid appearance
• Growth retardation in children
• Adrenal suppression after prolonged therapy

Important exam point

---

2. Calcineurin Inhibitors

Drugs

• Cyclosporine
• Tacrolimus

---

A. Cyclosporine

Mechanism

Uses

• Kidney, liver, heart and other organ transplantation
• Prevention and treatment of graft rejection
• Severe rheumatoid arthritis
• Severe psoriasis
• Atopic dermatitis
• Uveitis
• Nephrotic syndrome in selected patients

Adverse effects

1. Nephrotoxicity: most important dose-limiting toxicity
2. Hypertension
3. Tremor, headache, seizures at high levels
4. Hyperlipidaemia
5. Hyperuricaemia and gout
6. Hyperkalaemia
7. Gingival hyperplasia
8. Hirsutism
9. Increased risk of infections and lymphoma

Drug interactions

• Macrolides such as erythromycin and clarithromycin
• Azole antifungals
• Diltiazem and verapamil
• Grapefruit juice

• Rifampicin
• Phenytoin
• Carbamazepine
• St John's wort

Monitoring

---

B. Tacrolimus

Mechanism

Uses

• Prevention of rejection after kidney, liver and heart transplantation
• Topical tacrolimus for atopic dermatitis
• Selected autoimmune diseases

Adverse effects

• Nephrotoxicity
• Neurotoxicity: tremor, headache, seizures
• Hyperkalaemia
• Hypertension
• Increased risk of infection and malignancy
• Diabetes mellitus is more common than with cyclosporine
• Alopecia may occur

Cyclosporine versus Tacrolimus

---

3. Antimetabolites / Antiproliferative Drugs

---

A. Azathioprine

Mechanism

• Reduced proliferation of T and B lymphocytes
• Reduced antibody formation

Uses

• Kidney transplantation
• Rheumatoid arthritis
• SLE
• Inflammatory bowel disease, especially Crohn disease and ulcerative colitis
• Autoimmune hepatitis
• Steroid-sparing agent in chronic autoimmune disease

Adverse effects

• Bone marrow suppression: leucopenia, thrombocytopenia, anaemia
• Nausea, vomiting
• Hepatotoxicity
• Pancreatitis
• Increased infection risk
• Increased risk of malignancy with prolonged use

Important interaction

---

B. Mycophenolate Mofetil (MMF)

Mechanism

Uses

• Prevention of organ transplant rejection
• Usually combined with tacrolimus or cyclosporine and corticosteroids
• Lupus nephritis
• Some autoimmune disorders

Adverse effects

• Diarrhoea
• Nausea and abdominal pain
• Bone marrow suppression
• Infections
• Increased malignancy risk
• Teratogenicity: avoid in pregnancy

Key comparison

---

C. Methotrexate

Mechanism

Uses

• First-line disease-modifying drug for rheumatoid arthritis
• Psoriasis and psoriatic arthritis
• Some inflammatory bowel disorders
• Ectopic pregnancy and malignancy at different regimens

Adverse effects

• Stomatitis and mucositis
• Bone marrow suppression
• Hepatotoxicity
• Pneumonitis
• Teratogenicity
• Alopecia

Important points

• Folic acid reduces some adverse effects.
• Avoid in pregnancy.
• Avoid or use carefully in significant liver disease, renal dysfunction and heavy alcohol use.

---

4. mTOR Inhibitors

Drugs

• Sirolimus or rapamycin
• Everolimus

Mechanism

Difference from tacrolimus

• Tacrolimus blocks IL-2 production.
• Sirolimus blocks response to IL-2.

Uses

• Kidney transplant maintenance therapy
• Used with or as an alternative to calcineurin inhibitor regimens in selected recipients
• Drug-eluting coronary stents
• Lymphangioleiomyomatosis
• Everolimus is used in selected cancers and transplantation settings

Adverse effects

• Hyperlipidaemia
• Thrombocytopenia and leucopenia
• Delayed wound healing
• Mouth ulcers
• Proteinuria
• Pneumonitis
• Increased infection risk

Key point

---

5. Cytotoxic Drugs

A. Cyclophosphamide

Mechanism

• Cell-mediated immunity
• Humoral immunity

Uses

• Severe SLE, especially lupus nephritis
• Severe vasculitis, for example granulomatosis with polyangiitis
• Severe rheumatoid arthritis in rare cases
• Some cancers
• Conditioning before bone marrow transplantation

Adverse effects

• Bone marrow suppression
• Haemorrhagic cystitis due to acrolein metabolite
• Infertility
• Alopecia
• Nausea and vomiting
• Secondary malignancy, especially bladder cancer
• Serious infections

Prevention of haemorrhagic cystitis

• Adequate hydration
• Mesna, which binds toxic acrolein in urine

---

B. Chlorambucil

---

6. Biological Agents and Monoclonal Antibodies

---

A. Antilymphocyte Antibodies

1. Antithymocyte globulin, ATG

• Induction immunosuppression in transplantation
• Treatment of acute steroid-resistant transplant rejection
• Aplastic anaemia in selected cases

• Cytokine-release reaction: fever, chills, hypotension
• Leucopenia and thrombocytopenia
• Infection
• Serum sickness
• Anaphylaxis, rarely

---

2. Basiliximab

---

B. Anti-CD20 Antibody: Rituximab

Mechanism

Uses

• Non-Hodgkin lymphoma
• Rheumatoid arthritis
• ANCA-associated vasculitis
• Some cases of SLE and autoimmune haemolytic anaemia
• Antibody-mediated transplant rejection in selected protocols

Adverse effects

• Infusion reaction
• Serious infections
• Reactivation of hepatitis B
• Rare progressive multifocal leukoencephalopathy, PML

---

C. TNF-α Inhibitors

Drugs

• Infliximab
• Adalimumab
• Etanercept
• Golimumab
• Certolizumab

Mechanism

Uses

• Rheumatoid arthritis
• Ankylosing spondylitis
• Psoriasis and psoriatic arthritis
• Crohn disease
• Ulcerative colitis

Adverse effects

• Serious bacterial, fungal and viral infections
• Reactivation of tuberculosis
• Hepatitis B reactivation
• Infusion or injection-site reaction
• Rare demyelinating disorders
• May worsen heart failure

Important exam point

• Tuberculosis
• Hepatitis B
• Current serious infection

---

D. Other Important Cytokine-targeted Biologicals

---

E. Co-stimulation Blockers

Abatacept and Belatacept

• Abatacept: rheumatoid arthritis and selected autoimmune diseases.
• Belatacept: maintenance immunosuppression after kidney transplantation.

---

F. JAK Inhibitors

Drugs

• Tofacitinib
• Baricitinib
• Upadacitinib

Mechanism

Uses

• Rheumatoid arthritis
• Psoriatic arthritis
• Ulcerative colitis
• Atopic dermatitis, depending on drug and indication

Adverse effects

• Serious infections, including herpes zoster
• Cytopenia
• Hyperlipidaemia
• Thromboembolic and cardiovascular risk in certain high-risk patients

---

Clinical Uses of Immunosuppressants

1. Organ transplantation

Induction therapy

• Basiliximab
• Antithymocyte globulin
• High-dose corticosteroids

Maintenance therapy

• Tacrolimus or cyclosporine
• Mycophenolate mofetil
• Prednisolone, depending on protocol

Treatment of acute rejection

• High-dose corticosteroids
• Antithymocyte globulin if steroid-resistant or severe
• Adjustment of baseline regimen

---

2. Autoimmune and inflammatory diseases

---

General Adverse Effects of Immunosuppressants

1. Infections
   • Bacterial, viral, fungal and opportunistic infections
   • Latent TB or hepatitis B may reactivate with certain biological agents.
2. Malignancy
   • Lymphoma
   • Skin cancers
   • Virus-related cancers due to weakened immune surveillance
3. Bone marrow suppression
   • Leucopenia
   • Anaemia
   • Thrombocytopenia
4. Drug-specific organ toxicity
   • Nephrotoxicity: cyclosporine, tacrolimus
   • Hepatotoxicity: methotrexate, azathioprine
   • Haemorrhagic cystitis: cyclophosphamide
   • Hyperlipidaemia: sirolimus
   • Diabetes: corticosteroids and tacrolimus

---

B. Immunostimulants

Classification

---

1. Interferons

Types and actions

Mechanism

• Inhibit viral replication
• Increase MHC expression
• Enhance natural killer cell and macrophage activity
• Modify immune responses

Uses

IFN-α

• Some viral hepatitis regimens historically
• Hairy-cell leukaemia
• Kaposi sarcoma
• Some myeloproliferative disorders

IFN-β

• Relapsing forms of multiple sclerosis

IFN-γ

• Chronic granulomatous disease
• Severe congenital osteopetrosis in selected settings

Adverse effects

• Flu-like symptoms: fever, myalgia, fatigue
• Depression and neuropsychiatric effects
• Bone marrow suppression
• Thyroid dysfunction
• Hepatotoxicity
• Autoimmune phenomena

---

2. Interleukin-2: Aldesleukin

Actions

• Stimulates proliferation and activation of T lymphocytes
• Activates NK cells
• Enhances cytotoxic immune activity

Uses

• Metastatic renal cell carcinoma
• Metastatic melanoma, in specialized settings

Adverse effects

• Capillary-leak syndrome
• Hypotension
• Oedema
• Renal dysfunction
• Arrhythmias
• Fever and flu-like symptoms

---

3. Colony-Stimulating Factors

A. G-CSF

Drugs

• Filgrastim
• Pegfilgrastim

Action

Uses

• Chemotherapy-induced neutropenia
• After bone marrow transplantation
• Mobilisation of peripheral blood stem cells
• Severe chronic neutropenia

Adverse effects

• Bone pain
• Leucocytosis
• Splenic enlargement, rarely rupture
• Rare acute respiratory distress syndrome

---

B. GM-CSF

Drug

• Sargramostim

Action

Uses

• Bone marrow recovery after chemotherapy or transplantation
• Selected cases of marrow suppression

Adverse effects

• Fever
• Myalgia
• Bone pain
• Capillary leak and oedema
• Hypotension

G-CSF versus GM-CSF

---

4. BCG

Uses

1. Vaccine for tuberculosis in national immunisation programmes.
2. Intravesical BCG for superficial urinary bladder carcinoma.

Mechanism in bladder cancer

Adverse effects

• Cystitis symptoms
• Fever
• Haematuria
• Rare disseminated BCG infection

---

5. Immunoglobulins

A. Normal human immunoglobulin

Preparations

• Intravenous immunoglobulin, IVIG
• Subcutaneous immunoglobulin, SCIG

Uses

• Primary immunodeficiency states
• Immune thrombocytopenia
• Kawasaki disease
• Guillain-Barré syndrome
• Certain autoimmune neurological diseases

Mechanisms

• Replace missing antibodies
• Neutralize toxins or pathogens
• Modulate Fc receptors
• Reduce harmful autoantibody activity
• Alter complement activation

Adverse effects

• Headache, fever, chills
• Thrombosis
• Haemolysis
• Acute renal injury, rarely
• Anaphylaxis, particularly in some IgA-deficient patients

B. Specific immunoglobulins / antisera

• Rabies immunoglobulin
• Tetanus immunoglobulin
• Hepatitis B immunoglobulin
• Anti-D immunoglobulin
• Snake antivenom

---

High-yield Exam Table

---

Very Important One-liners for Viva

1. Cyclosporine and tacrolimus inhibit calcineurin and decrease IL-2 production.
2. Cyclosporine binds cyclophilin; tacrolimus binds FKBP.
3. Tacrolimus causes diabetes more frequently; cyclosporine causes hirsutism and gingival hyperplasia.
4. Mycophenolate inhibits IMPDH and blocks de novo guanine synthesis.
5. Sirolimus inhibits mTOR and blocks T-cell response to IL-2.
6. Azathioprine toxicity increases with allopurinol.
7. Cyclophosphamide can cause haemorrhagic cystitis, prevented by mesna.
8. Anti-TNF drugs can reactivate latent tuberculosis.
9. Rituximab is anti-CD20 and depletes B cells.
10. Filgrastim is G-CSF and is used for chemotherapy-induced neutropenia.

1. Drugs used in dermatology
   • Topical corticosteroids
   • Acne drugs
   • Psoriasis drugs
   • Antifungals
   • Antiscabies and pediculicides
   • Drugs for vitiligo and alopecia
2. Drugs used in ophthalmology
   • Mydriatics and cycloplegics
   • Miotics
   • Antiglaucoma drugs
   • Ocular local anaesthetics
   • Ocular antimicrobials and corticosteroids
3. Antiseptics and disinfectants
   • Alcohols
   • Iodine and chlorine compounds
   • Chlorhexidine
   • Oxidizing agents
   • Phenols
   • Aldehydes
   • Cationic detergents
4. Vitamins
   • Fat-soluble: A, D, E, K
   • Water-soluble: B-complex and C
   • Deficiency states, therapeutic uses and toxicity
5. Enzymes
   • Digestive enzymes
   • Thrombolytics: streptokinase, urokinase, alteplase
   • L-asparaginase
   • Hyaluronidase
   • Enzyme replacement therapy
6. Vaccines and sera
   • Active versus passive immunization
   • Types of vaccines
   • Immunoglobulins and antisera
   • Adverse effects, contraindications and storage

1. Drugs used in dermatology
   Topical corticosteroids, acne, psoriasis, fungal infections, scabies, pediculosis, vitiligo and alopecia.
2. Drugs used in ophthalmology
   Mydriatics, cycloplegics, miotics, antiglaucoma drugs, ocular antimicrobials and corticosteroids.
3. Antiseptics and disinfectants
   Classification, mechanism, uses, concentration, and examples such as alcohol, chlorhexidine, iodine, chlorine, phenols and aldehydes.
4. Vitamins
   Vitamin A, D, E, K; B-complex and vitamin C, including deficiency, therapeutic use and toxicity.
5. Enzymes
   Digestive enzymes, thrombolytics, L-asparaginase, hyaluronidase, rasburicase and enzyme replacement.
6. Vaccines and sera
   Active/passive immunization, vaccine types, immunoglobulins, antisera, contraindications and adverse effects.

Antiseptics and Disinfectants

Definitions

Antiseptic

Disinfectant

Sterilant

Important difference

---

Ideal Properties of an Antiseptic or Disinfectant

• Have broad antimicrobial activity
• Act rapidly
• Be active in the presence of blood, pus, and organic matter
• Have residual action where needed
• Be non-toxic and non-irritant to tissues
• Not corrode metals or damage rubber/plastic
• Be stable, inexpensive, water-soluble, and easy to use
• Have no unpleasant odour or staining effect

---

Factors Affecting Action

1. Concentration
   Higher concentration is not always better. For example, 70% alcohol is more effective than absolute alcohol because water helps protein denaturation and penetration into microbes.
2. Contact time
   The chemical must remain in contact for sufficient time.
3. Temperature and pH
   Higher temperature usually increases activity. Some compounds work better at a particular pH.
4. Type and number of microorganisms
   Spores, mycobacteria, non-enveloped viruses, and biofilm organisms are more resistant.
5. Presence of organic matter
   Blood, pus, faeces, serum, and dirt may reduce activity. Instruments should be cleaned before disinfection.
6. Nature of surface
   Cracks, crevices, fabrics, and biofilm make disinfection difficult.

---

Relative Resistance of Microorganisms

1. Bacterial spores
2. Mycobacteria
3. Non-enveloped viruses
4. Fungi
5. Vegetative bacteria
6. Enveloped viruses, for example influenza and HIV

---

Classification

---

1. Alcohols

Drugs

• Ethyl alcohol or ethanol
• Isopropyl alcohol

Effective concentration

Mechanism

• Denature proteins
• Dissolve lipid membranes
• Damage cellular integrity

Uses

• Hand rubs
• Skin preparation before injections, venepuncture, and minor procedures
• Cleaning stethoscopes and small equipment surfaces
• Surgical hand antisepsis in alcohol-based preparations

Advantages

• Very rapid action
• Cheap
• Easy to apply
• Leaves no residue
• Broad activity against bacteria, fungi, and enveloped viruses

Limitations

• Not sporicidal
• Poor activity against some non-enveloped viruses
• No significant residual activity after evaporation
• Inactivated or less effective when hands are visibly dirty
• Flammable
• Drying and irritating to skin with repeated use

High-yield point

---

2. Iodine and Iodophors

A. Iodine

Mechanism

• Iodinates cellular proteins
• Oxidizes essential enzymes
• Damages microbial cell components

Spectrum

• Gram-positive and gram-negative bacteria
• Mycobacteria
• Fungi
• Many viruses
• Some spores with sufficient concentration/contact time

Disadvantages

• Skin irritation and burns
• Staining
• Unpleasant odour
• Reduced activity in the presence of organic matter
• May cause iodine hypersensitivity

---

B. Iodophors

Example

• Povidone-iodine

Uses

• Preoperative skin preparation
• Surgical scrub
• Wound cleansing in selected situations
• Mucosal antisepsis

Adverse effects

• Contact dermatitis
• Chemical burns if used excessively or trapped under occlusive dressings
• Rare systemic iodine absorption, especially with extensive use on damaged skin

Important point

---

3. Chlorhexidine

Group

Preparations

• Chlorhexidine gluconate aqueous solution
• Chlorhexidine in alcohol
• Chlorhexidine-containing soap or hand wash
• Mouthwash
• Antiseptic creams

Mechanism

• Increases membrane permeability
• Causes leakage of intracellular substances

• Causes precipitation of cytoplasmic proteins
• Produces cell death

Spectrum

• Excellent against Gram-positive bacteria
• Good activity against many Gram-negative bacteria
• Active against fungi and enveloped viruses
• Less active against mycobacteria
• Not reliably sporicidal

Uses

• Surgical hand preparation
• Skin preparation before catheter insertion or surgery
• Hand antisepsis
• Oral rinse in gingivitis
• Antisepsis in burns and wounds in appropriate preparations

Major advantages

• Persistent or residual activity on skin
• Continued antimicrobial effect after application
• Less affected by organic matter than many other antiseptics

Adverse effects and precautions

• Skin irritation or contact dermatitis
• Rare serious allergic reaction or anaphylaxis
• Severe eye injury if it enters the eye
• Ototoxicity: avoid in middle/inner-ear procedures
• Neurotoxicity: should not contact meninges or neural tissue

High-yield comparison

---

4. Chlorine-Releasing Compounds

Examples

• Bleaching powder
• Sodium hypochlorite
• Calcium hypochlorite
• Chloramine-T
• Chlorine dioxide

Mechanism

Uses

• Disinfection of drinking water
• Swimming pools
• Blood spills
• Hospital surfaces
• Excreta and sewage
• Laundry and linen in suitable protocols

Advantages

• Cheap
• Broad antimicrobial spectrum
• Rapid action
• Effective against many viruses
• Can be sporicidal at suitable concentrations and contact time

Disadvantages

• Corrosive to metal
• Bleaching effect on fabrics
• Irritant to skin, eyes, and respiratory tract
• Reduced activity in the presence of organic matter
• Unstable after dilution
• Must not be mixed with acids or ammonia because toxic chlorine gas may be released

Important point

---

5. Oxidising Agents

A. Hydrogen Peroxide

Mechanism

Uses

• Wound cleansing in limited situations
• Oral cleansing/gargles in diluted preparations
• Surface and instrument disinfection
• Hydrogen peroxide vapour is used for environmental decontamination and sterilization systems

Adverse effects

• Tissue irritation
• Delayed wound healing if repeatedly used in wounds
• Can damage healthy cells
• Foaming may mechanically remove debris, but this does not mean it should be used routinely for all wounds

---

B. Potassium Permanganate

Mechanism

Uses

• Weeping eczema
• Fungal infections
• Certain superficial skin conditions

Adverse effects

• Irritant and caustic in concentrated form
• Brown staining of skin and clothes

---

C. Peracetic Acid

Uses

• High-level disinfection or sterilization of medical equipment, including heat-sensitive instruments in suitable systems.

Advantages

• Broad spectrum, including spores
• Rapid action

Disadvantages

• Corrosive and irritant
• Requires careful handling

---

6. Phenols and Phenolic Compounds

Examples

• Phenol
• Cresol
• Chloroxylenol, PCMX
• Hexachlorophene

Mechanism

• Damage cell membrane
• Denature proteins
• Cause leakage of cell contents

A. Phenol

Uses

• Disinfection of contaminated materials and surfaces
• Historically used as a disinfectant

Adverse effects

• Corrosive
• Toxic if absorbed
• Causes local anaesthesia followed by tissue damage
• Unpleasant odour

---

B. Cresols

Uses

• Surface and environmental disinfection
• Disinfection of excreta in selected settings

---

C. Chloroxylenol

Uses

• Skin cleansing
• Minor cuts and wounds
• Household antiseptic preparations

Limitations

---

D. Hexachlorophene

Limitation

---

7. Aldehydes

A. Formaldehyde

Mechanism

Uses

• Environmental fumigation in restricted circumstances
• Preservation of specimens
• Disinfection of rooms/equipment in older protocols

Adverse effects

• Strong irritant to skin, eyes, and respiratory tract
• Unpleasant smell
• Toxic
• Potential carcinogenic risk

---

B. Glutaraldehyde

Mechanism

Features

• Broad spectrum
• High-level disinfectant
• Can be sporicidal after prolonged contact

Uses

• Endoscopes
• Bronchoscopes
• Respiratory therapy equipment
• Anaesthetic equipment

Adverse effects

• Irritant vapours
• Dermatitis
• Eye and respiratory irritation
• Requires adequate ventilation and safety measures

High-yield point

---

8. Surface-Active Agents

A. Cationic Detergents

Examples

• Cetrimide
• Benzalkonium chloride
• Cetylpyridinium chloride

Mechanism

Uses

• Skin cleansing
• Minor wound antisepsis
• Mouthwash preparations
• Cleaning of certain surfaces

Limitations

• Mainly active against Gram-positive bacteria
• Weak action against Gram-negative bacilli, mycobacteria, spores, and some viruses
• Activity is reduced by soaps, hard water, and organic matter
• Not reliable for high-level hospital disinfection

---

B. Anionic Detergents

Examples

• Ordinary soaps
• Sodium lauryl sulfate

Important point

---

9. Heavy Metals

A. Silver Nitrate

Mechanism

Uses

• Historically used for neonatal conjunctivitis prophylaxis
• Limited topical antiseptic use

Limitation

---

B. Silver Sulfadiazine

Action

Use

• Topical prevention/treatment of infection in burns

Adverse effects

• Local irritation
• Delayed wound healing in some cases
• Rare systemic sulfonamide effects with extensive use
• Avoid or use carefully in sulfonamide allergy and near-term pregnancy/newborns according to clinical context

---

10. Dyes

Examples

• Gentian violet
• Acriflavine
• Brilliant green

Mechanism

Uses

• Limited topical use for superficial fungal infection or mucosal candidiasis
• Largely obsolete because better agents are available

Limitations

• Staining
• Irritation
• Narrow spectrum

---

Important Uses: Which Agent to Choose?

---

Antiseptic vs Antibiotic

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Frequently Asked KDT Exam Questions

1. Why is 70% alcohol preferred to absolute alcohol?

• Water promotes penetration into microbial cells.
• It improves protein denaturation.
• Absolute alcohol rapidly coagulates surface proteins, which may reduce deeper penetration.

2. Write uses of chlorhexidine.

• Surgical hand wash
• Preoperative skin preparation
• Catheter-site antisepsis
• Hand wash
• Oral rinse for gingivitis
• Burns/wound preparations in selected cases

3. Adverse effects of chlorhexidine.

• Contact dermatitis
• Rare anaphylaxis
• Corneal damage if introduced into eye
• Ototoxicity
• Neurotoxicity if it contacts meninges/neural tissue

4. Uses of glutaraldehyde.

• High-level disinfection of heat-sensitive instruments, especially endoscopes and respiratory equipment.

5. Uses of chlorine compounds.

• Drinking water
• Swimming pools
• Blood spills
• Environmental surfaces
• Excreta and sewage

6. Why are antiseptics ineffective in dirty wounds?

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Last-Minute Revision Table