Pyrexia

 

🔥 PYREXIA (FEVER) —

 

1. INTRODUCTION

• Pyrexia (Greek: pyretos = fire)
• Pyrogens = substances that induce fever

Types of Pyrogens:

1. Exogenous (external):

• Microbial products
• Lipopolysaccharide (Gram-negative bacteria)
• Toxins from Gram-positive bacteria (e.g., Staphylococcus aureus)

2. Endogenous (internal):

• Cytokines produced by immune cells
• IL-1, IL-6, TNF-α

2. DEFINITION

• Fever = regulated rise in body temperature due to increase in hypothalamic set point
• Normal: 36.5–37.5°C

3. TEMPERATURE MEASUREMENT

• Oral
• Axillary
• Rectal (most accurate in children)
• Tympanic membrane

4. TYPES OF FEVER

Type	Feature	Examples
Continuous	Persistent, minimal fluctuation	Typhoid, pneumonia
Intermittent	Fever + normal temperature phases	Malaria
Remittent	Fluctuates but never normal	Infective endocarditis
Relapsing	Fever returns after normal period	Borrelia infections

5. SIGNS & SYMPTOMS

• Shivering (rigors)
• Anorexia
• Dehydration
• Lethargy
• Headache
• Poor concentration
• Sleepiness

Severe cases:

• Irritability
• Confusion
• Delirium
• Convulsions (children)

6. DRUG-INDUCED FEVER

Class	Examples
Antimicrobials	Isoniazid
Antiarrhythmics	Procainamide, Quinidine
Antiepileptics	Phenytoin, Carbamazepine
Antihypertensives	Methyldopa
Antifungals	Amphotericin B
Others	Interferons, Sulfonamides

⚠️ Note:

• Cocaine/ephedrine → hyperthermia, not true fever

7. PATHOPHYSIOLOGY

Mechanism:

1. Infection → release of exogenous pyrogens
2. Activation of immune cells
3. Release of cytokines (IL-1, IL-6, TNF-α)
4. Stimulate hypothalamus → ↑ Prostaglandin E2 (PGE2)
5. Set point increases

Body response:

• Vasoconstriction → ↓ heat loss
• Shivering → ↑ heat production

👉 Result: Fever develops

8. FEVER vs HYPERTHERMIA (VERY IMPORTANT)

Feature	Fever	Hyperthermia
Set point	Increased	Normal
Cause	Pyrogens	Heat/drugs
Control	Regulated	Unregulated
Paracetamol effect	Works	No effect

9. MANAGEMENT

A. Non-Pharmacological

• Adequate hydration (ORS, fluids)
• Rest
• Light clothing
• Lukewarm sponging

❌ Avoid:

• Ice baths
• Alcohol rubs (increase shivering → worsen fever)

B. During Fever Care

• Maintain room temperature (not too hot/cold)
• Use fan if needed
• Remove excess clothing
• Lukewarm bath helps

C. Home Remedies (Supportive Only)

• Bed rest
• Fluids (herbal teas, lemon grass tea)
• Turmeric milk (symptomatic relief only)

⚠️ Note:

• No strong scientific evidence → not primary treatment

10. PHARMACOLOGICAL MANAGEMENT

Drug of Choice: Paracetamol

Adults:

• 500–650 mg every 6–8 hours
• Max: 3–4 g/day

Children:

• 10–15 mg/kg/dose every 6 hours

⚠️ Correction:

• Always use weight-based dosing in children

11. PREVENTION

• Hand hygiene
• Safe food and water
• Infection control
• Isolation of infected individuals

12. ROLE OF PHARMACIST

• Provide correct dose of paracetamol
• Assess severity of fever
• Advise hydration & rest
• Refer to doctor if:
• Fever persists >2–3 days
• Very high fever
• Associated severe symptoms

⚠️ Caution:

• Avoid overdose of paracetamol → hepatotoxicity
• Extra caution in alcoholics

13. CASE STUDY (EXAM FORMAT)

Case:

• Patient with fever (101°F)

Management:

1. Confirm temperature
2. Give Paracetamol 650 mg
3. Advise:
• Bed rest
• Fluids
4. Monitor symptoms
5. Refer if not improved

🔑 QUICK REVISION (LAST MINUTE)

• Fever = ↑ hypothalamic set point
• Key mediator = PGE2
• Cytokines = IL-1, IL-6, TNF-α
• DOC = Paracetamol
• Avoid ice/alcohol rub
• Fever ≠ Hyperthermia

 

 

Constipation

RESPONDING TO SYMPTOMS OF MINOR AILMENTS

5) CONSTIPATION

INTRODUCTION

Constipation is defined as infrequent bowel movements (≤2 per week) or difficulty in passing stools, often associated with:

• Hard stools
• Straining
• Pain
• Feeling of incomplete evacuation

Prevalence:

• Elderly: ~20%
• Middle-aged: ~8%
• Young: ~3%

Important:
Constipation is not a disease, but a symptom of an underlying condition.

Predisposing factors:

• Low-fiber diet
• Inadequate fluid intake
• Physical inactivity
• Disease conditions
• Polypharmacy (multiple drugs)

CAUSES OF CONSTIPATION

1. Gastrointestinal disorders

• Intestinal obstruction (ulcer, cancer)
• Irritable bowel syndrome (IBS)
• Diverticulitis
• Hemorrhoids
• Anal fissures
• Tumors

2. Metabolic & endocrine disorders

• Diabetes mellitus
• Hypothyroidism
• Panhypopituitarism
• Pheochromocytoma
• Hypocalcemia

3. Pregnancy

4. Neurogenic causes

• Head injury
• CNS tumors
• Stroke
• Parkinson’s disease

5. Psychogenic causes

• Psychiatric disorders
• Poor bowel habits

PATHOPHYSIOLOGY

·        The GI tract is divided into:

• Upper GI → digestion
• Lower GI → water absorption & stool formation

·        Peristalsis moves stool through the intestine

·        In constipation:

• Slower transit time
• ↑ Water absorption → hard stool
• ↓ Motility → difficult defecation

Key mechanisms:

• Reduced parasympathetic activity → ↓ motility
• Anticholinergic drugs → slow transit
• Opioids:
• ↑ smooth muscle tone
• ↓ peristalsis
• ↑ sphincter tone
• ↓ rectal sensitivity
  → Leads to severe constipation

MANAGEMENT

General Measures

• Treat underlying disease
• Review and adjust causative drugs
• Lifestyle modification

NON-PHARMACOLOGICAL TREATMENT

• Drink ~2 liters water/day
• Increase dietary fiber (fruits, vegetables, cereals)
• Regular exercise
• Develop regular bowel habits
• Avoid excessive coffee/tea

PHARMACOLOGICAL THERAPY

Types of laxatives based on action

Type	Onset	Examples
Stool softening (1–3 days)	Slow	Bulk laxatives, docusate, lactulose
Soft/semifluid stool (6–12 hrs)	Moderate	Senna, bisacodyl
Rapid evacuation (1–6 hrs)	Fast	Saline laxatives, castor oil, PEG

COMMONLY USED AGENTS

1. Bulk-forming laxatives

• First-line in chronic constipation
• Increase stool bulk → stimulate peristalsis

2. Emollient laxatives (Docusate)

• Soften stool by mixing fat & water
• Used for prevention, not treatment
• Useful when straining must be avoided

3. Lubricants (Mineral oil)

• Coat stool → easier passage
• Reduce water absorption

4. Osmotic laxatives

·        Lactulose

• Retains water in colon
• Useful in elderly
• Side effects: bloating, cramps

·        Sorbitol

• Similar to lactulose
• More economical

5. Saline cathartics

• Examples: Milk of magnesia, magnesium salts
• Rapid action (few hours)
• Use: bowel evacuation (not routine use)

6. Stimulant laxatives

• Senna, Bisacodyl
• Increase intestinal motility
• Used for short-term relief

7. Castor oil

• Strong purgative
• Acts within 1–3 hours
• Not for routine use

8. Glycerin suppositories

• Rectal osmotic action
• Works within 30 minutes
• Safe, especially in children

9. Enemas

• Tap water enema → quick relief
• Used in acute constipation

SPECIAL SITUATIONS

·        Acute constipation:

• Enema / glycerin suppository
• Mild laxatives

·        Chronic constipation:

• Bulk laxatives first-line
• Lactulose / osmotic agents if needed

·        Hospitalized patients:

• Due to anesthesia/opioids
• Use oral/rectal laxatives

WHEN TO REFER TO DOCTOR

• Constipation > 1 week
• Severe abdominal pain
• Blood in stool
• Sudden change in bowel habits
• Elderly patients with new symptoms

SAFETY MONITORING IN CLINICAL TRIALS

INTRODUCTION

• Clinical trials are essential for medical advancements and drug development.
• With progress in trial design and conduct, awareness of ethical issues and participant safety has increased.
• Therefore, systems must be in place to ensure protection of trial participants.
• Establishment of a Data Safety Monitoring Board (DSMB) is important, especially in trials involving potential risks.

ICH-GCP PRINCIPLE

• According to ICH-GCP guidelines:
  👉 “The rights, safety, and well-being of trial subjects are the most important considerations.”

WHO PERFORMS SAFETY MONITORING?

1. Investigator
2. Institutional Review Board / Independent Ethics Committee (IRB/IEC)
3. Sponsor
4. Monitor

1. INVESTIGATOR RESPONSIBILITIES

• Provide adequate medical care to participants during and after the trial.
• Manage and report adverse events (AEs).
• Ensure subject safety at all times.
• (Reference: ICH-GCP 4.3.2)

2. IRB / IEC RESPONSIBILITIES

• Safeguard rights, safety, and well-being of participants.
• Conduct continuing review of ongoing trials.
• Review should be done at least once per year.
• (Reference: ICH-GCP 3.1.1)

3. SPONSOR RESPONSIBILITIES

• May establish an Independent Data Monitoring Committee (IDMC/DSMB).
• Evaluate:
• Trial progress
• Safety data
• Decide whether to:
• Continue
• Modify
• Stop the trial
• (Reference: ICH-GCP 5.5.2)

4. MONITOR RESPONSIBILITIES

• Ensure proper reporting of adverse events within required timelines.
• Verify compliance with:
• GCP
• Protocol
• Regulatory requirements
• (Reference: ICH-GCP 5.18.4)

SAFETY MONITORING IN DIFFERENT PHASES

Phase I

• Small group (20–80 participants)
• Objective:
• Assess safety
• Determine dose range
• Identify side effects

Phase II

• Medium group (100–300 participants)
• Objective:
• Evaluate effectiveness
• Further assess safety

Phase III

• Large group (1000–3000 participants)
• Objective:
• Confirm effectiveness
• Monitor adverse effects
• Collect safety data

Phase IV

• Post-marketing studies
• Objective:
• Long-term safety
• Risk-benefit analysis
• Optimal drug use

SAFETY REPORTING (IND STUDIES)

• Under Investigational New Drug (IND) application:
• Strict reporting of serious and unexpected adverse events is required.
• Both investigator and sponsor are responsible.

DATA SAFETY MONITORING BOARD (DSMB)

Definition

• An independent group of experts that periodically reviews accumulating clinical trial data.
• Usually appointed by the sponsor.
• Common in randomized controlled trials (RCTs).

PURPOSE OF DSMB

• Protect participant safety
• Ensure study credibility and validity
• Identify:
• High dropout rates
• Protocol violations
• Ineligible participants
• Recommend continuation or termination

WHEN DSMB IS REQUIRED

• Large, multicenter randomized trials
• Trials evaluating:
• Mortality
• Major morbidity
• High-risk interventions

DSMB COMPOSITION

Includes:

• Clinicians (relevant specialty)
• Biostatistician
• Medical ethicist (if high risk)

May include:

• Epidemiologists
• Toxicologists
• Clinical pharmacologists
• Patient representatives

Selection Criteria

• Expertise and experience
• Availability
• Confidentiality
• No conflict of interest

RESPONSIBILITIES OF DSMB

1. Interim Monitoring

• Effectiveness
• Safety
• Study conduct
• External data

2. Monitoring for Effectiveness

• Recommend early termination if:
• Strong positive results
• Clear benefit
• Stop trial if:
• No chance of benefit (futility)

3. Monitoring for Safety

• Detect increased risk (e.g., mortality, disease progression)
• May recommend early termination if harm is observed
• Less strict proof needed for harm vs benefit

4. Monitoring Study Conduct

Review:

• Recruitment rates
• Protocol violations
• Dropouts
• Data quality and completeness

5. Consideration of External Data

• Evaluate findings from other studies
• May recommend:
• Trial modification
• Consent changes
• Trial termination

6. Special Cases

Less Serious Outcome Studies

• Usually short-term
• DSMB often not required

Early Phase Studies

• DSMB generally not required
• May be used if high-risk interventions

OTHER RESPONSIBILITIES

1. Making Recommendations

DSMB may recommend:

1. Continue study as planned
2. Terminate study
3. Modify protocol
4. Temporarily suspend study

2. Maintaining Records

• Keep detailed meeting minutes
• Provide written reports to sponsor
• Justify all recommendations

DSMB MEETINGS

• Held at least annually or as required

Meeting Structure

1.     Open Session

• Investigator may attend
• General updates

2.     Closed Session

• DSMB + statisticians
• Data analysis presented

3.     Executive Session

• DSMB only
• Final decisions and recommendations

✅ QUICK REVISION POINTS (EXAM)

• Safety is the top priority (ICH-GCP)
• DSMB = independent monitoring body
• Phase III = maximum safety data collection
• Early stopping reasons:
• Benefit
• Harm
• Futility

DIARRHEA –

1. Introduction

• Diarrhea = increase in frequency + fluidity of stool
• Normal stool: ~200 g/day
• Diarrhea:

o   250 g/day

• 70–95% water
• Frequency: 5–20 times/day
• Severe cases: >1.4 L fluid loss/day
• Main risk: Dehydration → morbidity & mortality

Dysentery

• Low-volume, painful, bloody diarrhea

2. Causes of Diarrhea

Infectious Causes

• Bacteria: Shigella, Salmonella, Vibrio, Campylobacter, Staphylococcus, Escherichia coli
• Viruses: Norovirus, Rotavirus
• Protozoa: Entamoeba histolytica

Non-Infectious Causes

• Contaminated food/water
• Poor hygiene, travel history
• Immunocompromised state
• Drugs:
• Antibiotics
• Magnesium antacids
• NSAIDs
• Prostaglandins
• Diseases:
• IBS
• Hyperthyroidism
• Diabetic neuropathy
• Carcinoid syndrome
• Surgical causes: Reduced gut length

3. WHO Classification

• Acute diarrhea: < 14 days
• Chronic diarrhea: > 14 days

4. Pathophysiology

Diarrhea occurs due to imbalance between absorption & secretion of fluids/electrolytes.

Mechanisms

• ↓ Sodium absorption / ↑ Chloride secretion
• Altered intestinal motility
• ↑ Luminal osmolarity
• ↑ Hydrostatic pressure
• Malabsorption

5. Types of Diarrhea

1. Secretory Diarrhea

• Cause: Toxins, hormones (VIP, serotonin, prostaglandins)
• Features:
• Stool > 500 mL/day
• Continues even during fasting

2. Osmotic Diarrhea

• Cause: Poorly absorbed substances (e.g., lactose intolerance, Mg antacids)
• Features:
• Stops with fasting
• High osmolarity stool

3. Exudative Diarrhea

• Cause: Inflammation (e.g., infections, IBD)
• Features:
• Blood, mucus, pus in stool
• Persistent even during fasting

4. Malabsorption Diarrhea

• Cause: Nutrient absorption defects
• Features:
• Bulky, fatty stool (steatorrhea)
• Improves with fasting

6. Management

A. Non-Pharmacological

• Fluid & electrolyte replacement is key
• ORS (Oral Rehydration Solution) – WHO recommended

Home ORS Formula

• 200 mL boiled & cooled water

·       

• 1 teaspoon sugar

·       

• pinch of salt

Diet Advice

• Bland diet
• Avoid:
• Dairy (initially)
• Solid/heavy foods (first 24 hrs)

B. Pharmacological Management

1. Anti-Motility Drugs

• Reduce intestinal motility → ↑ absorption

Examples:

• Loperamide
• Initial: 4 mg, then 2 mg after each loose stool
• Max: 16 mg/day
• Diphenoxylate
• 5 mg QID (max 20 mg/day)
• Opioids (Tincture opium)
• Risk: Addiction

2. Adsorbents

• Bind toxins & reduce symptoms

Example:

• Kaolin-pectin
• Dose: 30–120 mL after each stool

⚠️ Reduce absorption of other drugs

3. Anti-Secretory Agents

Bismuth Subsalicylate

• Used in traveler’s diarrhea
• Adverse effects:
• Black tongue/stool
• Tinnitus
• Encephalopathy (high dose)

Probiotics

• Restore gut flora

Examples:

• Lactobacillus acidophilus
• Lactobacillus bulgaricus

Dose:

• 2 tablets or 1 sachet 3–4 times/day

Octreotide

• Somatostatin analog
• Used in:
• Carcinoid syndrome
• VIP tumors

Dose: 100–600 mcg/day (SC)

Adverse effects:

• Nausea
• Abdominal pain
• Gallstones

4. Antibacterial Agents

Used in infectious/bloody diarrhea

Examples

• Metronidazole / Tinidazole (amoebiasis)
• Fluoroquinolones:
• Norfloxacin 400 mg
• Ciprofloxacin 500 mg
• Ofloxacin 200 mg

✔ Sometimes used in combination

7. Key Exam Points

• ORS = first-line treatment
• Avoid anti-motility drugs in bloody diarrhea
• Dehydration is the main complication
• Fasting helps differentiate:
• Osmotic (improves)
• Secretory (persists)

Data management and it's components

DATA MANAGEMENT & ITS COMPONENTS

1. Clinical Data Management (CDM)

Clinical Data Management involves:

• Collection, integration, and validation of clinical trial data
• Ensuring data is accurate, reliable, and statistically analyzable

Process Overview

• Investigators collect patient health data over a defined period
• Data is recorded in Case Report Forms (CRFs)
• Data is sent to the sponsor
• Sponsor performs statistical analysis on pooled data
• Data is stored in a Clinical Data Management System (CDMS)

2. Case Report Form (CRF)

• A CRF is a paper or electronic tool used to collect trial data for each subject
• It ensures standardized and consistent data collection across all sites

Functions of CRF

• Ensures accurate and efficient data recording
• Facilitates data processing, analysis, and reporting

STEPS IN DATA MANAGEMENT PROCESS

1. Data Design
2. Data Collection
3. Data Entry
4. Data Validation
5. Data Cleanup
6. Data Analysis
7. Data Reporting
8. Publication

SEQUENTIAL STEPS IN DATA MANAGEMENT

1. Data Design

• Database should allow:
• Accurate data storage
• Easy reporting and interpretation

Types of Databases

• Study Management Database
• Patient details, recruitment, follow-up tracking
• Clinical Database
• Clinical outcomes and study results

Key Functionalities

• Validation rules (range checks, skip logic, consistency checks)
• Query generation and reporting
• Audit trail

2. Data Collection

Key Principles

• Ensure validity and accuracy of data
• Source data must be correctly transcribed
• Regular monitoring (Source Data Verification - SDV)

Before Data Collection

Testing (Pilot Study)

• Test the system before use
• Maintain proper documentation

SOP (Standard Operating Procedures)

• Define:
• Data collection process
• System setup
• Roles and responsibilities

Privacy Risk Assessment

Includes:

• Personal data collected (e.g., Name, DOB)
• Access control
• Data storage and sharing procedures
• Data anonymization
• Risk of confidentiality breaches and mitigation

Training

• Train all users after system validation
• Maintain training records
• Provide workflow diagrams and instructions

During Data Collection

Audit Trail

• Maintain record of all data changes
• Ensure original entries remain traceable

Data Safety

• Protect against:
• Data loss
• Unauthorized access
• Ensure compliance with Good Clinical Practice (GCP)

3. Data Entry

Types

• Manual
• Optical Mark Recognition (OMR)
• Electronic (online/offline)

Important Points

• SOPs must define:
• Who enters data
• How data is entered
• Procedures must be tested and documented
• Staff must be trained
• Quality control checks are essential

Electronic Data Entry

• Data entered directly into electronic CRF (eCRF)
• Can be uploaded via internet/server
• Built-in validation rules prevent incorrect entries

4. Data Validation

Validation Checks

• Range checks
• Skip logic
• Missing data
• Inconsistencies

Output File Checks

• Correct variable names
• Proper coding of categories
• Data format accuracy (e.g., numeric vs text)
• Accurate export to formats like CSV/SPSS

5. Data Cleanup

• Identify:
• Errors
• Missing values
• Inconsistencies
• Corrections must:
• Be justified
• Maintain audit trail
• Queries should be documented

6. Data Analysis

• Conducted by trained statisticians
• Guided by Statistical Analysis Plan (SAP)

SAP Includes

• Primary and secondary outcomes
• Handling missing data
• Statistical methods
• Reporting format

Statistical Methods

• Hierarchical models
• Bayesian analysis
• Decision analysis
• Sequential analysis
• Meta-analysis
• Risk-based allocation

7. Data Reporting

Reports Include

• Recruitment progress
• Follow-up rates
• Data completeness
• Adverse event reconciliation (SAE)
• Withdrawals

8. Database Lock

• Final step before analysis
• Prevents any further data changes

Checklist Includes

• All queries resolved
• Data forms completed
• Coding finalized
• SAE reconciliation completed

9. Data Presentation

• Data presented using:
• Tables
• Graphs
• Statistical summaries

OBJECTIVES OF DATA MANAGEMENT

• Ensure data integrity and quality
• Maintain accuracy and completeness
• Enable valid statistical analysis
• Provide true representation of study results

Nausea and Vomiting

 

RESPONDING TO SYMPTOMS OF MINOR AILMENTS

2) NAUSEA & VOMITING

INTRODUCTION

·        Nausea and vomiting are common complaints, especially in:

• Gastrointestinal disorders
• Chronic diseases (e.g., cancer)

·        Nausea:

• Subjective, unpleasant sensation with an urge to vomit
• Associated with:
• Pallor
• Sweating
• Tachycardia
• Salivation
• Increased respiratory rate

·        Vomiting (Emesis):

• Reflex expulsion of stomach contents through the mouth

·        Retching:

• Involuntary, unsuccessful attempt to vomit

ETIOLOGY (CAUSES)

Common Causes

• Food allergies
• Gastrointestinal infections (e.g., food poisoning, viral gastroenteritis)
• Gastroesophageal reflux disease (GERD)
• Drugs (chemotherapy, radiation therapy)
• Migraine
• Pregnancy (morning sickness)
• Motion sickness
• Severe pain (e.g., kidney stones)
• Excess cannabis use

Serious Causes (Red Flags)

• Appendicitis
• Intestinal obstruction
• Tumors/cancer
• Poisoning or drug ingestion (especially in children)
• Peptic ulcers

CLINICAL PRESENTATION

• Dehydration
• Weight loss
• Mental confusion
• Reduced skin turgor
• Increased thirst
• Hypotension
• Muscle weakness
• Cardiac rhythm disturbances
• Metabolic alkalosis

PATHOPHYSIOLOGY

Phases of Emesis

1. Nausea – urge to vomit
2. Retching – muscular movements without expulsion
3. Vomiting – forceful expulsion of gastric contents

Mechanism

·        Controlled by the vomiting center in the brain

·        Inputs via:

• Vagus nerve
• Splanchnic nerves

·        Stimuli:

• Smell, sight
• Drugs, toxins
• Motion

·        Activation of Chemoreceptor Trigger Zone (CTZ) → initiates vomiting reflex

Key Neurotransmitters Involved

• Dopamine (D₂)
• Histamine (H₁)
• Serotonin (5-HT₃)
• Acetylcholine (Muscarinic)
• Substance P (NK₁ receptors)

PROCESS OF VOMITING

1. Deep inspiration
2. Contraction of abdominal muscles → ↑ intra-abdominal pressure
3. Closure of epiglottis (prevents aspiration)
4. Relaxation of esophagus & pyloric sphincter
5. Expulsion of gastric contents

MANAGEMENT

1) Non-Pharmacological Management

• Avoid triggering foods
• Eat small, frequent meals
• Maintain hydration
• Rest and fresh air
• Behavioral techniques (limited evidence)

2) Pharmacological Management

a) Antacids & Antisecretory Agents

• Neutralize gastric acid
• Example:
• Aluminum hydroxide
• Magnesium hydroxide

b) H₂-Receptor Antagonists

• Reduce acid secretion
• Examples:
• Cimetidine
• Famotidine
• Ranitidine
• Nizatidine

c) Proton Pump Inhibitors (PPIs)

• Strong acid suppression
• Examples:
• Omeprazole
• Esomeprazole
• Pantoprazole
• Rabeprazole
• Lansoprazole

d) Anticholinergics

• Block muscarinic receptors (vestibular system)
• Used in motion sickness
• Example:
• Scopolamine

e) Antihistamines (H₁ blockers)

• Useful in motion sickness, vertigo
• Side effects: sedation, blurred vision
• Examples:
• Diphenhydramine
• Meclizine

f) Dopamine Antagonists (D₂ blockers)

• Act on CTZ
• Side effects: sedation, hypotension, extrapyramidal symptoms
• Examples:
• Metoclopramide
• Domperidone
• Chlorpromazine
• Promethazine

g) Serotonin (5-HT₃) Antagonists

• Block serotonin receptors in CTZ & GI tract
• Used in chemotherapy-induced vomiting
• Example:
• Ondansetron

WHEN TO REFER TO DOCTOR

Immediate referral is needed if:

• Vomiting > 24 hours
• Blood in vomit
• Severe abdominal pain
• Severe headache or stiff neck
• Signs of dehydration:
• Dry mouth
• Reduced urination
• Dark urine
• Suspected poisoning

 

 

Dyspepsia

 

RESPONDING TO SYMPTOMS OF MINOR AILMENTS

3) DYSPEPSIA

INTRODUCTION

• The term dyspepsia is derived from the Greek word meaning “improper digestion.”
• It refers to upper abdominal discomfort usually related to:
• Food intake
• Alcohol consumption
• Common causes include:
• Certain drugs: NSAIDs, antibiotics, digoxin, bisphosphonates, theophylline
• Smoking
• Stressful lifestyle

TYPES

1. Acute (Infrequent) Dyspepsia

• Usually self-limiting
• Associated with:
• Irregular eating habits
• Alcohol intake
• Smoking
• Stress

2. Chronic Dyspepsia

• Recurrent symptoms such as:
• Epigastric pain
• Bloating
• Belching
• Nausea, vomiting
• Early satiety

CAUSES OF DYSPEPSIA

• Peptic ulcer disease
• Gastroesophageal reflux disease (GERD)
• Helicobacter pylori infection
• Gastric malignancy
• Functional (idiopathic) dyspepsia

Functional dyspepsia = No structural abnormality but persistent symptoms

PATHOPHYSIOLOGY

• Visceral hypersensitivity
• Impaired gastric accommodation
• Delayed gastric emptying
• Antral overdistension
• Abnormal gastroduodenal motility

CLINICAL FEATURES

Common Symptoms

• Epigastric discomfort
• Bloating
• Nausea
• Belching
• Early satiety

Alarm Symptoms (Require Endoscopy)

• Unexplained weight loss (>10%)
• Persistent vomiting
• Severe continuous pain
• Dysphagia
• Hematemesis or melena
• Anemia
• Jaundice

INVESTIGATION

·        Patients <55 years without alarm symptoms:

• Test for H. pylori (urea breath test)

·        Patients >35–55 years or with alarm symptoms:

• Upper GI endoscopy

MANAGEMENT OF DYSPEPSIA

1. NON-PHARMACOLOGICAL THERAPY

• Dietary modifications (bland diet)
• Avoid:
• Alcohol
• Smoking
• Caffeine
• Fatty foods
• Weight reduction
• Stress management

2. PHARMACOLOGICAL THERAPY

A. ANTACIDS

·        Example: Aluminum + Magnesium salts

·        Mechanism:

• Neutralize gastric acid
• Provide mucosal protection

·        Dose:

• 15 mL, 3–4 times daily

·        Note:

• Suspensions are more effective than tablets

B. H2 RECEPTOR ANTAGONISTS

·        Drugs:

• Ranitidine
• Famotidine

·        Mechanism:

• Block histamine (H2 receptors) → ↓ acid secretion

·        Dose:

• Famotidine: 20 mg BID or 40 mg OD
• Ranitidine: 150 mg BID or 300 mg OD

C. PROTON PUMP INHIBITORS (PPIs)

·        Drugs:

• Omeprazole 20 mg OD
• Rabeprazole 20 mg OD
• Lansoprazole 30 mg OD
• Pantoprazole 40 mg OD

·        Mechanism:

• Irreversibly inhibit H⁺/K⁺ ATPase (proton pump)

·        Key Point:

• Take 30–60 minutes before meals

D. MUCOSAL PROTECTIVE AGENT

Sucralfate

·        Mechanism:

• Forms protective barrier over ulcer
• Protects against acid, pepsin, bile

·        Dose:

• 1 g QID or 2 g BID

E. PROKINETIC AGENTS

Metoclopramide

·        Dose:

• 5–10 mg, three times daily

·        Mechanism:

• Dopamine (D2) receptor blockade
• ↑ Acetylcholine → ↑ gastric motility

·        Caution:

• Can cause neuropsychiatric side effects
• Use only under medical supervision

F. H. PYLORI ERADICATION

• Indicated if infection present
• Improves long-term symptoms

3. ALTERNATIVE THERAPIES

• Herbal options:
• Peppermint
• Caraway oil

SUMMARY (FOR QUICK REVISION)

• Dyspepsia = Upper abdominal discomfort
• Causes: Drugs, lifestyle, GERD, ulcers, H. pylori
• First step: Lifestyle modification
• Drugs:
• Antacids → Immediate relief
• H2 blockers → Moderate effect
• PPIs → Most effective
• Alarm symptoms → Endoscopy required