Exhaustive Facilitator Guide to Basic Pharmacology (NTA Level 4 Semester 2)

Background and Pharmaceutical Personnel Project

• Increasing Demand: There is a growing demand for pharmaceutical personnel in Tanzania due to expanded investment in public and private pharmaceutical sectors. Shortages in trained human resources contribute to poor service quality and low medicinal access.

• Project - "Supporting Training Institutions for Improved Pharmaceutical Services in Tanzania":

  • Partnership: Public-Private-Partnership (PPP) involving the Pharmacy Council (PC), development partners in Germany (GIZ), and Pharmaceutical Training Institutions (PTIs).

  • Goal: To improve the quality and capacity of PTIs, specifically focusing on lower-cadre pharmaceutical personnel.

  • Stakeholder Workshop: Conducted from 18th to 22nd August 2014 in Morogoro to initiate the project.

  • Key Activities: Situational analysis, curriculum review/harmonization, development of facilitator guides, assessment plans, training of trainers, and supportive supervision.

  • Writers’ Workshop (WW) Approach: Standardized teaching materials were developed starting in August 2015. This included two workshops (two weeks each) for drafting and a one-week workshop for reviewing, editing, and formatting.

• Collaborating Institutions and Personnel:

  • Lead Facilitators: Mrs. Stella M. Mpanda (Childbirth Survival International) and NACTE secretariat members.

  • Financial/Technical Support: St. Luke Foundation (SLF), John Snow Inc (JSI), GIZ, Merck Kgaa, Boehringer Ingelheim Gmbh, Bayer Pharma Ag, and action medeor.V.

  • Representatives: Tutors and experts from Pharmacy Council, NACTE, MoHCDGEC, HKMU, CUHAS, MUHAS, KSP, KCMC, and several regional hospitals and colleges.

Abbreviations and Acronyms

• AGS: Gas Gangrene Antitoxin

• ARS: Anti Rabies Serum

• ARV: Anti-Retroviral

• ATS: Tetanus antitoxin

• BCG: Bacillus Calmette Guerin

• CNS: Central Nervous System

• COCs: Combined Oral Contraceptives

• COPD: Chronic Obstructive Pulmonary Diseases

• CUHAS: Catholic University of Health and Allied Sciences

• DPT: Diphtheria Pertussis Tetanus

• E.L.C.T: Evangelical Lutheran Church in Tanzania

• HKMU: Hubert Kairuki Memorial University

• ICP: Increased Intra Cranial Pressure

• IGs: Immunoglobulins

• ITP: Idiopathic Thrombocytopenic Purpura

• JSI: John Snow Inc

• KCMC: Kilimanjaro College of Medical Sciences

• LZHRC: Lake zone Health Resource Centre

• MAO: Mono Amine Oxidase

• MEMS: Mission for Essential Medicine Supply

• MMR: Measles, Mumps and Rubella

• MoHCGC: Ministry of Health, Community development, Gender, Elderly and children

• MUHAS: Muhimbili University of Health and Allied Sciences

• NACTE: National Council For Technical Education

• NSAIDS: Non-steroidal anti-inflammatory drugs

• POPs: Progestogen Only Pills

• RuCU: Ruaha Catholic University

• SIBS: Spring Institute of Business

• SLF: Saint Luke Foundation

• USP: United States Pharmacopoeia

Module Overview and Organization

• Target Audience: Primarily tutors of pharmaceutical schools training Level 4 students.

• Session Structure: Each of the 45 sessions includes:

  • Session Title and Time: Estimated duration in minutes.

  • Pre-requisites: Prior modules or sessions required.

  • Learning Tasks: Expected outcomes for the student.

  • Resources Needed: Handouts, flip charts, markers, etc.

  • Session Overview: A box listing steps, timing, and methods.

  • Session Content: Detailed instructional steps and activities.

  • Key Points: A summary of major ideas.

  • Evaluation: Short questions based on learning tasks.

  • Handouts: Extra information for student reference.

• Instructional Guidance: Tutors are expected to use the Skill Laboratory, refer to the Standard Treatment Guidelines (2013), and involve students actively through real-life examples and locally available resources.

Introduction to Pharmacology

• Pharmacology Definition: The study of the effects of chemical substances on the function of living systems, or the study of substances interacting with living systems via chemical processes, particularly by binding to regulatory molecules (activation or inhibition).

• Drug: A substance that brings about changes in biological functions through chemical actions. It is a chemical substance of known structure, distinct from nutrients or essential dietary ingredients.

• Pro-drug: A chemical converted into an active drug form by biological processes within the body.

• Medicine: A chemical preparation containing one or more drugs, including excipients, stabilizers, and solvents, administered for therapeutic effect.

• Sources of Drugs:

  • Synthetic Chemicals: Laboratory-created reactions.

  • Plants: Morphine (opium), Quinine, Digitalis, Atropine, Ephedrine, Strychnine, Vinca alkaloids.

  • Fungal Sources: Penicillin, Streptomycin.

  • Animal Sources: Insulin, fish oil vitamins/fats.

  • Marine Organisms and Genetic Engineering.

  • Semi-synthetic: Chemical modification of natural products (e.g., Cephalosporins).

• Pharmacokinetics (PK): The quantitative, time-dependent study of plasma drug concentration and total drug amount in the body.

  • ADME Parameters:

    • Absorption (A): Bioavailability ($F$).

    • Distribution (D): Volume of Distribution ($Vd$).

    • Metabolism (M): Extraction Ratio ($ER$).

    • Elimination (E): Clearance ($CL$).

  • Bioavailability ($F$): The fraction of administered drug reaching systemic circulation. Example: if $100\,mg$ is given orally and $80\,mg$ is absorbed, $F = 80\%$ or $0.8$. For IV administration, $F = 1$ or $100\%$.

  • Half-life ($t_{1/2}$): The time required for blood concentration to reduce by half.

• Pharmacodynamics (PD): The actions of the drug on the body (concentration vs. effect relationship).

  • Receptor: A sensing macromolecule (on cell surface or intracellular) that mediates pharmacological actions.

  • Agonist: Binds to and activates a receptor.

  • Antagonist: Binds to a receptor but prevents activation, diminishing the effects of other molecules.

  • Synergy: Interaction where drugs enhance or magnify each other’s effects.

• Safety Measures:

  • Therapeutic Dose: Produces clinically desired response.

  • Toxic Dose: Produces toxicity.

  • Therapeutic Index ($TI$): $TI = \frac{\text{Toxic Dose}}{\text{Effective Dose}} = \frac{TD}{ED}$. A higher $TI$ indicates a wider safety margin.

• Usage Phenomenon:

  • Tolerance: Gradual decrease in responsiveness over days or weeks of repeated administration.

  • Dependence: Compulsive drug-taking (physical and psychological).

  • Addiction: A chronic, relapsing condition distinct from curable acute illness.

  • Habituation/Adaptation: Repeated use where cessation causes aversive effects.

General Classification of Medicines (NEMLIT Categories)

• Anaesthetics: Surgery/intubation (e.g., Halothane, Ketamine, Lignocaine).

• Muscle Relaxants: Surgery (e.g., Suxamethonium, Gallamine).

• Analgesics: Pain/fever (e.g., Paracetamol, Aspirin, Tramadol, NSAIDs like Diclofenac).

• Anti-allergies: Allergic reactions (e.g., Chlorpheniramine, Hydrocortisone, Adrenaline).

• Antidotes: Counteracting poisons (e.g., Activated charcoal, Antivenom).

• Anti-epileptics: Epilepsy (e.g., Carbamazepine, Phenobarbital, Diazepam).

• Anti-infectives: Various infections (Amoebicides, Anthelmintics, Antibacterials like Penicillins).

• Blood-affecting Drugs: Anemia management (e.g., Ferrous sulphate, Folic acid) and Anticoagulants (e.g., Heparin, Warfarin).

• Cardiovascular Medicines: Angina, arrhythmias, hypertension (e.g., Digoxin, Glyceryl trinitrate, Propranolol).

• Dermatologicals: Skin diseases (Topical steroids, Keratolytics, Fungicides).

• Gastro-intestinal Medicines: Ulcers, nausea, constipation (e.g., Antacids, Omeprazole, Loperamide).

• Hormones and Antidiabetics: Diabetes and hormonal disorders (e.g., Insulin, Metformin, Contraceptives).

• Sera, Immunoglobulins, and Vaccines: Immunological problems and prevention (e.g., BCG, DPT, Anti-D globulin).

• Ophthalmological, Ear, and Nose Preparations: Localized treatments (e.g., Chloramphenicol drops, Timolol).

• Psychotherapeutics: Psychiatric conditions (e.g., Chlorpromazine, Amitriptyline).

• Vitamins and Minerals: Deficiency management (e.g., Vitamin A, C, D).

Aminoglycoside Drugs

• Common Agents: Streptomycin, Neomycin, Kanamycin, Amikacin, Gentamicin, Tobramycin.

• Properties: Bactericidal; active against Gram-positive and many Gram-negative organisms. Amikacin, Gentamicin, and Tobramycin are active against Pseudomonas aeruginosa. Streptomycin is reserved for Mycobacterium tuberculosis.

• Contraindications: Myasthenia gravis, renal failure, hearing impairment, pregnancy.

• Dosages:

  • Gentamicin: Multiple daily dose regimen ($3\u20135\,mg/kg$ daily in divided doses every $8\,hours$ via IM or slow IV injection).

  • Neomycin: Oral bowel sterilization ($1\,g$ every $hour$ for $4\,hours$, then every $4\,hours$ for $2\u20133\,days$). Hepatic coma ($up\,to\,4\,g$ daily).

  • Amikacin: $15\,mg/kg$ daily in $2\,divided\,doses$; maximum $1.5\,g$ daily for $10\,days$ (max cumulative dose $15\,g$).

• Side Effects:

  • Ototoxicity: Hearing/balance loss (Neomycin is most ototoxic; Streptomycin and Gentamicin are most vestibulotoxic).

  • Nephrotoxicity: Renal damage (Neomycin, Tobramycin, and Gentamicin are the most potent).

• Interactions: Potentiated by loop diuretics (e.g., Furosemide) and other nephrotoxic agents (Vancomycin, Amphotericin).

Anaesthetics and Muscle Relaxants

• General Anaesthetics:

  • Halothane: Inhalation induction ($0.5\%–4\%$); side effect: severe fatal hepatotoxicity; caution in pharyngeal tumours.

  • Ketamine: Induction/maintenance ($6.5\u201313\,mg/kg$ IM or $1\u20134.5\,mg/kg$ IV); side effects: hallucinations, nightmares, tachycardia, hypertension.

  • Thiopental: Induction ($100\u2013150\,mg$ IV over $10\u201315\,seconds$); child induction ($4\,mg/kg$). Contraindicated in acute porphyria.

• Local Anaesthetics:

  • Bupivacaine: LaboUr/surgery ($2.5\,mg/mL$ solution). Side effects: inebriation, convulsions, bradycardia.

  • Lignocaine: Surface ($2\u20134\%$), nerve block ($max\,200\,mg$, or $500\,mg$ with adrenaline).

• Muscle Relaxants (Neuromuscular Blockers):

  • Depolarizing: Suxamethonium Chloride ($1\,mg/kg$ IV). Action enhanced by Donepezil.

  • Non-depolarizing: Gallamine ($1\u20131.5\,mg/kg$), Vecuronium, Pancuronium Bromide.

  • Contraindications (Suxamethonium): Family history of malignant hyperthermia, hyperkalaemia, major trauma, severe burns.

• Cholinesterase Inhibitors (Anticholinesterases):

  • Function: Reverses non-depolarizing blocks; prolongs polarizing blocks.

  • Agents: Neostigmine ($50\u201370\,micrograms/kg$ IV), Edrophonium (diagnosis of dual block).

  • Overdose Signs: Bronchoconstriction, miosis, excessive sweating, involuntary defecation, bradycardia.

Analgesics and Anti-allergies

• Analgesics/NSAIDs:

  • Aspirin: $300\u2013900\,mg$ every $4\u20136\,hours$. Contraindicated in children under $16\,years$ (Reye’s syndrome), hemophilia, and breast-feeding.

  • Paracetamol: $0.5\u20131\,g$ every $4\u20136\,hours$ ($max\,4\,g$ daily). High doses cause liver damage.

  • NSAIDs (Diclofenac, Ibuprofen, Naproxen): Side effects include GI irritation, bleeding, and renal impairment. They antagonize ACE inhibitors.

• Anti-allergies:

  • Chlorpheniramine: $4\,mg$ every $4\u20136\,hours$. Side effect: drowsiness (avoid driving).

  • Adrenaline: Emergency for acute anaphylaxis/cardiac arrest ($1\,in\,1000$ solution IM).

  • Corticosteroids (Hydrocortisone, Dexamethasone): Used for inflammatory/allergic suppression. Side effects: osteoporosis, diabetes, weight gain, hypertension. Must not be stopped abruptly.

Anti-infectives: Specialized Management

• Amoebicides: Metronidazole and Tinidazole. Must avoid alcohol (disulfiram-like reaction). Oral dose: $800\,mg$ every $8\,hours$ for $5\,days$.

• Anthelmintics:

  • Albendazole/Mebendazole: Single dose ($400\,mg$ and $500\,mg$ respectively). Teratogenic (avoid in 1st trimester).

  • Ivermectin: $150\,mcg/kg$ single dose for filariasis/onchocerciasis.

  • Niclosamide: $2\,g$ single dose for tapeworms (chew on empty stomach).

• Antimalarials:

  • ALU (Artemether $20\,mg$ + Lumefantrine $120\,mg$): $6-dose\,regimen$ over $3\,days$. Safe for multi-drug resistant strains.

  • Quinine: Rapid blood schizonticide. Side effects: Cinchonism (tinnitus, headache, visual disturbances) and hypoglycemia.

  • Chloroquine: Effective but resistance is high. Contraindicated in psoriasis.

• Antischistosomiasis: Praziquantel. Dose: $40\,mg\u201360\,mg/kg$ as a single dose. Contraindicated in ocular cysticercosis.

• Antituberculosis (TB):

  • Regimen: Combination of Rifampicin ($R$), Isoniazid ($H$), Pyrazinamide ($Z$), and Ethambutol ($E$).

  • Phases: Initial ($2\,months$) and Continuation ($4\,months$).

  • Side Effects: Rifampicin (jaundice, red urine), Isoniazid (peripheral neuropathy - treat with Pyridoxine $25\u201350\,mg$), Ethambutol (optic neuritis).

• Antifungals:

  • Amphotericin B: Severe systemic infections. High toxicity (renal).

  • Fluconazole: Vaginal candidiasis ($150\,mg$ single dose).

  • Griseofulvin: Scalp/nail infections. Long treatment ($up\,to\,12\,months$). Reduces effect of oral contraceptives.

Cardiovascular and Hypertension

• Anti-angina:

  • Nitrates (Nitroglycerin): Venodilators. Storage is critical ($6-week$ shelf life after opening). Interact severely with Phosphodiesterase inhibitors.

  • Beta-blockers (Atenolol): Reduce metabolic demand. Must be withdrawn gradually to avoid rebound hypertension.

• Antihypertensives:

  • Standard Classes: Thiazides (Bendroflumethiazide), Loop (Furosemide), ACEI (Captopril), ARB (Losartan), CCB (Nifedipine).

  • Compelling Indications: Stroke (Indapamide + ACEI), Diabetes (ACEI/ARB), Pregnancy (Methyldopa - ACEI/ARB are teratogenic).

• Cardiac Glycosides: Digoxin ($0.125\u20130.25\,mg/day$ loading). Toxicity: Arrhythmias, yellow vision, vomiting.

• Lipid Lowering: Statins (Simvastatin $10\u201380\,mg$). Avoid in liver disease and pregnancy.

Gastro-intestinal and Electrolytes

• Antacids: Weak bases. Magnesium trisilicate ($250\,mg$) causes diarrhea; Aluminium hydroxide causes constipation. They reduce absorption of Tetracyclines.

• Anti-ulcers: H2 blockers (Ranitidine $150\,mg\,BD$) and PPIs (Omeprazole $20\,mg\,daily$). Eradication of H. pylori utilizes PPI + Amoxicillin + Metronidazole for $7\,days$.

• Electrolyte Solutions:

  • Normal Saline ($0.9\%\,NaCl$): Resuscitation. Contraindicated in heart failure/hypertension.

  • Ringers Lactate: Burns, hypovolemic shock. Source of bicarbonate.

  • Dextrose ($50\%$): Emergency for hypoglycemia and status epilepticus.

Endocrine, Insulin, and Contraceptives

• Anti-diabetics:

  • Insulin: Subcutaneous ($0.5\u20131\,units/kg/day$). Risk: Hypoglycemia.

  • Metformin: Risk of Lactic Acidosis. Clearances reduced by Cimetidine.

• Thyroid: Levothyroxine for hypothyroidism. Antagonists (Carbimazole, Lugol’s solution) for hyperthyroidism.

• Contraceptives:

  • COCs: $21\,hormonal\,pills$ + $7\,non-hormonal$.

  • Morning-after pill: Within $72\,hours$ ($100\,mcg\,ethinylestradiol$ + $500\,mcg\,levonorgestrel$).

  • Injectables: Depo Provera ($150\,mg$ every $3\,months$).

Psychiatry and CNS

• Antipsychotics:

  • First-gen (Haloperidol, Chlorpromazine): Risk of Extrapyramidal Side Effects (Tardive dyskinesia).

  • Second-gen (Olanzapine, Risperidone): Weight gain and metabolic side effects.

• Anti-epileptics: Phenobarbital, Phenytoin (teratogenic), Carbamazepine. Do not stop abruptly as it precipitates rebound seizures.

Questions & Discussion

• Session 1 Evaluation: What is a pro-drug? (Answer: A chemical converted to active drug inside the body). What are the main sources of drugs? (Answer: Synthetic, plant, animal, fungal, marine, and genetic engineering).

• Clinical Application: What is the measure of a drug's safety? (Answer: Therapeutic Index - $TI = \frac{TD}{ED}$).

• Antituberculosis: Which drug causes red-green color blindness? (Answer: Ethambutol).

• Antimalarials: What is the timing for the 2nd dose of ALU? (Answer: Strictly after $8\,hours$).

• Immunization: Why is the ID route recommended for rabies vaccination? (Answer: Cost-effective according to WHO).

• Anaesthesia: What effect does using calcium channel blockers with isoflurane have? (Answer: Enhanced hypotensive effect).

• Tocalytics: What are the side effects of magnesium sulphate? (Answer: Respiratory paralysis, hypotension, depressed reflexes).