Maharashtra University of Health Sciences Courses

D.M. (Clinical Pharmacology)

Course Syllabus

Basic principles of clinical pharmacology:

• 1. Introduction:
  • The clinical Pharmacologist
    • Definition
    • Role of the clinical Pharmacologist in institutions / National / International setting.
    • Centers for clinical pharmacology – training / research.
      • Definition and scope of clinical Pharmacology
      • History and development of clinical Pharmacology
      • General principles in clinical Pharmacology
      • Aims of a clinical trial
      • Problems in clinical trials
• 2. Principles of drug actions; molecular mechanisms of drug action including:
  • Receptor theory and targets of drug action
  • Agonists and types of antagonism
  • Cellular basis of quantitative pharmacology
  • Principles of structure – activity and dose –response relationships
  • Mechanism by which drugs modulate signal transduction pathways
  • nteractions between drugs and ion channels
  •  Modulation of gene expression by drugs
  • Receptor – independent mechanisms of drug action e. g. inactivation of enzymes, interactions with structural components of the cell
  • Active and passive mechanisms by which drugs cross cell membranes
  • Molecular basis of inadequate or excessive drug actions including drug interactions
  • Mechanisms of termination of drug actions (e.g. uptake into cells; degradation)
• 3. Pharmacokinetics and Pharmacodynamic
  • Kinetics of absorption, distribution, biotransformation and excretion of drugs – use of
  • radioisotopes
  • Studies on bioavailability / bioequivalence of drugs new delivery system
  • Interaction between the drug and other drugs, physiological systems, disease and environment.
  • Role of a drug assay centre
  • Studies with single and multiple doses and multiple drug combination
  • Pharmacokinetic parameters, mathematical models single and multiple compartments
  • Molecular basis of drug action
  • Mechanism of drug action
  • Dose response relationship and effective therapeutic dose
• 4. Principles of Drug Therapy:
  • A. Principles of drug administration, drug action, and pharmacokinetics
    • Routes of administration
    • Mechanisms of absorption, distribution, metabolism and excretion of drugs
    • Desired and undesired actions of drugs
    • Principles of drug interactions and adverse drug reactions; emphasis on the global actions of the major drug groups in the whole body- multiple actions of single agents
    • Drug allergy – mechanisms and common examples of four types of allergic response; common clinical presentations and their management
    • Monitoring of plasma / tissue concentrations of drugs- when are these necessary; limitations
  • B. Variability in human response to drugs and influence of disease processes
    • Drug handling and prescribing in the elderly, infants and children: altered pathophysiology special problems with polypharmacy
    • Drug usage in pregnancy and in breast-feeding women: special concerns for drug toxicity, drugs of choice in common diseased
    • Prescribing for patients with renal or hepatic disease: altered pharmacokinetics and dynamics; drugs to be avoided; drug induced nephrotoxicity and hepatotoxicity
    • Influence of other concurrent diseases- e.g. asthma, gout, diabetes, hypertension, porphyria, hypercholesterolaemia, heart failure- on prescribing; and precipitation of the conditions by drugs
    • Pharmacogenetics: implications for altered or unusual drug handling, drug efficacy or toxicity, common and dangerous clinical examples, gene therapy
  • C. Knowledge of adverse drug reactions and interactions:
    • Epidemiology; mechanisms; pharmacologic and non-pharmacologic
    • How to recognize, how to avoid
    • Voluntary reporting systems, post- marketing surveillance
  • D. Elements of drug abuse, toxicology and poisoning
    • Overdose and addiction problems; epidemiology. recognition
    • Clinical toxicology, nature of toxic response
    • Food toxicology, additives, contaminants and components
    • Forensic aspects of poisoning
    • Management of common poisons (e.g. salicylate, paracetamol…)
• 5. Drug usage in special clinical condition:
  • Disease states
  • Renal failure
  • Hepatic failure
  • Cardiac failure
  • Different physiological states: neonatal, paediatric, geriatric, and pregnancy subjects.
• 6. Drug monitoring:
  • Monitoring drug therapy: How, why and when?
  • Drug surveillance, including post marketing drug
  • ADR monitoring.

Biostatistics

Statistical principles underlying clinical trials, data handling and role of biostatistician

• Sample size calculation
• Types of variables
• Type 1 error and type 11 errors
• Parametric and nonparametric tests
• Clinical significance versus statistical significance
• Correlation and regression analysis
• Probability
• Confidence intervals
• Intention to treat analysis
• Randomization

Methodologies for drug development, Drug evaluation and Clinical trials

• Drug Development:
  • Rationale/Need for a new drug
  • Source of new drugs and compounds for screening as a potential drug
  • General Pharmacological and systemic screening – preclinical / experimental
  • Toxicity studies – Teratology, carcinogenicity, mutagenicity
  • Role of government institutes, pharmacological housed, university centers of excellence and the government in drug development collaborative effort
• Assessment of Preclinical data:-
  • Animal Pharmacology- effectiveness and safety
  • ssessment of pre clinical data for adequacy of toxicity and efficacy studies as per
  • new drug development regulations for clinical evaluation
  • Pharmacokinetic studies in animals
  • Selection of initial human dose from animal data
  • Assessment of cost, benefit and risk ratio
  • Extrapolation of animal data to clinical situation
• Evaluation of drug actions in man
  • ICH and GCP guidelines, IRB, Ethics committee
  • Emergence of new drugs, drug design and discovery
  • Legislatory control of new drugs
  • The drug regulatory authorities’ point of view.
  • Pharmacological principles of therapeutics and systemic clinical pharmacology
  • Pharmacological basis of drug therapy of common and important diseases.
  • Clinical evaluation of difference classes of drugs. special problems and pitfalls and protocol designing of antianginal, antihypertensive, antiarrhythmic , diuretic, antiepileptic, hypnotic, analgesic, anti-inflammatory, neuropsychiatric disorders, antiasthmatic, drugs for peptic ulcer , anti- diabetic , antifertility , anti-cancer , chemotherapeutic agents , antiemetic , antiprotozoal , vaccines

Objectives

• Ability to assess critically commercial claims for established and new drugs
• Understanding of the pharmaceutical industry’s achievements and educational role
• Developing Clinical Trial Designs
• Developing and writing Clinical Protocols
• Planning special types of clinical trials
• Planning and conducting a single clinical trial
• Nonmathematical approach to statistics and data processing
• Fundamental principles, considerations, and techniques in the Interpretation of Clinical Data
• Interpretation of Safety and Efficacy Data
• Interpretation of Data from Special Trials, Modalities and Populations
• Issues and Problems of Clinical Data Interpretation
• Publishing Clinical Data and Evaluating Published Literature
• Planning and Conducting Multiple Clinical Trials
• Management of Multiple Clinical Trials
• Types of clinical studies envisaged:
  • Retrospective Vs Prospective trials
  • Single center Vs Multicentre trials
  • Fixed dosage Vs variable dosage
• Protocol designing: Broad principles and the role of industry in protocol designing
• Phases of clinical trials:
• Phase I, II, III and IV.
• Pre clinical, clinical requisites for Phase I, II, III and IV trials and their clinical significance
• Multicentric trials:
  • The placebo
  • Randomization
  • Withdrawals and dropouts of a study subjects
  • Washout period

International implications:

• Acceptance of data obtained in one country by the drug regulatory agency of another country for e of drug in another country (racial/genetic/nutritional differences)
• Drug regulations of India and some other countries
• Role of World Health Organization and the International Drug MonitoringCenter

Special features of clinical trials with plant products

• Ethical aspects –preclinical requisites
• Preparation and use of plant products
• Advantages and disadvantages
• Special problems in standardization of samples, selection of control etc.
• Collaboration with practitioners of alternative systems medicine
• General problems in organization and carrying out clinical trials

Ethical and legal aspects of clinical trials

• Ethical aspect of carrying out a clinical trial
• Formation of an ethical committee and its approval for clinical evaluation
• Legal aspects of carrying out clinical trials
• Informed consent of subject – written/verbal statement
• Subjects for clinical trials
• Investigator
• ther aspects
  • Drugs and the fetus
  • Payment to volunteers
  • Compensation to subjects for injury during participation in drugs trials
  • Insurance to investigator
  • Administration of drugs by non medical personnel
  • Assessment of risk and benefit
  • Historical perspectives in human experimentation experiments on prisoners at concentration camps, Helsinki Declaration, Nuremberg code.

Systemic Clinical Pharmacology and Therapeutics and Recent Advances

• Using drugs effectively:
  • Choice of therapy
  • When not to prescribe
  • Identification of therapeutic problem lists
  • Preparation of planned therapeutic regimens
  • Drug use in multiple illnesses
  • Combination therapies, tailored therapy
  • Reading and understanding prescriptions
  • Instruction in prescribing techniques
  • Awareness of iatrogenic disease
  • Principles of using approved names vs. brand names
  • Non – Text book information sources needed for effective uses of drugs e.g.
• National Formulary, Drug and Therapeutics Bulletin, Prescriber’s Journal
  • Communication with patients about their medication
  • Assessment of compliance problems and methods of enhancing compliance
  • Relationship between compliance and understanding
  • Essential drugs
  • Rational drug use
  • Evidence based medicine
  • Pharmacoeconomics
• Drugs and the autonomic nervous system:
  • Directly and indirectly acting cholinomimetics
  • Muscarinic and nicotinic receptor blockers
  • a/b – adrenoceptor agonist /antagonists
  • indirectly acting sympathomimetics
  • investigation of drug response in man – the action of beta – blockade in volunteers
  • the actions of nitrates and nicotine in man
  • drugs acting on the human eye - anticholinergic , cholinergic,sympathomimetic
• Drugscting primarily on the central nervous system
  • Antidressants
  • Anti- parkinsonian agents
  • Anxiolytics
  • Sedatives/hypnotics
  • Anti-convulsants
  • Anti-spastics
  • CNS stimulants
  • Appetite suppressants
  • Drugs of dependence, alcohol
  • Analgesics and pain control
  • Drugs for migraine
  • Neuroleptics
  • Drugs in affective disorders
  • Alzheimer’s disease
• Drugs and the cardiovascular system and blood:
  • Anti-hypertensives
  • Anti- anginals
  • Drugs used in heart failure and shock
  • Anti- dysrrhythmics
  • Diuretics
  • Lipid lowering drugs
• Drugs acting on the kidney:
  • Diuretics
  • Anti- diuretics
  • Drugs affecting urine pH
  • Uricosuric agents
• Drugs acting on the respiratory system:
  • Bronchodilators
  • Inhibitors of mast cell mediator release
  • Anti- inflammatory steroids
• Drugs for infection:
  • Antibacterial
  • Antiviral-including antiretrovirals - principles of vaccination
  • Anti malarial
  • Antifungal
  • Antiprotozoal and antihelminthic
• Cancer chemotherapy and immunosuppressive drugs
  • Neoplastic cell burden and principles of therapy
  • Cell cycle specific and non specific agents
  • Alkylating agents, antimetabolites, plant alkaloids, antibiotics, cisplatin, nitrosureas, hormonal agents
• Drugs affecting the GI tract
  • Autacoids
  • Ulcer healing drugs
  • Anti-spasmodic
  • Anti- diarrhoeal drugs
  • Laxatives
  • Motility stimulants
  • Anti- inflammatory
  • Anti- emetic
• Drugs and the blood
  • Drugs for anaemias
  • Anti- platelet agents
  • Anti- coagulants and fibrinolytic agents
• Drugs and endocrine systems (diabetes, thyroid disease, adrenal disorders, hypothalamus and pituitary disorders, bone metabolism)
  • Adrenocortical steroids, their analogues and drugs affecting their release
  • Thyroid and anti- thyroid drugs
  • Growth hormone and drugs affecting its release
  • Drugs affecting blood sugar
  • Drugs affecting Ca2+ homeostasis
  • Vasopressin and its analogues
• Drugs and reproduction
  • Gonadal steroids, their analogues and drugs affecting their release
  • Fertility drugs
  • Contraceptive drugs
  • Oxytoxics and tocolytics
  • Drugs suppressing lactation
• Autacoids and anti- inflammatory drugs
  • Aspirin, cyclo-oxygenase inhibitors, non-steroidal anti- inflammatory and disease modifying drugs
  • Eicosanoids, prostaglandins, thromboxane, leucotrienes and antagonists
  • Corticosteroids
  • Cytokines and anti- cytokines
  • Histamine, serotonin, kinins, platelet activating factor and antagonists
• Management of pain
  • Principles of pain relief
  • Analgesics – opioid and non-opioid
  • Techniques of analgesic administration
• Miscellaneous
  • Pre-anaesthetic medication
  • General anaesthetics, local anaesthetics
  • Skeletal muscle relaxants
  • Surgical prophylaxis

Practicals

• Pharmacodynamic exercises:
  • Central Nervous System
  • Cardiovascular system
  • Respiratory system