MONASH UNIVERSITY FACULTY HANDBOOKS

Pharmacy Handbook 1996

Published by Monash University
Clayton, Victoria 3168, Australia

Caution Copyright © Monash University 1996
ISBN 1037-0919

Authorised by Academic Registrar, April 1996


DETAILS OF UNDERGRADUATE STUDIES
Second Year

CONTENTS

  1. Pharmaceutics II
  2. Medicinal chemistry II
  3. Pharmacology I
  4. Pharmaceutical microbiology
  5. Pharmacy practice II

Pharmaceutics II

Dr Denis Morgan

36 lectures, 10 tutorials and 57 hours of practical work

The aim of the subject is to provide students with a detailed knowledge and understanding of the formulation, preparation, and basic pharmacokinetics of certain dose forms.

General objectives

In this teaching program students are expected to develop:

+ understanding of the factors influencing the absorption of drugs; the factors influencing the distribution and disposition of drugs in the body; the principles of drug metabolism and elimination; the production and use of powders, tablets and capsules; the formulation and use of suspensions; the principles underlying the production and use of foams; the formulation, properties and uses of aerosols;

+ abilities in the areas of performing pharmaceutical calculations; the preparation of pharmaceutical dose forms;

+ an appreciation of the need for accuracy and thoroughness in the preparation of pharmaceutical products; the factors which influence the design of pharmaceutical dose forms.

Syllabus

Biopharmaceutics. Structure and properties of membranes, mechanisms of drug transfer across membranes, effects of ionisation state, pH-partition hypothesis. Plasma protein binding of drugs, distribution and disposition of drugs, apparent volume of distribution, factors affecting drug accumulation in tissues, drug half-lives, pharmacokinetic modelling.

Tablets and powders. Particle size and distribution, particle size determination, flow properties. Mixing and mixers, granulation, tablets, manufacturing processes, special tablets, weight, content and physical uniformity, excipient interaction, in vitro disintegration and dissolution tests and requirements.

Disperse systems. Colloidal systems, kinetic, optical, electrical properties of solid-liquid dispersions, electrical and steric stabilisation of solid-liquid dispersions, nucleation and ageing.

Foams. Stability of foams, choice of surfactant, antifoaming agents.

Aerosols. Liquified and compressed aerosol propellants; two-phase aerosols; three-phase aerosols; aerosol formulation; aerosol stability; non-pressure pack aerosols, atomisers, packaging, containers.

Capsules. Hard and soft gelatin capsule walls, stability of macrocapsules, in vitro testing, in vitro/in vivo correlations. Manufacture of different types of microcapsules. Advantages and disadvantages of capsules.

Practical

Nineteen 3-hour practical sessions

Practical classes are designed to provide experience in the preparation of certain pharmaceutical dose forms and reinforcement of the principles of pharmaceutics covered in the lecture series.

Textbooks

Recommended texts

Reference books

Journal references

Assessment

Subject assessment will reflect the learning objectives outlined above. Methods of assessment will include:

+ Mid-year examination (June) (1 hour): 20%

+ Practical work: 10%

+ End-of-year examination (2.5 hours): 70%


Medicinal chemistry II

Dr Manuel Needleman

76 lectures, 13 tutorials and 66 hours of practical work. (An additional 6 hours of practical work is taught in conjunction with `Pharmacy practice II')

The aim of the subject is to build on the basic physical and organic chemistry taught in `Medicinal chemistry I', and to apply it to aspects of chemistry relevant to pharmacy.

General objectives

In this teaching program students are expected to develop:

+ understanding of the nomenclature and meaning of terms used to describe the three-dimensional structures (stereochemistry) of drug molecules; spectroscopic methods used in the analysis and structural determination of drugs; the theory and application of thermodynamics; the structural and mechanistic bases for the action of the autonomic neurotransmitters and related agents; factors affecting the physicochemical properties and reactivity of drugs based on aromatic frameworks; factors influencing the three-dimensional structures of proteins; the partition of substances between various phases as applied to both the analysis of drugs and their transport in the body; principles of electrochemistry applied in the analysis of drugs; the chemical principles underlying selected diagnostic aids relevant to pharmacy; the application of radioisotopes in pharmacy; the chemical principles relevant to the activity of selected antiviral compounds;

+ abilities in the areas of the measurement and recording of data relevant to the understanding of drug structure and reactivity; numerical calculations based on experimental or theoretical data; report writing or oral presentations based on the results of experimental work;

+ an appreciation of the general chemical principles of enzymatic catalysis; the importance of chemical reactions in determining drug transport and metabolism; the application of the principles of medicinal chemistry to the search for selectivity in therapeutic agents.

Syllabus

Stereochemistry. Molecular geometry, symmetry, isomerism, configuration, conformation, conformational analysis; the use of conformationally restricted analogues in determining receptor structure and the shape of active drugs; preparation of homochiral compounds, implications of stereo-chemistry for drug design and delivery.

Spectroscopy. NMR, IR, UV spectroscopy, mass spectrometry - underlying processes and applications in the pharmaceutical industry; interpretation of spectra; identification of compounds using spectroscopic techniques.

Aromatic chemistry. Differences between aromatic and aliphatic compounds; resonance theory and stabilisation, acid/base properties; linear free-energy relationships, Hammett plots, sigma and rho values, effect of substituents on drug stability; steric effects; structure-activity relationships in local anaesthetics; heterocyclic aromatic compounds - nomenclature and properties, role of heterocyclic compounds in biological systems.

Receptor structure. Chemistry of the peptide bond; factors affecting primary, secondary and tertiary structure of proteins; functional groups involved in binding of drugs to protein; thermodynamics of drug binding, stereochemistry, drug binding and the three-dimensional structure of proteins; techniques involved in determining protein structure.

Chemistry of enzymes. Catalysis of reactions, particularly ester and amide hydrolysis; pH rate profiles; transition-state stabilisation, general acid and general base catalysis, nucleophilic catalysis, metal-ion catalysis, and their role in reactions catalysed by enzymes; pyridoxal phosphate dependent enzymes; enzymes as targets for drugs.

Electrochemistry. Activity, ionic strength, junction potentials; Debye-Huckel theory, Ferguson principle for drug equi-action; ion-selective electrodes, pH measurements, amperometric electrodes, and their role in pharmacy/clinical chemistry; composition of pharmaceutical glasses; biological cell potentials.

Partition and chromatography. Liquid-liquid distribution, extraction efficiency; principles underlying HPLC, gas, gas-liquid, partition and thin-layer chromatography; relationship between pH, drug structure, dissolution medium and drug distribution, electrophoresis.

Diagnostic aids. Sampling techniques, clinical stick devices, tests for nitrate, pH, glucose, protein and cholesterol, and their clinical significance; tests for enzymes and lipoproteins; drug interferences in clinical tests.

Radiopharmacy. Types and units of radiation, maximum doses, background radiation; protection required for different forms of radiation; technetium generators and production of isotopes of pharmaceutical interest; preparation of radiopharmaceutical dose forms; X-ray and radio-isotopic imaging; the use of isotopes in sterilisation.

Antivirals. Targets for antiviral therapy and their relationship to structural features of antiviral drugs; structure, mode of action and uses of acyclovir, azidothymidine and ribavirin.

Autonomic nervous system agents. Cholinergic system: muscarinic and nicotinic receptors; structure and activity of acetylcholine and acetylcholinesterase; reversible and irreversible inhibition of acetylcholinesterase; treatment of anticholinesterase poisoning; cholinergic blocking agents and their use as muscle relaxants; degradation of muscle relaxants. Adrenergic system: structure and function of noradrenaline; inactivation of noradrenaline by monoamine oxidase and catecholamine-0-methyl transferase; a- and b-adrenoceptors; chemistry of a-adrenergic antagonists; chemistry and selectivity of b-active agents.

Thermodynamics. Reversible, irreversible and spontaneous processes; disorder, entropy, free energy; equilibrium constants; entropy and enthalpy-driven processes; coupled reactions; measurement of DG; calculation of free-energy changes, van't Hoff plots; applications of thermodynamic concepts to biochemical reactions, conformational equilibria, phase transitions, and drug-receptor interactions.

QSAR. The value of non-traditional approaches to drug design; Hammett, Hansch and Taft constants; use of pKa, partition and hydrolysis data to predict drug stability; multiparameter and non-mathematical approaches.

Consumer products chemistry. Swimming pool maintenance, antiseptics and disinfectants, pesticides and herbicides, polymeric materials in medicine and pharmacy, the photographic process.

Practical

66 hours of practical work

Practical classes are designed to reinforce chemical principles taught in the lecture series and to illustrate the analytical bases of quality assurance for pharmaceutical products. Emphasis is placed on technique and general methods. Performance in laboratory classes is taken into account in assessing students' results in this subject.

Textbooks

Recommended texts

Reference books

Assessment

Subject assessment will reflect the learning objectives outlined above. Methods of assessment will include :

+ Mid-year examination (June) (2 hours): 25%

+ Practical work: 10%

+ End-of-year examination (3 hours): 65%


Pharmacology I

Dr Ian Coupar

The overall subject consists of two components (i) a section dealing with systematic pharmacology and (ii) a basic course in biochemistry. The principal aim of the pharmacology course is to provide students with a knowledge of systematic pharmacology based on drug groups and to extend physiological and pathophysiological concepts in relation to the uses of drugs, their mechanisms of action and their side effects. The aim of the biochemistry course is to provide students with an understanding of biochemistry and of biochemical concepts as a base for later work in other subjects within the pharmaceutical sciences.

General objectives

In this teaching program students are expected to develop:

+ understanding of principles of receptor differentiation, drug-receptor interactions and receptor transduction mechanisms; pharmacological mechanisms by which drugs of various classes may alter biochemical, physiological or pathophysiological parameters to produce therapeutic or unwanted effects; the basic biochemistry of body constituents, metabolism, regulatory mechanisms and molecular biology;

+ abilities in the areas of observation and measurement of pharmacological and biochemical processes; assessment and integration of pharmacological information as it relates to wanted and unwanted effects produced by drugs;

+ an appreciation of integrated physiological functions, pathophysiological sequelae and pharmacological perturbations as they affect bodily functions; the differing pharmacological approaches available for the treatment of individual diseases; the pharmacists' role in optimising drug therapy.

Syllabus

Pharmacology

78 lectures, 10 tutorials and 54 hours of practical work

Pharmacology of neuroeffector systems. Humoral transmission. Historical background. Synthesis, storage, release, metabolism and termination of action of acetylcholine, noradrenaline and other transmitters. Modulation of transmitter release. Pharmacological actions of acetylcholine, noradrenaline and other neurotransmitters. Drugs which mimic and antagonise the muscarinic and nicotinic actions of acetylcholine. Skeletal neuromuscular function, myasthenia gravis, competitive and depolarising blocking drugs. Agonists and antagonists at a- and b- adrenoceptors. Drugs affecting the synthesis, storage, release and inactivation of neurotransmitters. The role of calcium in transmission and effector organ function. Membrane stabilisers and labilisers. Local anaesthetics. Neurotoxins and muscle toxins.

Autacoids. Synthesis, storage, release, metabolism and pharmacological actions of substances such as histamine, 5-hydroxytryptamine, kinins, prostaglandins and various peptides. Substances released during anaphylaxis. Antigen-antibody reactions as they affect allergic and inflammatory states. Drugs used in the treatment of allergies, acute inflammatory conditions and collagen diseases.

Drug-receptor interaction. Receptors. Theories of drug action. Kinetics of drug-receptor interactions. Agonists, antagonists, drug-receptor binding studies, receptor-response coupling, second messenger systems. Ion channels and their regulation.

Cardiovascular physiology and pharmacology. Cardiac output, its modulation, measurement and regulation. Circulation. Haemodynamics, pressures and flow in arteries, capillaries and veins, the systemic circulation, nervous and humoral control, auto-regulation. Blood flow through special regions, the pulmonary, coronary, splanchnic, muscle and skin circulation. Integrative analysis of the circulation. Hypertension and its consequences. Antihypertensive drugs, mechanisms of action, side effects and clinical uses.

Renal physiology and pharmacology. Ultrastructure of the kidney. The formation of urine. Active transport systems in the nephron, competition, saturation and inhibition. Regulation of acid-base and water balance. Diuretics, mechanisms of action. Mobilisation of oedema fluid. Treatment of diuretic-induced hypokalemia. Aldosterone and the renin-angiotensin system, spironolactone. Renal disease.

The central nervous system. Anatomy of the human brain, spinal cord and cranial nerves. Blood supply, cerebrospinal fluid. Location of sensory, motor and association areas. Somatic and autonomic reflex arcs. CNS transmitters and their function. Sensory pathways with particular relevance to pain. Pyramidal and extrapyramidal motor systems. Control of spasticity. Medullary and hypothalamic function. Basic pharmacology of morphine and opioids, benzodiazepines, phenothiazines, central muscle relaxants, antidepressants, hallucinogens and methylxanthines.

Practical

Practical classes are designed to provide experience through in vivo and in vitro experiments, seminars and discussion groups to illustrate and extend principles discussed in the lecture course.

Recommended texts

Reference books

Biochemistry

Dr Helen Irving

25 lectures, 4 tutorials and 15 hours of practical work

Biomolecules - structure and molecular properties

Water and bioenergetics. Physical and chemical properties, weak interactions, ionisation of water. Weak acids and bases, buffers. Free energy change, activation energy, equilibrium states. Coupled reactions, high energy compounds. Biological oxidation-reduction reactions, electron carriers.

Amino acids, peptides and proteins. Amino acid stereoisomerisation, amphoteric nature, classification by R groups, isoelectric point, pK1, pK2, pKR. Peptide bonds, peptides as active biological molecules. Proteins classified by different biological functions, polymorphisms. Covalent structure determined by amino acid composition, disulphide bonds. 3-D structure of proteins - secondary, tertiary and quaternary, a-helix, b-conformation, b-turns. Cooperativity. Protein denaturation/renaturation. Enzyme kinetics (role of enzymes and Michaelis-Menten kinetics). Mechanisms of enzyme action, inhibitors, enzyme regulation (allosteric, covalent, zymogens, isoenzymes), cofactors.

Carbohydrates. Monosaccharides (aldoses/ketones), stereo-isomerisation, ring structures, a/b configuration, reducing sugars. Derivatives, disaccharides, polysaccharides, peptideoglycans, glycosaminoglycans (hyaluronate), proteoglycans, glycoproteins, glycolipids.

Lipids and membranes. Fatty acids (saturated/unsaturated), triacylglycerols, waxes. Membrane lipids - glycerophospholipids, sphingolipids, sterols. Specific biological functions - steroid hormones, PIP2 hydrolysis, eicosanoids (prostaglandins, tromboxane, leukotrienes), fat soluble vitamins. Membrane fluidity and asymmetry (lipids and proteins). Peripheral and integral proteins.

Nucleotides/nucleic acids. Nucleotide structure, carry chemical energy, components of co-factors, monomers of nucleic acids. Nucleic acid structure. Phosphodiester bonds, sugar-phosphate backbone. DNA-strand complementarity, antiparallel strands, H-bonding between bases. Chromosome structure and DNA organisation. RNA single strand, irregular secondary structure. Palindromes - hairpins and cruciforms

Metabolism and information pathways

Oxidative phosphorylation and citric acid cycle. Mitochondrial structure, electron transfer chain, chemiosmotic theory, ATP production. Oxidation of acetylCoA to CO2 and production of reduced electron carriers, central role in metabolism, source of metabolic precursors, regulation within cycle.

Carbohydrate and fat metabolism. Glycolysis, fate of pyruvate - anaerobic and aerobic glycolysis; ATP production, regulation. Glycogen metabolism, pentose phosphate pathway, gluconeogenesis. Lipoproteins and role in lipid transport. -oxidation of fatty acids, ketogenesis, ATP and water production, fatty acid synthesis, cholesterol, phospholipids, hormonal influences and essential fatty acids. Hormonal regulation.

Nitrogen metabolism. Essential amino acids, transamination, role of alanine, glutamine, glutamate, deamination, urea cycle. Fate of carbon skeletons, sources of substrates for nutritionally non-essential amino acids, precursors of biologically active amines. Role of creatine. Nucleotide synthesis, degradation and regulation.

Information transfer. Gene structure, promoters, exons and introns. DNA replication, DNA repair, DNA recombination. RNA structure - ribosomal RNA, transfer RNA, messenger RNA. Transcription, primary transcripts, splicing, ribozyme. Ribosome structure. Translation. Polypeptide synthesis, post-translational modifications, protein targeting. Regulation of gene expression.

Molecular biology. Principles and techniques involved in recombinant DNA technology. Roles in diagnostics and medicine.

Practical

Practical classes are designed to provide experience through experiments and discussion groups to illustrate and extend principles discussed in the lecture course.

Recommended texts

Reference books

Assessment

Subject assessment will reflect the learning objectives outlined above. Methods of assessment will include:

+ Mid-year examination (June) (2 hours): 20%

+ Practical work: 15%

+ End-of-year examination (3 hours): 65%


Pharmaceutical microbiology

Dr Ian Griffith

78 lectures, 13 tutorials and 60 hours of practical work

The aim of the subject is to provide students with a detailed knowledge and understanding of the pharmaceutical aspects of microbiology, immunology, parasitology, general pathology and basic epidemiology.

General objectives

In this teaching program students are expected to develop:

+ understanding of the structure and classification of microorganisms and parasites of medical importance and the diseases caused by them; the techniques used to propagate and selectively culture microorganisms; the basic principles of microbial genetics, the mechanisms of gene transfer and the essential features of recombinant DNA technology; the structure and function of the immune system and its role in disease processes; the nature and uses of antiseptics, disinfectants and preservatives; sterilisation methods and contamination control; the principles of epidemiology; the nature and uses of anti-microbial agents;

+ abilities in the areas of handling and culturing microorganisms; conducting certain diagnostic tests; preventing contamination of pharmaceutical products;

+ an appreciation of the need for care, accuracy and thoroughness in the manufacture of sterile pharmaceutical products; the factors which influence the spread, course and control of diseases caused by microorganisms and parasites.

Syllabus

Introductory microbiology. Historical development: microorganisms as a cause of disease. Occurrence and role of microbes in the biosphere. Principles of classification. Basic morphological and physiological features of the main groups of microorganisms.

Host-parasite relationships. Nature of pathogens, parasites, commensals. Symbiosis. Transmissible disease, virulence, pathogenicity, invasiveness, infectivity, toxins, pyrogens. Barriers to infection: skin and mucosa, body secretions, resident microbial flora. Innate immunity: role of inflammation, complement, reticuloendothelial system.

Virology. Structure of viruses, methods of propagation, pathogenic mechanisms. Classification of viruses. Viral diseases of medical importance. Antiviral agents.

Bacteriology. Comparison of subcellular structures of the prokaryotic and eukaryotic cell. Summary treatment of microbial nutrition and energy production, and catabolic and anabolic processes. Synthesis of murein. Cell division and growth. Spore formation and germination.

Elementary microbial genetics. Population dynamics. Variation and adaptation. Expression and detection of mutation. Transfer of genetic information; conjugation, transformation, transduction. Extrachromosomal elements; lysogeny. Introduction to recombinant DNA technology.

Mycology. Classification of fungi. Medical mycology. Pathological reactions to fungi. Antifungal agents; selective toxicity. Fungi useful to humanity.

Parasitology. Parasites of medical importance; antiprotozoal agents and anthelminthics.

Infectious diseases. Principles of isolation and identification of infectious agents. Infections of the respiratory, gastro-intestinal and genito-urinary tracts; of the skin and eye; systemic infections. Important pathogens of domestic animals and plants. More detailed treatment of some problem pathogens.

Immunology. Active and passive immunity. Structural components of the immune system: bone marrow, thymus, lymph nodes, spleen, peripheral lymphoid tissue. Acquired specific immunity: humoral and cellular. Cytokines. Hypersensitivity reactions. Vaccines and blood products. The immunology of tissue and organ grafts, autoimmune disease. Cancer immunology. Immunological tests. Monoclonal antibodies.

Antisepsis. Nature of, and principles governing, the mechanism of action and use of antiseptics, disinfectants and preservatives.

Sterilisation. Principles and practice of sterilisation (filtration, heat, chemical, radiation), aseptic dispensing and sterility assurance. Control of particle and pyrogen levels.

Contamination control. Microbial contamination of the workplace: industrial, hospital and home environments. Aseptic techniques, monitoring contamination, clean room design and function.

Anti-microbial agents. Selective toxicity, spectrum and classification of antimicrobial agents. Concept of rational chemotherapy vis a vis identity of pathogen, acute/chronic/recurrent infections, site of infection, resistance, adverse drug reactions, and laboratory involvement. Roles of best-guess therapy, antibiotic prophylaxis, combined therapy and supportive treatment.

Epidemiology. Reservoirs of infection: means of transmission, carrier state, latent infections, alternate hosts, vectors. Epidemics and zoonoses. Methods of control. Quarantine: travel regulations.

Practical

Fifteen 3-hour and 1-hour practical classes

Practical classes are designed to provide experience of the principles taught in the lecture course and teach the skills required for the preparation of sterile pharmaceutical products and the handling and culture of microorganisms.

Textbooks

Recommended texts

Reference books

Assessment

Subject assessment will reflect the learning objectives outlined above. Methods of assessment will include:

+ Mid-year examination (June) (2 hours): 20%

+ Practical work: 15%

+ End-of-year examination (3 hours): 65%


Pharmacy practice II

Mr Arthur Pappas

13 lectures, 8 tutorials and 27 hours of practical work (an additional 6 hours of practical work is taught in conjunction with `Medicinal chemistry II')

This subject follows on from `Pharmacy practice I' but concentrates more on the patients and their environment with particular attention spent on communications skill between pharmacist and patient. It also introduces the concept of problem solving from the point of view of pharmacist/patient/provider interactions and the role of the pharmacist in intervening in the therapeutic situation. Accordingly, the major aims of this subject are to provide students with a knowledge and understanding of the principles of counselling, illness behaviour, compliance and problem solving situations in the therapeutic environment.

General objectives

In this teaching program students are expected to develop:

+ understanding of the methods of effective communication with patients and providers; the problems of medication non-compliance and means of overcoming them; patient education in the broad sense of the pharmacist being a health provider; illness behaviour, normal and abnormal; the placebo effect and how it fits into pharmacy practice; the concepts of self role and the sick role;

+ abilities in the areas of written and oral communication; counselling; problem-solving in clinically oriented situations; the recording of prescriptions and the use of patient profiles through the use of pharmacy computers;

+ an appreciation of the relationships existing between drugs, medicines, patients and society; problem-solving in clinically oriented situations and an awareness of the pharmacist's role in therapeutic intervention.

Syllabus

Counselling and communications. Communication skills, professional/patient communication, professional/professional communication. Listening skills, barriers to communication, rapport, empathy, interviewing skills. Advanced counselling skills.

Patient compliance. The problem of noncompliance to health oriented regimens. Statistics and reasons for non-compliance to therapeutic regimens. The patient, the health provider, the social milieu, the therapeutic regimen, the health belief system. Methods of improving compliance.

Patient education. Definition of health education, methods of health education, improving compliance. Practical recommendations to improve comprehension, recall and compliance. The principles of brevity, organisation, primacy, readability, repetition and specificity.

Social pharmacy. The influence of others on behaviour. Categorisation and its dangers in the patient-provider situation. Groups and behaviour, obedience and behaviour. Person perception, behaviour and the patient.

Illness behaviour. What is illness behaviour? Parson's concept of role; the sick role; the well role. Social class and the sick role. Mechanic's Help Seeking Process. Suchman's five stages of the illness experience.

The placebo. Historical perspective, definitions, incidence, mechanisms, practitioner behaviour and placebo effect, patient characteristics and placebo effect, patient-practitioner communication and placebo effect, situational determinants of placebo effects, social norms and the placebo effect, generalisability and the placebo effect, the placebo as a methodological tool, alternative therapies and the placebo effect.

Practical

Practical classes are designed to provide experience in dispensing, communication and counselling, oral presentations (following on from `Pharmacy practice I'), prescription-solving situations and computers in pharmacy. In addition, sessions on aspects of pharmaceutical chemistry related to the practice of pharmacy and a pharmaceutical industrial visit will be organised.

Textbooks

Recommended texts

Reference books

Journal references

Assessment

Subject assessment will reflect the learning objectives outlined above. Methods of assessment will include:

+ Practical work and counselling assignment: 10%

+ Open book practical examination (October) (3 hours): 90%

The theoretical aspects of the lectures on social pharmacy and illness behaviour will be examined in the `Pharmacy practice III' annual examination

Dispensing: Students are required to reach a satisfactory level of competence in dispensing by the end of the course


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