CONTENT OUTLINE AND LEARNING TASK

Pharmacology is defined as the study of substances that interact with living systems through chemical processes, especially by binding to regulatory molecules and activating or inhibiting normal body processes. These substances commonly known as drugs. Drugs might produce more than one effect, beneficial therapeutic effects or, in the other hand, undesirable effects on living systems adverse or toxic effects. Pharmacology refers to a very broad area of study. Pharmacokinetics and pharmacodynamics are two basic subject area of pharmacology. There are several sources of drugs, including plant, animal, microorganism and chemical synthesis. Drug candidates undergo several tests for screening their pharmacologic profile and activity as well as their selectivity. The safety and efficacy of drugs must be defined before they can be marketed; therefore some preclinical pharmacologic and toxicity testing including invitro and animal studies, as well as clinical study phase 1 – 4 must be performed. Many factors affecting the action of drug in our body including the route of drug administration which is related to drug preparation or drug form, age, sex, weight, genetic variation, the presence of other disease or interaction with other drug drug interaction. Drug interaction refers to the effects that occur when the actions of one drug are affected by another drug. Drug interaction might affect the pharmacokinetic or pharmacodynamics process of drug that subsequently affects the drug action or effect. Related to the regulation of drug distribution in Indonesia, Indonesian Ministry of Health has already classified marketed drugs into five groups of drugs free drug, limited free drug, hard drug, psychotropic drug and narcotics. Generally, in the world, drugs are divided into prescription and nonprescription drugs over the counter drugs OTC drugs. Drugs can also be classified into patent drugs, generic drugs and branded generic drugs. Vignete A 25 years old woman came to public health center PHC complaining fever since 3 days ago. Patients also complained sore throat, cough, cold and headache. After doing anamnesis and physical examination, doctor decided to prescribe Demacolin® and Amoxsan® tablet. Learning Task 1 1. What are the categories of those two drugs? 2. What are the advantages and disadvantages of this route of administration? 3. What processes undergone by such oral drug in our body? Learning Task 2 A few hours later, patient came back to PHC complaining rash and itchy in her whole body. 1. What condition possibly happened to this patient? 2. What information should be given to the patient related to her condition? Udayana University Faculty of Medicine, DME, 2016 10

11. CONTENT OUTLINE AND LEARNING TASK

Lecture 1-2. Introduction to Pharmacology, Drug Development The aim of studying pharmacokinetic is to understand the term that commonly used in pharmacology and the fate of drug in the body. The action of the body to drug is called pharmacokinetics, that are including absorption, distribution, metabolism and excretion of drug. If the drug is given to patient, the first reaction of the body is absorption of the drug. The drug is absorbed from the site of administration, pass through the cell membrane. In blood or plasma part of drug will bound to protein especially albumin and orosomucoid, and the others are free. So in plasma there are two kind of drugs, free drug unbound drug and bound drug. Each drug have its specific protein bound eg.warfarin, only 2 in the form of free, while penicilline 50 are bound. Only free drug will be distributed, produce effects, metabolized and excreted. The very common route of administration is oral route, although absorption may be slower and less complete. Ingested drugs are subject to the first pass effect, in which a significant amount of drug is metabolized in the gut wall and the liver before the drug reaches the systemic circulation. The drug then distributed to all part of the body and reaches its receptor to produce its effects. An important pharmacokinetic parameter that reflect of dug distribution is apparent volume of distribution Vd. The bigger the value of Vd, the greatest amount of drugs distributed to body organ. After distribution process the drug will be metabolized. Metabolism of drug sometimes terminate its action. The action of many drugs eg.phenothiazine is terminated before they are excreted, but prodrugs eg.Levodopa are inactive as administered and must be metabolized in the body to become active. The other drugs eg.benzodiazepine are active as administered and have active metabolites as well. On the other hand lithium is not metabolized by the body, so lithium still active in the body until it is excreted. Elimination is not the same with excretion of drug. Elimination means that an active drugs are metabolized to become inactive, although it metabolites are still in the body, and excreted means that molecules of drugs are excreted from the body. But for drugs that are not metabolized, excretion is the mode of elimination. For most drugs and it’s metabolites, excretion is primarily by kidney and intestine. Anesthetic gases are excreted primarily by the lungs. Vignete A 40 years old patient came to private practice doctor with complain of cough, wheezing, chest tightness andor dyspnoea breathlessness, which are often worse at night or early in the morning. The patient was diagnosed with Bronchial Asthma. Salbutamol Beta 2 agonist is given to patient. Learning Task 1. Describe the definition of : Drug, Pharmacology, Pharmacokinetic, Pharmacodynamic, Volume of distribution Vd, Half life t ½ , Bioavailability, Minimum Effective Concentration MEC, Therapeutic window, First Pass Effect Presystemic elimination, 2. Differentiate drug elimination and drug excretion, first order elimination and zero order elimination. 3. Describe the fate of drug, if taken orally. 4. Name and discuss the common route of drugs administration. Udayana University Faculty of Medicine, DME, 2016 11 Lecture 3-4. Drug Pharmacokinetics Lecture 5-6. Drug Pharmacodynamics Pharmacodynamics is the study of the biochemical and physiological effects of drugs on the body or on microorganisms or parasites within or on the body and the mechanisms of drug action and the relationship between drug concentration and effect. Pharmacodynamics is often summarized as the study of what a drug does to the body. Pharmacodynamics is sometimes abbreviated as PD. The majority effect of drugs on the body either: a mimic or inhibit normal physiologicalbiochemical processes or inhibit pathological processes in animals or b inhibit vital processes of endo- or ectoparasites and microorganisms. There are 7 main drug actions:  Stimulating action through direct receptor agonism and downstream effects  Depressing action through direct receptor agonism and downstream effects ex.: inverse agonist  Blockingantagonizing action as with silent antagonists , the drug binds the receptor but does not activate it  Stabilizing action, the drug seems to act neither as a stimulant or as a depressant ex.: some drugs possess receptor activity that allows them to stabilize general receptor activation, like buprenorphine in opioid dependent individuals or aripiprazole in schizophrenia, all depending on the dose and the recipient  Exchangingreplacing substances or accumulating them to form a reserve  Direct beneficial chemical reaction as in free radical scavenging  Direct harmful chemical reaction which might result in damage or destruction of the cells, through induced toxic or lethal damage cytotoxicity or irritation The desired activity of a drug is mainly due to successful targeting of one several sitetarget of actions. The targets are c ellular membrane disruption, c hemical reaction with downstream effects, interaction with enzyme proteins, interaction with structural proteins, interaction with carrier proteins, interaction with ion channels , l igand binding to receptors h ormone receptors, n euromodulator receptors, n eurotransmitter receptors. In principle, a pharmacologist would aim for a target plasma concentration of the drug for a desired level of response. In reality, there are many factors affecting this goal. Pharmacokinetic factors determine peak concentrations, and concentrations cannot be maintained with absolute consistency because of metabolic breakdown and excretory clearance. Genetic factors may exist which would alter metabolism or drug action itself, and a patients immediate status may also affect indicated dosage. The therapeutic window is the amount of a medication between the amount that gives an effect effective dose and the amount that gives more adverse effects than desired effects. For instance, medication with a small pharmaceutical window must be administered with care and control, e.g. by frequently measuring blood concentration of the drug, since it easily loses effects or gives adverse effects. The duration of action of a drug is the length of time that particular drug is effective. Duration of action is a function of several parameters including plasma half-life , the time to equilibrate between plasma and target compartments, and the off rate of the drug from its biological target . Receptors are macromolecules involved in chemical signaling between and within cells; they may be located on the cell surface membrane or within the cytoplasm. Activated receptors directly or indirectly regulate cellular biochemical processes e.g., ion conductance, protein phosphorylation, DNA transcription, enzymatic activity. Molecules e.g., drugs, hormones, neurotransmitters that bind to a receptor are called ligands. A ligand may activate or inactivate a receptor; activation may increase or decrease a particular cell function. Each ligand may interact with multiple receptor subtypes. Few, if any, drugs are absolutely specific for one receptor or subtype, but most have relative selectivity. Selectivity is the degree to which a drug acts on a given site relative to other sites; selectivity relates largely to physicochemical binding of the drug to cellular receptors. A drug’s ability to affect a given receptor is related to the drug’s affinity probability of the drug occupying a receptor at any given dose and intrinsic efficacy intrinsic activity—degree Udayana University Faculty of Medicine, DME, 2016 12 to which a ligand activates receptors and leads to cellular response. A drug’s affinity and activity are determined by its chemical structure. The pharmacologic effect is also determined by the duration of time that the drug-receptor complex persists residence time. The lifetime of the drug-receptor complex is affected by dynamic processes conformation changes that control the rate of drug association and dissociation from the target. A longer residence time explains a prolonged pharmacologic effect. Drugs with long residence times include finasteride and darunavir. A longer residence time can be a potential disadvantage when it prolongs a drugs toxicity. For some receptors, transient drug occupancy produces the desired pharmacologic effect, whereas prolonged occupancy causes toxicity. Receptor up-regulation and down-regulation affect adaptation to drugs e.g., desensitization, tachyphylaxis, tolerance, acquired resistance, postwithdrawal supersensitivity. The structures of receptors are very diverse and can broadly be classified into the following categories: 1. Type 1: L ionotropic-receptors – These receptors are typically the targets of fast- neurotransmitters such as acetylcholine nicotinic and GABA; and, activation of these receptors results in changes in ion-movement across a membrane. They have a hetero-structure. Each subunit consists of the extracellular-ligand-binding domain and a transmembrane-domain where the transmembrane-domain in turn includes four transmembrane-alpha helixes. The ligand-binding cavities are located at the interface between the subunits. 2. Type 2: G protein-coupled receptors metabotropic – This is the largest family of receptors and includes the receptors for several hormones and slow transmitters e.g. dopamine, metabotropic-glutamate. They are composed of seven transmembrane- [alpha helix|alpha helices]]. The loops connecting the alpha-helices form extracellular and intracellular-domains. The binding-site for larger peptidic-ligands is usually located in the extracellular-domain whereas the binding-site for smaller non- peptidic ligands is often located between the seven alpha-helices and one extracellular-loop. The aforementioned receptors are coupled to different intracellular-effector systems via G-proteins. 3. Type 3: kinase linked and related receptors see r eceptor tyrosine kinase , and e nzyme-linked receptor - They are composed of an extracellular-domain containing the ligand-binding site and an intracellular-domain, often with enzymatic- function, linked by a single transmembrane-alpha helix. e.g. the insulin-receptor. 4. Type 4: nuclear receptors – While they are called nuclear-receptors, they are actually located in the cytosol and migrate to the nucleus after binding with their ligands. They are composed of a C-terminal -ligand-binding region, a core- DNA- binding domain DBD and an N-terminal -domain that contains the AF1 activation function 1 region. The core-region has two zinc-fingers that are responsible for recognizing the DNA sequences specific to this receptor. The N-terminal interacts with other cellular-transcription factors in a ligand-independent manner; and, depending on these interactions it can modify the bindingactivity of the receptor. Steroid and thyroid-hormone receptors are examples of such receptors. Ligands bind to precise molecular regions, called recognition sites, on receptor macromolecules. The binding site for a drug may be the same as or different from that of an endogenous agonist hormone or neurotransmitter. Agonists that bind to an adjacent site or a different site on a receptor are sometimes called allosteric agonists. Nonspecific drug binding also occurs—ie, at molecular sites not designated as receptors e.g., plasma proteins. Drug binding to such nonspecific sites, such as binding to serum proteins, prohibits the drug from binding to the receptor and thus inactivates the drug. Unbound drug is available to bind to receptors and thus have an effect. Learning Task Udayana University Faculty of Medicine, DME, 2016 13 1. Plasma concentration of the drug for a desired level of response are very important. In reality, there are many factors affecting this goal. Mention and explains each of its 2. Please explain about the concept of therapeutic window Medication with a small therapeutic window must be administered with care and control, e.g. by frequently measuring blood concentration of the drug. Why? The autonomic nervous system ANS is the involuntary portion of the nervous system. The ANS consists of sympathetic SANS and parasympathetic nervous system PANS. Both of these systems regulates many important bodily functions to maintain homeostasis, such as heart rate, blood pressure, and respiratory function. It involves neurotransmitters as it hallmark in regulating those functions. The synthesis, storage, release, receptor interaction, reuptake, and metabolism of the involved neurotransmitters can be modulated by many drugs. Hence, it is very important for undergraduate medical students to comprehend and master the knowledge of ANS pharmacology as a basis of rational therapy and good clinical practice. Vignete A man, 21 years old, accompanied by his parents, came to the emergency room of RSUP Sanglah complaining about breathing difficulty and dizziness. Those symptoms commenced about an hour after he took amoxicillin prescribed previously by a GP due to the diagnosis of upper respiratory tract infection. He said that he frequently take amoxicillin when he think that he get pharyngitis. He denied the history of drug allergy, but admitted that he has allergy to seafood. Physical examination revealed urticaria in both of the volar aspects of his lower arms, blood pressure of 8050 mmHg, heart rate of 124 xminute, breathing rate of 30 xminute, wheezing on chest auscultation, and O 2 saturation of 90. The emergency physician diagnosed him with anaphylactic shock. After being administered with epinephrine injection, he showed dramatic clinical improvements. He was then hospitalized for 3 days for clinical observation and stabilization under the supervision of a clinical allergo- immunologist. Learning Task 1. What receptors and neurotransmitters are involved in the pathomechanism of the case above? Please explain their functions 2. Why does the emergency physician administer epinephrine, and not dopamine, when he treat the shock? 3. Please explain the neurotransmitter aspect of the SANS 4. Please explain the neurotransmitter aspect of the PANS 5. What are the steps in autonomic transmission? Please give an example of drug and its pharmacodynamics for each step Penicillins and chepalosporins are the major antibiotics that inhibit bacterial cell wall synthesis. They are called beta-lactams because of the unusual 4-member ring that is common to all their members. The beta-lactams include some of the most effective, widely used, and well-tolerated agents avaliable for the treatment of microbial infections. Vancomysin, fosfomycin, and bacitracin also inhibit cell wall synthesis but for various reasons are not nearly as important as the beta-lactams drugs. The Selective toxicyti of the drug discussed in this chapter is mainly due to specific actions on the synthesis of a cellular structure that is unique to the microorganism. More than 50 antibiotics that acts as cell wall Udayana University Faculty of Medicine, DME, 2016 14 Lecture 7-9. Drug Act on Autonomic Nervous System Lecture 10. Antibacterial Drugs synthesis inhibitors are currently avaliable, with individual spectra of activity that afford a wide range of clinical applications. The antimicrobial drugs reviewed in this chapter selectively inhibit bacterial protein synthesis. The mechanism of protein synthesis in microorganism are not identical to those of mammalian cells. Bacteria have 70S ribosomes, whereas mammalian sell have 80S ribosomes. Differences exist in ribosomal subunits and in the chemical composition and functional specificities of component nucleic acids and proteins. Such differences from the basis for the selective toxicity of these drugs against microorganisms without causing major effect on protein synthesis in mammalian cells. Aminiglycosides are also capable of exerting a postantibiotic effect such that their killing action continues when their plasma levels have declined below measurable levels. Consequently, aminoglycosides have greater efficacy when administered as a single large dose than whwn given as multiple smaller doses. The toxicity in contrast to the antibacterial efficacy of aminoglycosides depends both on critical plasma concentration and on the time that such a level is exceeded. The time above such a single large dose of an aminoglyciside than when multiple smaller doses are given. These concepts from the basis for once-daily aminoglycoside dosing protocols, which can be more effective and less toxic than traditional dosing regimens. Sulfonamides and trimethoprim are antimetabolites selectively toxic to microorganisms because they interfere with folic asid synthesis. Sulfonamides continue to be used selectively as individual antimicrobial agents , altough resistance is common. The combination of a sulfonamide with trimethoprin causes a sequential blockade of folic acid synthesis. This results in a synergistic actions againts a wide 1Fluoroquinolons, which selectively inhibit microbial nucleic asid metabolism, also have a broad spectrum of antimicrobial activity that includes many common pathogens. Resistance has emerged to the older antibioticsin this class, but has been offset to some extent by the introduction of newer generations of fluoroquinolones with expanded activity against common pathogenic organism. Learning Task 1. A 36- year-old woman recently treated for leukemia is admitted to the hospital with malaise, chills, and high fever. Gram stain of blood reveals the presence of gram-negative bacilli. The initial diagnosis is bacteremia, and parenteral antibiotics are indicated. The records of the patient reveal that she had a severe urticarial rash, hypotension, and respiratory difficulty after oral penicillin V about 6 mo ago. The most appropriate drug for empiric treatment is: A. ampicillin plus sulbactam B. aztreonam C. Cefazolin D. imipenem plus cilastatin E. ticarcillin plus clavulanic acid 2. A 2-year-old child is brought to the hospital after ingesting pills that a parent had used for bacterial dysentery when traveling outside the United States. The child has been vimiting for more than 24 h and has had diarrhea with green stools. He is now lethargic with an ashen color. Other signs and symptoms include hypothermia, hypotention, and abdominal distention. The drug most likely to be the cause of this problem is: A. Ampicillin B. Chlorampenicol C. Clindamycin D. Doxicicline E. Erythromycin Udayana University Faculty of Medicine, DME, 2016 15 3. A 24-year- old woman has primary syphilis. She has a history of penicillin hypersensitivity, so tetracycline will be used to treat the infection. Which one of the following statements about the proposed drug treatment of this patient is false ? A. She will have to take the drug for 15 days B. She should avoid taking antacids at the same time as she takes the drug C. She may experience anorexia and gastrointestinal distress D. She should eat plenty of yogurt to prevent vaginal candidiasis E. She should call her physician if she develop severe diarrhea 4. A 31-year-old man has gonorrhea. He has no drug allergies, but a few years ago while in Afrika acute hemolysis followed use of an antimalarial drug. The physician is concerned that the patient has an accompanying urethritis caused by C trachomatis, although no cultures or enzyme tests have been perfomed. Which of the following drug is most likely to be effective against gono cocci and to eradicate C trachomatis in this patient? A. Cefixime B. Ciprofloxacin C. Ofloxacin D. Spectinomycin E. Sulfamethoxazole The treatment of patients with inflammation involves two primary goals: first, the relief of pain, which is often the presenting symptom and the major continuing complaint of the patient; and second, arrest of the tissue-damaging process. Reduction of inflammation with nonsteroidal antiinflamatory drugs NSAIDs often results in relief of pain for signifificant periods. Furthermore, most of the non-opiod analgesicsaspirin, etc. also have anti-inflammatory effects, so they are apppropriate for the treatment of both acute and chronic inflammatory conditions. The glucocorticoids also have powerful anti-inflammatory effects and when first introduced were considered to be the ultimate answer to the treatment of antiinflammatory arthritis. Unfortunately, the toxicity associated with chronic corticosteroid therapy limits their use except in the control of acute flare-up of joint disease. Therefore, the nonsteroidal anti- inflammatory drugs have assumed a major role in the long term-term treatment of arthritis. Another important group of agents are characterized as slow-acting antirheumatic drugs SAARDs or disease-modifying antirheumatic drugs DMARDs. They may slow the bone damage associated with rheumatoid arthritis and are thought to affect more basic inflammatory mechanism than do the NSAIDs. Vignete A 25-year-old woman presented with intense pain in her stomach. The physician diagnoses her with dysmenorrhea. Which of the following drugs is used in the treatment of dysmenorrhea? A. Allopurinol B. Colchicine C. Leflunomide D. Naproxen E. Sulfinpyrazone Udayana University Faculty of Medicine, DME, 2016 16 Lecture 11. Analgesic Antiinflammation Learning Task 1. List NSAIDs, non-opioid analgesics and drugs used in gout 2. Describe the mechanisms of action of anti-inflammatory drugs, non-opiod analgesics and drugs used in gout 3. Describe the pharmacokinetics of anti-inflammatory drugs, non-opioid analgesics and drugs used in gout 4. Describe the toxic effects of anti-inflammatory drugs, non-opioid analgesics and drugs used in gout 5. Describe of the clinical uses of anti-inflammatory drugs, non-opioid analgesics and drugs used in gout 6. Describe the advantages of the disease-modifying antirheumatic drugs in the treatment of arthritis 7. List the disease-modifying antirheumatic drugs DMARDs When a drug is administered, a response occurs; if a second drug is given and the response to the first drug is altered, a drug interaction is said to have occurred. A drug interaction may be beneficial or harmful. It is deliberately sought in multidrug treatment of tuberculosis and when naloxone is given to treat morphine overdose. It is an embarrasment when a woman taking a combined estrogen progesteron oral contraseptive for a desired interaction is prescibed a drug that is a metabolic enzyme inducer, with the result that she becomes pregnant. Although dramatic unintended interactions attract most attention and are the principal subject of this section, they should not distract attention from the many therapeutically useful interactions that are the basis of rational polypharmacy. Vignete Report of cardiac arrhythmias caused by unusually high blood level of 2 antihistamines, terfenadine and astemizole . These effect were best explained by? A. Concomitant treatment with phenobarbital B. Use of these drugs by smokers C. A genetic predisposition to metabolize succinylcholine slow D. Concomitant treatment with procainamide E. Treatment of these patients with ketoconazole, an antifungi agent Learning Task 1. What is pharmacodynamic interaction ? 2. What is pharmacokinetic interaction ? 3. Describe the antagonism 4. Describe the synergism 5. Describe the drug interactions that occur outside the body 6. Describe the drug interactions that occur at site of absorption 7. Describe the drug interactions that occur during distribution 8. Describe the drug interactions that occur directly on receptors or on body systems 9. Describe the drug interactions that occur during metabolism 10. Describe the drug interactions that occur during excretion Adverse drugs reactions ADRs, put simply, are noxious, unintended, and undesirable effects that occur as a result of drug treatment at doses normally used in man for diagnosis, prophylaxis, and treatment. Although there are many terms indicating the harmful and undesirable effects of drug treatment, the term ‘adverse drug reaction’ describes them best. Udayana University Faculty of Medicine, DME, 2016 17 Lecture 12. Drug Interaction Lecture 13. Adverse Drug Reaction During the course of treatment, drugs prescribed to patients produce certain effects other than the desired or expected effects. These cause concern both to the physician and the patient. They not only add to spiralling costs of medical treatments, but also cause a great deal of morbidity and mortality. These are generally referred to as ‘side effects’. People usually attribute these abnormal effects to either overdose or inappropriate medications prescribed by the doctor or the attending specialists. The unwanted effects are categorised into many types such as toxic effects, side effects, adverse reactions, and adverse drug events etc., depending upon the taxonomic classification used. Worldwide, studies have shown them to be a major cause of morbidity and mortality. Therefore, incidence of the adverse drug reactions is likely to be same as that of the West, or more. Unfortunately, inspite of presence of five wellorganised centres for drug monitoring in the country, the number of reports sent annually are dismal. Most of the adverse drug reactions are, fortunately, preventable. This calls for the urgent need to reinforce the monitoring of adverse reactions to drugs; public education against self-medication, inclusion of reaction monitoring, and an introduction to drug-safety in the curriculum of medical undergraduates, and systemic and periodic continuing medical education of health professionals. This multi- pronged strategy can lead to reduction in the incidence of adverse drug reactions Learning Task 1. D.W. is a 9-year-old boy with osteosarcoma, which is being treated with ifosfamide and etoposide. He has no history of allergy. After two courses of chemotherapy, D.W. develops an upper arm deep venous thrombosis because of the chemotherapy. He is admitted to the hospital and initiated on heparin, omeprazole, and prophylactic antibiotics piperacillintazobactam. On the third day of treatment, the swelling and pain in his upper arm have decreased significantly. Which one of the following best classifies D.W.’s chemotherapy adverse drug reaction ADR? A. Type A. B. Type B. C. Type C. D Type D. 2. On the third hospital day, D.W.’s platelet count has dropped by 50 from baseline, and his alkaline phosphatase has increased to twice the normal value. He also begins to have some oozing of blood from his central catheter line site. The team agrees that these events are ADRs and asks you to narrow the suspected drugs to two agents. Which two- drug option is most likely causing these ADRs in D.W.? A. Omeprazole and heparin. B. Heparin and ifosfamide. C. Ifosfamide and omeprazole. D. Omeprazole and piperacillintazobactam. 3. You have been asked by your department’s director to compile a listing of your institution’s reported ADRs for review by your health system’s quality committee. Which one of the following metrics would be most helpful to ADR prevention? A. Rate of ADRs per 100 admissions. B. Rate of ADRs per 100 discharges. C. Number of ADRs by therapeutic drug classification. D. Number of ADRs resulting in harm. Udayana University Faculty of Medicine, DME, 2016 18 Once a patient with a clinical problem has been evaluated and a diagnosis has been identified, the doctor can often select from a variety of therapeutic approaches, including drug therapy. This requires the writing of prescription. According to definition from WHO, a drug therapy is considered to be rational if patient receive medication in appropriate clinical indication, in appropriate dosage, in adequate duration of treatment and reachable cost. Therefore rational drug therapy must follow several basic principles including right indication, right drug, right patient, right dosage, right route of administration, right interval of treatment, right duration of treatment and caution for adverse effect. Medication error is defined as any preventable event that may cause or lead to inappropriate medication use or patient harm, while the medication is in the control of the healthcare professional, patient or consumer. This might be derived from prescription by a doctor, from preparation and dispension by pharmacist as well as from administration by nurse. Some issues related to medication error included incomplete prescription, wrong technique, poor communication, unreadable prescription, off label prescription, preparation error, excessive treatment, excessive cost, look alike and sound alike medication. Vignete A 30 years old man came to general practitioner due to fever since 4 days ago. Patient also complained headache, cough, cold and sore throat. Patient has already taken paracetamol but the complaints not getting better. After complete examination, patient was prescribed Demacolin® and Amoxsan® tablet. Patient was also still taken his previous medication paracetamol along with drugs given by the doctor because doctor didn’t instruct him to stop his previous medication. Learning Task 1. Is there any irrational treatment happened in this patient? 2. What medication error has occurred in this patient? 3. Mention other type of medication error or irrational therapy. 4. How to avoid medication error? 5. What are the basic principles must be followed to perform rational drug therapy to the patient? GENERAL DIRECTIONS  The aims of practicum  Direct observation on the effects of drugs in vivo  Comparing the practicum results with existing theories and making conclusion based on the comparation  Helping the students to comprehend the basics of pharmacology  The implementation of practicum by the students  By using this manual, the students are expected to work independently, in a solemn and systematic manner  The students are expected to take notes on the practicum results in a good way to optimize their way of studying  The lectures are only facilitators during the practicum Udayana University Faculty of Medicine, DME, 2016 19

12. GUIDELINE FOR PRACTICAL SESSION