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MINISTRY OF HEALTH OF UKRAINE Vinnitsa National Medical Univercity after N.I.Pirogov “Approved” on methodological conference Clinical pharmacy and clinical Pharmacology department Head of department ______prof. Yakovleva О.A. «___»___________20___y. Guidelines for students for practical lessons (seminar) Academic discipline Clinical pharmacology Informal module №2 Subject classes № 9 Clinical pharmacology of drugs that affect the bronchial patency. Anti-inflammatory drugs.Antibacterial drugs Anti-inflammatory drugs. Course 5-th Faculty Medical Vinnitsya – 2013 Anti-inflammatory drugs 1. Background: Non-steroidal anti-inflammatory drugs used to treat inflammation, reduce fever and as anesthetics. Inflammation is a universal reaction of the organism to the action of various exogenous and endogenous destructive factors, which include the causative agents of bacterial, viral and parasitic infections, and allergens, physical and chemical stimuli. Drug eliminate inflammation by acting on the prostanoids (prostaglandins and thromboxane). Analgesic effect associated with inhibition of the enzyme cyclooxygenase and decreasing the synthesis of prostaglandins. Glucorticosteroids have various effects on the body. The biological activity of glucocorticoids can use them in the most difficult clinical situations. Often they include a set of emergency measures of assistance in urgent situations. Specific Tasks: 1. Analyze the causes of inflammation, the mechanism bolvogo feeling rise in body temperature. 2. Analyze the mechanisms of action of nonsteroidal anti-inflammatory drugs that eliminate signs of inflammation, especially depending on the selectivity. 3. To analyze the pharmacological effects of nonselective nonsteroidal antiinflammatory drugs. 4. To analyze the pharmacological effects of selective NSAIDs. 5. To analyze the pharmacological effects of highly selective non-steroidal antiinflammatory drugs. 6. To characterize the pharmacological effects of nonsteroidal anti-inflammatory drugs. 7. Interpreting the indications for use of NSAIDs different groups. 8. Analyze the possibility of side effects of medicines to prevent them. 9. To make the algorithm of care to patients with fever, bolvomu syndrome. 10. Write down and analyze recipes for Drug, used to reduce elevated body temperature, elimination of inflammation and reduce pain. 11. Analyze the mechanism of action and physiological effects of glucocorticoids. 12. To analyze the pharmacokinetics of natural glucocorticoids. 13. Analyze the pharmacokinetics of synthetic glucocorticoids. 14. To analyze the pharmacokinetics of inhaled glucocorticoids. 15. Interpreting the evidence and the administration schedule systemic glucocorticoids. 16. Interpreting the evidence and the administration schedule of inhaled glucocorticoids. 17. Analyze the contraindications and side effects of glucocorticoids. 18. To make the algorithm of care to patients with anaphylactic shock, asthmatic status. 2. Basic knoledges, skills, practices to study (interdisciplinary integration). Name of previous courses 1. Latin These skills Section "Pharmacological and medical terminology." Posses ability to write correct Latin names of drugs according to grammar. Know about endings of nouns and adjectives of different declinations in genitive case when writing drug in recipes 2.Physiology Section «The body temperature and its regulation», section «Physiology of the endocrine and respiratory systems» - apply the knowledge in this section. 3. Biological Chemistry Determine the role of the enzyme cyclooxygenase and metabolism of arachidonic acid, glucocorticoids in humans. Apply knowledge of this section when considering the mechanisms of action of individual drug. 4. Pharmacology Section «Pharmacology of anti-inflammatory drugs». Section «Pharmacology of hormonal drugs». Apply knowledge of this section when considering the pharmacodynamics and pharmacokinetics of the individual drug. 3.List of base terms, parameters, characteristics that students should learn in preparation for the lession Term NSAIDs Finding Drugs used to relieve depression and signs of inflammation, relieve pain and fever. For the treatment of patients using drugs of different chemical groups. COX Enzymes that involved in the formation of prostaglandins from arachidonic acid. Inhibition of this enzyme leads to increased utilization of arachidonic acid by lipoxygenase path and improve formation leukotrienes and limit exudation. Aspirin-induced The result of preferential formation of leukotrienes and asthma thromboxane A2 from arachidonic acid. In the case of this complication prescribe ozagrelya hydrochloride, the decrease of formation tromboxane synthetase, reduces the formation of thromboxane A2. Reye's syndrome Toxic encephalopathy, acute fatty degeneration of the liver, brain and kidney. Glucocorticoids group of drugs that are structural and functional analogs of hormones that are synthesized in zona fasciculata of the adrenal cortex. Pulse-therapy scheme ultrahigh doses of corticosteroids administration for shortterm patients with severe and life threatening diseases or conditions (eg, systemic collagen, vasculitis, severe rheumatoid arthritis with a lesion of the internal orgnans, multiple sclerosis). Drug of choice is methylprednisolone. Chronotherapy Section of Medicine, which is based on the improvement of patient care by reducing the one-time, daily, course of doses of medicines, reducing the severity of side effects, taking into account the variability of pharmacodynamic, pharmacokinetic parameters, depending on the time factor (period of day, month, season, etc.). 4. Theoretical questions to lesson. 1. Signs of inflammation, the effect on each link of inflammation. 2. Classification of non-steroidal anti-inflammatory drugs, depending on the chemical origin, anti-inflammatory activity, analgesic activity, antipyretic activity. 3. Classification of NSAIDs according to the selectivity of action on COX. 4. The mechanism of action of nonsteroidal anti-inflammatory drugs, unlike antiinflammatory effects of GCS. 6. Pharmacological effects of nonsteroidal anti-inflammatory drugs and their practical application in clinics. 7. The pharmacokinetics of NSAIDs. 8. The interaction of NSAIDs with drugs from other groups. 9. Side effects of NSAIDs and the ways of its treatment and prevention. 10. Indications for use of NSAIDs. 11. Criteria of evaluating the effectiveness and safety of NSAIDs. 12. Classification of glucocorticoides. 13. Regulation of the functions of the hypothalamic-pituitary-adrenal system. 14. The mechanism of action and physiological effects of glucocorticoids. 15. Pharmacokinetics of systemic and inhaled glucocorticoides. 16. Impressions and administration schedule of systemic and inhaled glucocorticoids. 17. Contraindications and side effects of glucocorticoides. 18. Interaction of glucocorticoides with drugs of other groups. 5. Practice. This stage provides for carring out without assistance by each student following practical work. A. Materials for self-control Task 1 Prescription and to hold their pharmacotherapeutic analysis (indicate group membership, indications for use, possible complications) 1. Ibuprofen tablets 2. Diclofenac sodium intablets and capsules 3. Paracetamol in tablets and suppositories 4. Nimesulide 5. Celecoxib in tablets 6. Rofecoxib in tablets 7. Meloxicam in tablets 8. Hydrocortisone in ampule 9. Prednisolone in tablets and capsules 10. Methylprednisolone in tablets and capsules 11. Triamcinolone in tablets and capsules 12. Dexamethasone in tablets and capsules 13. Beclomethasone dipropionate for inhalation 14. Flunisolide for inhalation 15. Budesonide for inhalation 16. Fluticasone for inhalation. Task 2 Look through the training drug collection on the subject, to determine their beloning to the pharmacological group, and indications for use. Task 3 Confirm the choice of the drug, its pharmaceutical form, dosage, concentration and route of drug introduction. 1. Drug for removal of headache. 2. Drug for removal of pain in the joints. 3. Drug to lower elevated body temperature. 4. Drug for the relief of pain with radiculitis. 5. Drug of NSAIDs to contra aggregate e of the patient's coronary artery disease. 6. Drug to stimulate the closure of the open Bottalo's duct in preterm infants provided left-right shunt. 7 Drug for emergency assistance by anaphylactic shock. 8. Drug for emergency care for asthmatic status. 9. Drug for emergency care for cerebral edema. 10. Drug for local therapy in articular syndrome. 11. Drug substitution therapy for adrenal insufficiency. Task 4 Indicate NSAIDs: • contraindicated for use for children • contraindicated in pregnant women • contraindicated in patients older through hondrotoksichnist B. Tasks for self-control. Task 1 Mode of action of acetylsalicylic acid: a) Anti-inflammatory, hemostatic, uricosuric b) Antipyretic, anti-inflammatory, fibrinolytic c) Antipyretic, anti -inflammatory, contra -aggregate d) Wound healing, anti -inflammatory Task 2 NSAIDs are used for: a) Arthritis, radiculitis, myalgia, neuritis, connective tissue diseases b) Connective tissue diseases, neuritis, colic, toothache c) Radiculitis, arthritis, myalgia, thrombosis, spastic states d) Bleeding, colic Task 3 Suppositories with anti-inflammatory, analgesic and antipyretic action: a) Metindol, revodin, paracetamol b) Anuzol c) Voltaren d) Posterizan, Ekonazol-HL Task 4 Combined NSAIDs include: a) Diclocaine, reopyrin b) Reopyrin, meloxicam c) Piroxicam, diclocaine d) Voltaren, mefenamic acid Task 5 For NSAIDs include: a) Meloxicam, diclofenac sodium, analgin, paracetamol, and prednisone b) Indomethacin, mefenamic acid, piroxicam, movalis, voltaren c) Piroxicam, indomethacin, Sedalgin, tramadol d) Retabolil, ephedrine hydrochloride, tramadol Task 6 Diseases in which contraindicated the use of NSAIDs: a) Stomach ulcer, myocardial damage, bleeding in the digestive tract b) Stomach ulcer, diabetes, arthritis c) Hyperacid gastritis, bleeding from the gastrointestinal tract, bronchial asthma, stomach ulcer d) Diabetes mellitus, myocardial infarction Task 7 Distinctive feature of NSAIDs selective inhibitors of COX-2 is less expressed: a) Anti-inflammatory action b) Ulcerogenic effect c) Antipyretic action d) Analgesic actions Task 8 With simultaneous use of NSAIDs and alcohol increases the risk: a) Bronchospasm b) Nephrotoxicity action c) Allergic reaction d) Ulcerogenic effect Task 9 Of the group of anti-inflammatory action of NSAIDs during pregnancy allowed to use: a) Ibuprofen b) Aspirin c) Acetaminophen d) Analgin Task 10 Drugs of natural glucocorticoids are biologically inactive. Activated in the liver, turning into hydrocortisone and have a short-term effects. In comparison with other glucocorticoids is most pronounced mineralocorticoid action. Name the drug and the dominant display to use it. (Answer: Cortisone) Task 11 Natural glucocorticoid on glucocorticoid activity in 4 weaker than prednisolone at mineralocorticoid - a few ahead of him. Name the drug. How is not recommended to assign to patient this drug. (Answer: Hydrocortisone) Task 12 Drug, which is fluorinated glucocorticoids, 7 times more glucocorticoid activity of prednisolone, has no mineralocorticoid activity. Cause significant inhibition of the hypothalamic-pituitary-adrenal system. Call the drug, and particularly the testimony to its destination. (Answer: Dexamethasone) Task 13 The synthetic glucocorticoid,which in comparison with prednisolone has a few more (20%) of glucocorticoid activity, minimal mineralocorticoid effects. Indicate the drug, especially its use. (Answer: Methylprednisolone) Task 14. Adverse effects of glucocorticoids include: a) Osteoporosis b) Hypotension a) Glaucoma d) Dysphonia d) Hyperkalemia Task 15. What pharmacodynamic effects typical of glucocorticoids? E) Neutrophilic leukocytosis. b) Increase blood pressure a) Lymphocytopenia c) Eosinopenia d) Decrease in circulating blood e) Inhibition of basal secretion of hydrochloric acid B. Problems for self-control The final stage - 15 min. Active ultimate test control The problem according to the base Krok 2 Test Center MoH Ukraine NSAIDs 1. The patient, 46 years, with exacerbation of rheumatoid arthritis, who has spent NSAIDs revealed leukopenia. What drug could cause this effect is most likely? A. Ibuprofen B. butadion C. Meloxicam D. Celecoxib E. Diclofenac sodium 2. By the pharmacist asked the patient, which recommended acceptance of acetylsalicylic acid as antiaggregants. What is the daily dose should be recommended for continuous use? A. 0,1-0,3 B. 0,5-1,0 C. 1,0-2,0 D. 2,0-3,0 E. More than 4,0 3. Which of the pharmacodynamic effects are not characteristic of non-steroidal anti-inflammatory drugs? A. Inhibition of exudative manifestations of inflammation B. Inhibition of synthesis of interleukin-2 C. Inhibition of synthesis of thromboxane A2 D. Inhibition making macroergastic substrates E. Inhibition of synthesis of hyaluronidase 4. What complication may arise in the prescribing of acetylsalicylic acid, a patient with deficiency of glucose-6-phosphodiesterase? A. Lyell’s syndrome B. Anaphylaxis C. Asthma D. Intravascular hemolysis E. Thrombocytopenic purpura 5. In the pharmacy turned a pregnant woman with a fever. Recommend safest drug. A. Diclofenac sodium B. Acetylsalicylic acid C. Paracetamol D. Ibuprofen E. Indomethacin 6. In the pharmacy called mother of 3 month-old baby, with a request to extradite antipyretic drug. Which drug you recommend for a child? A. Coldrex B. Panadol C. Acetylsalicylic acid D. Indomethacin E. Diclofenac sodium 7. A pregnant woman (III trimester), which the flu for 3 days, in order to reduce the temperature took acetylsalicylic acid on 0,5 twice a day. What side effects may result acetylsalicylic acid on the fetus? A. Violation of protein metabolism B. Teratogenic C. Embryotoxicity D. Violation of carbohydrate metabolism E. Violation of fat metabolism 8. Newborn E., admitted to the neonatal center with the diagnosis: Pulmonary hypertension, premature closure of the Strait Batalova. What kind of friend that were applied a woman during pregnancy could cause these complications? A. Chloroquine B. Penicillamine C. Vitamin E D. Indomethacin E. Chlorpromazine 9. Patient P., aged 38, of rheumatoid arthritis in adjuvant therapy took diclofenac sodium 0.01 g / day. Evaluating the effectiveness of nonsteroidal anti-inflammatory agents occurs in all except the following criteria? A. Index nabryaklivosti sites joints B. Power compression hand C. Laboratory tests D. Range of motion in joints E. The emergence of agranulocytosis 10. The activity of cyclooxygenase can be inhibited by the application of certain drugs. Which of them has an irreversible inhibitory effect on this enzyme? A. norsulfazol B. Diclofenac sodium C. Sulfodimezin D. Aspirin E. Tocopherol Glucorticosteroids 11. The woman, 38 years, 6 years suffer from asthma. Works in the room where the walls are covered with mold. Allergy to aspirin, analginum, Tylenol. At the present time - 4 attacks of breathlessness at night, often at night. Nasal breathing is difficult. In the lungs, breathing weakened, dry rales on vidosi. Cutaneous allergic to house dust samples - +, feather pillows on - "on maple and alder - +. Assign treatment with regard to the shape and severity of the disease. A. Deksametozon and teopek inside B. Claritin eufillina intravenously and orally. C. Implementation of specific desensitization to the allergen house dust and feather pillows. D. Ingakort to 2 inhalations, 2 times a day after preliminary inhalation ofFenoterol. E. Teofedrin inside and astmopent in ingalyatsyayah in attack 12. The patient, 23 years old, suffers from lupus, acute with the passage of a primary lesion of the myocardium, kidney, esophagus, designed pathogenetic treatment. In the analysis of blood erythrocytes - 3,8 * 102 / l, Hb - 120 g / l, WBC 2 * 109 / l, platelets - 150 * 109 / l, bilirubin - 19 mEq / liter. Select the correct Variant treatment. A. Prednisone - 60 mg / day B. Cyclophosphamide 200 mg / day in a C. Timalin - 10 mg / m daily D. Laferon 5 million / m 2 twice a week E. Levamisole 150 mg / day according to the scheme 13. Patient, 20 years after zhaleniya axis developed angioedema, rash on the trunk appeared in the form of blisters, papules. Emergency aid should begin with: A. Norepinephrine, mezaton B. Reopolyglukine, gemodez C. Epinephrine, prednisolone, antihistamines, drugs D. Fresh frozen plasma, E-aminocaproic acid E. Hypothiazid, furosemide 14. According to WHO recommendations, the daily dose of inhaled corticosteroids for persistent mild bronchial asthma in adults is? A. 150-300 mcg B. 200-500 mg C. 800-2000 mcg D. More than 2000 mcg 15. The patient, 28 years old, 2 months after suffering from angina. Complaints of morning stiffness, pain, proximal interphalangeal II and III of the fingers, knees, elbows. In laboratory examination - hypochromic anemia, ESR 40 mm / h, the reaction Vaaler-Rose 1:128. Which drug should be used for local therapy? A. Kenalog-40 B. Afluton C. Arteparon D. Rumalon E. Lidasa 16. The patient K., age 28, was admitted in serious condition in the nephrology department, a fast-diagnosed idiopathic glomerulonephritis, nephrotic syndrome (proteinuria of up to 12 g / day), secondary hypertension. Which of the proposed treatment regimens must assign the patient: A. Prednisone 1 mg / kg / day 8 weeks. + Cyclophosphamide 2 mg / kg / day for 8 weeks. B. Trimethoprim-sulfamethoxazole 160/800 mg 2 times a day for 14 days. C. Cefazolin 2 g / 3 times a day for 10 days. D. Methylprednisolone 30 mg / kg (up to 3g) in / in a day NN3, then prednisone 2 mg / kg oral for 2 months. E. Kidney. 17. Female patient, 30 years, during the year received substitution treatment prednisolone (10 mg / day after meals) on the chronic adrenal insufficiency. Following the discovery of focal pulmonary tuberculosis worsened appetite in zvyazku reception than with prednisolone was stopped. The next day there adynamia, vomiting, psychotic disorders (disorientation). Glycemia 3.1 mmol / l, blood pressure 110/80 mm Hg. Required treatment: A. Hydrocortisone gemisuktsinat, rn sodium chloride 0.9%, glucose 5% / drip, treatment of tuberculosis. B. Mineralocorticoid Drug (ftorgidrokortizon inside), ftivazid. C. Only TB therapy with corticosteroids after removal of tuberculous intoxication. D. 40% rr glucose and 10% p-r sodium chloride w / jet, treatment of tuberculosis. E. Drug potassium and specific TB treatment. 18. Patients with bronchial asthma, which for years had been treated Bekotid and SEREVENT emerged redness and swelling of the gums, white patches on the tongue. What could it be? What not to do ill and what to do? A. Glossitis, stomatitis due to stimulation of the oral cavity. B. Side effects SEREVENT. Cancel drug. C. Allergic reaction to Bekotid. Cancel drug D. Gribkov impression of the oral cavity as a result of prolonged use Bekotid. Arose from the fact that the patient does not rinse your mouth after inhaling Bekotid. In the next (after treatment of mycosis), this should be done. E. Not associated with asthma disease. It should be thoroughly examined patients. 19. A man aged 36, who suffers from bronchial asthma, severe persistent currents, for 16 years and regularly took salbutamol during seizures, Formoterol 2 times per day, Bekotid 400 mg 2 times / day, Teotard 1 time per day, there was severe asthma. On-no: cyanosis, heart rate = 95/hv, BH = 28/hv. Dry whistling rales are heard at a distance, auscultation - "silent" light. Condition was bought w / the introduction of hydrocortisone and eufillina. What is the further patient treatment in the future is most appropriate? 1. Go to hydrocortisone tablets 2. Take salbutamol regularly 3. Increase the dose of beclomethasone 4. Exchange w / introduction eufillina 5. Increase number of intakes formotorelu 20. A man aged 36, who suffers from bronchial asthma, severe persistent currents, for 16 years and regularly took salbutamol during seizures, Formoterol 2 times per day, Bekotid 400 mg 2 times / day, Teotard 1 time per day, there was severe asthma. On-no: cyanosis, heart rate = 95/hv, BH = 28/hv. Dry whistling rales are heard at a distance, auscultation - "silent" light. What type of glucocorticoid therapy is the most shown in this situation? A. Inhalation therapy B. Intensive short-term C. Alrenating therapy D. Intermittent therapy E. Pulse therapy Solve a pharmacological problem (10) and write in the form of recipes 1. Drug for relieving headache. 2. Drug for removal of joint inflammation in rheumatoid arthritis. 3. Drug for reducing elevated body temperature in lactating women. 4. Antiagregantnymi effect of NSAIDs. 5. Drug for the elimination of acute inflammation in gouty arthritis. 6. Highly selective NSAIDs for the treatment of inflammation in patients with stomach ulcer in the anamnesis. 7. Highly selective NSAIDs, caution should be taken for the elderly with cardiovascular pathology. 8. Gel to relieve pain syndrome of the cervical spine with pain and antiinflammatory effect. 9. NSAIDs for the treatment of the manifestations of dysmenorrhea. 10. Drug for the treatment of inflammation and pain in osteoarthritis. 11. Drug group of SCS to provide emergency assistance in anaphylactic shock. 12. Glucorticosteroid for emergency care of asthmatic status. 13. Glucorticosteroid for emergency care of cerebral edema. 14. Glucorticosteroid for local therapy of articular syndrome. 15. Glucorticosteroid for substitution therapy of adrenal insufficiency. At the end of the session to review and analysis of our results with the exhibiting relevant points and assessment. Algorithm for evaluating students' knowledge 1. Baseline knowledge 2. The final level of knowledge. - Tests for KROK-2 - Prescribing of recipes and solving of pharmacological problems 3. Situational problem Students learning activities assess by a 4-point traditional scale, which then converted into points by «Scale convertion of traditional marks in rating points for discipline that finish by final module control», approved by Academic Council of VNMU. 1. 2. 3. Recommended literature: Basic & Clinical Pharmacology/ edited by Bertram G. Katzung. - 10th edition. – USA, 2007. Goodman & Gilman's the pharmacological basis of therapeutics / edited by Laurence L. brunton. - 11th ed. – USA, 2006. Color atlas of Pharmacology/ edited by Heinz Lullmann, Klaus Mohr, Albrecht Ziegler, Detlef Bieger. - 2nd edition. - New York, 2000.