METHODICAL INSTRUCTIONS TO LESSON № 3 FOR STUDENTS
THEME: CLINICAL PHARMACOLOGY OF DRUGS FOR CENTRAL NERVOUS SYSTEM DISORDERS.CLINICAL PHARMACOLOGY OF DRUGS FOR GASTROINTESTINAL DISORDERS.
Aim: To acquaint with actions, pharmacokinetics, therapeutic uses, adverse effects, concomitant use of drugs affecting the CNS: Neuroleptic Drugs, Anxiolytic and Hypnotic Drugs, Antidepressant Drugs, CNS Stimulants; agents influencing on gastrointestinal tract, their clinical usage and complications.
Professional Motivation: Primary and secondary affective disorders are said to be among the most common conditions found in the practice of medicine. The chance of developing a depression during the course of a lifetime ranges from 8 to 20 percent. However, only 20 to 25 percent of depressed people receive treatment for their depression. Twice as many females as males suffer from mood disorders. All clinically used antidepressant drugs (also called thymoleptics) potentiate, either directly or indirectly, the actions of norepinephrine, dopamine, and/or serotonin in the brain.
Disorders involving anxiety are the most common mental disturbances. The symptoms of severe, chronic, debilitating anxiety may be treated with antianxiety drugs (sometimes called anxiolytic or minor tranquilizer), and/or some form of psycho- or behavioral therapy. Since all of the antianxiety drugs also cause some sedation, the same drugs often function clinically as both anxiolytic and hypnotic (sleep-inducing) agents.
Many drugs have applications in the treatment of gastrointestinal diseases. The treatment of GI disease have been profoundly modified by recent development of medicine. Therapeutically, the H2 antihistamine preparations, with their potent antacid effects, have changed the management of peptic ulcer disease. The discovery of the role of Campylobacter pylori in bowel disease has led to advances in its treatment. hepatic and biliary disorders need specific therapy, such as hepatoprotectors, bile drugs, enzyme agents etc.
Basic Level:
Students’ Independent Study Program
I. Objectives for Students’ Studies
You should prepare for the practical class using exist textbooks and lectures. Special attention should be paid to the following:
ANXIOLYTIC AND HYPNOTIC DRUGS
Benzodiazepines: anxiolytics: alprazolam, chlordiazepoxide, clonazepam, clorazepate, diazepam, lorazepam; hypnotics: quazepam,
midazolam, estazolam, flurazepam, temazepam, triazolam.
Other anxiolytic drugs: buspirone, hydroxyzine, zolpidem
Benzodiazepines are the most widely used anxiolytic drugs. They have largely replaced barbiturates and meprobamate in the treatment of anxiety, since the benzodiazepines are more effective and safer.
The benzodiazepines have no antipsychotic activity, nor any analgesic action and do not affect the autonomic nervous system. All of the benzodiazepines exhibit the following actions to a greater or lesser extent:
1. Reduction of anxiety
2. Sedative and hypnotic actions.
3. Anticonvulsant.
4. Muscle relaxant.
ANTIDEPRESSANT DRUGS
Antidepressants (thymoleptics):
TRICYCLIC/POLYCYCLIC antidepressants – amitriptyline, amoxapine, desipramine, doxepin, imipramine, maprotiline, nortriptyline, protriptyline, trimipramine.
SELECTIVE SEROTONIN REUPTAKE INHIBITORS – fluoxetine, fluvoxamine, nefazodone, paroxetine, sertraline, trazodone, venlafaxine.
MONOAMINE OXIDASE INHIBITORS – isocarboxazid, phenelzine, tranylcypromine
DRUGS used to treat MANIA – lithium salts.
CNS STIMULANTS:
Psychomotor stimulants: amphetamine, caffeine, cocaine, methylphenidate, nicotine, theobromine, theophylline.
Psychotomimetic drugs: lysergic acid diethylamide, phencyclidine, tetrahydrocannabinol.
ANTIULCER AGENTS
There are three major landmarks in the management of peptic ulcer disease. The first was the introduction of the H2 receptor antagonists (H2RA) of which the first was cimetidine. This gave effective acid suppression for the first time. The second was the introduction of the proton pump inhibitors (PPI) of which omeprazole was the first. This gave more profound and more prolonged suppression of gastric acid. The third was the discovery that Helicobacter pylori is associated with much peptic ulcer disease, and with this came the rationale for eradication of the organism. As a result of these innovations, the need for surgery for peptic ulcer has been dramatically reduced. H pylori infection is associated with about 95% of duodenal ulcers and 80% of gastric ulcers.
Prevention and treatment of NSAID-induced ulceration and related complications: Where possible, the NSAID should be discontinued when GI ulceration or another GI complication occurs. Misoprostol is considered the drug of choice for preventing NSAID-related ulcers and related GI events. The PPIs and H2-blockers appear to be effective at preventing and also treating NSAID-induced GI complications, but the PPIs may be preferred over H2-blockers based on a recent trial. At least one recent study has shown that the PPIs are as effective as misoprostol in healing NSAID-induced ulceration and that PPI therapy may be better tolerated.Some experts suggest that a PPI should be utilized for the treatment of an active NSAID-induced ulceration, and that combination treatment of a PPI with misoprostol should be reserved for refractory ulcers. There is no rational for combining a PPI with an H2-blocker.
II. Tests and Assignments for Self-assessment:
Multiple Choice:
Choose the ONE best answer.
1. Which one of following is an appropriate therapeutic use for imipramine?
A. Insomnia.
B. Epilepsy
C. Bed—wetting in children
D. Glaucoma.
E. Mania
2. MAO inhibitors are contraindicated with all of the following EXCEPT:
A. Indirect adrenergic agents, such as ephedrine.
B. Tricyclic antidepressants.
C. Beer and cheese.
D. Aspirin.
E. Dopamine.
3. All of the following are observed in patients taking neuroleptic agents EXCEPT:
A. Sexual dysfunction.
B. Increased blood pressure.
C. Altered endocrine function.
D. Constipation.
E. Orthostatic hypotension.
Real-life Situations to be solved:
1. A very agitated young male was brought in the emergency room by the police. Psychiatric examination revealed that he had snorted cocaine several times in the past few days, the last time being 10 hours previously. He was given a drug which sedated him and he fell asleep. What drug should be used in treating cocaine withdrawal?
2. A very upset mother brings in her 10 year old son to ask help in dealing with his bed-wetting. Which agents might alleviate this problem?
III. Answers to the Self-assessment:
Multiple Choice:
Real-life Situations to be solved:
1. The anxiolytic properties of benzodiazepines, such as lorazepam, make them the drugs of choice in treating the anxiety and agitation of cocaine withdrawal. Lorazepam also has hypnotic properties.
2. The tricyclic antidepressants and especially imipramine are effective in this condition because it contracts the internal sphincter of the bladder.
A. Which of the following substances has its major activity as a saline cathartic?
1) Sodium bicarbonate
2) Aluminium hydroxide
3) Magnesium sulfate
4) Calcium carbonate
5) All of above
B. In general, mechanisms of laxation include
1. adding bulk to the stool
2. increasing peristaltic activity
3. emulsifuing aqenons and fatty substances with stool
4. lubricating the passage of stool
5. all of the above
C. Drug which exerts anti-peptic effects through histamine-2 receptor antagonism:
1. Denol
2. Ranitidine
3. Omeprasole
4. Aluminium hydroxide
5. All of above
1. Real-life situation to be solved .
For treatment of heartburn patient regularly used some powder. After a week of drug using vomiting, nausea, abdomen pain, fibrillation, shallow and slow breathing. Biochemical examination show alkalosis. What drug used patient?
III. Answer to the self-assessment
1. A-3: B-5: C-2
2. Natrii hydrocarbonas
Visual Aids and Material Tools: Medical documents, tables, slides.
Students Practical Activities
Student must know:
· clinical pharmacology of neuroleptic drugs (actions, therapeutic uses, adverse effects, cautions and contraindications);
· clinical pharmacology of anxiolytic and hypnotic drugs;
· clinical pharmacology of antidepressant drugs;
· clinical pharmacology of CNS stimulants.
· Mechanism of stimulative activity of sitters on appetite and bowel secretion. Uses of bitters.
· Agent that can stimulate appetite (anorexogenic drugs), mechanism of action, use, side effects, contraindication.
· Principle action, pharmacodymic and usage of agents that reduce gastric secretion.
· Comparative characteristic and usage of antacids.
· Agents of substitute therapy of gastric secretion insufficient.
· Agents increasing gastric secretion.
· Principles of combine usage of different drugs for gastritis, ulcer disease management.
· Drugs’ characteristics that used for reduced pancreatic secretion treatment.
· Characteristic, mechanism of action and usage of agent stimulate bale run out (cholikinetics).
· Pharmacodynamic mechanism of action, use and toxicity of cholagogue drugs, stimulating the producing of bile.
· Agent influencing on intestinal motility.
· Vomiting and antiemetic remedies, mechanism of action, usage, side effects, contraindication.
· Classification of laxative preparations mechanism of their action, use, contraindications.
Student must be able to write a prescription on following drugs: diazepam, oxazepam, flurazepam, lorazepam, zolpidem, pentobarbital, chlorpromazine, thioridazine, haloperidol, amitriptyline, imipramine, maprotiline, fluoxetine, phenelzine; tincture Absinthii herb Centraurii, Phepranonum, Succus gastricus naturalis, Acidum hydrochloricum dilute, Atropini Sulfas, Magnesii oxydum, Aluminii hydroxydum, Denol, Natrii hydrocarbonas, Ranitidinum, Phamotidinum, Gastrocepinum, Plantaglucidum, herba Plantagims majoris, extractun and tincture Belladonae, Pavarerini hydrochoridum, Aceclydinum, Proserinum, Apamorphini hydrochloridum, Aethaperazinum, Scopolamini hydrochloridum, Metoclopramide, “Aeronum”, “Alcoholum” Cholosasum, Nicodinum, Cholagolunu, Magnessi sulfas, Oleum Ricini, Bisacodinum, Phenolphthaleinum, Isapheninum, Isamanum, Extractum Fraugulae, Folium Sennae, Senadexunum, Lopamidum, Nospanum.
Referenses:
1. Bateson AN: The benzodiazepine site of the GABA A receptor: An old target with new potential? Sleep Med 2004;5(Suppl 1):S9.
2. Mohler H, Fritschy JM, Rudolph U: A new benzodiazepine pharmacology. J Pharmacol Exp Ther 2002;300:2.
3. Fricchione G: Generalized anxiety disorder. N Engl J Med 2004;351:675.
4. Bytzer P, O'Morain C: Treatment of Helicobacter pylori. Helicobacter 2005;10(Suppl 1):40.
5. Capell MS: Clinical presentation, diagnosis, and management of gastroesophageal reflux disease. Med Clin North Am 2005; 89:243.
6. Chan FK, Leung WK: Peptic-ulcer disease. Lancet 2002;360:933.
Prepared by ass. prof. Meretskyy V.M.
Methodical instruction was discussed
and adopted at the Department sitting
4.01.2013,
Minute № 7
Methodical instruction was adopted
and reviewed at the Department sitting
27.08.2013 Minute № 1