1. INTRODUCTION AND GENERAL PROBLEMS OF MODERN MEDICAL THERAPY. THERAPY OF DISEASES OF THE NERVOUS SYSTEM

2. KINDS OF TREATMENT Ethiotropic treatment (antibacterials, antidotes) Pathognomonic treatment (antihypertensive, antiarrhythmic, antiinflammatory agents, antidepressants) Symptomatic treatment (pain-killers, antipyretics) Substitutional therapy (enzymes, hormonal medicines, vitamines) Preventive treatment (vaccines, antiviral drugs)

3. Terminology Symptom - any sensation or change in bodily function that is experienced by a patient and is associated with a particular disease SYNDROME - a pattern of symptoms indicative of some disease (Reye's syndrome - acquired brain disorder following acute viral infections (especially influenza or chicken pox) in young children )Reye's syndrome

4. FACTORS THAT INFLUENCING ON TREATMENT EFFECTICITY Exogenic Chemical structure and physical&chemical characteristics of agents, medicinal form, ways of using, drug dose, dietery, environmental factors (metheorological, etc.) Endogenic Age, sex, menstruation, pregnancy, combined pathological stages

5. MEDICINAL FORM AND WAYS OF USING Biofarmaciya is engaged in the study of influence of medical form on a pharmacodynamics and pharmacokinetics of medications. Bioavailability of medications – complex of pharmacokinetic processes due to which the effective concentration of medication is created in the area of specific receptors (part of preparation, which got in blood, in relation to a that amount which was applied)

6. INFLUENCE OF PATIENT’ S SEX ON DRUGS ACTION Morphin, nicotine, strychnin - the sensitiveness of women is more high Changes of metabolism of theophyllin, methylprednisolon, paracetamol in the different phases of menstrual cycle Pregnancy – absorbtion gets worse, biotransformation of medications is slowed Menstruation - anticoagulants can cause the massive uterine bleeding

7. INFLUENCE OF BIOLOGICAL RHYTHMS Administration of GKS between 6-8 h. of morning At night maximal sensitiveness of bronchial tubes to histamin and acetilcholin, it is that is why expedient to appoint the prolonged forms of theophyllin in the evening Hypertensive crises more frequent develop between 16-24 hours Maximal diuretic action at the reception of diuretic preparations is observed in the morning (to 10 h.) Toxicity of haloperidol for a day long differs in 5 times

8. INFLUENCE OF PATHOLOGICAL PROCESSES ON MEDICATIONS ACTION Diminishing of tolerance to cardiac glycosides - at miocarditis Cardiac glycosides operate in the conditions of cardiac insufficiency Paracetamol and other antipyretics reduce a temperature only at hyperpyrexia Slowing of metabolism, growth of toxicity of medications at pathology of liver Slowing of leadingout of medications at pathology of kidneys Inhibition of absorbtion of fat-disolved vitamins at violation of biliation At smoking the risk of tromboembolic complications grows at the reception of anticoagulants, hormonal contraceptives

9. BASIC SYMPTOMS AND SYNDROMES OF DEFEAT OF NERVOUS SYSTEM PAIN DIZZINESS INCREASE OF INTRACRANEAL PRESSURE AND HYDROCRANIUM DEMENCIYA VIOLATION OF CONSCIOUSNESS COMMA

10. PAIN Development of sharp pain is related to the pain irritations of superficial and deep fabrics and internalss or parafunction smooth musculature of internalss without the damage of fabrics. The neurological reasons of sharp pain - traumatic, infectious, dismetabolic and other damages of CNS. The mechanisms of chronic pain depending on a prevailing role in its genesis of different departments of the nervous system divide into peripheral, central, united peripheral and central, psycological

11. Headache Headache— one of the most frequent symptoms of different diseases. It is arisen up as a result of irritation of nervous completions of vessels of chairman or brain-tunics and depending on reason has the features. Nosotropic types of headache: it is vascular – headache of muscular tension ;- liquorodynamic ; - neuralgic; - hallucinogenic (psychalgya); headache of the mixed genesis.

12. Dizziness Dizziness is feeling of loss of orientation of body in space. Meets at disfunction of the sensory antihunt systems - vestibular, visile and somatosensor. Dizzinesses are quite often accompanied by : falling nystagmus an ataxia in extremities visceral violations (paleness, sweating, change of pulse and AP, nausea, vomitting, diarhea).

13. Increasing of intracraneal pressure The increase of intracraneal pressure can be conditioned: – by the presence of intracraneal volume process; – by the increase of volume of cerebrum (edema of the brain); – by the increase of level of cerebrospinal liquid at a hydrocephaly – by the increase of volume of blood at vasodilatation in the conditions of hypercapnia.

14. DEMENTIA Dementia is the state, which arises up as a result of organic defeat of cerebrum and characterized violation of intellectual activity, worsening of memory of thought, understanding, language, cognitive functions. Dementia meets for old years people (more senior 65 years -10 %, more senior 80 years - 20 %). Select dementia, associated with degenerative neurological diseases and those which develop on a background various neurological and somatic diseases (intoxications, tumours, craniocerebral trauma, metabolic violations, epilepsy, neuroinfection, internalss conditioned illnesses, and by the inherited somatic and neurological diseases).

15. CONFUSED CONSCIOUSNESS Under confusing of consciousness understand impossibility to think with sufficient speed and clarity. Patients do not perceive that surrounds them, can not estimate a situation and does not control the function of pelvic organs. Types of violation of consciousness: stupor, sopor coma, delirium, twilight state of consciousness

16. Stupor - is a partial exception of consciousness with the maintainance of verbal contact on a background enhanceable perception of all external irritants decline of own activity. Sopor - psychical and physical activity expressed to the minimum, a reaction on linguistic commands absents and is inadequate. Coma characterized the protracted oppression and loss of consciousness with the making progress deepening of disorders vitally of important organs, up to death of brain. Death of brain is the state at which the brain is damaged nonreversible and does not function, and cardiac and respiratory functions are supported artificially.

17. COMA The comatose states can be conditioned: — by violations of exchange and intoxications of endogenous or exogenous character; — by cerebral defeats.

18. Types of the comatose states A diabetic coma Hypoglycemia coma Cerebral coma Uremic coma Hepatic coma Coma at Addison illness Thyroid coma

19. NERVOUS SYSTEM DISEASES Divided on: disease of the central, peripheral and vegetative nervous system. In dependence on pathogeny of nervous disease divide into three groups: Inflammatory diseases (meningitis, encephalitis, myelities). Vascular diseases (ischemic and hemorragic strokes of cerebrum, migraine, sharp necrotizing hemorragic stroke). Demyelinating (degenerative distrophical) diseases (disseminated sclerosis, sharp disseminated encephalomyelitis, syringomyelia, lateral amyotrophic sclerosis)

20. MENINGITIS Meningitises are sharp infectious diseases with the overwhelming defeat of arachnoid and soft shells of cerebral and (or) spinal brain. Meningitises can run across in form leptomeningitis (inflammation of soft and arachnoid shells), to the arachnoiditis (isolated inflammation of arachnoid shell, meets rarely) and pachymeningitis (inflammation of hard cerebral shell)

21. MENINGITIS. CLINICAL SYMPTOMS Meningeal syndrome: headache, intoxication, meningeal symptom, change of composition of neurolymph and immunity. Headache- holding apart, mainly in frontal, temporal or cervical areas. Meningeal symptoms: Kernig symptom, Brudzinsky. Kernig symptom: overhead is rigidity of cervical muscles; lower: initial position: a patient lies on the back, a leg is arcuated at right angles in hip and knee joints. At the attempt of straightening there is tension of muscles of back surface of thigh in a knee-joint. Brudzinsky symptom: overhead: consists in bending of thigh and shin at an attempt to incline a chairman lying on the back of patient forward; lower— in bending of contralateral leg at the attempt of straightening and raising of other leg. An important symptom of meningeal syndrome is general hiperesthesia. Patients painfully react on any external irritants — bright light, loud sound, touch. Level of lg А, Ig G, Ig М changes in blood serum

23. Brudzinsky symptom

25. Central Nervous System Stimulants Stimulants are drugs that exert their action through excitation of the central nervous system. Psychic stimulants include caffeine, cocaine, and various amphetamines. These drugs are used to enhance mental alertness and reduce drowsiness and fatigue. Stimulants increase alertness, attention, and energy, which are accompanied by increases in blood pressure, heart rate, and respiration.

27. Amphetamine Amphetamine Levoamphetamine (Benzedrine), dextroamphetamine (Dexedrine), and methamphetamine (Methedrine) These agents produce a feeling of well being and euphoria. Cocaine and amphetamine have a significant abuse potential because of these mood enhancing effects. Tachyphylaxis or tolerance to the stimulating actions of these agents can develop. These agents produce an increase in systemic arterial blood pressure. Heart rate can either decrease or increase depending on the levels of the drug. Drug toxicity effects multiple organ systems and can result in arrhythmias, hypertension, psychosis and convulsions. The local anesthetic activity of cocaine can also contribute to rhythm disturbances. Clinical Therapeutics of CNS Stimulants 1) Because of its local anesthetic activity, cocaine has some limited uses as a oral, nasal and ophthalmic local anesthetic. 2) Appetite suppression - amphetamine and analogs 3) Narcolepsy - methylphenidate, amphetamine analogs 4) Attention deficient disorder with hyperactivity (ADHD) - methylphenidate, amphetamine and analogs

28. Tolerance and Dependence Regular use of amphetamines induces tolerance to some effects, which means that more and more of the drug is required to produce the desired effects. Tolerance does not develop to all effects at the same rate, however; indeed, there may be increased sensitivity to some of them. Chronic users may also become psychologically dependent on amphetamines. Psychological dependence exists when a drug is so central to a person's thoughts, emotions, and activities that the need to continue its use becomes a craving or compulsion. Experiments have shown that animals, when given a free choice, will readily operate pumps that inject them with cocaine or amphetamine. Animals dependent on amphetamines will work hard to get more of the drug. Physical dependence occurs when the body has adapted to the presence of the drug, and withdrawal symptoms occur if its use is stopped abruptly. The most common symptoms of withdrawal among heavy amphetamine users are fatigue, long but troubled sleep, irritability, intense hunger, and moderate to severe depression, which may lead to suicidal behavior. Fits of violence may also occur. These disturbances can be temporarily reversed if the drug is taken again.

30. Antidepressant Drugs All are effective in relieving depression, but they differ in their adverse effects. All must be taken for 2 to 4 weeks before depressive symptoms improve. They are given orally, absorbed from the small bowel, enter the portal circulation, and circulate through the liver, where they undergo extensive first-pass metabolism before reaching the systemic circulation. They are metabolized by the cytochrome P450 enzymes in the liver. Many antidepressants and other drugs are metabolized by the 2D6 or 3A4 subgroup of the enzymes.

31. Antidepressant Drugs indications for use Antidepressant drug therapy may be indicated if depressive symptoms persist at least 2 weeks, impair social relationships or work performance, and occur independently of life events. In addition, antidepressants are increasingly being used for treatment of anxiety disorders. TCAs may be used in children and adolescents in the management of enuresis (bedwetting or involuntary urination resulting from a physical or psychological disorder). In this setting, a TCA may be given after physical causes (eg, urethral irritation, excessive intake of fluids) have been ruled out. TCAs are also commonly used in the treatment of neuropathic pain. MAOIs are considered third-line drugs, largely because of their potential for serious interactions with certain foods and other drugs.

33. Tranquilizers Tranquilizers are divided into a Major Tranquilizer and Minor Tranquilizer group. Major Tranquilizers include phenothiazines, indoles, thioxanthenes, butyrophenones, piperazine compounds, and piperidine compounds. Trade names include drugs such as Thorazine, Haldol, Clozaril and Risperdal. These drugs are referred to as Neuroleptics and are most commonly prescribed as anti-psychotics. This type of tranquilizer is not widely abused. Minor Tranquiliers are the more common of the tranquilizers. These include the Benzodiazepines, known by trade names such as Valium, Xanax, Serax, Ativan, Klonopin, Librium and Tranxene. There are also combination drugs such as Librax. These drugs are very commonly prescribed as anti-anxiety drugs, or anxiolytics. They are often referred to as Sedative/Hypnotics. They are central nervous system depressants with specific sites of action. Slang references to these drugs include Libs, Tranks, Benzos, and Vees. The primary route of administration for these medications is oral, swallowed as a tablet, capsule, or liquid. They are also available in solution form for intravenous use.

34. Effects The minor tranquilizers induce a feeling of calm and relaxation. Depending on the medication and dosage this can range from feelings of mild euphoria to states of drowsiness, confusion, and lightheadedness. Effects can include hostility, blurred vision, hallucinations, lethargy, headaches, memory loss, disorganized thinking, and irritability. Other common effects include impaired motor function, dry mouth, nausea, vomiting, and sweating. Certain Benzodiazepines, including Valium, can produce toxic reactions when combined with alcohol. The Benzodiazepines (Minor Tranquilizers) can be addictive even at prescribed dosages if the medication is administered for long periods of time. The withdrawal process can be painful and even life-threatening with some of the Benzodiazepines. Physical withdrawal symptoms can include general pain, stomach cramps, diarrhea, flu-like symptoms, and heart palpitations. There is also the possibility of seizure with certain medications. The withdrawal can also produce psychosis, hallucinations, delusions, paranoia, and depression.

35. SEDATIVE - HYPNOTIC AGENTS Drug Classes of Sedative-Hypnotics Barbiturates Benzodiazepines Alcohols/Imidazopyridine Barbiturates: Duration of Action Onset -PhenobarbitalLong (6-12 h) 20 min -PentobarbitalIntermediate (4-6 h) 3 min -SecobarbitalShort-Intermediate (3-6 h) 2 min -Thiopental/Short (15- 30 min) few seconds Methohexital [All are derivatives of barbituric acid]

36. 1.Sites of Action: Barbiturates act at multiple levels of the CNS. Sedative-Hypnotic effect involves, in particular, the reticular activating system. 2.Mechanism of Action: -facilitate the action of GABA at GABAA receptors by increasing the duration of channel openings (bind at a distinct site from that bound by benzodiazepines) -reduce glutamate-induced depolarization via inhibitory action on AMPA- type glutamate receptors -at high doses, reduce the responsiveness of voltage-dependent Na+ channels and directly active GABAA receptors

37. 3.CNS effects: Dose-dependent progression: (lower margin of safety) Sedation → ‘Hypnosis’ → Anesthesia → Coma → Death* Anticonvulsant/antiepileptic -all barbiturates stop convulsions in progress if given IV at high enough dosage -some can prevent seizures (eg. phenobarbital), but are not drugs of first choice owing to sedative effect (except for children); used to maintain control of status epilepticus For animal surgery, methohexital may be used as an induction agent only. Pentobarbital (Nembutal®) used, but has a very low margin of safety in rodents and guinea pigs (consequently, often agent of choice for rapid, humane euthanasia)

38. Adverse effects: -respiratory depression via action on respiratory center in the medulla is the usual cause of death with overdose; depression occurs at supra-hypnotic doses -generalized CNS depression: impaired motor and cognitive skills -uncommon: rash, dermatitis, decreased red blood cells and platelet -physiological and psychological dependency: significant incidence of abuse

39. Benzodiazepines: Duration of Action -FlurazepamLong (30-100h) [pro-drug] -Diazepam “ [active metabolites] -TemazepamIntermediate (10- 40h) -TriazolamShort (1-3h)

41. Effects and uses: -drugs of choice for sedation and ‘hypnosis’ (higher margin of safety) flurazepam: long-acting pro-drug temazepam: slowly absorbed, intermediate acting drug with no active metabolites; most highly prescribed hypnotic triazolam: rapid but short-acting drug diazepam (Valium®): long-acting drug; may be useful as adjunct in animal surgery -at sedative doses may cause euphoria and ‘disinhibition’ -anticonvulsant (primary drug for initial treatment of status epilepticus) -anxiolytic -muscle relaxation (used in spasticity; largely via effect in spinal cord) -ethanol withdrawal

42. Adverse reactions: -‘hangover’ (esp. with benzodiazepines with long half-lives: diazepam) -early morning awakening for benzodiazepines with short half-lives: triazolam -impaired motor and cognitive skills -anterograde amnesia -chronic use/dependence: more intense withdrawal symptoms with benzodiazepines having short half-lives ‘rebound’ insomnia (and/or anxiety), restlessness and even seizures (severity and frequency of dependence less than that found for barbiturates)

43. Alcohols/Imidazopyridine: Duration of Action -Chloral HydrateLong (6-10h) [pro-drug] -ZolpidemShort (several hours) -ZaleplonShort (1-3h)

44. 1.Chloral hydrate rapidly metabolized in liver to triethanolamine - pharmacologically active (also metabolized to trichloroacetic acid, which is toxic and may accumulate); mechanism of action is not known -oft-used sedative-hypnotic for animals undergoing surgery -institutional use 2.Zolpidem: non-benzodiazepine that acts via subtype of GABAA receptor -an effective, short-acting hypnotic agent (most highly prescribed hypnotic) -much lower risk of tolerance and dependency; but some mild cognitive impairment during onset -little anticonvulsant or muscle relaxant effects 3.Zaleplon: an alternative non-benzodiazepine that also acts via the GABAA receptor -similar to Zolpidem, but without effects on cognitive function

45. Narcotic Analgesic Drugs