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CNS Stimulants 1. Analeptics 2. Anorexiants 3. Antidepressants 4. Serotonin agonists CNS Stimulants: Adverse effects • CVS: Palpitation, tachycardia, hypertension, angina, dyshythmia • CNS: Nervousness, restlessness, anxiety • Endocrine: Hypoglycemia, hyperglycemia • GIT: Nausea, vomiting,diarrhea Analeptic • Used to stimulate respiration when natural reflex is lost • H-cholinomimetic (reflex analeptic) • Central analeptic (Aminophyllin, theophylline,Caffeine, Doxapram) Did You Know? • Caffeine is a xanthine alkaloid compound that acts as a stimulant in humans. Caffeine is sometimes called guaranine when found in guarana, mateine when found in mate, and theine when found in tea. It is found in the leaves and beans of the coffee plant, in tea, yerba mate, and guarana berries, and in small quantities in cocoa, the kola nut and the Yaupon Holly. Overall, caffeine is found in the beans, leaves, and fruit of over 60 plants, where it acts as a natural pesticide that paralyzes and kills certain insects feeding upon them. Chemical Properties Molar Mass = 194.19 g mol−1 Density: 1.2 g/cm³ Phase: Solid Melting Point: 237 °C Boiling Point: 178 °C Uses of Caffeine • Caffeine is a central nervous system (CNS) stimulant, having the effect of temporarily warding off drowsiness and restoring alertness. Beverages containing caffeine, such as coffee, tea, soft drinks and energy drinks enjoy great popularity: caffeine is the world's most widely consumed psychoactive substance. In North America, 90% of adults consume caffeine daily. Metabolizing Of Caffeine • Caffeine is completely absorbed by the stomach and small intestine within 45 minutes of ingestion. After ingestion it is distributed throughout all tissues of the body and is eliminated by first-order kinetics. The half-life of caffeine varies widely among individuals according to such factors as age, liver function, pregnancy, some concurrent medications, and the level of enzymes in the liver needed for caffeine metabolism. In healthy adults, caffeine's halflife is approximately 3-4 hours. In women taking oral contraceptives this is increased to 5-10 hours, and in pregnant women the half-life is roughly 9-11 hours. Caffeine can accumulate in individuals with severe liver disease when its half-life can increase to 96 hours. Caffeine • • • • AP Hate rate Respiratory stimulation Adjunctive effect Doxapram • over dosage of CNS depressant • COPD (chronic obstructive pulmonary disease • Respiratory depression in postoperative recovery period Doxapram: Contraindication • • • • Newborn Epilepsy Hypertension Stroke Amphetamines • Produce mood elevation or euphoria, increase mental alertness and capacity for work, decrease fatigue and drowsiness, prolong wakefulness. Amphetamines usage • Narcolepsy • ADHD (attention-deficit/hyperactivity disorder Amphetamines • Tolerance • Psychological dependence • High abuse potential (under Control Substance Act Methylxanthines • COPD (chronic obstructive pulmonary disease • Respiratory depression in postoperative recovery period Anorexants • Central acting (Benzphetamine, diethylpropion, Sibutramine) • Metabolism acting (orlistat) Antidepressants • Used to treat depression • Depression, common feelings – Pessimism – Worry – Intense sadness – Loss of concentration – Slowing of mental processes – Problems with eating and sleeping Serotonin agonist (Sumatriptan) • Treatment of migraine Antidepressants Common Symptoms of Depression – Loss of interest in usual activities – Low self-esteem – Self-pity – Significant weight loss or gain – Insomnia or hypersomnia – Extreme restlessness – Loss of energy – Feelings of worthlessness – Diminished ability to think – Feelings of guilt – Recurrent thoughts of death – Suicide attempts Antidepressants Depression • Women are affected more often than men • When men are affected, it is usually later in life • Levels of neurotransmitters in the brain may be a causative factor Mood Disorders • Mania • Bipolar Disorder • Unipolar Disorder Mood Disorders • Mania Mood of extreme excitement, excessive elation, hyperactivity, agitation, and increased psychomotor activity • Bipolar Disorder • Unipolar Disorder Mood Disorders • Mania • Bipolar Disorder Mood swings alternate between major depression and mania • Unipolar Disorder Mood Disorders • Mania • Bipolar Disorder • Unipolar Disorder Major depression with no previous occurrence of mania Treatment for Depression Electroconvulsive Therapy • Introduction of brief, but convulsive electrical stimulation through the brain • Can induce seizures • Effective for major and delusional depression Antidepressants • Selective Serotonin Reuptake Inhibitors (SSRIs) • Cyclic Antidepressants • Monoamine Oxidase Inhibitors (MAOIs) Antidepressants Selective Serotonin Reuptake Inhibitors (SSRIs) – Block the reuptake of serotonin, with little effect on norepinephrine – Fewer side effects than older meds Treatments Cyclic Antidepressants – Two Types • Tricyclic antidepressants (TCAs) • Tetracyclic antidepressants – Prevent reuptake of norepinephrine and/or serotonin – Agents in this class differ in adverse effects, cost, and response Treatments Monoamine Oxidase Inhibitors (MAOIs) Allows for buildup of norepinephrine at the synapse Drug List SSRIs for Depression • • • • • • • citalopram (Celexa) escitalopram (Lexapro) fluoxetine (Prozac, Sarafem) fluvoxamine paroxetine (Paxil) sertraline (Zoloft) venlafaxine (Effexor) Dispensing Issues Warning! Look-Alike Drugs – Prozac and Proscar (urinary drug) – Zoloft and Zocor (high cholesterol) – Celexa and Cerebyx (seizures) and Celebrex (arthritis) SSRI Dispensing Issues Warning! • Do not discontinue abruptly • Alcohol consumption should be avoided while taking these medications fluoxetine (Prozac) • Indicated for major depression and obsessive-compulsive disorder (OCD) • Anorexia is a possible adverse effect • Take in the morning to avoid insomnia paroxetine (Paxil) • Indicated for depression, obsessivecompulsive disorder, and panic disorder venlafaxine (Effexor) • Blocks reuptake of serotonin and norepinephrine • Indicated for depression • May cause increase in blood pressure and blurred vision sertraline (Zoloft) • Indicated for depression and obsessivecompulsive disorder • Primary side effect is nausea • May also cause drowsiness citalopram (Celexa) • Indicated for depression and obsessivecompulsive disorder • Minimal drug interactions escitalopram (Lexapro) • Similar to Celexa • More potent with fewer side effects Drug List Cyclic Antidepressants Tricyclic • amitriptyline (Elavil) • clomipramine (Anafranil) • desipramine (Norpramin) • doxepin (Sinequan) • imipramine (Tofranil) Drug List Cyclic Antidepressants Tricyclic • nortriptyline (Aventyl, Pamelor) • protriptyline (Vivactil) • trimipramine (Surmontil) Tetracyclic • maprotiline Tricyclic Antidepressants Dispensing Issues Warning! • Improvements are usually seen in 10 to 21 days • Can be cardiotoxic in high doses • May cause postural hypotension Tricyclic Antidepressants Dispensing Issues Warning! Do not discontinue abruptly. Cyclic Antidepressants Side Effects • Sedation is common, but tolerance usually occurs • Have many anticholinergic effects Discussion Why would cyclic antidepressants be prescribed for bed wetting in children? Discussion Why would TCAs be prescribed for bed wetting in children? Answer They may be prescribed because of their anticholinergic side effects. Drug List MAOIs • phenelzine (Nardil) • selegiline (Eldepryl) • tranylcypromine (Parnate) MAOI Dispensing Issues Warning! Be cautious of many interactions with foods such as aged cheeses, concentrated yeast extracts, pickled fish, sauerkraut, broad bean pods, chocolate, and alcohol. MAOI Dispensing Issues Warning! If changing to another class of antidepressant, patient must have a two-week “wash out” period before starting the new medication. Drug List Other Antidepressants • bupropion (Wellbutrin, Zyban) • mirtazapine (Remeron) • trazodone (Desyrel) trazodone (Desyrel) • Prevents reuptake of serotonin and norepinephrine • Has a better side effect profile than TCAs • Caution: possible interaction with Ginkgo bupropion (Wellbutrin, Zyban) • Dopamine-uptake inhibitor • Does not cause sedation, blood pressure changes, or ECG changes • Do not discontinue abruptly • Approved in the aid of smoking cessation Other Antidepressant Dispensing Issues Warning! • Wellbutrin SR = BID dosing • Wellbutrin XL = QD dosing Bipolar Disorders Signs or Symptoms – Decreased need for sleep – Elevated or irritable mood – Excessive involvement in pleasurable activities with a big potential for painful consequences – Grandiose ideas – Pressure to keep talking – Racing thoughts Discussion What is the drug of choice for treating bipolar disorders? Discussion What is the drug of choice for treating bipolar disorders? Answer Lithium Discussion What is the two-fold objective of drug therapy for bipolar disorder? Discussion What is the two-fold objective of drug therapy for bipolar disorder? Answer Treat acute episodes Prevent subsequent attacks Drug List Drugs to Treat Bipolar Disorders • • • • • carbamazepine (Epitol, Tegretol) divalproex (Depakote) lithium (Eskalith, Lithobid) olanzapine-fluoxetine (Symbyax) valproic acid (Depakene) PSYCHOTROPIC DRUGS PSYCHOTROPIC DRUGS Drugs with depressive type of action 1. 2. 3. 4. Neuroleptics (antipsychotics) Tranquilizers (anxiolytics) Sedative drugs Normotymics (tymoleptics, tymoanaleptics) Drug with stimulative action 1. 2. 3. 4. Antidepressants Psychomotor stimulants Nootropic drugs Drugs which increase general tone (adaptogens) Psychotomimetics (psychodysleptics) 1. 2. LSD Cannabis sativa L. NEUROLEPTICS • Derivatives of phenotiazine: aminasine, triftiazine, etaperasine, tioridazine • Derivatives of tioxanten: chlorprotixen • Derivatives of butyrophenon: galoperidol, droperidol • Derivatives of piperasinedibenzodiazepine: clozapine • Derivatives of indole: reserpin, sulpyrid (eglonil) NEUROPLEPTICS “Typical” – derivatives of phenotiazine, tioxanten, butyrophenon – they cause disorders of extrapyramidal system function – syndrome of parkinsonism “Atypical” – derivatives of indole, benzodiazepine – they cause those negative reactions very rarely Aminasine (chlorpromasine) • 1951 – aminasine was introduced into clinical practice • It brought considerable changes into situations of psychiatric clinics • Before appearance of aminasine for treatment of psychologically sick patients insulin or electric shock were widely used, in some cases - lobotomy Mechanism of action of neuroleptics Influence on dopamine (D2), noradrenergic, serotoninergic, GABAergic, cholinergic receptors Properties of neuroleptics • Antipsychotic action - they eliminate productive symptoms of psychosis (delirium and hallucinations), affective disorders • They eliminate psychomotor excitation with condition of consciousness Administration of antipsychotic action of neuroleptics Treatment of psychosis • • • • Schizophrenia Maniac-depressive psychosis Alcohol psychosis Reactive psychosis In a case of psychomotor excitation of various etiology Delirium tremens – alcohol psychosis Influence of neuroleptics on psychical activity 1. Drugs with psychosedative action – they cause condition of psychomotor indifference (apathy, decreasing of moving activity, retarded emotions and wishes, disappearance of initiative) Aminazine, clozapine (leponex), chlorprotyxen, haloperidol, droperidol Peculiarities of usage: psychosis with manifestations of excitation Contraindications: psychosis with retardness, inertia, depression, stupor, apatho-abulic syndrome Neuroleptics with psychosedative action Influence of neuroleptics on psychical activity 2. Drugs which stimulate psychical activity (increase mimics and liveliness, increase moving activity, improve the mood) Triftazin, ethaperazin, moditen, majeptil Peculiarities of usage: psychosis with psychomotor retardness, apatho-abulic conditions, stupor conditions Contraindications: affective disturbances, mania, psychomotor excitation Other properties and indications for administration of neuroleptics • Drugs with psychosedative action – for potentiation of action of soporifics, opioid and nonopioid analgesics, drugs for general anesthesia, local anesthetics, for example, neuroleptanalgesia • Anti-emetic action (elimination of vomiting of central origin): brain tumors, radial and chemical therapy, intestinal impassability, intoxication with heart glycosides, apomorphine and other drugs • Decreasing of body temperature (only in the case of simultaneous hypothermia) • Decreasing of blood pressure (alpha-adrenoblocking properties – aminasine, droperidol) – in case of hypertensive crisis, lungs edema Side effects of neuroleptics • Extrapyramidal disorders: muscular hypertonus, general constraint, tremor of hands, tongue, mandible, head, seizure contractions of muscles, vegetative crisis For treatment – cyclodol (levodopa is contraindicated because it diminishes therapeutic effect of neuroleptics) • Orthostatic collapse • Complicated nose breathing, hypostatic, aspirate pneumonia • Dyspeptic disorders: anorexia, changes of taste • Abdominal pain • Constipation • Damage of the liver (cholestasis) • Granulocytopenia (especially clozapin) • Hyperglycemia, dysmenorrhea, galactorrhea, hyperthyrosis, gynecomastia, impotence • Aminasine has a considerable irritable action syndrome of parkinsonism TRANQUILIZERS • Agonists of benzodiazepine receptors: - derivatives of benzodiazepine – chlozepid, sybazon, phenazepam, gidazepam • Agonists of serotonine receptors: buspyrone • Drugs with other mechanisms of action: - derivatives of diphenilmethan: amisyl - derivatives of propanediole: meprotan Properties of tranquilizers • Anxiolytic properties – eliminate feeling of anxiety, restlessness, fear, aggressiveness, irritability, cause peace, careness, decreasing of moving activity • Hypnotic (somnolent) action • Myorelaxing action (of central genesis) • Antiseizure action Duration of action of tranquilizers • Drugs of long lasting action: diazepam, phenazepam, chlozepid • Drugs of medium action duration: lorazepam, alprazolam • Drugs of short action duration: midazolam “DAY” TRANQUILIZERS Gidazepam Mezapam (rudotel) Grandaxyn (tophizopam) Trioxazyn Buspyron Administration of tranquilizers Anxiolytic action • Treatment of neurosis, accompanied by fear, anxiety, exertion, increased irritability, insomnia • In case of headache and heart pain of neurotic origin, so called organic neurosis • In case of abstinence in alcohol and drugs addicts • In case of diencephalons crisis (sybazon) Tranquilizers do not diminish productive symptoms of psychosis! Usage of tranquilizers • Hypnotic action – they cause sleep, which is very close to physiological one according to its parameters Nitrazepam Phenazepam Diazepam Chlozepid • Depression of CNS – for atharalgesia Sybazon Midazolam Administration of tranquilizers Anti-seizure and myorelaxing action (depression of CNS structures, braking polysynaptic spinal reflexes) sybazon, fenazepam • In a case of seizures of any etiology (epileptic status, tetanus, poisoning with seizure causing poisons) sybazon is introduced intravenously (intramuscularly) – 2-4 ml of 0,5 % solution repeatedly (maximal daily dose – 14 ml) • To eliminate muscle tension in a case of radiculitis, arthritis, myositis, bursitis Seizures (tetanus) drug of a first choice - Sibazon SIDE EFFECT OF TRANQUILIZERS • Psychological and physical addiction Prophylaxis: 1. Duration of treatment course should not be more than 2 months 2. Repeated course – not earlier than after 3 weeks break • Sleepiness, reeling walk, retarded reactions tranquilizers should not be administered in ambulatories to people whose professions are connected with quick reactions • Paradox reaction of excitation, insomnia • Dizziness, decreasing of libido, disturbances of menstrual cycle • Uncontrolled urination, defecation, ataxia, dysartria • Acute poisoning in case of overdosing FLUMAZENIL (ANEXAT) ANTAGONIST OF TRANQUILIZERS Combination of tranquilizers with alcohol-containing drinks is absolutely contraindicated (pathological alcohol intoxication) LITHIUM DRUGS LITHIUM CARBONATE INDICATIONS FOR ADMINISTRATION OF LITHIUM DRUGS • Prophylaxis and treatment of endogen (affective) psychosis: maniac-depressive, schizo-affective, organic affective • Prophylaxis and treatment of affective disturbances in patients with epilepsy, chronic alcoholism, in psychopaths Method of lithium drugs administration • It is administered orally • Treatment concentration of lithium in blood – 0,6-0,8 mmol/l (not more than 1,5-1,6 mmol/l) • The effect develops after few days – 5-6 months • Small width of therapeutic action (treatment with lithium drugs needs the same attentiveness from the doctor as treatment with insulin) Acute poisoning with lithium drugs It develops if the concentration is over 1,5-2 mmol/l Development of constant nausea and tremor during treatment with lithium means that the dose should be decreased SYMPTOMS OF POISONING • Nausea, vomiting, diarrhea • tremor, general muscular weakness, twitching muscles • Noise in the ears, unclear vision, somnolence, dysartria • Changes of handwriting: massive, bold • Local neurological symptoms, meningism • Oliguria • Changes in ECG, arrhythmia, decreasing of BP • Sopor, coma • Death – from hypostatic pneumonia Treatment of intoxication with lithium drugs • A lot of drinking, 10% solution of sodium chloride (till 300 ml/day), 5% solution of sodium hydrocarbonate (till 300 ml / day) intravenously • Mannit, urea (saluretics are contraindicated!) • Pyracetam, vinpocetin • Prophylaxis of pneumonia – antibiotics • Control of water-electrolyte balance, acid-base balance • Symptomatic therapy, for example, in case of seizures - sybazon • Haemodialysis if necessary Prophylaxis of intoxication with lithium drugs • Salt in day ration should not be limited • A lot of drinking • Do not indicate saluretics, sweatstimulating drugs • Heavy physical work or other situations, accompanied by considerable sweating should be avoided SEDATIVE DRUGS • Bromides • Drugs of plant origin: valerian, dog nettle, melissa, passiflora etc. They do not cause addiction, somnolence, myorelaxation, ataxia Valeriana PASSIFLORA Leonurus L. dog nettle ADMINISTRATION OF SEDATIVE DRUGS • • • • • • Neurosis Neurasthenia Hysteria Increased irritability Insomnia Primary stages of essential hypertension Bromism • Cause – accumulation of bromide ions in organism in case of their prolonged administration as a result of material accumulation • Symptoms: rhinitis, cough, conjunctivitis, skin rash, general weakness, memory disorders • Treatment: sodium chloride (10-20 g / day), a lot of drinking (3-5 l / day), regular and frequent cleaning of skin and digestive tract DRUGS FOR GENERAL ANESTHESIA General anesthesia = Narcosis (from the Greek narkosis – numbness, rigidity) – Generalized reversible depression of the central nervous system such that perception of all senses is ablated, condition which is characterized by loss of consciousness, pain feelings, depression of reflexes and relaxation of skeletal muscles and which is obtained by administration of drugs for general anesthesia “Gentlemen, this is no humbug.” 1846 TG Morton: First public demonstration of ether administration for excision of neck mass Desirable Components of Anesthesia 1. 2. 3. 4. 5. 6. 7. Immobility in response to noxious stimulus Amnesia Analgesia Unconsciousness Muscle relaxation Loss of autonomic reflexes Anxiolysis CLASSIFICATION OF GENERAL ANESTHETICS Inhalational agents primarily used for maintenance •Volatile agents Isoflurane Sevoflurane Desflurane Halothane (Ftorothane) Enflurane •Anesthetic gases Nitrous Oxide - currently used CLASSIFICATION OF GENERAL ANESTHETICS Intravenous agents primarily used for induction •Barbiturates (Thiopental-sodium) •Benzodiazepines (Midasolam, diazepam) •Etomidate •Ketamine •Propofol •Propanidid •Sodium oxybutyrate •Predion Unitary Hypothesis General anesthesia can be caused by a remarkable number of structurally diverse molecules Molecular Mechanism(s) of General Anesthesia Xe Isoflurane Halothane ...... Molecular (lipids & receptors) Cellular (synapses) A Working Hypothesis • Anesthetics enhance inhibitory postsynaptic channel activity (GABAA and glycine receptors) • Anesthetics inhibit excitatory synaptic channel activity (nicotinic acetylcholine and glutamate receptors) Effects of General Anesthesia Low Dose Effects High Dose Effects •Amnesia •Deep sedation •Euphoria •Muscle relaxation •Analgesia •Diminished motor responses •Hypnosis •Diminished autonomic responses •Excitation •Hyperreflexia •Myocardial protection from ischemia •Cardiovascular/respiratory depression •Hypothermia Measures of Anesthetic Potency • MAC: minimum alveolar concentration • MAC is the concentration of anesthetic that produces immobility in 50% of patients exposed to a noxious stimulus. • MACawake: MAC at which response to commands are lost • amnesia, loss of awareness • • MACBAR: blunt autonomic response MACintubation: response to intubation Stages of narcosis І. Stage of analgesia Loss of pain feelings along with normal or dimmed consciousness Duration from the beginning of inhalation of narcosis substance and till the moment of loss of patient’s consciousness Sometimes during this stage small surgical interventions are performed (opening of abscesses, teeth extraction, taking of the stitches etc.) ІІ. Stage of excitation (no desirable!!! dangerous) Duration from the moment of loss of patient’s consciousness till the stage of surgical narcosis Complications language and motor excitement, increasing of secretor activity of salivary and bronchial glands, vomiting, variation of arterial pressure, changes of breathing frequency Heavy complications Laryngospasm, bronchospasm, respiratory arrest, cardiac arrhythmias, cardiac arrest ІІІ. Stage of surgical anesthesia 1st level Skeletal muscles aren’t relaxed, conjunctive and pharyngeal reflexes disappear (it is possible to perform intubations) 2nd level Reaction of frequent breathing as a respond cut on the skin disappear (deep analgesia), laryngeal reflexes disappear (it is possible to perform endotracheal intubation); good miorelaxation 3rd level Decreasing of blood pressure, Full relaxation of muscles, step by step intercostal muscles get turned off, Type of breathing changes into abdominal; Corneal and pupil reflexes disappear 4th level muscular tone is low, full paralysis of intercostal muscles; decreasing of blood pressure; dilated pupil which don’t react on light IV. Agony stage (occurs in a case of overdosing of drugs for narcosis) Characteristics decreasing of breathing and vaso-motor centers of medulla oblongata Typical manifestations full paralysis of breathing muscles, respiratory arrest, collapse; cardiac arrest Surgical interventions are performed on 1st and 2nd levels, approximately till half of 3rd level of third stage of narcosis Drugs for inhalative narcosis Ether for narcosis Narcosis develops after 10-20 min, stage of excitation - 10-20 min, strongly expressed after-narcosis depression, high width of narcotic action (broad therapeutic window) Side effects and complications bright stage of excitation Increasing of tone of n. vagi Increasing of secretion of salivary, bronchial glands, coughing; laryngospasm, bronschospasm, vomiting with the following aspiration of the masses bradycardia, stop of heart beat Increasing of tone of sympathetic nervous system Tachycardia, hyperglycemia Ftorothane (halothane) Power of narcosis action of ftorothan is higher than of ether, it has a large width of narcotic action, doesn’t irritate mucous membranes of breath tracts, doesn’t cause laryngeal and bronchial spasm, speed of development of narcosis – 3-5 min., after narcosis depression is not expressed Side effects and complications • hypotension and cardiac arrest, • sensitization (increased sensitivity) of myocardium towards catecholamines • acute damage of liver – halothane hepatitis, • teratogenic action Nitrogenous oxide Small power and width of narcosis action, stage of excitation is present, quick entry and exit from narcosis (1-2 min) Administration as an analgesic: pregnancy, teeth extraction, bandaging in case of burns, cleaning and revisions of wounds, iscemic heart attacks and myocardium infarction, colics, traumas, acute pancreatitis, pain relief in post-operative period Induction Speed Anesthetic of the Future: Xenon •Rare gas extracted from air •Very expensive to produce •Close to ideal anesthetic •Low blood and tissue solubility (rapid induction/recovery) •Potent •Not metabolized •Nonflammable •Minimal side effects Drugs for noninhalative narcosis Thiopental-sodium After administration of the drug narcosis develops in 1-2 min., awakening occurs in 20-30 min. Administration • introduction narcosis, • basis narcosis, • mononarcosis in case of short-lasting operative interventions (dentistry, gynecology, traumatology), • anti-seizure drug. Side effects cough, laryngeal and bronchial spasm In case of rapid introduction – depression of centers of medulla oblongata . In case of contact of the drug with skin, it’s separation may occur, contact with nervous trunk or near it – irreversible paralysis, contact with an artery – thrombosis with the following gangrene of the extremity Propanidid (sombrevin) Narcosis develops after 30-40 sec from the beginning of intravenous introduction of the drug (“on the edge of the needle”). Stage of surgical narcosis lasts for 3-4 min Administration for mononarcosis during short operative interventions in surgery, dentistry, gynecology, urology, painful diagnostic procedures, sometimes – for introduction into narcosis Side effects and complications Frequent breathing (tachypnoe) with the following stopping of breathing (apnoe), phlebitis and thrombosis in the place of introduction anaphylactic reactions Sodium oxybutyrate in case of intravenous introduction narcosis develops after 15-40 min. id administered orally sleep comes after 30-60 min. duration of narcosis is 1,5-3 hours. It manifests antihypoxia properties Administration • mononarcosis – to perform long-lasting surgeries but with small traumatic effect • premedication, • introduction and basis narcosis. • drug of choice for narcosis in case of intoxications, sepsis, disturbance of functions of parenchymatous organs, • analgesia during child-delivery. • to decrease psycho-motor excitation, seizures, • insomnia Side effects motor excitation seizure twitching of extremities and tongue vomiting hypopotassiumemia. Ketamine hydrochloride (ketalar, kalipsol) During intravenous introduction of the drug narcosis develops after 1530sec, lasts for 8-10 min, during intramuscular introduction – after 2-3 min, lasts for 20-30 min Administration • introduction and basis narcosis • mononarcosis during surgeries which don’t need muscular relaxation • as a part of combined narcosis Side effects during coming out of narcosis – unpleasant dreams, delirium, hallucination, seizures, nausea, vomiting, increasing of blood pressure, increasing of frequency and power of heart contractions The drug is able to raise intracranial pressure, oxygen consumption by brain and intraoccular pressure PROPOFOL (DIPRIVAN) drug with ultra-short action Narcosis develops after 30-40 sec after intravenous introduction, lasts for 3-5 min Administration • Mononarcosis • Polycomponent narcosis • Artificial ventilation of lungs Positive moments: can’t be accumulated, doesn’t have afternarcosis depression, possesses anti-vomiting action Negative moments: doesn’t have analgesic action (it is often combined with fentanil, ketamine), possible hypotension, short apnoe Ethomidate (hipnomidate) drug of ultra-short action During introduction into vein effect develops after 1 min and lasts for 3-5 min Administration • Introduction narcosis • Mononarcosis during short-lasting surgeries • Performing of diagnostic manipulations Disadvantages: doesn’t have analgesic activity, promotes vomiting, in case of long lasting introduction depending on dose it depresses synthesis of hormones of adrenal cortex Mononarcosis (simple, single-component) Polynarcosis (multicomponent, combined) Induction narcosis most frequently is achieved by intravenous introduction of noninhalative narcosis drugs which don’t cause excitation stage: ketamine, thiopental-sodium, propofol (diprivan), ethomidate (hypnomidate) Basis - narcosis – element of combined analgesia (most often it is an intravenous narcosis, which acts during all the surgery) Following drugs are used: Sodium oxybutyrate Tiopental-sodium Ketamine Potentiated narcosis – is a kind of general analgesia,during which for potentiation of action of main narcosis substance drugs which don’t have narcosis activity but depress CNS are used : Neuroleptics Tranquilizers Opioid analgesics Antihistamine drugs Scopolamine Myorelaxants Neuroleptanalgesia – method of general analgesia when narcoleptic (droperidol) and narcotic analgesic (fentanyl) are combined. Combined drug - talamonal Advantages of neuroleptanalgesia • • • • • • • • inconsiderable toxicity large therapeutical width, deep analgesia, anti-shock action, considerable anti-vomiting effect, stability of hemodynamics, quick developing of narcosis, quick coming out of narcosis Ataralgesia Combined administration of narcotic analgesic and tranquilizer (diazepam or midasolam) Advantages Tranquilizing action (until full turning off consciousness under the influence of midasolam), anterograde amnesia (the patient doesn’t remember events which happened after introduction of the drug), relaxation of the muscles, anti-seizure effect, minimal influence on blood circulation