CNS Stimulants 1.Analeptics 2.Anorexiants 3.Antidepressants 4.Serotonin agonists.

CNS Stimulants

1. Analeptics2. Anorexiants

3. Antidepressants4. 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 half-life 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

• ManiaMood of extreme excitement, excessive elation, hyperactivity, agitation, and increased psychomotor activity

• Bipolar Disorder

• Unipolar Disorder

Mood Disorders

• Mania

• Bipolar DisorderMood swings alternate between major depression and mania

• Unipolar Disorder

Mood Disorders

• Mania

• Bipolar Disorder

• Unipolar DisorderMajor 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

SSRIs for Depression• citalopram (Celexa)

• escitalopram (Lexapro)

• fluoxetine (Prozac, Sarafem)

• fluvoxamine

• paroxetine (Paxil)

• sertraline (Zoloft)

• venlafaxine (Effexor)

Drug List

Dispensing Issues

Look-Alike Drugs

– Prozac and Proscar (urinary drug)

– Zoloft and Zocor (high cholesterol)

– Celexa and Cerebyx (seizures) and Celebrex (arthritis)

Warning!

SSRIDispensing Issues

• Do not discontinue abruptly

• Alcohol consumption should be avoided while taking these medications

Warning!

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, obsessive-compulsive 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 obsessive-compulsive disorder

• Primary side effect is nausea

• May also cause drowsiness

citalopram (Celexa)

• Indicated for depression and obsessive-compulsive disorder

• Minimal drug interactions

escitalopram (Lexapro)

• Similar to Celexa

• More potent with fewer side effects

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

Drug List

Tricyclic Antidepressants Dispensing Issues

• Improvements are usually seen in 10 to 21 days

• Can be cardiotoxic in high doses

• May cause postural hypotension

Warning!

Tricyclic AntidepressantsDispensing Issues

Do not discontinue abruptly.Warning!

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.

MAOIs

• phenelzine (Nardil)

• selegiline (Eldepryl)

• tranylcypromine (Parnate)

Drug List

MAOI Dispensing Issues

Be cautious of many interactions with foods such as aged cheeses, concentrated yeast extracts, pickled fish, sauerkraut, broad bean pods, chocolate, and alcohol.

Warning!

MAOI Dispensing Issues

If changing to another class of antidepressant, patient must have a two-week “wash out” period before starting the new medication.

Warning!

Other Antidepressants

• bupropion (Wellbutrin, Zyban)

• mirtazapine (Remeron)

• trazodone (Desyrel)

Drug List

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

• Wellbutrin SR = BID dosing

• Wellbutrin XL = QD dosing

Warning!

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

Drugs to Treat Bipolar Disorders

• carbamazepine (Epitol, Tegretol)

• divalproex (Depakote)

• lithium (Eskalith, Lithobid)

• olanzapine-fluoxetine (Symbyax)

• valproic acid (Depakene)

Drug List

PSYCHOTROPIC DRUGS

PSYCHOTROPIC DRUGSDrugs with depressive type of action

1. Neuroleptics (antipsychotics)2. Tranquilizers (anxiolytics)3. Sedative drugs4. Normotymics (tymoleptics, tymoanaleptics)

Drug with stimulative action1. Antidepressants 2. Psychomotor stimulants3. Nootropic drugs4. Drugs which increase general tone (adaptogens)

Psychotomimetics (psychodysleptics)1. LSD 2. Cannabis sativa L.

NEUROLEPTICS• Derivatives of phenotiazine: aminasine,

triftiazine, etaperasine, tioridazine

• Derivatives of tioxanten: chlorprotixen

• Derivatives of butyrophenon: galoperidol, droperidol

• Derivatives of piperasine-dibenzodiazepine: 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, GABA-

ergic, 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 excitationof 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 drugsIt 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

decreasedSYMPTOMS 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, sweat-stimulating 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. Immobility in response to noxious stimulus

2. Amnesia

3. Analgesia

4. Unconsciousness

5. Muscle relaxation

6. Loss of autonomic reflexes

7. Anxiolysis

Inhalational agentsInhalational agentsprimarily used for maintenanceprimarily used for maintenance

•Volatile agentsVolatile agentsIsofluraneIsofluraneSevofluraneSevofluraneDesfluraneDesfluraneHalothaneHalothane ( (FtorothaneFtorothane)) EnfluraneEnflurane

•Anesthetic gasesAnesthetic gasesNitrous Oxide Nitrous Oxide - currently used- currently used

CLASSIFICATION OF GENERAL ANESTHETICS

Intravenous agentsIntravenous agentsprimarily used for inductionprimarily used for induction

•Barbiturates (Thiopental-Barbiturates (Thiopental-sodium)sodium)•Benzodiazepines (Benzodiazepines (Midasolam, Midasolam, diazepam)diazepam)•EtomidateEtomidate•KetamineKetamine•PropofolPropofol•PropanididPropanidid•Sodium oxybutyrateSodium oxybutyrate•PredionPredion

CLASSIFICATION OF GENERAL ANESTHETICS

General General anesthesia can be anesthesia can be caused by a caused by a remarkable remarkable number of number of structurally structurally diverse moleculesdiverse molecules

Unitary Hypothesis

Xe

Isoflurane

Halothane

......Cellular (synapses)Cellular (synapses)

MolecularMolecular(lipids & (lipids &

receptors)receptors)

Molecular Mechanism(s) of General Molecular Mechanism(s) of General AnesthesiaAnesthesia

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 EffectsLow Dose Effects

•AmnesiaAmnesia

•EuphoriaEuphoria

•AnalgesiaAnalgesia

•HypnosisHypnosis

•ExcitationExcitation

•HyperreflexiaHyperreflexia

High Dose EffectsHigh Dose Effects

•Deep sedationDeep sedation

•Muscle relaxationMuscle relaxation

•Diminished motor responsesDiminished motor responses

•Diminished autonomic Diminished autonomic responsesresponses

•Myocardial protection from Myocardial protection from ischemiaischemia

•Cardiovascular/respiratory Cardiovascular/respiratory depressiondepression

•HypothermiaHypothermia

• MAC: MAC: mminimum inimum aalveolar lveolar cconcentration oncentration

• MAC is the concentration of MAC is the concentration of anesthetic that produces anesthetic that produces immobility in 50% of patients immobility in 50% of patients exposed to a noxious exposed to a noxious stimulus.stimulus.

• MACMACawakeawake: MAC at which response : MAC at which response to commands are lost to commands are lost

• amnesia, loss of awarenessamnesia, loss of awareness

• MACMACBARBAR: : bblunt lunt aautonomic utonomic rresponseesponse• MACMACintubationintubation: response to intubation: response to intubation

Measures of Anesthetic Potency

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 anesthesia1st level

Skeletal muscles aren’t relaxed, conjunctive and pharyngeal reflexes disappear (it is possible to perform intubations)

2nd levelReaction 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 levelDecreasing 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 levelmuscular 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 manifestationsfull 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 narcosisNarcosis 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 complicationsbright stage of excitation

Increasing of tone of n. vagiIncreasing 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 systemTachycardia, 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 oxideSmall power and width of narcosis action, stage of excitation

is present, quick entry and exit from narcosis (1-2 min)

Administration Administration as an as an analgesicanalgesic:: pregnancypregnancy,, teeth extractionteeth extraction,, bandaging in case of burnsbandaging in case of burns, , cleaning and revisions of woundscleaning and revisions of wounds,, iscemic heart attacks and iscemic heart attacks and myocardium infarctionmyocardium infarction,, colicscolics,, traumastraumas,, acute pancreatitisacute pancreatitis,, pain relief in post-operative periodpain relief in post-operative period

Induction Speed

Anesthetic of the Future: Xenon

•Rare gas extracted from airRare gas extracted from air

•Very expensive to produceVery expensive to produce

•Close to ideal anestheticClose to ideal anesthetic

•Low blood and tissue solubilityLow blood and tissue solubility

(rapid induction/recovery)(rapid induction/recovery)

•PotentPotent

•Not metabolizedNot metabolized

•NonflammableNonflammable

•Minimal side effectsMinimal side effects

Drugs for noninhalative

narcosis

Thiopental-sodiumAfter 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 effectscough, 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 introductionanaphylactic 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 effectsmotor excitationseizure twitching of extremities and tonguevomiting hypopotassiumemia.

Ketamine hydrochloride (ketalar, kalipsol)

During intravenous introduction of the drug narcosis develops after 15-30sec, 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 after-narcosis 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 manipulationsDisadvantages: 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 (multi-component, 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 analgesicsAntihistamine 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)

AdvantagesTranquilizing 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