1. General CNS depressants (neuroleptics, tranquillisers, sedative, lithium salts)
Lector prof. Posokhova K.A.

2. PSYCHOTROPIC DRUGS Drugs with depressive type of action
Neuroleptics (antipsychotics)
Tranquilizers (anxiolytics)
Sedative drugs
Normotymics (tymoleptics, tymoanaleptics)
Drug with stimulative action
Antidepressants
Psychomotor stimulants
Nootropic drugs
Drugs which increase general tone (adaptogens)
Psychotomimetics (psychodysleptics)
LSD
Cannabis sativa L.

3. NEUROLEPTICS
Derivatives of phenotiazine: aminasine, triftiazine, etaperasine, tioridazine
Derivatives of tioxanten: chlorprotixen
Derivatives of butyrophenon: haloperidol, droperidol
Derivatives of piperasine-dibenzodiazepine: clozapine
Derivatives of indole: reserpin, sulpyrid (eglonil)

4. NEUROLEPTICS
“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

5. 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

6. Mechanism of action of neuroleptics
Influence on dopamine (D2), noradrenergic, serotoninergic, GABA-ergic, cholinergic receptors

7. Properties of neuroleptics
Antipsychotic action - they eliminate productive symptoms of psychosis (delirium and hallucinations), affective disorders
They eliminate psychomotor excitation
consciousness is present

8. 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

9. Delirium tremens –
alcohol psychosis

10. 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

11. Neuroleptics with psychosedative action

12. 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

13. 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

14. 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

15. syndrome of parkinsonism

16. 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

17. 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

18. 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

19. Grandaxyn (tophizopam)
“DAY” TRANQUILIZERS
Gidazepam
Mezapam (rudotel)
Grandaxyn (tophizopam)
Trioxazyn
Buspyron

20. 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!

21. 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
Sibazon Midazolam

22. 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) sibazon 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

23. Seizures (tetanus) drug of a first choice - Sibazon

24. SIDE EFFECT OF TRANQUILIZERS
Psychological and physical addiction
Prophylaxis:
Duration of treatment course should not be more than 2 months
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, dysarthria
Acute poisoning in case of overdosing

25. FLUMAZENIL (ANEXAT) ANTAGONIST OF TRANQUILIZERS

26. (pathological alcohol intoxication)
Combination of tranquilizers with alcohol-containing drinks is absolutely contraindicated
(pathological alcohol intoxication)

27. LITHIUM DRUGS
LITHIUM CARBONATE

28. 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

29. 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)

30. 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

31. 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

32. 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

33. They do not cause addiction, somnolence, myorelaxation, ataxia
SEDATIVE DRUGS
Bromides
Drugs of plant origin: valerian, dog nettle, melissa, passiflora etc.
They do not cause addiction, somnolence, myorelaxation, ataxia

34. Valeriana

35. PASSIFLORA

36. Leonurus L. dog nettle

37. ADMINISTRATION OF SEDATIVE DRUGS
Neurosis
Neurasthenia
Hysteria
Increased irritability
Insomnia
Primary stages of essential hypertension

38. 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

39. DRUGS FOR GENERAL ANESTHESIA

40. General anesthesia = Narcosis (from the Greek narkosis – numbness, rigidity) –
-one of the greatest discoveries in medicine of all time
-made modern surgery possible
-rare to go through life without being anesthetized at least once
-scary: low TI, unknown mechanism of action
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

41. “Gentlemen, this is no humbug.”
1846 TG Morton: First public demonstration of ether administration for excision of neck mass

42. Desirable Components of Anesthesia
Immobility in response to noxious stimulus
Amnesia
Analgesia
Unconsciousness
Muscle relaxation
Loss of autonomic reflexes
Anxiolysis

43. CLASSIFICATION OF GENERAL ANESTHETICS
Inhalational agents
primarily used for maintenance
Volatile agents
Isoflurane
Sevoflurane
Desflurane
Halothane (Ftorothane)
Enflurane
Anesthetic gases
Nitrous Oxide - currently used
Most anesthetic procedures today involve the combination of different anesthetic drugs which are being used in concentrations that are considerably smaller than those needed if the drug were to be used all by itself.
Halogenated anesthetics:
(1) rapid and pleasant induction of, and recovery from, anesthesia;
(2) rapid changes in the depth of anesthesia;
(3) adequate relaxation of skeletal muscles;
(4) the absence of toxic effects or other adverse properties in normal doses;
(5) a wide margin of safety.
Advantages of using intravenous drugs:
(1)high potency and rapid reversibility
(2) adds flexibility and permits the administration of lower doses of inhalational agents;
(3) permit more precise control of the effect required.

44. CLASSIFICATION OF GENERAL ANESTHETICS
Intravenous agents
primarily used for induction
Barbiturates (Thiopental-sodium)
Benzodiazepines (Midasolam, diazepam)
Etomidate
Ketamine
Propofol
Propanidid
Sodium oxybutyrate
Predion
Most anesthetic procedures today involve the combination of different anesthetic drugs which are being used in concentrations that are considerably smaller than those needed if the drug were to be used all by itself.
Halogenated anesthetics:
(1) rapid and pleasant induction of, and recovery from, anesthesia;
(2) rapid changes in the depth of anesthesia;
(3) adequate relaxation of skeletal muscles;
(4) the absence of toxic effects or other adverse properties in normal doses;
(5) a wide margin of safety.
Advantages of using intravenous drugs:
(1)high potency and rapid reversibility
(2) adds flexibility and permits the administration of lower doses of inhalational agents;
(3) permit more precise control of the effect required.

45. Unitary Hypothesis
General anesthesia can be caused by a remarkable number of structurally diverse molecules
Different size, different chemical properties.
Suggests single site, common mechanism.

46. Molecular Mechanism(s) of General AnesthesiaXe
Isoflurane
Halothane
......
Cellular (synapses)
Molecular
(lipids & receptors)
The difficulty to determine the site of action in the CNS for GA:
we have no consensus of opinion regarding the region or regions of the brain responsible for the maintenance of consciousness.
the brain area responsible for the control of consciousness:
cerebral cortex? No. Large regions of the cortex could be ablated without loss of consciousness
brainstem? No.
Although much data exist on anesthetic effects in various brain regions, no set is sufficiently complete or consistent to allow one to conclude that exert their actions through one specific effect in one CNS region.
Since it’s difficult to define gA comprehensively and quantitatively, there has been from the beginning a search for in-vivo and in-vitro model systems capable to either reflect gA completely, to describe partial aspects of it or to measure it indirectly.

47. A Working Hypothesis
Anesthetics enhance inhibitory postsynaptic channel activity (GABAA and glycine receptors)
Anesthetics inhibit excitatory synaptic channel activity (nicotinic acetylcholine and glutamate receptors)

48. Effects of General Anesthesia
Low Dose Effects
Amnesia
Euphoria
Analgesia
Hypnosis
Excitation
Hyperreflexia
High Dose Effects
Deep sedation
Muscle relaxation
Diminished motor responses
Diminished autonomic responses
Myocardial protection from ischemia
Cardiovascular/respiratory depression
Hypothermia

49. 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
Besides conventional EC50 for the drug potency measurement, MAC is more popularly used in the field.

50. Stages of narcosis

51. І. Stage of analgesia Duration
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.)

52. 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

53. 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

54. Typical manifestations
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

55. Surgical interventions are performed on 1st and 2nd levels, approximately till half of 3rd level of third stage of narcosis

56. Drugs for inhalative narcosis

57. Ether for narcosis Side effects and complications
Narcosis develops after min, stage of excitation 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

58. 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

59. 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

60. Induction Speed

61. 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

62. Drugs for noninhalative narcosis

63. cough, laryngeal and bronchial spasm
Thiopental-sodium
After administration of the drug narcosis develops in 1-2 min., awakening occurs in 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

64. Propanidid (sombrevin) Side effects and complications
Narcosis develops after 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

65. Sodium oxybutyrate Administration Side effects premedication,
in case of intravenous introduction narcosis develops after min. id administered orally sleep comes after 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.

66. 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 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

67. PROPOFOL (DIPRIVAN) drug with ultra-short action
Narcosis develops after 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

68. 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

69. (simple, single-component) Polynarcosis (multi-component, combined)
Mononarcosis
(simple, single-component) Polynarcosis (multi-component, combined)

70. ethomidate (hypnomidate)
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)

71. Following drugs are used:
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

72. Potentiated narcosis Neuroleptics Tranquilizers Opioid analgesics
– 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

73. Advantages of 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

74. Ataralgesia Advantages (diazepam or midasolam)
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