Download (neuroleptics, tranquillisers, sedative, lithium salts)

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. Immobility in response to noxious stimulus
2. Amnesia
3. Analgesia
4. Unconsciousness
5. Muscle relaxation
6. Loss of autonomic reflexes
7. 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