Central Nervous System Depressants

ANTIPSYCHOTIC AGENTS

“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

Aminazine (chlorpromazine)

• 1951 – aminazine was introduced into clinical practice

• It brought considerable changes into situations of psychiatric clinics

• Before appearance of aminazine for treatment of psychologically sick patients insulin or electric shock were widely used, in some cases - lobotomy

Phenothiazine derivatives

Thioxanten derivatevesThioxanten derivateves

Butyrophenon derivativesButyrophenon derivatives

piperasine-dibenzodiazepine derivatives(Clozapin, Clozapine, FazaClo, Leponex, Zaponex, Clopin

Eco.)

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

• consciousness is present

1 Lung Cancer, 2 Criminality, 3 Stroke, 4 Breast Cancer, 5 Same Sex Attraction, 6 Leukemia, 7 Malformation, 8 Alzheimer’s, 9 Ulcerative

Colitis, 10 Rheumatoid Arthritis, 11 Alcoholism, 12 Schizophrenia, 13 Depression, 14 Suicide attempt,

15 Diabetes type I, 16 Divorce, 17 Crohn’s disease, 18 Asthma, 19 Hypertension, 20 Co twin is best friend, 21 Diabetes type II, 22 Autism,

23 Opposite Sex Attraction, 24 Phenylketonuria

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

Drugs which stimulate psychical activity

Other properties and indications for administration of neuroleptics

• Drugs with psychosedative action – for potentiation of action of hypnotic drugs, 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 – aminazine, droperidol) – in case of hypertensive crisis, lungs, brain 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• Aminazine has a considerable irritative action

syndrome of parkinsonism

Parkinsone syndrome treatment

Cyclodolum Levodopa is contraindicated

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

TRANQUILIZERS

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

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!

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 (maximum 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,

dysarthria • Acute poisoning in case of overdosing

FLUMAZENIL (ANEXAT) ANTAGONIST OF TRANQUILIZERS

Combination of tranquilizers with alcohol-containing drinks is absolutely

contraindicated(pathological alcohol

intoxication)

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

Hypnotic agents

CNS Depressants

Hypnotics

• Calm or soothe the CNS to the point that they cause sleep

Sedative-Hypnotics—dose dependent:• At low doses, calm or soothe the CNS

without inducing sleep• At high doses, calm or soothe the CNS• to the point of causing sleep

Epilepsy

• In the U.S., 2.5 million people are affected.

• Not all seizure disorders are epilepsy.

Epilepsy

SeizureAbnormal electrical discharges in the cerebral cortex caused by sudden, excessive firing of neurons

– Result in a change in behavior of which the patient is not aware

– While conscious, the patient may or may not lose movement control

– Loss of body control may affect one area or the entire body

Anticonvulsants

• lamotrigine (Lamictal)

• levetiracetam (Keppra)

• lorazepam (Ativan)

• oxcarbazepine (Trileptal)

• phenobarbital (Luminal Sodium)

• phenytoin (Dilantin)

• primidone (Mysoline)

• topiramate (Topamax)

• valproic acid (Depakene)

• zonisamide (Zonegran)

Drug List

• carbamazepine (Epitol, Tegretol)

• clonazepam (Klonopin)• diazepam (Valium)• divalproex (Depakote)• ethosuximide (Zarontin)• Fosphyenytoin (Cerebyx) • gabapentin (Neurontin)

valproic acid (Depakene) and divalproex (Depakote)

• Increases the availability of GABA (inhibitory)

• Take with water, not a carbonated drink

• Do not use aspirin

Dispensing Issues

• Depakote and Depakene can easily be confused.

• Be careful with Depakote and Depakote ER.

• Depakote ER is only once a day.

Warning!

Parkinson’s Disease

Physiology• Normal muscle movement requires balance of

dopamine (inhibitor) and ACh (stimulator)• In the substantia nigra, enough dopamine is

released to counteract the effects of ACh• In parkinsonism, enough dopamine is not released

which leads to excessive motor nerve stimulation

Substantia Nigra

Parkinson’s Disease

Drug Therapy• Improves the functional ability and clinical

status of patients• Aims at symptomatic relief, does not alter

the disease process• Patients may have temporary or prolonged

remission• Side effects can be a problem