Pharmacology drugs depressing central nervous system

1. PHARMACOLOGY OF DRUGS WHICH INFLUENCE ON THE CENTRAL NERVOUS
SYSTEM. GENERAL ANESTHETICS, HYPNOTICS, ANTICONVULSION,
ANTIPARKINSONIC DRUGS. NEUROLEPTICS, TRANQUILIZERS
National Pirogov Memorial Medical University
Department of Pharmacology
Lecturer:
Saenko Andrew Victorovich
professor assistant, ph.d.
Lecture №2

2. Plan of lecture:
• Central Nervous System
• Drugs for Narcosis
• Preanesthetic medication
• Hypnotic drugs
• Antiseizure drugs
• Antiparkinsonic drugs
• Neuroleptics
• Tranquilizers
• Sedative drug

3. CENTRAL NERVOUS SYSTEM

4. NEURON

5. Central neurotransmitters
Biogenic amines: dopamine, nor-adrenaline, adrenaline, serotonin, histamine
Acetylcholine; mainly excitatory (e) in CNS vs., inhibitory (i) effects in the PNS
Amino acids: GABA (i), glycine (i), glutamate (e), aspartate (e)
Neuropeptides: vasopressin, oxytocin, endorphins, enkephalines
Purine nucleotides: adenosine, ATP
Neurolipids: anandamide, 2-arachidonoyl glycerol, ceramide

6. DRUG ACT IN CNS
Drug for narcosis
Hypnotic drugs
Neuroleptic
Tranquilizers
Sedative drug
Analgesics
Psychostimulants
Antidepressants
Nootropic drug
Analeptic
Adaptogens

7. DRUGS FOR NARCOSIS
Narcosis Greek word ναρκωσις (narcosis) is derived from narke, is a state of drug-induced reversible inhibition of central
nervous function, during which surgical procedures can be carried out in the absence of consciousness, responsiveness to pain,
defensive or involuntary movements, and significant autonomic reflex responses.
Main characteristic:
 Loss of consciousness
 Pain feelings
 Depression of reflexes
 Relaxation of skeletal muscles
 Postnarcosis amnesia

8. DRUGS FOR NARCOSIS
Characteristics of the ideal anesthetic
Rapid, pleasant induction and recovery of anesthesia
Rapid changes in the depth of anesthesia
Adequate skeletal muscle relaxation to perform surgery
Production of amnesia
Ability to provide analgesia
A wide safety margin
Nontoxic

9. GENERAL ANESTHETICS
Inhalational
agents
Injectable
agents
The modern practice of anesthesiology relies on the use of combinations
of intravenous and inhaled drugs ( balanced anesthesia techniques) to take advantage
of the favorable properties of each agent while minimizing their adverse effects. The
choice of anesthetic technique is determined by the type of diagnostic, therapeutic,
or surgical intervention to be performed.

10. GENERAL ANESTHETICS
Inhalational agents
Inhalation Anesthetics :
- gases:
Nitrogenium oxydulatum
- volatile liquids:
Aether pro narcosi, Ftorotanum, Halotanum Sevfluranum
Inhalation anesthetics have advantages over intravenous agents in that the
depth of anesthesia can be changed rapidly by altering the inhaled
concentration and, because of their rapid elimination, they do not
contribute to postoperative respiratory depression.

11. ETHER FOR NARCOSIS
Narcosis develops after 10-20 min, stage of excitation - 10-20 min, strongly expressed after-narcosis
depression, high width of narcosis action
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

12. FTOROTAN (GALOTAN)
Power of narcosis action of ftorotan is higher than of ether, it has a large width of narcosis
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 heart stop,
sensibilization (increased sensitivity) of myocardium towards catecholamines
acute damage of liver – halothane hepatitis,
teratogenic action

13. NITROGEN 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,
 traumas, burns,
 attacks of stenocardia and myocardium infarction,
 colics,
pain relieving in post-operative period

14. XENON
• Xenon interacts with many different receptors and ion channels, and like many theoretically multi-modal inhalation
anesthetics, these interactions are likely complementary. Xenon is a high-affinity glycine-site NMDA receptor
antagonist. However, xenon is different from certain other NMDA receptor antagonists in that it is not neurotoxic and
it inhibits the neurotoxicity of ketamine and nitrous oxide, while actually producing neuroprotective effects.
• Xenon inhibits nicotinic acetylcholine α4β2, plasma membrane Ca2+ ATPase, 5-HT3 receptor. While neither anesthetic
nor antinociceptive, this reduces anesthesia-emergent nausea and vomiting.
• Xenon has a minimum alveolar concentration (MAC) of 72% at age 40, making it 44% more potent than N2O as an
anesthetic. Thus, it can be used with oxygen in concentrations that have a lower risk of hypoxia.

15. INTRAVENOUS ANESTHETICS:
Short-acting drugs (10- 15 min):
- Ketaminum (Kalipsol, Ketanest)
- Propofol (Diprivan)
- Propanididum (Sombrevin)
Drugs with medim duration of action (20 - 50 min):
- Thiopental-natrium
Long-acting drugs:
- Natrii oxybutyras
Cause rapid loss of consciousness and induction is pleasant. However, they produce little muscle relaxation and
frequently do not obtund reflexes adequately. Repeated administration results in accumulation and prolongs
the recovery time. Since these agents have little if any analgesic activity, they are seldom used alone except in
brief minor procedures.

16. THIOPENTAL-NATRIUM
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 –
nonreversible paralysis, contact with an artery – thrombosis with the following gangrene of the extremity

17. KETAMINUM (KALIPSOL, KETANEST)
Ketamine hydrochloride injection is indicated as the sole anesthetic agent for diagnostic and surgical procedures
that do not require skeletal muscle relaxation. Ketamine hydrochloride injection is best suited for short procedures
but it can be used, with additional doses, for longer procedures.
Usual Adult Dose for Anesthesia
IV:
-Induction: 1 to 4.5 mg/kg IV; alternatively, 1 to 2 mg/kg IV at a rate of 0.5 mg/kg/min; (2 mg/kg dose
provides 5 to 10 minutes of surgical anesthesia within 30 seconds)
IM:
-Induction: 6.5 to 13 mg/kg IV; (9 to 13 mg/kg IV provides 12 to 25 minutes of surgical anesthesia)
-Maintenance: The maintenance dose should be adjusted according to the patient's anesthetic needs
and whether an additional anesthetic is employed. Increments of one-half to the full induction dose may
be repeated as needed for maintenance of anesthesia.

18. PROPOFOL (DIPRIVAN)
Usual Adult Dose for Anesthesia
Most adult patients under 55 years of age and classified as ASA-PS I or II
require 2 to 2.5 mg/kg of Propofol injectable emulsion for induction when
unpremedicated or when premedicated with oral benzodiazepines or
intramuscular opioids. For induction, Propofol injectable emulsion should
be titrated (approximately 40 mg every 10 seconds) against the response of
the patient until the clinical signs show the onset of anesthesia.
Propofol is an intravenous sedative-hypnotic agent for use in the induction and maintenance of anesthesia
or sedation. Intravenous injection of a therapeutic dose of Propofol induces hypnosis with minimal
excitation, usually within 40 seconds from the start of injection (the time for one arm-brain circulation)

19. PREANESTHETICS MEDICATION
“It is the term applied to the administration of drugs prior to general anaesthesia so as to make anaesthesia
safer for the patient” & to minimize adverse effects of anaesthesia
AIMS:
 Relief of anxiety & apprehension preoperatively &
facilitate smooth induction
 Amnesia for pre- & post-operative events
 Potentiate action of anaesthetics, so less dose is needed
 Antiemetic effect extending to postoperative period
 Decrease secretions & vagal stimulation caused by
anaesthetics
 Decrease acidity & volume of gastric juice to prevent
reflux & aspiration pneumonia

20. DRUGS USE FOR PREMEDICATION
М-cholinoblockers
Atropini sulfas
Narcotic analgesics
Morphini hydrochloridum,
Promedolum
Antihistaminic
Dimedrolum, Suprastinum
Tranquilizers
Diazepamum
Decrease secretion of salivary glands
Prophylaxis of laryngo- and
bronchospasm
Prophylaxis of vagotony
Potentiation of drugs for
nacrosis
Prophylaxis of allergic reactions
Decrease of anxiety, potentiation
of nacrosis

21. NEUROLEPTANALGESIA – SPECIAL TYPE OF GENERAL ANALGESIA WHICH INCLUDE
NEUROLEPTIC (DROPERIDOL) AND NARCOTIC ANALGESIC (FENTANIL). COMBINED
DRUG IS TALAMONAL
Main peculiarities
 Low toxicity
 Potent antishock action
 Evident antivomiting
effect
 Stability of hemodynamics
 Rapid onset (1-3 min),
rapid termination of
action (20-30 min)
Usage:
 Extensive
traumas, burns
(the prophylactic
of pain shock)
 Myocardium
infarction
 Initial narcosis

22. HYPNOTIC DRUGS
These drugs are able to cause sedation (with concomitant relief of anxiety) or to encourage
sleep.
Chemical classes of sedative-hypnotics
Barbiturates: Hexobarbital, Phenobarbital, Thiopental.
Benzodiazepines: Chlordiazepoxide, Diazepam, Nitrazepam, Oxazepam
Carbamates: Meprobamate
Quinazolones: Methaqualone
Alcohols: Ethanol

23. SLEEP PHASES

24. HYPNOTIC DRUGS
therapeutic classification
Sedative/Hypnotics
• Lormetazepam,
• Temazepam,
• Nitrazepam,
• Flurazepam
 Anxiolytics
• Diazepam
• Oxazepam
• Lorazepam
Anticonvulsants
• Diazepam,
• Nitrazepam,
• Clonazepam
• Lorazepam
Central muscle relaxants
• Diazepam,
• Flurazepam,
• Clonazepam

25. HYPNOTIC DRUGS
Indication for usage of hypnotic drugs
• For relief of anxiety
• For sedation and amnesia before medical and surgical procedures
• Treatment of epilepsy and seizure states.
• Premedication prior to anesthesia
• Intravenous administration, as a component of balanced anesthesia
• For control of ethanol or other sedative hypnotic withdrawal states
• For muscle relaxation in specific neuromuscular disorders

26. ADVERSE EFFECTS OF HYPNOTIC DRUGS
 CNS – drowsiness, impaired concentration, mental and physical sluggishness
 Drug hangover: hypnotic doses produce a feeling of tiredness well after the patient awakes. This
drug hangover leads to impaired ability to function normally for many hours after waking.
Occasionally, nausea and dizziness occurs.
Precautions. Barbiturates induce the P-450 system and therefore may decrease the effect of drug
that metabolized by these hepatic enzymes.
 Addiction. Abrupt withdrawal from barbiturates may cause tremors, anxiety, weakness,
restlessness, nausea and cardiac arrest.
 Drug dependence (physiological and psychological). Poisoning leads to severe depression of
respiration and central cardiovascular depression.

27. ANTISEIZURE DRUGS
Classification of seizure types.
 Partial seizures
• Simple partial seizures
• Complex partial seizures
• Partial seizures secondarily generalized
 Generalized seizures
• Generalized tonic-clonic (grand mal) seizures
• Absence (petit mal) seizures
• Tonic seizures
• Atonic seizures
• Clonic and myoclonic seizures

28. ANTISEIZURE DRUGS
by groups
• AMPA receptor antagonists
• Barbiturate anticonvulsants
• Benzodiazepine anticonvulsants
• Carbamate anticonvulsants
• Carbonic anhydrase inhibitor anticonvulsants
• Dibenzazepine anticonvulsants
• Fatty acid derivative anticonvulsants
• Gamma-aminobutyric acid analogs
• Gamma-aminobutyric acid reuptake inhibitors
• Hydantoin anticonvulsants
• Miscellaneous anticonvulsants
• Neuronal potassium channel openers
• Oxazolidinedione anticonvulsants
• Pyrrolidine anticonvulsants
• Succinimide anticonvulsants
• Triazine anticonvulsants

29. ANTISEIZURE DRUGS
by disease
Antiepileptic
Сarbamazepinum (Finlepsin, Tegretol)
Ethosuximidum (Suxilep)
Natrii valproas (Convulex)
Antiparkinsonic
 Dopaniergic system activators
• Levodopa
• Mіdantanum
• Nakom
 Central cholinoblockers
• Cyclodolum (Parkopan)

30. ANTIPARKINSONIC DRUGS
Parkinson’s disease (PD) is a progressive neurodegenerative
disorder. It is caused by degeneration of substantia nigra in the
midbrain, and consequent loss of DA-containing neurons in the
nigrostrial pathway. Two balanced systems are important in the
extrapyramidal control of motor activity at the level of the corpus
striatum and substantia nigra; in the first the neurotransmitter is
ACh, in the second – DA.

31. ANTIPARKINSONIC DRUGS CLASSIFICATION
 Drugs acting on dopaminergic system:
• Dopamine precursors – Levodopa (l-dopa)
• Peripheral decarboxylase inhibitors – carbidopa and
• benserazide
• Dopaminergic agonists: Bromocriptyne, Ropinirole and
• Pramipexole
• MAO-B inhibitors – Selegiline, Rasagiline
• COMT inhibitors – Entacapone, Tolcapone
• Dopamine facilitator - Amantadine
 Drugs acting on cholinergic system
• Central anticholinergics – Teihexyphenidyl (Benzhexol),
• Procyclidine, Biperiden
• Antihistaminics – Orphenadrine, Promethazine

32. ANTIPARKINSONIC DRUGS CLASSIFICATION
Dopamine and Tyrosine Are Not Used for Parkinson Disease Therapy, Why?
 Dopamine Doesn't Cross the Blood Brain Barrier
 Huge amount of tyrosine decreases activity of rate limiting enzyme Tyrosine Hydroxylase

33. NEUROLEPTICS
Antipsychotics, also known as neuroleptics or major tranquilizers, are a class of
medication primarily used to manage psychosis (including delusions,
hallucinations, paranoia or disordered thought), principally in schizophrenia and
bipolar disorder. They are increasingly being used in the management of non-
psychotic disorders. Antipsychotics are usually effective in relieving symptoms of
psychosis in the short term.
Main effect:
Antipsychotic – they reduce main symptoms of psychosis (delirium, hallucination,
psychomotor activity). These drugs also have a calming effect &
they keep consciousness

34. CLASSIFICATION OF NEUROLEPTICS
• Derivatives of phenotiazine: aminasine, triftazine, etaperasine,
• Derivatives of tioxanten: chlorprotixen
• Derivatives of butyrophenon: haloperidol, droperidol
• Derivatives of piperasine-dibenzodiazepine: clozapine
• Derivatives of indole: reserpin, sulpyrid (eglonil)
“Typical” – derivatives of phenotiazine, tioxanten, butyrophenon
– they cause disorders of extrapyramidal system
function – syndrome of parkinsonism
“Atypical” – derivatives of indole, piperasine-dibenzodiazepine –
they cause those negative reactions very rarely

35. THE MECHANISM OF ACTION OF NEUROLEPTICS
1. Block a adreno-, dopamino-, cholino-, histamino- and serotoninergic receptors.
Typical antipsychotics block postsynaptic dopamine receptors in the limbic system and increase dopamine turnover by
blockade of the D2 receptor. The decrease in dopamine neurotransmission has been correlated to the antipsychotic
effects of the phenothiazines. This D2 blockade is also responsible for their extrapyramidal and antiemetic effects.
2. Decrease the permeability of cell membranes for electrolytes
3. They inhibit the enzyme tyrozine-hydroxylase, which convert aminoacid tyrosine to DOPA, one of the precursors of
main mediators dopamine and norepinephrine.
4. They inhibit the calmoduline activity. This enzyme converts Са++ into its active form, and influence on the main
processes in the cells.
5. They decrease the release of exciting aminoacids which can interfered with NMDA receptors and have activating action
on the neurons.

36. USE OF ANTIPSYCHOTIC ACTIVITY OF NEUROLEPTICS
Treatment of psychoses
 schizophrenia
 manic-depressive psychosis
 alcoholic psychosis
 reactive psychosis
psychomotor agitation of different etiology
Used for potentiation of action of hypnotic, narcotic and nonnarcotic analgesics, drugs for narcosis, local anesthetics, neuroleptanalgesia.
Anti-emetic action (elimination of vomiting of central genesis): brain tumors, radial and chemical therapy, intestinal impassability, intoxication with heart glycosides,
apomorphine and other drugs
Decreasing of body temperature in case of hypothermia
Decreasing of blood pressure (alpha-adrenoblocking properties – aminasine, droperidol) – in case of hypertensive crisis, lungs edema
Complex treatment of epilepsy (myorelaxation of skeletal muscles) In combination with narcotic analgetics for treatment of chronic pain with severe anxiety.

37. ADVERSE 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)
 Orthostatic collapse
 Dyspeptic disorders: anorexia, changes of taste
 Abdominal pain
 Damage of the liver (cholestasis)
 Granulocytopenia (especially clozapin)
 Hyperglycemia, dysmenorrhea, galactorrhea, gynecomastia, impotence
 Aminasine has a considerable irritable action

38. TRANQUILIZERS
A tranquilizer is a drug that acts on the central nervous system and is used to calm, decrease anxiety, or help a
person to sleep. Often called depressants because they suppress the central nervous system and slow the
body down, they are used to treat mental illness as well as common anxiety and sleeplessness. Available only
by prescription, they can cause dependence and certain ones can easily be abused.
Type of actions
Hypno-
sedative
Correct
vegetative
status
Anticonvulsive Myorelaxant
Potent anxiolytic
(anti-anxiety)

39. TRANQUILIZERS
Anxiolytic action
 Treatment of neurosis, accompanied by fear, anxiety, tenseness,
increased irritability, insomnia
 In case of headache and heartache of neurotic origin, so called
organic neurosis
 In case of abstinence in alcohol and drugs addicts
 In case of diencephal crisis (sibazon)
Tranquilizers do not eliminate productive symptoms of psychosis!
Hypnotic action – they cause sleep, which is very close to
physiological one according to its parameters (Nitrazepam,
Phenazepam, Diazepam, Chlozepid

40. INDICATION FOR USAGE OF TRANQUILIZERS
Depression of CNS – for atharalgesia (Sibazon, Midazolam)
Anti-seizure and myorelaxing action (depression of CNS structures, braking
polysynaptic spinal reflexes) - Sibazon, Phenazepam
In case of seizures of any etiology (epileptic status, tetanus, poisoning with seizure
causing poisons) Sibazon is introduced i.v (i.m.) – 2-4 ml of 0,5% solution
To eliminate muscular tension in case of radiculitis, arthritis, myositis bursitis –
drugs which practically don’t have myorelaxing properties

41. ADVERSE EFFECTS OF TRANQUILIZERS
Psychological and physical dependence
Prophylaxis: Duration of treatment course should not be more than 2 months
Repeated course – not earlier than after 3 weeks
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

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

43. SEDATIVE DRUG
Drugs which increase inhibition processes and decrease excitation processes in
brain cortex and thus cause calming effect on the CNS
Bromides (KBr, NaBr)
Drugs of plant origin: valerian, dog nettle, melissa, pasiflora etc.
Combine drugs: Corvalolum, Novo-pasit, Persen
They do not cause addiction, somnolence, myorelaxation, ataxia

44. INDICATION FOR USAGE
OF SEDATIVE DRUGS
 Neuroses
 Neurasthenia
 Hysteria
 Hyperexcitability
 Insomnia
 Initial stages of hypertony, ischemia, tachycardia

45. Thank for your attention