Pharmacology Psychotropic drugs neuroleptics

Psychotropic Drugs

Psychotropic Drugs

drugs with exciting type of action: psychostimulants antidepressants, lithium, nootropic drugs

drugs with inhibitory type of action: neuroleptics, tranquilizers and sedative drugs

Neuroleptics (Antipsychotic Drugs)• exert antipsychotic action, that is manifested in

elimination of delirium and hallucinations and slowing down of further development of the disease. The mechanism of antipsychotic action is blockade of D2-dopamine receptors of the limbic system of the brain. The characteristic effect of these drugs is the sedative one, that is manifested by elimination of affective reactions, decrease of anxiety and motor activity.

• "typical" and "atypical" Neuroleptics –• "typical" drugs often cause such side-effect as

impairment of functions of the extrapyramidal system (parkinsonism and other motor disorders).

"Typical" neuroleptics• 1) phenothiazine derivatives

— aminazinum [chlorpromazine], triftazinum [trifluoperazine], phthorphenazinum [fluphenazine], aethaperazine [perphenazine], levomepromazine, periciazine;

• 2) thioxanthene derivatives— chlorprothixene, flupenthixole

• 3) butyrophenone derivatives — haloperidol, droperidol

"Atypical" neuroleptics

• 1) benzamids — sulpiride, amisulpiride;

• 2) diazepine, oxazepine and thiazepine derivatives — azaleptine [clozapine], olanzapine, quetiapine;

• 3) other drugs — risperidone.

Neuroleptics are used: 1) for the treatment of psychoses and acute psychomotor excitement; 3) for neuroleptanesthesia;4) for premedication before general anesthesia;5) for the treatment of vomiting and durable hiccup; 6) for the treatment of drug dependence; 7) for the cupping of hypertensive crises.

Effects of neuroleptics (Aminazinum)• antipsychotic and sedative;• decrease of motor activity (central

myorelaxation action);• inhibition of the centre of thermoregulation;• antiemetic action;• ability to potentiate the action of general

anesthetics, hypnotic drugs, opioid analgesics;

• adrenoblocking action leads to• dilation of arteries and decrease of blood

pressure;• M-cholinoblocking properties• local action - significant irritation of the tissues• antihistamine activity• spasmolytic action.

Side-effects:• decrease of psychomotor activity, apathy,

sleepiness, dryness in the mouth, discomfort in the cardiac area, in the epigastric area, hypotension, orthostatic collapse (all these signs are observed most commonly in taking of aminazinum).

• The characteristic side-effects are extrapyramidal disorders (parkinsonism).

• In long taking of phenothiazine derivatives (during many months or years) there is possibility of the development of so called "late dyskinesia". It is manifested by involuntary contractions of the muscles of face, tongue, extremities and torso.

Tranquilizers (anxiolytics, ataractics or antiphobic drugs)

• eliminate long-lasting negative emotions - the symptoms of neurosis (internal tension, anxiety, fear, etc.)

DIVISION OF TRANQUILIZERS • I) agonists of benzodiazepine receptors: 1.

long-acting drugs (24-48 hours) — phenazepsm, chlozepidum [chlordiazepoxide], sibazonum [diazepam], flurazepam, mezapanum;

• 2. intermediate-duration drugs (6-24 hours) - nitrazepam, oxazepam, lorazepam, alprazolam; 3. short-acting drugs (< 6 hours) — midazolam, triazolam.

• II) agonists of serotonin receptors — Buspirone.

• blockers of the central M-cholinoceptors — amizylum (benactizine).

• miscellaneous tranquilizers — meprobamate, oxylidinum [benzoclidine], trioxazinum [trimethozine], mebicar, hydroxyzine.

"daily" tranquilizers

• - Benzodiazepines: mezapam, clorazepam, tofizopam, gidazepam

• - non-benzodiazepine agents: mebicar, buspiron, trioxazinum.

The mechanism of benzodiazepine’s action

• is stimulation of benzodiazepine receptors which are located in the limbic system and closely connected with GABA receptors. The interaction of benzodiazepines with the corresponding receptors leads to GABA-mimetic effect which causes the inhibition of neuronal activity in the limbic system, that leads to inhibition of negative emotion centres.

BENZODIAZEPINES' EFFECTS• sedative effect• tranquilizing action• contribute to development of

sleep• myorelaxation • anticonvulsive action• development of amnesia

(high doses)• promotion of the action of

general anesthetics, opioid analgesics, hypnotics.

SIDE-EFFECTS: • sleepiness, • slowing down of the motor

reactions,• decrease of memory, • weakness, • headache, • nausea, etc. • In taking of benzodiazepines

more than 6 months - the tolerance and drug dependence.

• A specific antagonist of benzodiazepines - flumazenil.

Indications for use:• treatment of neuroses, • as hypnotic drugs, • for the treatment of

different forms of epilepsy,

• some forms of parkinsonism,

• for potentiation of the action of general anesthetic and opioid analgesics in surgical operations.

Sedative Drugs• 1) bromides — natrium

bromide, kalium bromide;• 2) agents obtained from

plants: Valeriana, Motherwort (Leonurus), Passiflora, Peony, etc.;

• 3) combined drugs: bromated camphor, corvalole, barboval, cardiovalen, novo-passit, persen, sanason.

The mechanism of action: • exert calmative action

owing to decrease of the processes of internal inhibition, that leads to the predominance of inhibition upon excitation in the CNS.

Sedatives• As against of the tranquilizers sedative

drugs do not eliminate the negative emotions (internal tension, anxiety, fear, etc.), do not provide the myorelaxation action and do not potentiate the effects of other neurotropic drugs. They also do not cause drug dependence. This group of drugs is used in low neuroses, increased irritability, insomnia

Drugs with exciting type of action:

• Antidepressants, • Psychostimulants, • Nootropic Drugs. • Analeptics • Adaptogens.

• Antidepressant drugs are the drugs used for the treatment of psychical depressions. The main manifestations of psychical depression are dreary spirits, feeling of hopelessness and desperation, tendency to the suicide.

• There are 3 types of depression: • 1) "reactive" depression — it occurs in

response to real stimuli (grief, illness, etc.); 2) "endogenous" depression -genetically determined biochemical disorder manifested by inability to cope with ordinary stress;

• 3) depression in maniac-depressive psychosis.

Antidepressants• 1) drugs which inhibit the neuronal

reuptake of monoamines (noradrenaline and serotonin):— imizinum [imipramine], amitriptyline, azaphenum [pipofezine], phthoracizinum[fluacizine];

• — fluoxetine,fluvoxamine, paroxetine, sertraline, trazodone— maprotiline,desipramine.

• 2) MAO inhibitors:— nialamide, transaminum

• — moclobemide, pyrasidole, incazanum [metralindol].

Psychostimulants• Psychostimulants are

the drugs which increase the capacity for mental and physical work,

• increase the ability to perceive external tired

• Slightly improve the mood and decrease the feeling of tiredness, the need of sleep and food.

Classification • 1) phenylalkylamine derivatives

— phenaminum [amphetamine];

• 2) piperidine derivatives — pyridrolum [pipradole], meridilum [metylphenidate];

• 3) sidnonimine derivatives — sydnocarbum [mesocarbe], sydnophenum [pheprosidine];

• 4) methylxanthine derivatives — coffeinum [caffeine].

Coffeinum• The mechanism of action –• the inhibition of the enzyme phosphodiesterase, that leads

to accumulation of cAMP,• - blockade of the adenosine receptors. • direct stimulating action upon the cortex of the brain.

Coffeinum stimulates the psychical activity, increases the mental and physical capacity for work, the motor activity. After its taking the cheerfulness arises and fatigue, sleepiness are eliminated or decreased.

• The influence upon the higher nervous activity is significantly dependent on the dose of coffeinum and the type ofthe nervous system. In low doses it exerts the stimulating action and in high doses — the inhibitory effect. For the "weak" type of the nervous system the effect of excitement is reached by introduction of low doses of coffeinum and the "strong" type requires higher doses.

Coffeinum• The analeptic activity is associated with the influence upon the

centres of medulla oblongata - exerts direct stimulating influence upon the respiratory, vasomotor centres.

• - stimulates neurons of the spinal cord increasing motor reflexes and muscular tone.

• exerts direct stimulating action upon myocardium, but at the same time it excites the centres of vagus nerves. That's why the heart activity is not almost changed. Only high doses of coffeinum may cause tachycardia.

• Has direct influence upon the smooth muscles of vessels: coronary, cerebral and renal arteries are dilated but the tone of the veins is increased. In arterial hypotension the BP is normalized, in normal blood pressure it is not changed,

• stimulates lipolysis and glycogenesis • intensify the secretion of gastric juice• increases the glomerular filtration - increase of diuresis.

Coffeine

Nootropic drugs• These are the drugs

which enhance cognitive functions of the brain, they improve the processes of memorizing and cognitivity in their impairment. That is why this group is also called the cognitive enhancers

Nootropic drugs

• They improve the aerobic and anaerobic glycolysis,

• reduce the reserves of noradrenaline in cerebral vessel wall,

• stimulate the inhibitory processes in the CNS,

• increase of the neuronal stability to hypoxia and improvement of the cerebral blood supply. Effects: antihypoxic, antioxidant, membrane-protective, anticonvulsive and

• antiedematic

Adaptogens• This group of drugs

include various agents mainly of plant origin which exert slight stimulating influence upon the CNS, endocrine system and functions of other systems and organs. These agents include powders, tinctures, extracts of Ginseng, Schizandra, Aralia, Eleutherococcus, Rhodiola, Leuzea, etc.

Indications for use• asthenia, • weakening of organism's

functions in overstrain, after diseases.

• They also increase capacity for physical and psychical exertion.

• These agents are low-toxic, well tolerated and may be used for a long time.