CNS Stimulants

1. CNS Stimulants

2. PSYCHOTROPIC DRUGS Drugs withdepressivetype of actoin • Neuroleptics (antipsychotic) • Tranquilizers (anxiolytics) • Sedative drugs • Normotymics (tymoleptics, tymoanaleptics) Drug withstimulativeaction • Antidepressants • Psychomotor stimulants • Nootropic drugs • Drugs which increase general tone (adaptogens) Psychotomimetics(psychodysleptics) • LSD • Cannabis sativa L.

3. ANTIDEPRESSANTS

4. DEPRESSION Types Symptoms Diagnosis Causes Treatment

5. TYPES OF DEPRESSION Major depression Chronic depression (Dysthymia) Atypical depression Bipolar disorder/Manic depression Seasonal depression (SAD)

6. CAUSES OF DEPRESSION Genetics Death/Abuse Medications

7. SYMPTOMS persistently sad, anxious, or empty moods loss of pleasure in usual activities (anhedonia) feelings of helplessness, guilt, or worthlessness crying, hopelessness, or persistent pessimism fatigue or decreased energy loss of memory, concentration, or decision-making capability restlessness, irritability sleep disturbances change in appetite or weight physical symptoms that defy diagnosis and do not respond to treatment (especially pain and gastrointestinal complaints) thoughts of suicide or death, or suicide attempts poor self-image or self-esteem (as illustrated, for example, by verbal self-reproach)

8. More than 50 % of patients with depressive disorders don’t realize that they have any psychological problems and complain only on certain somatic discharges Most frequent complaints of patients with depression Feeling of hopelessness, indifference, fear, panic Tiredness, weakness, headache, dizziness, dream disorders, dyspepsia, unpleasant feelings and pain in different parts of the body Depressive conditions “mask” as vegetovascular, neurocirculative dystonia (various vegetative disorders), gastro-intestinal pathology, pathology of cardio-vascular, respiratory systems, manifest as diskinesia, functional motor disorders, insomnia, toothache, disorders of sexual activity, recidivate eczema and many other disorders

9. TREATMENT FOR DEPRESSION • Psychotherapy • Electroconvulsive therapy • Natural alternatives • Medication • SSRIs • MAOIs • TCAs • SNRIs • NDRIs • TeCAs

10. NEUROTRANSMITTERS AND THE CATECHOLAMINE HYPOTHESIS Neurotransmitters pass along signal Smaller amount of neurotransmitters causes depression

11. Function of adrenergic synapse in physiological conditions

12. ANTIDEPRESSANTS Drugs which inhibit neuronal uptakeof monoamines • Nonselective action (blockuptakeof noradrenaline and serotonine): imisin, amitriptilin • Selective action: а) heterocyclic compounds (block neuronaluptakeof noradrenaline): amoxapin, maprotilin (ludiomil); б) selective blockers of neuronal uptake of serotonin: fluoxetin (prozak, framex), sertralin (zoloft), paroxetin (rexetin) Inhibitors of monoaminoxidase (IMAO) • nonselective (block МАО-А and МАО-В): а) irreversibleaction – nialamid; b) reversible action – transamin • Selective ІМАО (block МАО-А): moklobemid, pirasidol

13. TCAS MECHANISM OF ACTION TCAs inhibit serotonin, norepinephrine, and dopamine transporters, slowing reuptake TCAs also allow for the down regulation of post-synaptic receptors All TCAs and SSRIs contain an essential amino group that appears to interact with Asp-98 in hSERT

14. TCAS SIDE EFFECTS Muscarinic M1 receptor antagonism - anticholinergic effects including dry mouth, blurred vision, constipation, urinary retention and impotence Histamine H1 receptor antagonism - sedation and weight gain Adrenergic α receptor antagonism - postural hypotension Direct membrane effects - reduced seizure threshold, arrhythmia Serotonin 5-HT2 receptor antagonism - weight gain (and reduced anxiety)

15. TCAS SIDE EFFECTS • Nonselectivity results in greater side effects • TCAs can also lead to cardiotoxicity • Increased LDH leakage • Slow cardiac conduction • High potency can lead to mania • Contraindicated with persons with bipolar disorder or manic depression

16. MONOAMINE OXIDASE (MAO) AND DEPRESSION • MAO catalyze deamination of intracellular monoamines • MAO-A oxidizes epinephrine, norepinephrine, serotonin • MAO-B oxidizes phenylethylamine • Both oxidize dopamine nonpreferentially • MAO transporters reuptake extracellular monoamine

17. MAOIS MECHANISM OF ACTION MAO contains a cysteinyl-linked flavin MAOIs covalently bind to N-5 of the flavin residue of the enzyme

19. Mechanism of action of IMAO

20. Blockers of neuronaluptake of serotonin Modern point of view on mechanism of development of depression Primary deficiency ofserotoninin synaptic gap Compensatory growing of quantity and sensitivity of postsynaptic5-НТ2receptors Compensatory decreasing of quantity and sensitivity of presynaptic5-НТ1receptors in hippocampus and nuclei row (these structures play an important role іn development of depression)

21. Blockers of neuronaluptake of serotoninfluoxetin, sertralin, paroxetin Mechanism of action Increasing of active concentration of serotonin in synaptic gapon a level of postsynaptic 5-НТ2 serotonin receptors of cerebral structures

22. Blockers of neuronaluptake of serotoninfluoxetin, sertralin, paroxetin

23. SSRIS SIDE EFFECTS Anhedonia (disambiguation) Apathy Nausea/vomiting Drowsiness or somnolence Headache Bruxism (involuntarily grinding of the teeth) Extremely vivid and strange dreams Dizziness Fatigue Changes in sexual behavior Suicidal thoughts

24. SSRIS SIDE EFFECTS • Many disappear within 4 weeks (adaption phase) • Side effects more manageable compared to MAOIs and TCAs • Sexual side effects are common • SSRI cessation syndrome • Brain zaps • Sexual dysfunction

25. SEROTONIN-NOREPINEPHRINE REUPTAKE INHIBITORS (SNRIS) • Slightly greater efficacy than SSRIs • Slightly fewer adverse effects than SSRIs • Current drugs • Venlafaxine (Effexor) • Duloxetine (Cymbalta) • Mechanism of Action • Very similar to SSRIs • Works on both neurotransmitters • Side effects • Similar to SSRIs • Suicide

27. Usage of antidepressants Schizophrenia, Bipolar disease Atherosclerosis of brain Reactive depressions Parkinsonism Organic diseases of CNS Oncology patients General somatic diseases

28. Psychotropic action of antidepressants • Drugs withpsychosedativeaction: Аmitriptilin, maprotilin, asafen, fluvoxamin 2. Drugs withpsychostimulativeaction: Imisin, nialamid, fluoxetin 3. Drugs withregulativeinfluence Pirasidol

29. Principles of antidepressants usage • Endogen depression – the deeper it is, the larger doses, rate of their increasing and duration of treatment should be administered • Step-by-step dose increasing till obtaining of effect, administration of effective dose during 4-6 weeks – 3-6 months, gradual decreasing of dose (during 5-6 weeks) • Effect can appear only after 7-14 days after beginning of therapy (this fact should be taken into consideration in patients with suicidal dispositions) • In case of rapid abolishing withdrawal syndrome may develop

30. Side effects of antidepressants • М-cholinoblocking action: dry mouth, increasing of intraocular pressure, disturbance of accommodation, constipation, ischuria (important in a case of adenoma of prostatic gland!), tremor, hallucinations, disorders of consciousness, excitation • Alpha-adrenoblocking, papaverine-like effect: sharp hypotension, orthostatic collapse (especially in combination of amitriptiline with clopheline), for correction of which adrenomimetics can’t be used (it is necessary to increase volume of circulating blood, put the legs up)

31. Side effects of antidepressants • Acute attacks of epilepsy • Cardiotoxicaction (sudden death), three- cyclic antidepressants increase arrhythmogenic activity of drugs for general anesthesia, antihistamines etc. • Combination of three-cyclic antidepressants with IMAO is absolutely contraindicated:danger of development of hypertensive crisis, seizures, rapid excitation, tachycardia, cardiac arrhythmias, increasing of temperature

32. Rules of transferring from one kind of antidepressants to another • From three-cyclic to IMAO – break time– 2-3 days • From IMAO to three-cyclic – break time – not less than 2 weeks

33. It is absolutely contraindicated to administer adreno(sympato)mimetics in case of treatment with antidepressants Even small doses of adrenomimetic (sympatomimetic) substances in such patient can cause hypertensive crisis: • Nose drops for rhinitis • If few drops were added to solutions of local anesthetics • In case of administration of drugs which contain pseudoephedrine

34. Diet in case of administration of IMAO It is necessary to excludesuch products which contain DOPAandthiramine(which is formed from casein during the process of transforming under the influence of bacteria) aged cheese, kefir Marinated herring Smoked meat, fish Red vine, beer, yeast Beans Any BAA are also dangerous In case of treatment with IMAO new products should be introduced intoration very carefully

36. In case of administration of inhibitors of uptake of serotoninthe previously indicated side effects are observed much more rarely • Administration of antidepressants with any other drugs should be performed only after precise studying of possible negative consequences of their interaction

37. PSYCHOMOTOR STIMULANTS

38. PSYCHOMOTOR STIMULANTS • Derivatives of purine – caffeine • Phenilalkilamines – phenamine (amphetamine) • Phenilalkilsydnonimins - sydnocarb

39. Properties of psychomotor stimulants • Stimulate intellectual activity, speed up thinking processes, temporarily eliminate tiredness, somnolence • Eliminate such manifestations of neurosis as: subdepression, fatigue, retardness • Aren’t able to eliminate endogen depression, which accompanies psychical diseases

40. Caffeine

41. Did You Know? • Caffeine is a xanthine alkaloid compound that acts as a stimulant in humans. Caffeine is sometimes called guaranine when found in guarana, mateine when found in mate, and theine when found in tea. It is found in the leaves and beans of the coffee plant, in tea, yerba mate, and guarana berries, and in small quantities in cocoa, the kola nut and the Yaupon Holly. Overall, caffeine is found in the beans, leaves, and fruit of over 60 plants, where it acts as a natural pesticide that paralyzes and kills certain insects feeding upon them.

42. Chemical Properties Molar Mass = 194.19 g mol−1 Density: 1.2 g/cm³ Phase: Solid Melting Point: 237 °C Boiling Point: 178 °C

43. Uses of Caffeine • Caffeine is a central nervous system (CNS) stimulant, having the effect of temporarily warding off drowsiness and restoring alertness. Beverages containing caffeine, such as coffee, tea, soft drinks and energy drinks enjoy great popularity: caffeine is the world's most widely consumed psychoactive substance. In North America, 90% of adults consume caffeine daily.

44. Metabolizing Of Caffeine • Caffeine is completely absorbed by the stomach and small intestine within 45 minutes of ingestion. After ingestion it is distributed throughout all tissues of the body and is eliminated by first-order kinetics. The half-life of caffeine varies widely among individuals according to such factors as age, liver function, pregnancy, some concurrent medications, and the level of enzymes in the liver needed for caffeine metabolism. In healthy adults, caffeine's half-life is approximately 3-4 hours. In women taking oral contraceptives this is increased to 5-10 hours, and in pregnant women the half-life is roughly 9-11 hours. Caffeine can accumulate in individuals with severe liver disease when its half-life can increase to 96 hours.

45. Caffeine Mechanism of action • Binds to adenosine (“purine”) receptorsin brain (endogen ligand of these receptors – adenosine decreases processes of excitation in CNS) • Inhibiting of phosphodiesterase, which leads to accumulation of cAMP and stimulation of many physiological processes and metabolism

46. Usage of psychostimulating influence of caffeine • For stimulation of psychological processes, workability, to eliminate somnolence • Enuresis, narcolepsy • In case of poisoning with alcohol • To speed up awakening after narcosis

47. Influence of caffeine on cardiac-vascular system Vessels • Stimulation of vasomotor center – contraction of vessels, increasing of AP • Peripheral myotropic spasmolytic action – dilation of vessels, decreasing of AP Heart • Central action (increasing of n. vagus tone) – bradycardia • Peripheral action (direct influence on heart) – tachycardia, possible extrasystolia

48. Influence of caffeine on cardio-vascular system • Contraction of brain vessels • Dilation of kidney vessels, increasing of diuresis • Dilation of coronary vessels In case of depression of centers of brain stem (medulla oblongata) caffeine shows stimulating properties, increases blood pressure, stimulates breathing –analeptic action

49. SIDE EFFECTS OF CAFFEINE • If administered regularly – psychological addiction – theism, which is accompanied by development of abstinent syndrome (retardness, fatigue, somnolence, depression) • Tolerance • Teratogenic action (innate abnormalities) • Increasing of frequency of IHD, essential hypertension • Acute attacks of ulcer disease(it increases gastric secretion) • Acute poisoning in case of overdosing

50. CNS STIMULANTS • Medically approved use is for the treatment of Attention deficit/hyperactivity disorder (ADHD), narcolepsy, obesity & reversal of respiratory distress • Drugs used to treat migraine headache