CNS Stimulants

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• CNS Stimulants

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PSYCHOTROPIC DRUGS

• Drugs with depressive type of actoin
• Neuroleptics (antipsychotic)
• Tranquilizers (anxiolytics)
• Sedative drugs
• Normotymics (tymoleptics, tymoanaleptics)
• Drug with stimulative action
• Antidepressants
• Psychomotor stimulants
• Nootropic drugs
• Drugs which increase general tone (adaptogens)
• Psychotomimetics (psychodysleptics)
• LSD
• Cannabis sativa L.

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ANTIDEPRESSANTS
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DEPRESSION

• Types
• Symptoms
• Diagnosis
• Causes
• Treatment

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TYPES OF DEPRESSION

• Major depression
• Chronic depression (Dysthymia)
• Atypical depression
• Bipolar disorder/Manic depression
• Seasonal depression (SAD)

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CAUSES OF DEPRESSION

• Genetics
• Death/Abuse
• Medications

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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)

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More than 50 of patients with depressive
disorders dont 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

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TREATMENT FOR DEPRESSION

• Psychotherapy
• Electroconvulsive therapy
• Natural alternatives
• Medication
• SSRIs
• MAOIs
• TCAs
• SNRIs
• NDRIs
• TeCAs

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NEUROTRANSMITTERS AND THE CATECHOLAMINE HYPOTHESIS

• Neurotransmitters pass along signal
• Smaller amount of neurotransmitters causes
  depression

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Function of adrenergic synapse in physiological
conditions
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ANTIDEPRESSANTS

• Drugs which inhibit neuronal uptake of monoamines
• Nonselective action (block uptake of
  noradrenaline and serotonine) imisin,
  amitriptilin
• Selective action ?) heterocyclic compounds
  (block neuronal uptake of noradrenaline)
  amoxapin, maprotilin (ludiomil) ?) selective
  blockers of neuronal uptake of serotonin
  fluoxetin (prozak, framex), sertralin (zoloft),
  paroxetin (rexetin)
• Inhibitors of monoaminoxidase (IMAO)
• nonselective (block ???-? and ???-?) ?)
  irreversible action nialamid b) reversible
  action transamin
• Selective ???? (block ???-?) moklobemid,
  pirasidol

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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

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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 a receptor antagonism - postural
  hypotension
• Direct membrane effects - reduced seizure
  threshold, arrhythmia
• Serotonin 5-HT2 receptor antagonism - weight gain
  (and reduced anxiety)

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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

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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

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MAOIS MECHANISM OF ACTION

• MAO contains a cysteinyl-linked flavin
• MAOIs covalently bind to N-5 of the flavin
  residue of the enzyme

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Mechanism of action of IMAO
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Blockers of neuronal uptake of serotonin

• Modern point of view on mechanism of development
  of depression
• Primary deficiency of serotonin in synaptic gap
• Compensatory growing of quantity and sensitivity
  of postsynaptic 5-??2 receptors
• Compensatory decreasing of quantity and
  sensitivity of presynaptic 5-??1 receptors in
  hippocampus and nuclei row (these structures play
  an important role ?n development of depression)

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Blockers of neuronal uptake of serotonin
fluoxetin, sertralin, paroxetin

• Mechanism of action
• Increasing of active concentration of serotonin
  in synaptic gap on a level of postsynaptic
• 5-??2 serotonin receptors of cerebral structures

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Blockers of neuronal uptake of serotonin
fluoxetin, sertralin, paroxetin
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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

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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

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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

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Usage of antidepressants

• Schizophrenia, Bipolar disease
• Atherosclerosis of brain
• Reactive depressions
• Parkinsonism
• Organic diseases of CNS
• Oncology patients
• General somatic diseases

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Psychotropic action of antidepressants

• Drugs with psychosedative action
• ?mitriptilin, maprotilin, asafen, fluvoxamin
• 2. Drugs with psychostimulative action
• Imisin, nialamid, fluoxetin
• 3. Drugs with regulative influence
• Pirasidol

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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

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Side effects of antidepressants

• ?-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 cant be used (it is necessary to
  increase volume of circulating blood, put the
  legs up)

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Side effects of antidepressants

• Acute attacks of epilepsy
• Cardiotoxic action (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

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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

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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

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Diet in case of administration of IMAO

• It is necessary to exclude such products which
  contain
• DOPA and thiramine (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 into ration very carefully

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• In case of administration of inhibitors of uptake
  of serotonin the 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

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PSYCHOMOTOR STIMULANTS
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PSYCHOMOTOR STIMULANTS

• Derivatives of purine caffeine
• Phenilalkilamines phenamine (amphetamine)
• Phenilalkilsydnonimins - sydnocarb

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Properties of psychomotor stimulants

• Stimulate intellectual activity, speed up
  thinking processes, temporarily eliminate
  tiredness, somnolence
• Eliminate such manifestations of neurosis as
  subdepression, fatigue, retardness
• Arent able to eliminate endogen depression,
  which accompanies psychical diseases

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Caffeine
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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.

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Chemical Properties
Molar Mass 194.19 g mol-1
Density 1.2 g/cm³ Phase Solid
Melting Point 237 C Boiling Point 178 C
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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.

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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.

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Caffeine

• Mechanism of action
• Binds to adenosine (purine) receptors in
  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

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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

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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

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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

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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

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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

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Pathophysiology

• ADHD may be caused by disregulation of the
  neurotransmitters serotonin, norepinephrine
  dopamine. This occurs in children less than 7
  y/o but may persist through the teenage years.
  More common in boys. Characterized by
  inattentiveness, inability to concentrate,
  restlessness, hyperactivity, inability to
  complete tasks impulsivity.

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A My son is hyperactive.B Kids are like that
sometimes.A No, I''m serious. He is constantly
on the go from 5 a.m. to 10 p.m.
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Pathophysiology

• Narcolepsy is characterized by falling asleep
  during normal waking activities. Sleep paralysis
  usually accompanies it affects voluntary
  muscles.

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AMPHETAMINE-LIKE DRUGS

• MOA stimulate the release of NE Dopa
• For the treatment of ADHD Narcolepsy
• increases attention span, cognitive performance
  to decrease impulsiveness, hyperactivity
  restlessness
• SE restlessness, insomnia, tachycardia,
  hypertension, palpitation, dry mouth, anorexia,
  weight loss, diarrhea, impotence
• Antihypertensive barbiturates decrease action
  Caffeine increase its action
• Methylphenidate (Ritalin)
• Pemoline (Cylert)

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Analeptics (Bemegridum, Camphora, Cordiaminum)
Camphora
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ANALEPTICS

• CNS stimulants mostly affecting the brainstem
  spinal cord but also affects the cerebral cortex
• Primary use is to stimulate respiration like in
  newborns with respiratory distress
• SE nervousness, restlessness, tremors,
  palpitations, insomnia, diuresis, GI irritation
• Methylxanthines caffeine, theophylline

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RESPIRATORY CNS STIMULANT

• CNS respiratory stimulant used to treat
  respiratory depression caused by drug overdose,
  pre- postanesthetic respiratory depression
  chronic obstructive pulmonary disease (COPD)
• Doxapram HCl (Dopram)

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NOOTROPIC DRUGS(NEUROMETABOLIC
CEREBROPROTECTORS)
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Neurometabolic cerebroprotectors

• Derivatives of pyrrolidone pyracetam
  (nootropil)
• Derivatives of GABA aminalon, sodium
  oxybutyrate
• Neuropeptides melatonin, sinacten-depot
• Cerebrovascular drugs sermion (nicergolin),
  cavinton (vinpocetin), stugeron (cinnarisin),
  pentoxyphylline (trental, agapurine), xantynole
  nicotinate
• Derivatives of piridoxine piritinol
  (encephabol)
• Antioxidants mexidol, tocopherole acetate
• Other cerebrolysine, actovegin, solkoseryl,
  plant preparations

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Properties of nootropic drugs

• Improvement of brain blood circulation, promotion
  of collaterals development
• Psychostimulating effect, antiasthenic action
• Sedative, antidepressive action
• Antiepileptic, antiparkinsonic action
• Nootropic action
• Mnemotropic action
• Vasovegetative action
• Antihypoxic action

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Administration of nootropic drugs

• Atherosclerosis of brain, vascular parkinsonism,
  Alzheimer's disease
• Disorders of brain blood circulation in case of
  traumas and intoxications, vascular diseases of
  brain
• Diseases of CNS, accompanied by decreasing of
  intellect, memory
• Disorders of psychology (in elderly with
  schizophrenia, depressions)
• To decrease manifestations of abstinence
  (alcoholism, drug addiction)
• In neurology (neurasthenia, migraine, neuralgias,
  radiculitis)
• In pediatrics in case if mental insufficiency

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Piracetam (nootropil)
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Cerebrolysin
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Cinnarizin (stugeron)
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ADAPTOGENS
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Adaptogens

• Drugs of
• Ginseng, Schizandrum, Rodiola, Eleutherococcus,
  Leusea, Echinacea
• Apilac, propolis, mumie,
• heparin, dybazol

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GINSENG
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RODIOLA
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Eleutherococc
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Schizandrum
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Echinacea purpurea Maxima
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ADAPTOGENS

• Increase general resistance of the organism
  towards unfavorable factors
• Stimulating action
• Antistress action
• Anabolic action

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Side effects of adaptogens

• Increasing of AP
• disturbance of sleep if administered in evening
  time, overwhelming excitation, psychic dependence