CNS Stimulants
PSYCHOTROPIC DRUGS
Drugs with depressive type of actoin
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2.
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4.
Neuroleptics (antipsychotic)
Tranquilizers (anxiolytics)
Sedative drugs
Normotymics (tymoleptics, tymoanaleptics)
Drug with stimulative action
1.
2.
3.
4.
Antidepressants
Psychomotor stimulants
Nootropic drugs
Drugs which increase general tone
(adaptogens)
Psychotomimetics (psychodysleptics)
1.
2.
LSD
Cannabis sativa L.
ANTIDEPRESSANTS
DEPRESSION
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Types
Symptoms
Diagnosis
Causes
Treatment
TYPES OF DEPRESSION
• Major depression
• Chronic depression
(Dysthymia)
• Atypical depression
• Bipolar disorder/Manic
depression
• Seasonal depression (SAD)
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)
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
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TREATMENT FOR
DEPRESSION
Psychotherapy
Electroconvulsive therapy
Natural alternatives
Medication
• SSRIs
• MAOIs
• TCAs
• SNRIs
• NDRIs
• TeCAs
NEUROTRANSMITTERS AND
THE CATECHOLAMINE
HYPOTHESIS
• Neurotransmitters pass along signal
• Smaller amount of neurotransmitters causes
depression
Function of adrenergic synapse in
physiological conditions
ANTIDEPRESSANTS
Drugs which inhibit neuronal uptake of
monoamines
1.
2.
Nonselective action (block uptake of noradrenaline and
serotonine): imisin, amitriptilin
Selective action: а) heterocyclic compounds (block neuronal
uptake of noradrenaline): amoxapin, maprotilin (ludiomil); б)
selective blockers of neuronal uptake of serotonin: fluoxetin
(prozak, framex), sertralin (zoloft), paroxetin (rexetin)
Inhibitors of monoaminoxidase (IMAO)
1.
2.
nonselective (block МАО-А and МАО-В): а) irreversible
action – nialamid; b) reversible action – transamin
Selective ІМАО (block МАО-А): moklobemid, pirasidol
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 Asp98 in hSERT
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)
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
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
MAOIS MECHANISM OF
ACTION
• MAO contains a
cysteinyl-linked
flavin
• MAOIs covalently
bind to N-5 of the
flavin residue of the
enzyme
Mechanism of action of IMAO
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-НТ2 receptors
Compensatory decreasing of quantity and sensitivity of
presynaptic 5-НТ1 receptors in hippocampus and
nuclei row (these structures play an important role іn
development of depression)
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-НТ2 serotonin receptors of cerebral
structures
Blockers of neuronal uptake of serotonin
fluoxetin, sertralin, paroxetin
SSRIS SIDE EFFECTS
• Anhedonia
(disambiguation)
• Apathy
• Nausea/vomiting
• Drowsiness or
somnolence
• Headache
• Bruxism
(involuntarily
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grinding of the teeth)
Extremely vivid and
strange dreams
Dizziness
Fatigue
Changes in sexual
behavior
Suicidal thoughts
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
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
Usage of antidepressants
Schizophrenia, Bipolar disease
Atherosclerosis of brain
Reactive depressions
Parkinsonism
Organic diseases of CNS
Oncology patients
General somatic diseases
Psychotropic action of
antidepressants
1. Drugs with psychosedative action:
Аmitriptilin, maprotilin, asafen,
fluvoxamin
2. Drugs with psychostimulative action:
Imisin, nialamid, fluoxetin
3. Drugs with regulative influence
Pirasidol
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
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)
Side effects of antidepressants
• Acute attacks of epilepsy
• Cardiotoxic action (sudden death), threecyclic 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
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
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
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
• 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
PSYCHOMOTOR
STIMULANTS
PSYCHOMOTOR STIMULANTS
• Derivatives of purine – caffeine
• Phenilalkilamines – phenamine
(amphetamine)
• Phenilalkilsydnonimins - sydnocarb
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
Caffeine
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.
Chemical Properties
Molar Mass = 194.19 g mol−1
Density: 1.2 g/cm³
Phase: Solid
Melting Point: 237 °C
Boiling Point: 178 °C
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.
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 halflife 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.
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
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
Influence of caffeine on
cardiac-vascular system
Vessels
1. Stimulation of vasomotor center –
contraction of vessels, increasing of AP
2. Peripheral myotropic spasmolytic action
– dilation of vessels, decreasing of AP
Heart
1. Central action (increasing of n. vagus
tone) – bradycardia
2. Peripheral action (direct influence on
heart) – tachycardia, possible
extrasystolia
Influence of caffeine on cardiovascular 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
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
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
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.
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.
Pathophysiology
• Narcolepsy is characterized by falling
asleep during normal waking activities.
Sleep paralysis usually accompanies it &
affects voluntary muscles.
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)
Analeptics (Bemegridum, Camphora,
Cordiaminum)
Camphora
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
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)
NOOTROPIC DRUGS
(NEUROMETABOLIC
CEREBROPROTECTORS)
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
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
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
Piracetam (nootropil)
Cerebrolysin
Cinnarizin (stugeron)
ADAPTOGENS
Adaptogens
Drugs of
Ginseng, Schizandrum, Rodiola,
Eleutherococcus, Leusea,
Echinacea
Apilac, propolis, mumie,
heparin, dybazol
GINSENG
RODIOLA
Eleutherococc
Schizandrum
Echinacea purpurea Maxima
ADAPTOGENS
Increase general resistance of the organism
towards unfavorable factors
Stimulating action
Antistress action
Anabolic action
Side effects of adaptogens
Increasing of AP
disturbance of sleep if administered
in evening time, overwhelming
excitation, psychic dependence