PSYCHOTROPIC DRUGS

PART II
PSYCHOANALEPTICS

1. ANTIDEPRESSANTS DRUGS
2. PSYCHOSTIMULANT DRUGS
3. NOOTROPIC DRUGS
4. GENERAL TONIFYING, ADAPTOGENS
5. ANALEPTIC DRUGS.
An antidepressant is a psychiatric
medication used to alleviate mood
disorders, such as major depression,
dysthymia and anxiety disorders such as
social anxiety disorders.
 S/S DEPRESSION
Sense of inadequacy and helplessness
Maybe unresolved grief
Psychomotor retardation
“Vegetative signs”
Weight loss
Constipation
Early morning awakening
TYPES OF DEPRESSION
Depression can be classified as:
Reactive (i.e., response to grief or illness)
Endogenous (i.e., genetically determined
biochemical condition)
Bipolar affective (i.e., manic-depressive
disorder)
NEUROTRANSMITTERS AND THE
CATECHOLAMINE HYPOTHESIS
 Neurotransmitters pass along signal
 Smaller amount of neurotransmitters causes
depression
THE RECEPTOR SENSITIVITY
HYPOTHESIS
 Supersensitivity and up-regulation of post-
synaptic receptors leads to depression
 Suicidal and depressed patients have
increased 5HT-α2 receptors
MONOAMINE OXIDASE (MAO)
AND DEPRESSION
 MAO catalyzes deamination of intracellular
monoamines
 MAO-A oxidizes epinephrine, norepinephrine,
serotonin
 MAO-B oxidizes phenylethylamine

 Both oxidize dopamine nonpreferentially

 MAO transporters reuptake extracellular

monoamine
Classification of Antidepressants
A. Amine reuptake blocking drugs
nonselective: imipramine, amitriptyline,
clomipramine, pipofezine
selective:
a). selective serotonin reuptake inhibitors (SSRIs)
fluoxetine, duloxetine
paroxetine, venlafaxine
sertraline, dapoxetine
b).selective noradrenalin reuptake inhibitors
maprotiline
desipramine
atomoxetine
B. Monoamine oxidase (MAO) inhibitors
ireversible drugs
phenelzine
tranylcypromine
nialamide
reversible drugs
a) selective (MAO A)
moclobemide
pirlindol
b) non selective – methyltriptamine, caroxazon
C. The drugs from various groups with undefined
mechanism of action
alprasolam (xanax)
mianserin
feprozidine,
cefedrine
 Amine reuptake blocking drugs
MECHANISM OF ACTION
a. TCAs and atypical antidepressant drugs potentiate the actions
of norepinephrine, serotonin, or both by blocking their uptake by
transporters into prejunctional nerve endings, the major route for
their physiologic inactivation.
b. Exceptions include
(1) Amoxapine, which also blocks dopamine receptors
(2) Trazodone and nefazodone, which are antagonists at postjunctional 5-
HT2-receptors and also block prejunctional serotonin 5-HT1-autoreceptors
(3) Mirtazapine, which has serotonin 5-HT2-receptor antagonist activity and
also blocks a2-adrenoceptors
(4) Bupropion, the mechanism of action of which is unclear.
c. SSRIs are selective inhibitors of serotonin uptake.
d. also allow for the downregulation of post-synaptic receptors
 Monoamine oxidase inhibitors
(MAOI): MECHANISM OF ACTION
a. MAOIs inhibit the activity of enzymes MAO-A and
MAO-B. Inhibition of MAO-A, which preferentially
degrades norepinephrine and serotonin, is
responsible for the therapeutic efficacy of MAOIs as
antidepressants (MAO-B degrades dopamine
preferentially).
b. MAOIs act as ‘‘suicide’’ enzyme inhibitors, with
inhibition continuing for up to 2–3 weeks after their
elimination from the body.
 Therapeutic efficacy
a. All antidepressant drugs have similar therapeutic efficacy, although
individual patients may respond better to one drug than another.
Selection is often based on associated adverse effects.
b. Therapeutic efficacy of these drugs occurs after several weeks of
antidepressant administration and is closely associated with
adaptive changes over the same time period, including decreased
cyclic AMP (cAMP) accumulation and a reduction (down-
regulation) of postjunctional b-adrenoceptors, as well as an
increase in responsiveness of postjunctional serotonin 5-HT1A-
receptors. Adaptive desensitization of prejunctional norepinephrine
and serotonin autoreceptors may also be factors.
c. Adaptive changes in neurotropic factors have also been implicated.
 How to start
antidepressants?
Start low to assess tolerance of side
effects
Increase dosage rapidly as tolerated
Maintain typical dose for at least 4 to 8
weeks
 Effects:
Antidepressant,
Activator,
Sedative,
analgesic and potentiation of analgesia,
M-Cholinoblocking,
-adrenoblocking,
Orexigenic effect
H1-blocking
Cardiovascular effects ( hypotension,
depression of cardiac conduction,
arrhythmias)
 Therapeutic uses (Indications):
1. Major depressive disorder
a. Antidepressant drugs elevate mood,
increase physical activity and mental
alertness, increase appetite and sexual drive,
improve sleep patterns, and reduce
preoccupation with morbid thoughts.
b. These drugs are effective in 70% of
patients.
c. SSRIs are preferred over TCAs because of
their more limited toxicity.
d. MAOIs are used rarely, usually only when
TCAs have proved ineffective or for
‘‘atypical’’ depression.
 Therapeutic uses (Indications):
2. Bipolar affective disorder. The depressed
phase of bipolar affective disorder is often
treated with antidepressants given in
combination with lithium or other drugs used
to control mania.
3. Anxiety disorders (SSRIs, although unlike
benzodiazepines, their full efficacy may not
be seen for weeks).
a. Generalized anxiety disorder (GAD) and panic
disorder (PD)
b. Obsessive–compulsive disorder (OCD), which is
also treated with clomipramine.
c. Social phobia (SP), situational anxiety disorder
(SAD), and post-traumatic stress disorder (PTSD).
 Therapeutic uses (Indications):
4. Attention-deficit/hyperactivity disorder
(ADHD). TCAs (e.g., imipramine,
desipramine) are useful in patients
unresponsive or intolerant to stimulants;
however, there is some concern regarding
reports of toxicity in preadolescents.
Atomoxetine, a selective inhibitor of
norepinephrine reuptake that has some
structural similarities to TCA, is also approved
for the treatment of ADHD.
 Therapeutic uses (Indications):
5. Chronic pain
a. TCAs (Amitryptiline) and SNRIs venlafaxine are
often used for chronic pain of unknown origin.
SSRIs are ineffective. Duloxetine is approved for
treatment of neuropathic pain associated with
diabetes.
b. These drugs may work directly on pain pathways,
but the exact mechanism of action is unknown.
6. Other indications
a. Bulemia
b. Premenstrual dysphoric disorder (fluoxetine,
sertraline)
c. Smoking cessation (Bupropion)
d. Enuresis (Imipramine)
e. Early ejacullation
 Contraindications;
glaucoma, urinary retention,
old persons,
Arterial pressure instability,
liver and kidney failure,
epilepsy,
pregnancy,
heart diseases.
 SIDE EFFECTS of
Amine reuptake blocking drugs
The adverse effects of TCAs are often accounted for by
their antagonist activity at alpha-adrenoceptors,
muscarinic cholinoceptors, histamine H1-receptors,
and others.
a. CNS
(1) Sedation is common and probably due to antagonist activity at
CNS histamine H1 receptors.
(2) Confusion and memory dysfunction are central anticholinergic
effects and are more common in the elderly.
(3) Mania occasionally occurs in patients with an underlying bipolar
affective disorder (‘‘switch’’ reaction).
(4) Agitation and psychosis may worsen in psychotic patients.
(5) Tremor occurs in 10% of patients and is managed with propranolol.
(6) Seizures occur occasionally because of lowered seizure threshold;
they are more common with tertiary amines.
7) Movement disorders are occasionally produced by amoxapine; these effects
are due to dopamine–receptor antagonist activity.
 SIDE EFFECTS of
Amine reuptake blocking drugs
b. Cardiovascular system
(1) Postural hypotension, which may be severe and
may be temporary, is probably due to peripheral
a1-adrenoceptor blockade; it may result in reflex
tachycardia.
(2) Tachycardia, conduction defects, and
arrhythmias
(a) These effects are particularly common with
overdose, particularly with imipramine.
(b) Patients with preexisting heart block or
compensated cardiac output are at risk.
 SIDE EFFECTS of
Amine reuptake blocking drugs
c. Autonomic nervous system
(1) Autonomic nervous system effects reflect the
muscarinic cholinoceptor antagonist activity of
TCAs. The effects may be temporary.
(2) TCA use commonly produces dry mouth, blurred
vision, difficulty in urination, and constipation.
(3) TCAs more rarely may precipitate narrow-angle
glaucoma or paralytic ileus or cause urine
retention.
(4) These effects are more common in the elderly.
 SIDE EFFECTS of
Amine reuptake blocking drugs

d. Rebound/discontinuation effects
(1) Common effects include dizziness,
nausea, headache, and fatigue.
(2) The effects may persist for up to 2
months.
(3) Tapered withdrawal minimizes effects.
 SIDE EFFECTS of
Amine reuptake blocking drugs
e. Other adverse effects
(1) TCAs often produce weight gain that can be
extensive.
(2) TCAs can cause sexual dysfunction.
(3) TCAs may increase suicidal ideation for children,
adolescents, and young adults;
(4) These drugs produce rare but serious hematologic
changes, including hemolytic anemia and
agranulocytosis.
(5) TCAs infrequently cause allergic reactions and
obstructive jaundice.
(6) Atomoxetine may increase suicidal thoughts in
children and adolescents.
 Overdose and toxicity.
• Overdose of TCAs produces severe
anticholinergic and antiadrenergic signs,
respiratory depression, arrhythmias,
shock, seizures, coma, and death.
• Treatment is supportive and includes
sodium bicarbonate for cardiac toxicity,
benzodiazepines for seizures, and IV
fluids and norepinephrine for
hypotension.
 Adverse effects of SSRIs
Overall, SSRIs produce fewer serious adverse effects
than TCAs, including little sedation, postural
hypotension, anticholinergic activity, and
cardiovascular toxicity.
a. Headache that is generally temporary
b. Sexual dysfunction in up to 40% of all patients, which is a
leading cause of noncompliance
c. Gastric irritation that is generally transient and includes nausea
and heartburn
d. Weight loss initially followed in some patients by weight gain
e. Stimulation that is mild and often transient, may be
experienced as dysphoria, and is marked by agitation,
anxiety, increased motor activity, insomnia, tremor, and
excitement
f. Apathy (flattened affect) occurs in some patients.
g. Rebound/discontinuation effects like those for TCAs are most
likely to occur with Paroxetine.
Overdose and toxicity of
SSRIs
With only a few reported seizures in
overdose, SSRIs are remarkably safe in
comparison to other antidepressants. This
accounts for their relative popularity.
However, SSRIs may increase suicidal
ideation for children, adolescents, and young
adults.
SSRIs have a rare and potentially fatal
interaction with MAOIs called ‘‘serotonin
syndrome’’ that includes tremor,
hyperthermia, muscle rigidity, and
cardiovascular collapse.
SIDE EFFECTS of Amine reuptake blocking drugs
 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)
 MAOIs SIDE EFFECTS

• Adverse effects include postural hypotension,

headache, dry mouth, sexual dysfunction
(phenelzine), weight gain, and sleep disturbances.

• Overdose and toxicity. Uncommon results of

overdose of MAOIs include agitation,
hyperthermia, seizures, hypotension, or
hypertension.
 MAOIs SIDE EFFECTS
•Drug interactions
a. MAOIs may result in headache, nausea, cardiac arrhythmias,
hypertensive crisis, and, rarely, subarachnoid bleeding and
stroke in the presence of indirectly acting sympathomimetics
(e.g., tyramine from certain foods). These effects are due to
the release of increased stores of catecholamines resulting
from inhibition of monoamine oxidase.
b. These can potentiate the pressor effect of high doses of
directly acting sympathetic amines.
c. MAOIs may cause a ‘‘serotonin syndrome’’ in the presence of
SSRIs, certain TCAs, and opioids such as meperidine.
d. MAOIs result in additive sedation and CNS depression in the
presence of barbiturates, alcohol, and opioids.
 MAOIs SIDE EFFECTS
• Patients who are taking MAO inhibitors should not take meperidine,
dextromethorphan, TCAs, or SSRIs: they produce "serotonin syndrome“.
• Most serotonergic antidepressants should be discontinued at least 2
weeks before starting an MAOI. Fluoxetine, because of its long half-life,
should be discontinued for 4–5 weeks before an MAOI is initiated.
Conversely, an MAOI must be discontinued for at least 2 weeks before
starting a serotonergic agent.
Potentially very severe reactions, characterized by:
(1) Excitation (2) Sweating (3) Myoclonus and muscle rigidity
(4) Hypertension (5) Severe respiratory depression
(6) Coma (7) Vascular collapse (8) Possibly resulting in death
 MAOIs SIDE EFFECTS

Treatment of "serotonin syndrome“:

•Anticonvulsants
•Muscle relaxants
•cyproheptadine (antagonist of 5-HT
receptors)
Pharmacokinetics of Antidepressants

 Absorption is rapid
 Metabolism: extensive 1st pass
 Oxidation, hydroxylation, demethylation
 5% = “slow acetylators”
 Protein bound: 90 – 95%
 Psychostimulants
are psychoactive drugs which induce
temporary improvements in either
mental or physical function or both.
Classification:

Phenylethylamine - Amphetamine,
Methamphetamine
Piperidines: Methylfenidat, Piridrol
Sydnonimines: Mesocarb
(Sidnocarb)
Methylxanthines: Caffeine
 Amphetamine
Mechanism of action
increases the levels of norepinephrine and
dopamine in the brain via reuptake inhibition;
cause stimulation through the direct release
of catecholamines from storage vesicles in
cells.
Amphetamines are known to cause elevated
mood and euphoria as well as rebound
depression and anxiety.
Effects:
Psychomotor stimulant effect,
Euphoria, improving mood
Increased arousal, locomotion,
Cardiovascular effect (tachycardia,
hipertension)
Diminished requirement for food (anorexigen
effect)
Metabolic effect (increasing of the glucose
and lipids quantity)
Diminished requirement for sleep.
Indications:
 To reduce sleepiness and to keep the person
awake when necessary, as well as to treat
narcolepsy.
 To decrease appetite and promote weight
loss, as well as to treat obesity.
 To improve concentration and focus while at
work or school, especially for those with
attentional disorders.
 Occasionally, they are also used off label to
treat clinical depression, more particularly,
non-typical depression and treatment-
resistant depression.
Side effects:
 medical, psychiatric and psychosocial
deterioration.
 tolerance, dependence, sensitization as well
as a withdrawal syndrome can occur.
 tachycardia and hypertention
 anxiety, insomnia
 heart failure
 pulmonary edema
Contraidications:
 Hypertension
 Insomnia
 Angina pectoris
 Renal failure
 Atherosclerosis
 Maniac-depression disease
 Glaucoma
 Association with MAO inhibitor
 Schizophrenia
 Pregnancy
Caffeine

is a nonselective antagonist of
adenosine receptors (Blocks
Adenosine receptors)

Adenosine is a calming
neurotransmitter
 Aspects of Caffeine
Desirable effects
Stimulant, increased alertness, concentrate,
energy, bronchial dilator
Toxicity
Restlessness, jitters, anxiety, insomnia,
elevated or irregular heart rate
No tolerance
Most develop little or no tolerance to the
nervous system effects
Withdrawal effects
Transient but persistent, headache, low
energy, in ability to concentrate
 Indications:
In Hypotension
In diagnosis of some specific diseases
Migraine
Potency of analgesia
As psychostimulant
 Caffeine Content

1 Cup of coffee – 65-175 mg

1 Cup of tea – 50 mg
Can of soda (12 oz) – 40-50 mg
Bar of chocolate (30 g) – 1-35 mg
 Methylphenidate
CNS stimulant.
MA is thought to block the reuptake of
norepinephrine and dopamine into the
presynaptic neuron and increase the
release of these monoamines into the
extraneuronal space.
 Methylphenidate
hydrochloride
• INDICATIONS
Attention deficit hyperactivity disorder
Narcolepsy
 Methylphenidate

https://www.cchrint.org/2014/11/13/adhd-drugs-have-never-been-proven-safe-or-effective/
 Nootropics
Drugs that improve mental functions
such as cognition, memory, intelligence,
motivation, attention, and concentration
Classification
Pirolidones : Piracetam (nootropil)
Vitamin’s derivates : Pirithinol, Pantogam,
Picamilone
GABA derivates: GAMA-aminobutiric acid,
Fenibut
Dimetylaminoethanol: Meclofenoxat
Various groups: Vinpocetine, Cinarizine,
Nicergoline, Pentoxipylline
 Proposed mechanism

Nootropics are said to alter cerebral

supplies of neurotransmitters,
enzymes, and hormones by
improving the brain's oxygen supply
or by stimulating nerve growth.
 Effects:
Enhances Brain Metabolism (By increasing
Glucose Utilization, Blood & Oxygen Flow)
Increases Cerebral Phospholipids & Cellular
Membrane Fluidity
Supports Cognitive Receptors
Stimulates the Corpus Callosum, an area of the
brain that controls communication between the left
and right hemispheres {Involved in speech and
creative thinking}.
Stimulates the Locus Coeruleus, (specialized
neurons) {Involved in information processing,
attention, cortical/behavioral arousal, learning and
memory}
Inhibits Platelet Aggregation
Has a significant antioxidant effect.
 Indications:
post stroke,
organic brain syndrome,
Alzheimer's disease
cerebrovascular insufficiency.
in pediatrics
alcoholism
migraine
coma
prophylaxis in stress situations
Contraindications: Side effects:
pregnancy and allergy
lactation neurosis
liver and kidney excitation
failure insomnia or
psychoses somnolence
systemic diseases (nausea, vomiting
allergy leucopoenia,
eusinofilia etc.
 CNS STIMULANTS
1. Spinal cord stimulants
Strychnine,Securenine
2. Bulb stimulants
Bemegrid, Niketamine, Pentetrazol
Camphor, Sulphocomphocaine, Ethimizol
3. General tonizants and adaptogens
a) Tonizants: Schizandra, Streculia,
Leuzeea, Echinopanax, Panttocrine,
Rantarine
b).Adaptogens: Panax (Ginseng),
Bioginseng, Eleuterococcus, Rodiola
 Strychnine
It primarily affects the motor nerves in the
spinal cord which control muscle contraction
Since the whole nervous system is excited,
convulsions affect all the muscles.
used as a pesticide, particularly for killing
small vertebrates such as birds and rodents.
Strychnine poisoning can be fatal to humans
and animals.
 Bulb stimulants –
Indications:
Newborn asphyxia;
Respiratory arrest caused by trauma or surgery.
After general anesthesia (speed up awakening and
stimulates breathing);
Slight poisonings with barbiturates and opioids.
Hypoventilation after drowning;
Collapse of central origin;
Syncope;
Obstructive chronic bronchitis;
The elderly:
Heart failure in the elderly after infectious diseases,
pneumonia;
Hypotension.
Neuro circulatory dystonia
56
 Bulb stimulants –
Side effects
Cough;
Nausea, vomiting, restlessness;
Hypertension, tachycardia,
arrhythmias;
Headache, feeling hot, tremor;
Muscular hypertonus;
Convulsions.

57
 Bulb stimulants –
Contraindications
 Brain traumas, coma, hypoxia;
 In poisonings:
 with convulsive toxins (strychnine);
 drugs that excite the CNS and / or may cause
convulsions (antidepressants, antihistamines,
opioids, penicillins, fluoroquinolones, etc..)
 with barbiturates and opioids (medium and
severe gravity)
 Meningitis, tetanus;
 Epilepsy history.
58
 General tonics and
adaptogens drugs

Medicines that increase

resistance to stress, trauma,
anxiety, and fatigue.
 Mechanism OA GTA
Several mechanism of action;
hypothalamic-pituitary-adrenal (HPA)
axis and the regulation of key
mediators of the stress response,
such as molecular chaperons (e.g.,
Hsp70), stress-activated c-Jun N-
terminal protein kinase (JNK1),
Forkhead box O (FoxO) transcription
factor, cortisol and nitric oxide (NO).
Mechanism OA GTA (including
ginseng, eleuterokokka) due to:
the weakening of negative biochemical
and functional changes in the stress-
reactions
the activation of the adaptive synthesis
Ribo-nucleic acid (RNA) and proteins,
resulting in improved energy
metabolism and recovery processes.
For the development of a noticeable
effect requires a long time, and regular
admission (peak after 4-6 weeks).
 EFFECTS
induce increased attention and
endurance in situations of decreased
performance caused by fatigue and/or
sensation of weakness.
reduce stress-induced impairments and
disorders related to the function of
stress (neuroendocrine and immune
systems).
 Indications;
elderly people
post-surgery recovery,
asthenia,
chronic obstructive pulmonary
disease
neurodegenerative diseases,
 ADVERSE EFFECTS
are generally considered safe,
increased heart rate,
nausea,
headaches,
insomnia, restlessness.
Possible effects in women may
include swollen breasts and vaginal
bleeding.