Learning Objectives

The student will be able to:

Classify psychotropics.
List different types of antipsychotics
Acquire knowledge in neuroleptic toxicokinetics
Recognize toxic effects of neuroleptics.
Determine the investigations required for each case.
Apply measures for management of poisoned patients.
Illustrate some case reports
Acquire knowledge about the serious side effect of
neuroleptics; NMS.
 Anti Anti Sedative Mood CNS
psychotic anxiety Hypnotics stabilizing stimulants
Effect of Antipsychotic drugs

Therapeutic effects: Many

Many
side
side
Antipsychotic
effects
effects
Anti-anxiety effect
Anti-emetic effect
Hypothermic effect
sedative effects NO
NO
addiction
addiction
..habituation
habituation
 Neuroleptic drugs

Typical A typical
Traditional agents Novel agents

Less EPS
Less TD
Effective in R
 :Catecholamine-1

Glycine -1 Epinephrine
GABA -2 Nor-epinephrine
Dopamine

Serotonin -2
Absorption, Metabolism and Excretion of Neuroleptics drugs

Absorption

Distribution They
Theyarearehighly
highlylipophilic.
lipophilic.
85%
85% of the drug inplasma
of the drug in plasma
isisbound to albumin.
bound to albumin.

Excretion
Metabolism
 Pathophysiology
of
Neuroleptic Agents

Block other Quinidine-like action

Block neuroreceptors: on the heart
Dopamine 2-receptors

Anterior pituitary M1 H1 α1 ventricular

ventriculararrhythmias
arrhythmias
Basal ganglion
CRTZ Anticholinergic
Anticholinergic hypotension,
hypotension,
Hypothalamus effects
effects meiosis
meiosis
Limbic .s sedation
sedation
hypotension
hypotension
Pathophysiology of Neuroleptic Agent
 ,tachycardia Clinical
hypotension picture of
arrhythmias acute poisoning
ECG changes

-Anti
Neurological Cardiovascular Coma
cholinergic

dry Mouth and skin Hypotension

constipation hypothermia
dilated pupils Mellaril ,arrhythmia
Extra N.B PPP
convulsions
pyramidal PPP Chlorpromazine .Resp
.( block)
 Extra pyramidal Manifestations

--11 --22 3-
3- --44
Parkinsonism Akathisia Tardive
Tardive
Parkinsonism Dystonia
Dystonia Akathisia
dyskinesia
dyskinesia

.Masked face-1 Feeling

Feelingof
of
.Tremor-2 restlessness
restlessness
.Rigidity-3
1- Torticollis (neck),
Slowness of-4
2-occulogyriccrises.
.Movements
3- Arched back
Dopamine in-5
4- dysphagia
B.G
5- dysarthria,
6- peri-oral-spasm
Rabbit syndrome
Parkinsonism occulogyriccrises.

arched back
Torticollis
Investigations:
Toxicological analysis: Non-toxicological
1-Qualitative and semi- investigations:
quantitative 1- Abdominal x-ray
estimation by TLC.  radio-opaque
2- Quantitative shadow in the
estimation by the use stomach.
of HPLC. 2- ECG arrhythmia
3- Color test : Forrest
Rapid Urine.
 Treatment of Acute Poisoning
3- Decontamination (D):
1- Care of respiration. No emesis (antiemetic ) ?
If the patient is conscious or
2- Care of circulation comatosed: do
gastric lavage
* Hypotension first with warm water
circulatory shock. then with NaHCO3 5%.
* Treat cardiac arrhythmias powdered activated charcoal
repeated dosing)
sodium sulphate as cathartic
3-Treat extra pyramidal manifestations
By the use of antiparkinsonian drugs e.g.
Benztropine Mesylate (cogentin) 1-2 mg IV .
4-If there is cardiac arrhythmias
Treat by phenytoin sodium.
with monitoring for 2 days.
5- No role of elimination (E):
Diuresis, peritoneal or hemodialysis are
ineffective in removing the drug as it is
highly bound to plasma proteins.
 Neuroleptic Malignant Syndrome (NMS)

 Definition:
Is a serious complication of neuroleptic treatment
Lithium , TCAs , stopping of Levo-dopa or Carbidopa
used in treatment of Parkinsonism .
 Cause : diminution of dopamine neurotransmitter.
 It is characterized by:
 Hyperpyrexia.
 Autonomic dysfunction.
(tachycardia, sweating, salivation, hypertension).
 Fluctuation of the level of consciousness.
 Tremors, Rigidity.
 Treatment : Bromocriptine (Parlodel) as it stimulates synthesis
of dopamine.
 They have the following effects:

::Therapeutic
Therapeutic effects
effects .. 11
::Anti-
Anti- anxiety
anxiety effect
effect
inin the
the treatment
treatment of
of
.Neurosis
.Neurosis
.Anti-
.Anti- spasmodic
spasmodic effect
effect
Anti-
Anti- convulsant
convulsant effect
effect
.).)Diazepam
Diazepam = = valium
valium((
hypnotic
hypnotic effect
effect
.Lorazepam
.Lorazepam (Ativan)
(Ativan)
 Important member of anti-anxiety drugs

I- Meprobamate group
Equanil.

II- Benzodiazepine group

Diazepam ( Valium)
Lorazepam ( Ativan)
Rohypnol
 Absorption, Metabolism and Excretion
of ANTI ANXIETY DRUGS

Absorption

Distribution

Excretion

Metabolism
 Pathophysiology of Benzodiazepine

GABA
 Clinical picture of acute poisoning

 CNS: headache, drowsiness, apathy, ataxia

coma.
 Cardiovascular : hypotension and syncope.

 Gastrointestinal: nausea, may be vomiting.

 Allergic reactions : urticaria, skin rash.

 Suicidal attempt with large doses may lead to rapid sleep,

later coma due to vasomotor and respiratory depression.
 Investigations :
1-Toxicological analysis 2- Routine investigations

 Qualitative and Blood gases

semiquantitative
acid-base status
detection of benzo.
metabolites in urine
using immunoassay
techniques.
 Quantitative estimation
of the blood level.
Treatment of Benzodiazepine overdose:

1- Care of respiration ( A - B ).
2- Care of circulation (C).
3-Decontamination (D) .
conscious: induce vomiting.
comatosed: endotracheal tube before
gastric lavage.
powdered activated charcoal,
sodium sulphate as cathartics.
4- No role of elimination (E ) :
Diuresis.
peritoneal dialysis.
Hemodialysis are
5- Antidote Flumazenil = Anexate

Mechanism:
It is a Competitive Benzodiazepine Receptor Antagonist
it displaces Benzodiazepines from the receptors and binds
to them).
Dose:
A
the dose is 0.5 mg IV or by I.V infusion
B.R

repeated after half to one hour until the patient awakes

or up to a total of 1-2 mg.
The onset of action occurs within 1-2 minutes
with a peak at 6-10 minutes.
Withdrawal syndrome :

Time :
After prolonged administration of benzodiazepines.
From 3- 6 days following cessation of Benzodiazepines.
S &S:
Anorexia, nausea, vomiting.
Apprehension, restlessness, insomnia.
Tremors may be convulsions.
To avoid:
Gradual dose reduction over a period of 10-15 days
should be done.