Antipsychotics used to treat bipolar disorder include:

Abilify (aripiprazole)
Clozaril (clozapine)
Geodon (ziprasidone)
Latuda (lurasidone)
Risperdal (risperidone)
Saphris (asenapine)
Seroquel (quetiapine)
Zyprexa (olanzapine)
Drug Interactions

Additive effects with sedatives.

Additive effects with anticholinergics.

Additive effects with antihistaminergics.

Additive effects with -AR blocking drugs.

Additive effects with drugs with quinidine-like action (thioridazine).

Side Effects of Antipsychotic Drugs

Certain antipsychotic drugs cause significant weight gain and high cholesterol levels, and they
may increase the risk of diabetes. People considering an antipsychotic for bipolar disorder should
be screened for their risk of heart disease, stroke, and diabetes, according to a study published
in Diabetes Care.
Common side effects of antipsychotic medications include:

Blurred vision
Dry mouth
Drowsiness
Muscle spasms or tremors
Weight gain
Pseudodepression and Schizophrenia-like syndrome.
Seizures.
Cardiac toxicity and endocrine effects.
Other side-effects (dry mouth, constipation, blurred vision, hypotension, etc.) are due to
block of other receptors, particularly adrenoceptors and muscarinic ACh receptors.

Contact dermatitis, blood dyscrasias, obstructive jaundice sometimes occurs with

phenothiazines.
Sedation - initially considerable; tolerance usually develops after a few weeks of therapy;
dysphoria

Postural hypotension - results primarily from adrenergic blockade; tolerance can

develop

Anticholinergic effects - include blurred vision, dry mouth, constipation, urinary

retention; results from muscarinic cholinergic blockade

Endocrine effects - increased prolactin secretion can cause galactorhea; results from
antidopamine effect

Hypersensitivity reactions - jaundice, photosensitivity, rashes, agranulocytosis can

occur

Idiosyncratic reactions - malignant neuroleptic syndrome

Weight gain

Neurological side effects

) cause anorexia.

(2) precipitate mania or hypomania.

(3) result in nausea, nervousness, headache, and insomnia.

(4) cause 5-HT syndromes (hyperpyrexia, convulsions, and coma) when combinated with
and MAO inhibitor.

EFFECTS OF ANTIPSYCHOPTIC DRUGS

1.Central Nervous System

Effects of antipsychotic drugs differ in normal and psychotic individuals.

In normal individuals they produce indifference to surrounding, paucity of thought,

psychomotor slowing, emotional quiet, reduction in initiative and tendency to go off to
sleep. Spontaneous movements are minimized, but slurring of speech, ataxia or motor
uncoordination does not occur. This has been referred to as the neuroleptic syndrome
and is quite different from the sedative action of barbiturates and other similar drugs.
The effects are appreciated as neutral and unpleasant by most normal individuals

Catalepsy arises primarily from acute blockade of postsynaptic D2 receptors in basal

ganglia.
Chlorpromazine lowers seizure threshold and can precipitate fits in untreated epileptics.
The piperazine side chain compounds have a lower property for this action. The
temperature control is knocked off at relatively higher doses rendering the individual
poikilothermic body temperature falls if surrounding are cold. The medullary
respiratory and other vital centers are not affected, except at high doses. It is very difficult
to produce coma with these drugs. Neuroleptics, except thioridazine, have potent
antiemetic action exerted through the central trigger zone. However, they are ineffective
in motion sickness.
3.Local anaesthetic
Chlorpromazine is as potent a local anaesthetic as procaine. However, it is not used for
this purpose because of its irritant action. Others have weaker membrane stabilizing
action.
5.Skeletal muscle
Neuroleptics have no effects on muscle fibers or neuromuscular transmission. They
reduce certain types of spasticity: the site of action being in the basal ganglia or medulla
oblongata. Spinal reflexes are not affected.
ANWANTED EFFECTS
Neuroleptic drugs are replete with side effects. Many side effects occur early
during treatment and result from neuroleptic blockade of receptors in the central and
peripheral nervous systems; others appear later in the course of treatment (fig.12).
1.Extrapyramidal reactions include
Parkinsonism, which can mimic idiopathic Parkinsons disease but is usually of mild
degree. It responds to anticholinergic drugs or amantadine;
Akatisia is a subjective sense of restlessness usually accompanied by wild to moderate
motor hyperactivity. It is among the most common of side effects and usually responds to
-adrener gic receptor antagonists, anticholinergics, antihistamines or amantadine.
Akathisia is sometimes misinterpreted as increased agitation, leading to increased
neuroleptic dosing, resulting in greater akathisia.
2.Endocrine effects
DA, released in the median eminence by neurons of the tuberohypophyseal pathway
acts physiologically via D2 receptors as an inhibitor of prolactin secretion. The result of
blocking D2 receptors by antipsychotic drugs is therefore to increase the plasma prolactin
concentration, resulting breast swelling, pain and lactation, which can occur in men as
well as women. Other less pronounced endocrine changes including a decrease of growth
hormone secretion, but these, unlike the prolactin response, are unimportant clinically.
Sedation, which tends to decrease with continued use, occurs with many antypsychotic
drugs. Antihistamine (H1) activity is a property of phenothiazines and contributes to their
sedative and antiemetic properties, but not to their antipsychotic action.

REACTION

FEATURES

TIME OF
MAXIMAL
RISK

PROPOSED
MECHANISM

TREATMENT

Acute dystonia

Spasm of muscles
of tongue, face,
neck, back; may
mimic seizures;
not hysteria

1 to 5 days

Unknown

Antiparkinsonian
agents are
diagnostic and
curative

Akathisia

Motor restlessness;
not anxiety or
"agitation"

5 to 60 days

Unknown

Reduce dose or
change drug:
antiparkinsonian
agents,b
benzodiazepines
or propranololc
may help

Parkinsonism

Bradykinesia,
rigidity, variable
tremor, mask
facies, shuffling
gait

5 to 30 days

Antagonism of
dopamine

Antiparkinsonian
agents helpful

Neuroleptic malignant
syndrome

Catatonia, stupor,
fever, unstable
blood pressure,
myoglobinemia;
can be fatal

Weeks; can
persist for
days after
stopping
neuroleptic

Antagonism of
dopamine may
contribute

Stop neuroleptic
immediately:
dantrolene or
bromocriptined
may help:
antiparkinsonian
agents not
effective

Perioral tremor ("rabbit"

syndrome)

Perioral tremor
(may be a late
variant of p
arkinsonism)

After
months or
years of
treatment

Unknown

Antiparkinsonian
agents often help

Tardive dyskinesia

Oral-facial
dyskinesia;
widespread

After
months or
years of

Excess function
of dopamine
hypothesized

Prevention
crucial; treatment
unsatisfactory

choreoathetosis or
dystonia

treatment
(worse on
withdrawal)

Many drugs have been claimed to be helpful for acute dystonia. Among the most commonly employed
treatments are diphenhydramine hydrochloride, 25 or 50 mg intramuscularly, or benztropine mesylate, 1 or 2
mg intramuscularly or slowly intravenously, followed by oral medication with the same agent for a period of
days to perhaps several weeks thereafter. b. For details regarding the use of oral antiparkinsonian agents, see
the rest of slides c. Propranolol often is effective in relatively low doses (20-80 mg per day). Selective beta1adrenergic receptor antagonists are less effective. d. Despite the response to dantrolene, there is no evidence
of an abnormality of Ca2+ transport in skeletal muscle; with lingering neuroleptic effects, bromocriptine
may be tolerated in large doses (10-40 mg per day).

6.Various idiosyncratic and hypersensitivity reaction can occur, the most important being.
Jaundice, which occurs with older phenothizines, such as chlorpromazine. The jaundice is
usually mild, and of obstructive origin; it disappears quickly when the drug is stopped of
substituded by an antipsychotic of different class.
Details on two main extrapyramidal disturbances (EPS):

Parkinson-like symptoms

tremor, rigidity

direct consequence of block of nigrostriatal DA2 R

reversible upon cessation of antipsychotics

Tardive dyskinesia

involuntary movement of face and limbs

less likely with atypical antipsychotics (AP)

appears months or years after start of AP

? result of proliferation of DA R in striatum

treatment is generally unsuccessful

Phenothiazines - Side effects

presynaptic?

Weight gain 40% - weight gain now attributed to ratio of binding to D2 and 5-HT2 receptors;
possibly also histamine (for newer antipsychotics anyway)
Sexual dysfunction

result from NE and SE blockade

erectile dysfunction in 23-54% of men

retrograde ejaculation in

loss of libido and anorgasmia in men and women

Seizures - <1% for generalized grand mal

ESTIMATED MEAN WEIGHT GAIN AT 10 WEEKS

A comprehensive literature search identified 78 studies that included data on weight

change in patients treated with a specific antipsychotic.

For each agent a meta-analysis and random effects regression estimated the change in
weight at 10 weeks of treatment.

Phenothiazines - Side effects

Neuroleptic malignant syndrome (1-2% early in trt)

combination of motor rigidity, hyperthermia, and autonomic dysregulation of blood

pressure and heart rate (both go up)

can be fatal in 5-20% of cases if untreated

treatment discontinue meds; give trts for fever and cardiac problems

Sensitivity to sun

some phenothiazines collect in skin (chlorpromazine)

sunlight causes pigmentation changes grayish-purple splotching (look bruised)

can also occur in eye and cause brown in cornea

this produces a brownish cloud to vision and possibly permanent impairment

Agranulocytosis - <1%

reduced white blood cell count

lowered resistance to infection

can be fatal

Jaundice elevated bilirubin in liver - < %

Neuroleptic Malignant Syndrome
Is a rare but serious side effect of neuroleptic (antipsychotic) therapy that can be lethal. It can
arise at any time in the course of treatment and shows no predilection for age, duration of
treatment, antipsychotic medication, or dose.

Occurs in pts. hypersensitive to the Ex.Py. effects of antipsychotics.

Due to excessively rapid blockade of postsynaptic dopamine receptors.

The syndrome begins with marked muscle rigidity.

If sweating is impaired, a fever may ensue. The stress leukocytosis and high fever
associated with this syndrome may be mistaken for an infection.

Autonomic instability with altered blood pressure and heart rate is another midbrain
manifestation.

Creatinekinaseisozymes are usually elevated, reflecting muscle damage.

Tranquilizer effects, both adverse and therapeutic, are generally less extreme than those of
barbiturates. Tolerance may develop within a few weeks if the drug is continually kept in the

bloodstream by three-times-a-day ingestion. Side effects may include apathy, low blood pressure,
blurred vision rashes, disorientation, confusion, muscle weakness, head aches, upset stomach,
fainting, lack of coordination, dizziness; menstrual, bladder, and ovulary irregularities;: anxiety,
and hallucinations. Some users experience stimulation rather than sedation, which results in
hyperex citability, insomnia, hostility, and rage. Large doses can lead to tremors, loss of muscular
coordination, and convulsions with time and heavy dosage, habituation, psychological
dependence, and withdrawal symptoms may occur.
Tranquilizers can kill when potentiated by other central nervous-system depressants such as
alcohol, barbiturates, opiates, hypnotic-sedatives, and synthetic narcotics. Accidental poisoning
or suicide is almost impossible with tranquilizer unless the drug is combined with anon
depressant.
Alcohol and tranquilizers have a synergistic effect on eachother, creating an additive result when
they are together. Since the liver processes alcohol first, the tranquilizer must wait its turn,
circulating through the system many times over, damaging organs with each visit. Body func
tions, including breathing, heartbeat, and mum - ad reasoning powers, slow down and may
eventually stop, causing death.
In addition to alcohol, minor tranquilizers should not be used with anti-depressants or
antihistamines and may decrease the effectiveness of birth-control pills; Major tranquilizers
should be avoided when using anti-depressants,
antihistamines, barbiturates, other tranquilizers and sedatives, blood-pressure medication, or
diuretics. These sub stances, along with anti-convulsants, anti-coagulants, and MAO inhibitors,
should also be avoided in combination with try-cyclic anti-depressants, which remain in the
system for two weeks after their use is discontinued. All drugs should be temporarily avoided
after the user has stopped taking tri-cyclics.
Since tranquilizers depress the central nervous system and relax muscles, they cause the user's
reaction time to increase Operating machinery or power tools, driving a car, or riding a bike in
traffic may all be hazardous to the health of the user, as alteration of vision and time, and- space
judgment greatly multiplies the chance of accident.
Pregnant women should avoid use of tranquilizers, which penetrate the placental barrier. Birth
defects, fetal death, congenital heart disease, and skeletal l abnormalities have all been attributed
to use of the drug, which also infiltrates the mother's milk. The most publicized case of
tranquilizer;
danger to fetal development was that of Thalidomide, a non- barbiturate sleeping pill, originally
thought harmless, which resulted in severe birth defects. Tranquilizers are also ranked third
among drugs causing damage to the stomach lining, trailing only aspirin and alcohol.

Street tranquilizers are even more dangerous, since they are sometimes cut with unknown
substances, or crudely manufactured in amateur laboratories, adding to the unpredictability of an
already unpredictable drug. Tranquilizers' shelf lives with some pills becoming impotent while
others become more toxic with the passage of time.
Addiction, both physical and psychological, may occur with prolonged heavy use. Selfmedication is often the culprit when tranquilizers -are abused. The need to increase dosage to
achieve the same effect signifies tolerance has set in.
An addictive personality may find the drug to be alegitimate" source to feed-his-habit, not
realizing that withdrawal from tranquilizers maybe as difficult as from alcohol, opiates, or
barbiturates. Sedative, users should take precautions. Do -not use tranquilizers for minor
temporary problems or refill prescriptions without consulting your doctor. Do not use the drug
over long periods of time, follow directions exactly, and do not self-medicate.
Prolonged medication-'should not be stopped abruptly.' Tranquilizer use must be gradually
discontinued to avoid unpleasant withdrawal symptoms. A dependent user may experience such
symptoms within four to eight hours after cessation. Hyperexcitability and anxiety, insomnia,
'respiration and pulse reductions, coordination impairment, -slurred' speech, nausea, vomiting,
tremors, and convulsions may occur, depending on the drug's potency, the victim's metabolism,
and the length and frequency of use.
Medical supervision is necessary for safe withdrawal from tranquilizers. Get the overdoser to a
hospital, or, if he is conscious, induce vomiting. Do not force an unconscious person to throw up,
but turn him on his side in case he does. Do not give him amphetamines or coffee. Keep` him
awake and walking. Find out exactly what he took, how much, and what it looked like, if
possible.
Tranquilizers are regulated under Schedule IV of the Controlled Substances Act. Prescriptions
are not refillable more than five times within six months, and the drug's production and
distribution 'must be recorded and supervised by manufacturers.

Tranquilizer Effects
Unfortunately, an addiction to tranquilizers will be costly to you or your loved one. While the
physical signs of addiction may be the most evident, the ramification of tranquilizer abuse does
not stop there. An addiction to tranquilizers can impact your life in the following ways:

Physically: The recreational use of tranquilizers can harm your body physically as it interferes
with the normal mechanisms. In severe cases, death can occur, especially in the instance of
overdose. These are possible physical effects that may result from a tranquilizer addiction:

Irregular sleep patterns

Disorientation, confusion

Restlessness

Inability to relax

Respiratory distress or arrest

Cardiac arrest

Gastrointestinal distress

Unconsciousness or sedation

Psychologically: A tranquilizer addiction can confuse an abusers perception of reality as well as

disturb their mental and emotional well being. The following are some psychological effects that
may result from the abuse of tranquilizers:

Risk of anxiety or paranoia attacks

Mood disorders, personality shifts

Feelings of rage or aggressiveness

Dulled emotional responses

Delusions or Hallucinations

Social Impact: The prolonged use of tranquilizers will have a negative impact on an individuals
social life. If you or a loved one is abusing tranquilizers, you may observe these social effects:

Estranged relationships with family and friends

Difficulty engaging in social functions

Isolation and increased seclusion from loved ones

Seclusion from loved ones

Men and women abusing tranquilizers will incur damage to the other facets of their lives as well,
such as in their financial responsibilities, career, and work and familial duties. For the duration of
time that tranquilizers are abused, addicts will continually experience these consequences until
professional help is sought and appropriate treatment is received.
Tranquilizer Withdrawal
The withdrawal from tranquilizers can be a dangerous process as the body has become dependent
on the drug and a variety of unpleasant symptoms can be induced once the drug is no longer in
the bodys systems. Symptoms can vary from person to person depending on how long
tranquilizers have been abused. Because of the severity of the symptoms that can result, it is
important that the withdrawal process take place under medical supervision. Withdrawal
symptoms will usually begin anywhere from 6-36 hours after the last use of the drug and can
include the follow:

Seizures

Convulsions

Psychotic episodes

Chills

Hot flashes

Loss of appetite

Night sweats

Rapid breathing

Confusion, altered reality

Muscle aches

Irritability, Rage

It is usually expected that symptoms worsen and reach the peak of discomfort around the first to
second day of the withdrawal process. In certain situations, physicians may be able to prescribe a
medication to help ease the discomfort that is experienced while withdrawing from tranquilizers.
Treatment programs tailored specifically for tranquilizer addictions will have the necessary
resources to help individuals safely withdraw from these substances, and having this support is
invaluable during the recover process.
Tranquilizer Treatment And Help
With adequate support and with the proper resources, you can be well on your way towards
recovery from a tranquilizer addiction. If you or a loved one is struggling with a tranquilizer
addiction, take comfort in knowing that you are not alone. There is nothing more valuable than
your life, wellness, and peace and you are deserving of the freedom that is experienced apart
from dependence on a drug. Though it might feel painfully difficult or impossible to break your
addiction, take hope in knowing that recovery is always an achievable option. You should find
treatment centers that work with a tranquilizers addiction. You will ultimately have the ability to
overcome this addiction by receiving the help you.
ANTIPSYCHOTICS
(Called Major Tranquilizers or Neuroleptics)
BRAND NAMES: (Older Antipsychotics)
Amidate
Arvynol
Dalmane
Demerol
Depakote
Doriden
Dormalin
Geodon
Haldol
Largon
Lidone
Loxitane
Mellaril
Moban
Navane
Nembutal
Neurontin
Nozinan
Orap
Permitil
Phenergan

Proketazine
Prolixin
Proscom
Quide
Repoise
Serlect
Seroquel
Sparine
Stelazine
Taractan
Tegretol
Thorazine
Tindal
Topamax
Trancopal
Triclos
Trilafon
Versed
Vesprin
BRAND NAMES: (Newer Antipsychotics)
Abilify
Ambien
Clozaril
Compazine
Lamictal
Reserpine
Risperdal
Serentil
Zyprexa
Side Effects:
Akathisia*
Abnormal gait (manner of walking)
Birth defects
Blindness
Blood disorders
Blood-sugar
abnormalities
Blurred vision
Cardiac arrest
Confusion
Death from liver failure

Depression
Diabetes
Drowsiness
Extreme inner-anxiety
Fatal blood clots
Headache
Heart arrhythmia
Heart failure
Heart palpitation
Heat stroke
Hemorrhage
Hostility
Hyperglycemia (abnormally high blood sugar)
Hypoglycemia (abnormally low blood sugar)
Impotence
Insomnia
Involuntary movements
Light-headedness
Manic reaction
Muscle rigidity
Nausea
Nervousness
Neuroleptic malignant
Syndrome*
Nightmares
Painful skin rashes
Pancreatitis (inflammation of pancreas, a gland near the stomach that helps digestion)
Poor concentration
Restlessness
Seizures
Sexual dysfunction
Sleepiness
Spasms
Suicidal thoughts
Swollen and leaking breasts
Tachycardia (heart irregularity)
Tardive dyskinesia*
Tremors
Violence
Vomiting

Weakness
Weight gain68
*Akathisia: A, meaning without and kathisia, meaning sitting, an inability to keep still.
Patients pace about uncontrollably. The side effect has been linked to assaultive,
violent behavior.69
*Neuroleptic malignant syndrome: A potentially fatal toxic reaction where patients break into
fevers and become confused, agitated, and extremely rigid. An estimated 100,000 Americans
have died from it after taking the older antipsychotics.70
*Tardive Dyskinesia: Tardive, meaning late and dyskinesia meaning, abnormal movement of
muscles. Tardive Dyskinesia is a permanent impairment of the power of voluntary movement of
the lips, tongue, jaw, fingers, toes, and other body parts.71

Tranquilizers: Physiological effects

Last modified: Saturday, 20. June 2009 - 3:47 pm
Beneficial Physiological effects of the major and minor tranquilizers include:
anesthesia
anticonvulsant effects
blood vessel dilation
decreased contrasctability of the heart
decreased hyperactivity, impulsivity, and aggression
muscle relaxation
pain relief
reduced muscle spasms
relaxation
sedation
slowed heart rate
Harmful side effects
At high doses, both the major and minor tranquilizers are severely toxic and may cause coma,
respiratory arrest, convulsions, acute renal failure, speech impairment, or death. However, at
therapeutic doses, the neu-roleptics have been associated with more
Atypical antipsychotic agent Distinctive features Aripiprazole partial agonist at D2 and 5HT1A receptor It is minimally sedating, may even cause insomnia Metabolized by CYP2D6
and CYP3A4. ADR: nausea, dyspepsia, constipation and light-headedness.
hyperprolactinaemia, hypotension and Q-T prolongation are not frequent. Ziprasidone D2 + 5HT2A/2C + H1 + 1 receptor blocking activity. Efficacy in schizophrenia has been related
equivalent to haloperidol Amisulpiride Congener of sulpiride (typical antipsychotic) High
affinity to D2 (and D3) receptor and has low affinity for 5- HT2 receptor. Not sedative.

Zotepine D1+D2 and 5-HT2, 1 receptor blocking activity. It also inhibits NA reuptake.
Both positive and negative symptoms of schizophrenia appear to be benefited. It has lower
seizure threshold. ADR: Weight gain, hyperglycemia.
34. Adverse events CNS: Drowsiness, lethargy, mental confusion, weight gain (not with
haloperidol), aggravation of seizures in epileptics. CVS: Postural hypotension, palpitation,
inhibition of ejaculation (especially with thioridazine) are due to a adrenergic blockade; Q- T
prolongation and cardiac arrhythmias are risk of overdose with thioridazine, pimozide and
ziprasidone. Anticholinergic Dry mouth, blurring of vision, constipation, urinary hesitancy
in elderly males. Endocrine Hyperprolactinemia (due to D2 blockade) is common with
typical neuroleptics and risperidone. This can lower GH levels, but amenorrhoea, infertility,
galactorrhoea and gynaecomastia occur infrequently after prolonged treatment. Metabolic
effect: Elevation of blood sugar and triglyceride.
35. Adverse events Extrapyramidal disturbances: Dose-limiting side effects. The inhibitory
effects of dopaminergic neurons are normally balanced by the excitatory actions of cholinergic
neurons in the striatum. Blocking dopamine receptors alters this balance, causing a relative
excess of cholinergic influence, which results in extrapyramidal motor effects. Parkinson-like
symptoms of bradykinesia, rigidity, and tremor usually occur within weeks to months of
initiating treatment. Tardive dyskinesia, which can be irreversible, may occur after months or
years of treatment. Hypersensitivity reaction: Chlestatic jaundice, myocarditis, agranulocytosis.
Miscellaneous: Weight gain often occurs with long term antipsychotic therapy; blood sugar and
lipids may tend to rise. Risk of worsening of diabetes and blue pigmentation of exposed skin, and
retinal degeneration. Tardive dyskinesia is a disorder that involves involuntary movements,
especially of the lower face (tongue, lips, face, trunk, and extremities).
1. 36. Therapeutic uses Treatment of schizophrenia Prevention of severe nausea and
vomiting Other uses: Treatment of mania, organic brain syndromes, anxiety.
Chlorpromazine is used to treat intractable hiccups. Risperidone and haloperidol are
also commonly prescribed for this tic disorder. Also, risperidone and aripiprazole are now
approved for the management of the disruptive behavior and irritability secondary to
autism (is a disorder of neural development characterized by impaired social interaction).
REFERENCES
1. Pharmacology, Fourth Edition, H.P.Rang, M.M.Dale, J.M.Ritter, CHURCHILL
LIVINGSTONE, 2001.
2. Human Pharmacology, Molecular to Clinical, Third Edition, T.Brody, J.Larner,
K.Minneman, Mosby, 1998 by Mosby-Year Book,Inc.
3. Basic & Clinical Pharmacology. A LANGE medical book. 8 EDITION, B.G.Katzung,
2001, McGraw-Hill Comp.

4. Lippincotts Illustrated Reviews: Pharmacology, 2nd Edition, M.J.Mycek, R.A.Harvey &

P.C.Champe, LIPPINCOTT WILLIAMS & WILKINS, 2000.