Antipsychotics

(Neuroleptics, Major Tranquilizers)

All antipsychotic drugs tend to block D2 receptors in the dopamine pathways

of the brain.

Dopamine released in these pathways has less effect.

Excess release of dopamine in the mesolimbic pathway has been linked to

psychotic experiences. It is the blockade of dopamine receptors in this
pathway that is thought to control psychotic experiences.

Dopamine
In the brain, dopamine functions as a neurotransmittera chemical released
by nerve cells to send signals to other nerve cells.
The human brain uses five known types of dopamine receptors, labeled D1,
D2, D3, D4, and D5. Dopamine is produced in several areas of the brain,
including the substantia nigra and the ventral tegmental area.
The Reward Circuit
MESOLIMBIC PATHWAY
the bundle of dopaminergic fibres associated with the reward circuit.
It is the most significant neural pathway in the brain in which changes occur
in all known forms of addiction.
By blocking this pathway, antipsychotic drugs reduce the intense emotions caused
by conditions such as schizophrenia.
Mesocortical Pathway

also originates in the ventral tegmental area, but projects to the frontal
cortex and surrounding structures.
evidence indicates that a malfunction in this pathway might be the cause of
some of the symptoms of schizophrenia, such as hallucinations and
disordered thinking.
This pathway may be the brain system that is abnormal or functioning
abnormally in psychoses, such as schizophrenia.

It is thought to be associated with the negative symptoms of schizophrenia,

which include avolition, alogia and flat affect.
This pathway is closely associated with the mesolimbic pathway, which is also
known as the mesolimbic reward pathway.
Medications that block this pathway reduce psychotic delirium, but also
reduce the overall activity of the frontal lobes
Nigrostriatal Pathway
Involved in motor control.
Degeneration of the neurons in this pathway is associated with the trembling
and muscular rigidity symptomatic of Parkinsons disease.
Dopamine releasing neurons of this pathway release several other
neurotransmitters, including glutamate and GABA.
This pathway is also implicated in producing tardive dyskinesia, one of the
side-effects of antipsychotic drugs. These medications (in particular the

older typical antipsychotics) block D2 dopamine receptors in multiple

pathways in the brain.
The desired clinical effect of reducing psychotic symptoms is thought to be
associated with blocking dopamine function in the mesolimbic pathway only.
However, as many of these drugs are not selective, they block dopamine in
all pathways. When this happens in the nigrostriatal pathway, similar
movement problems to those found in Parkinson's disease can occur.
Tuberoinfundibular Pathway,
which connects the hypothalamus to the pituitary gland,
Dopamine released at this site regulates the secretion of prolactin from
the anterior pituitary gland
antipsychotic drugs block dopamine in the tuberoinfundibular pathway, which
can cause an increase in blood prolactin levels (hyperprolactinemia). This can
cause abnormal lactation (even in men), disruptions to the menstrual cycle in
women, visual problems, headache and sexual dysfunction.
Extrapyramidal Side Effects
Acute Dystonia
Abnormal postures caused by involuntary spasm
Manifestations
Muscular rigidity & cramping
Stiff or thick tongue w/ difficulty of swallowing
Laryngospasm & respiratory difficulties
Opisthothonus; tightness in the entire body w/ the head back and arched
neck
Oculogyric crisis; eyes rolled back in a locked position
Torticollis; twisted head & neck
Writers cramp; fatigue spasm affecting a hand
Occurence
First week of treatment
Younger than 40 years old
Males
Receiving high potency drugs e.g. haloperidol & thiothixene
MANAGEMENT
Give anticholinergic medications such as benztropine mesylate (cogentin) IM
or dipenhydramine (benadryl) IM or IV
Akathisia
reported by the client as an intense need to move about.
Manifestations
Restless or anxious & agitated
w/ rigid posture or gait
Inability to sit still
Management
Change medication
Oral meds of beta-blocker, anticholinergics or benzodiazepines

Akinesia/Bradykinesia
absence of movement / slowed movement
Manifestation
Weakness
Fatigue
Painful muscles
Anergia
Management
Give anticholinergic medications such as benztropine mesylate (cogentin) IM
or dipenhydramine (benadryl) IM or IV
Pseudoparkinsonism
resembles Parkinsons disease
Manifestations
Stooped posture
Mask-like facies
Decrease arm swing
Shuffling gate
Cogwheel rigidity
Drooling
Tremors
Coarse pill rolling movements of the thumb & fingers while at rest
Management
Change medication to an antipsychotic drug with lower incidence of EPS
Add oral anticholinergic
Give amantadine (dopamine agonist)
Neuroleptic Malignant Syndrome
Potentially fatal idiosyncratic reaction to a neuroleptic
Rigidity
High fever
Unstable BP
Diaphoresis
Pallor
Delirium
Elevated CPK
Confused & mute
Agitated or stuporous
Occurrence
First two weeks of therapy
After an increase in dosage
Dehydration
Poor nutrition
Concurrent medical illness
Management
Immediately discontinue medication
Treat dehydration & hyperthermia
May change medication
Dantrolene (Dantrium) and bromocriptine (parlodel) are the drugs of choice
Antipsychotics should not be administered at least two weeks after symptom
resolution
Tardive Dyskinesia

A syndrome of permanent involuntary movements that is most commonly

caused by long term use of conventional typical antipsychotics
Irreversible
No effective treatment
Management
No substantial management available yet.
Vitamin E has helped improve the condition in minority of patients
Anti-adrenergic Side effects
Hypotension
Reflex tachychardia: compensatory mechanism for lower extremity
Ask pt to get out of bed or change position slowly
Management of hypotension resolves this

Endocrine Side Effects

Inhibition of dopamine causes HYPERPROLACTINEMIA
Men
Impotence
Loss of libido
Gynecomastia
Low sperm count
Feminization
Women
Amenorrhea
Loss of libido
Galactorrhea
Risk for osteoporosis
Change in menstrual cycle
METABOLIC SYNDROME or insulin resistance leading to type 2 DM
Hyperglycemia
Obesity
Elevated lipid levels
Coagulation abnormalities
Hypertension
Sexual Side Effects
Decreased libido
Impotency
Impaired ejaculation
GI Side effects
Weight gain atypical anti psychotics specially with clozapine and
olanzapine; except with ziprasidone
Carbohydrate craving
Management:
Choose an appropriate diet
Advise not to take diet pills

CLOZAPINE (SIDE EFFECTS)

Can cause agranulocytosis which is characterized by leukopenia,
malaise, sore throat and fever
Obtain patients baseline WBC count and differential before
initiation of treatment
WBC count should be done weekly for 4 weeks after discontinuation
of the drug
Electrocolvulsive therapy
Action
Unclear at present
Voltage
70-150 volts
Duration
.5-2 seconds
Dose
6-12 treatments
Frequency interval of 48hrs for each treatment
Effectiveness
occurrence of generalized tonic-clonic seizure
Indications depression, mania, catatonic schizophrenia
Contraindication
increased ICP
fever, cardiac arrythmias, TB w/ hx of hemorrhage, recent
fracture
Retinal detachment, pregnancy
Consent
Yes
Pre-meds
Atropine Sulfate
Anectine (succinylcholine)
Methohexital Sodium (Brevital)
Complications
Loss of memory
Headache
Apnea
Fracture
Respiratory Depression

ANTIDEPRESSANTS
Selective
Serotonin
Reuptake Inhibitors (SSRI)
Generic Name
Trade Name
Fluoxetine
Prozac
Fluvoxamine
Luvox
Paroxetine
Paxil
Sertraline
Zoloft
Citalopram
Celexa
Escitalopram
Lexapro
Tricyclic Compounds (TCA)
Generic Name
Imipramine
Desipramine
Amitriptyline
Nortriptyline
Doxepine
Trimipramine
Protriptyline
Maprotiline
Mirtazipine
Amoxapine
Clomipramine
Other

compounds
Bupropion
Venlafaxine
Trazodone
Nefazodone
Duloxetine

Trade Name
Tofranil
Norpramin
Elavil
Pametor
Sinequan
Surmontil
Vivactil
Ludiomil
Remeron
Asendin
Anafranil

Wellbutrin
Effexor
Desyrel
Serzone
Cymbalta

Monoamine Oxidase Inhibition (MAOI)

Generic Name
Phenelzine
Tranylcypromine
Isocarboxazid

Trade Name
Nardil
Parnate
Marplan

Indications
Major depressive disorder
Anxiety disorder
Depressed phase of bipolar disorder
Psychotic depression
Panic disorder
Eating disorder
Given:
Early in the morning
Mechanism of Action
Exact mechanism is unknown
Interacts with norepinephrine and serotonin that are responsible for arousal,
attention, mood and appetite
SSRIs block serotonin reuptake
Cyclic antidepressants and venlafaxine primarily blocks norepinephrine and
to some extent, serotonin
Antidepressants take effect in
SSRI
2-3 weeks
Cyclic compounds 4-6 weeks
MAOI
2-3 weeks
Side Effects: SSRI
Anxiety
Agitation
Akathisia
Nausea
Insomnia
Sexual dysfunction
Headache
Diarrhea
Diminished sexual drive
Difficulty achieving orgasm or erection
Weight gain
Sedation (paroxitine)
Sweating
Handtremors
Management
For akathisia give propanolol (inderal) or a benzodiazepine
For insomnia, a sedative-hypnotic or low-dose trazodone may be given
Sweating and Continued Sedation indicate the need for change in
medication
TCA

Side effects
Dry mouth
Constipation
Urinary retention
Dry nasal passage
Blurred near vision
Sedation
Orthostatic hypotension
Weight gain
Tachycardia
Sexual dysfunction
Management

Caution when driving or performing activities requiring sharp and alert

reflexes
Calorie-free beverages or hard candy and taking frequent sips of water for
dry mouth
Stool softeners, increase fluid intake, and inclusion of grains and fruits in the
diet for constipation
Avoid exposure to extreme heat if there is decreased sweating
For patients w/ blurred vision, advise pt to avoid potentially dangerous tasks.
Reassure that normal vision will return in a few weeks. Pilocarpine eye drops
may be used.
Advise wearing of sunglasses outdoors for those with photophobia
For urinary retention, encourage frequent voiding & voiding when urge is
present
For urinary hesitancy, provide the patient privacy

MAOI
Side Effects

Daytime sedation
Insomnia
Weight gain
Dry mouth
Orthostatic hypotension
Sexual dysfunction
Hypertensive Crisis

Management: MAOI
Inform client of the possibility of hypertensive crisis
Implement dietary restrictions by giving the client a food list of what to avoid
Instruct client not to take any OTC without consulting the consultant or
pharmacist

Hypertensive Crisis
Results when the client who is taking MAOI ingested tyramine-containing food such
as the following:
Mature or aged cheese
Aged meats like pepperoni, salami, meat extracts, sausages
tofu, over ripe fruit, avocado
All tap beer
Soysauce, or soybean condiments
Yogurt, sour cream, peanuts MSG
Hypertensive Crisis
Signs & Symptoms
Hypertension
Hyperpyrexia
Tachycardia
Diaphoresis
Cardiac dysrhythmias
Fatal

Drug Interactions
Another MAOI
TCA
Demerol
Antihypertensives
General anesthesia
SSRI
Serotonergic syndrome: agitation, fever, tachycardia, hypotension,
hyperreflexia, rigidity)

Mood Stabilizing Drugs

Generic
Lithium
Carbamazepine
Valproic
Gabapentin
Topiramate
Oxcarbazepine
Lamotigrine

Trade Name

Tegretrol
Depakote,Depakene
Neurontin
Topamax
Trileptal
Lamictal

Indication
Treatment of Acute Episode of Mania
Mechanism of Action
Lithium normalizes reuptake of serotonin, norepinephrine, acetylcholine and
dopamine
Valproic acid & topiramate increase GABA level
Valproic & carbamazepine stabilize mood through KINDLING PROCESS
(snowball-like effect that raises the level of threshold to minor manic
episodes thus preventing full-blown mania

Topiramate Side Effects

Dizziness
Sedation
Weight Loss
Increased incidence of renal calculi
Management
Monitor blood levels periodically, time of the last dose must be accurate so
that plasma levels can be checked 12 hours after the last dose has been
taken
Take medication w/ meals to prevent nausea
Advise client not to drive until dizziness, lethargy, fatigue or blurring of vision
has subsided
Toxic Effects
Valproic Acid
Can cause hepatic failure, liver function test before start of therapy &
frequent intervals specially for the first six months
Can produce teratogenic neural tube defects (spina bifida)
Can cause pancreatitis
Carbamazepine
Can cause aplastic anemia & agranulocytosis. Monitor WBC & platelet counts
Lamotigrine
Can cause Stevens-Johnson syndrome and rarely, toxic epidermal necrolysis

Antianxiety / Anxiolytics/
Minor Tranquilizers

Generic Name

Trade Name

Alprazolam

Xanax

Chlordiazepoxide

Librium

Clonazepam

Klonopin

Chlorazepate

Tranxene

Diazepam

Valium

Flurazepam

Dalmane

Lorazepam

Ativan

Oxazepam

Serax

Temazepam

Restoril

Triazolam

Halcion

BUSPIRONE

BUSPAR

Indications
Used to treat anxiety and anxiety disorders, insomnia, obsessive compulsive
disorders, depression, PTSD and alcohol withdrawal
Mechanism of Action
Benzodiazipines mediate the actions of the amino acid GABA
Buspirone acts as a partial agonist at serotonin receptors which decreases
serotonin turnover
Side Effects
Can cause physical dependency
Drowsiness
Sedation/next-day sedation
Poor coordination
Impaired memory
Clouded sensation
Management
Advise client not to drink alcohol because benzodiazipines potentiate its
effects
Advise client to be aware of decreased response time, slower reflexes and
possible sedative effects
Advise not to discontinue the drug abruptly and without order from the
physician
Stimulants
Generic Name
Trade Name
Methyphenidate
Ritalin
Dextroamphetamine
Dexedrine
Amphetamine
Adderall
Pemoline
Cylert
Selective Norepinephrine Reuptake Inhibitor

Atomoxetine

Strattera

Indications
For treatment of ADHD and narcolepsy
Mechanism of Action
Acts as cortical and RAS stimulants by increasing the release of
norepinephrine, dopamine and serotonin from the presynaptic neurons and
block their reuptake
Paradoxical effect of calming by hyperexcitability through CNS stimulation is
related to increase stimulation of an immature RAS
Adverse Effects
Nervousness
Insomnia
Dizziness and headache
Blurred vision and difficulty with accommodation
GI effects nausea and vomitting
CV effects hypertension, arrythmias and angina
Side Effects

 Anorexia
Weight loss
Nausea
Irritability
Growth and weight suppression (long-term)
Management
Advise to take medications w/ meals to avoid anorexia and nausea
Clients should avoid caffeine, sugar & chocolates
Amphetamines & Methyphenidate
Potential for abuse is high
Pemoline
Cause-life threatening liver failure