PSYCHOPHARMACOLOGY

RAINIER B. UMALI, M.D.

I. Antipsychotics

-Dopamine Receptor Antagonists

-Serotonin-Dopamine Antagonists
Dopamine Receptor Antagonists

- Typical, traditional, conventional

antipsychotics
- Differentiates these drugs from newer
“atypical” antipsychotics
- Refers to target symptoms
- Highlights strong dopamine activity and
tight binding at D2 receptors
Serotonin-Dopamine Antagonists

- Novel or atypical antipsychotics

- Improves negative and positive
symptoms
- Smaller risk of EPS
- All are considered first line except
for Clozapine
DOPAMINE RECEPTOR
ANTAGONISTS
 Dopamine Hypothesis:

- Schizophrenia results from too much

dopaminergic activity.
Developments in the
Treatment of Schizophrenia

1.1930s to 1940s
-Electroconvulsive therapy

First Generation Antipsychotics

1.1940s to 1950s
-Chlorpromazine
Developments in the
Treatment of Schizophrenia
First Generation Antipsychotics
1.1950s to 1960s
-Haloperidol
-Fluphenazine
-Thioridazine
-Loxapine
-Perphenazine
Developments in the
Treatment of Schizophrenia

Second Generation Antipsychotics

1.1970
-Clozapine
Developments in the
Treatment of Schizophrenia
Second Generation Antipsychotics
1.1990 to 2000
-Risperidone
-Olanzapine
-Quetiapine
-Ziprasidone
-Aripiprazole
Developments in the
Treatment of Schizophrenia
Second Generation Antipsychotics

1.2006 to 2008
-Asenapine
-Bifeprunox
-Paliperidone
-Iloperidone
I. ANTIPSYCHOTICS

A.Dopamine Receptor Antagonists

1. Phenothiazines
2. Thioxanthenes
3. Dibenzoxazepines
I. ANTIPSYCHOTICS

A.Dopamine Receptor Antagonists

1.Dihydroindoles
2. Butyrophenones
3. Benzamides
4. Diphenylbutylpiperidines
I. ANTIPSYCHOTICS

A.Serotonin-Dopamine Antagonists

1.Risperidone
2.Olanzapine
3.Quetiapine
I. ANTIPSYCHOTICS

A.Serotonin-Dopamine Antagonists

1.Clozapine
2.Ziprasidone
3.Aripiprazole
CLASSIFICATIONS:
A.According to chemical structure

1. Phenothiazines
a. alipathic (Chlorpromazine)
b. piperazine (Fluphenazine)
c. piperidine ( Thioridazine)

2. Thioxanthenes - Thiothixene
A. According to chemical
structure

3. Dibenzoxazepines
-Loxapine

4. Dihydroindoles
-Molindone: does not induce
weight gain and is less
epileptogenic.
A. According to chemical
structure

5. Butyrophenones
-Haloperidol is one of the most
widely used antipsychotics.
-Droperidol is approved only
as an adjuvant to
anesthetics
-Spiroperidol is used in basic and
clinical research studies to
mark dopamine receptors
in PET.
A. According to chemical
structure

6. Diphenylbutylpiperidines
-Pimozide (Orap): approved for
the treatment of Tourette’s
disorder.
A. According to chemical structure

7. Benzamides
-Sulpiride (Dogmatil)
-Raclopide: used as a radiolabeled
ligand (an ion or molecule that
binds to a central metal atom
to form a coordination complex) in
research studies, particularly
in PET studies.
A.According to potency

1. Low potency agents

2. Medium potency agents

3. High potency agents

• Also blocks histamine-1, alpha-1, and
muscarinic receptors to varying degrees.
TYPICAL EFFECTS ON DOPAMINE AND
CLINICAL EFFECTS
A.According to absorption

- Erratic, ⇑ first-pass metabolism

- Oral administration – incomplete
absorption
- Liquid form – more efficient
absorption
- Peak plasma concentration – 1 to 4
hours after oral; 30 to 60 min
after parenteral administration.
A.According to distribution
- Highly protein bound

A.According to metabolism /
elimination
- Metabolized hepatically
- Long t1/2 allowing OD dosing
– 10 to 20 hours
THERAPEUTIC INDICATIONS:
1.Primary Psychotic Disorders -
Schizophrenia and Bipolar Disorders
2.Secondary Psychosis
3.Severe Agitation and Violent Behavior
4.Tourette’s Disorder
5.Non-psychiatric indications: nausea,
emesis, intractable hiccups and pruritus,
ballismus and hemiballismus
 NON-NEUROLOGICAL ADVERSE
EFFECTS:
1.Cardiac effects – low potency more cardiotoxic
than high-potency

2.Sudden Death
- Chlorpromazine – prolongs QT and PR
intervals depresses ST segment
- Thioridazine – malignant arrythmias
(Torsade de Pointes)
- Pimozide + Macrolide – potentiates
prolongation of QT interval
*do not use with Clarithromycin,
Erythromycin, Azithromycin
and Dirithromycin
 NON-NEUROLOGICAL ADVERSE
EFFECTS:
1.Orthostatic (Postural) Hypotension – most
common in low-potency DRA; results in
alpha-adrenergic blockade.

* DO NOT GIVE EPINEPHRINE

– paradoxical worsening of hypotension
– breast enlargement, galactorrhea,
impotence in men, amenorrhea
and inhibited orgasm in women.
 NON-NEUROLOGICAL ADVERSE
EFFECTS:

1.Hematological Effects – transient,

leukopenia
*Agranulocytosis

1.Peipheral anticholinergic effects – dry

mouth, blurred vision, constipation, urinary
retention and mydriasis; can be severe if
Low-potency DRA + tricyclics
 NON-NEUROLOGICAL ADVERSE
EFFECTS:
1.Endocrine – breast enlargement, galactorrhea,
impotence in men, amenorrhea and
inhibited orgasm in women.

2.Sexual – 50% of men experience ejaculatory

and erectile dysfunction; priaprism and painful
orgasm
- Thioridazine – decreased libido and
retrograde ejaculation

1.Weight gain
 NON-NEUROLOGICAL ADVERSE
EFFECTS:
1.Dermatological

2. Ophthalmological
Thioridazine – irreversible pigmentation of
retina

1. Jaundice

1. Overdoses - Haloperidol is the safest DRA in

overdose
NEUROLOGICAL ADVERSE EFFECTS:

1.Neuroleptic-induced Parkinsonism

2.Neuroleptic-induced Acute Dystonia

3.Neuroleptic-Induced Acute Akathisia

4.Neuroleptic-Induced Tardive Dyskinesia

NEUROLOGICAL ADVERSE EFFECTS:

1.Neuroleptic Malignant Syndrome

2.Epileptogenic Effects

3.Sedation – Chlorpromazine is the most

sedating

4.Central anticholinergic effects – severe

agitation, disorientation to time,person and
place, hallucinations, seizures, high fever,
dilated pupils, stupor and coma
USE IN PREGNANCY AND LACTATION:

1.If possible, should be avoided esp. in first

trimester

2.Only Chlorpromazine has data about

congenital malformation

3.High-potency DRA preferable

4.Haloperidol and Phenothiazines pass in

breastmilk
 DRUG INTERACTIONS:

1.Antacids – reduce absorption

2.Anticholinergics – anticholinergic toxicity

3.Anticonvulsants – Thioridazine decrease

metabolism of diphenylhydantoin – toxic
levels; barbiturates increase metabolism of
DRA;
 DRUG INTERACTIONS:

1.Antidepressants – tricyclics; Fluoxetine

and Paroxetine

2.Antihypertensives – DRA inhibits uptake of

guanethidine and inhibit effects of clonidine
and methyldopa

3.CNS depressants – DRA potentiates effect

 CONTRAINDICATIONS:
1.History of serious allergic response

2.Possible ingestion of substance that

may interact with the AP to induce
CNS depression or anticholinergic
delirium

3.Presence of severe cardiac

abnormality
 CONTRAINDICATIONS:

1.High risk for seizures

2.Presence of narrow-angle glaucoma

or prostatic hypertrophy – high
anticholinergic activity

3.Presence or history of tardive

dyskinesia
SEROTONIN–DOPAMINE
ANTAGONISTS
 RISPERIDONE
1.5HT2a, D2, @-1, @-2, H1

2.Lower incidence of EPS than Haloperidol (dosage-

dep.)

3.Use with phenytoin or SSRI may produce EPS

4.Use in opioid dependents may precipitate

withdrawal symptoms

5.a/e: weight gain, anxiety, nausea and vomiting,

rhinitis, erectile dysfunction, orgasmic dysfunction,
increased pigmentation.
 OLANZAPINE

1.Thienobenzodiazepine derivative of
Clozapine

2.5-HT2a, D1, D2, D4, @-1, muscarinic and

H1

3.More likely than risperidone to cause

weight gain
 OLANZAPINE

1.Fluvoxamine increase serum

concentration

2.No significant drug-drug interaction

3.a/e : somnolence, dry mouth, dizziness,

constipation, dyspepsia, increased appetite
and tremors.
 QUETIAPINE

1.5-HT2, 5-HT6, D1, D2, H1, @-1, @2

2.Does not block muscarinic or

benzodiazepine receptors

3.Not associated with EPS;

 QUETIAPINE

1.Use with Phenytoin increases clearance

fivefold; with Thioridazine increases
clearance by 65%; Cimetidine by 20%

2.It reduces Lorazepam clearance by 20%

3.a/e: somnolence, postural hypotension,

dizziness
 CLOZAPINE

1.5-HT2a, D1, D3, D4, @ receptors

2.Relatively low as D2 – does not cause EPS

3.Agranulocytosis
 CLOZAPINE

1.Should not be used with Carbamazepine,

Phenytoin, PTU, sulfonamides and Captopril

2.With Paroxetine – clozapine-asso.

Neutropenia

3.With Lithium- ↑ risk of seizures, confusion

and movement disorder.
 ZIPRASIDONE

1.5-HT1d,5-HT2a, 5-HT2c, D2, D3, D4, @-

1, H1
2.Agonist at 5-HT1a; serotonin reuptake
inhibitor and norepinephrine reuptake
inhibitor;
3.No clinically significant drug interaction
4.a/e: somnolence, headache, dizziness,
nausea and lightheadedness.
5.QT prolongation
 ARIPIPRAZOLE

1.Not an SDA; Partial agonist at D2

receptor.

2.Compete at D2 receptors for endogenous

dopamine – functional reduction

3.A quinoline derivative

4.Non-sedating
THERAPEUTIC INDICATIONS:
1.Psychotic Disorders

2.Mood Disorders

3.AIDS Dementia

4.Autistic spectrum disorders

THERAPEUTIC INDICATIONS:
1.Dementia-related psychosis

2.Tourette’s disorder

3.Huntington’s disease

4.Lesch-Nyhan syndrome
 ADVERSE EFFECTS:
1.Neuroleptic Malignant Syndrome – more
likely to occur if Clozapine is given
together with Lithium. It has been
reported with CLOZAPINE,
RISPERIDONE AND OLANZAPINE.

2.Tardive Dyskinesia – rare; associated with

Risperidone; SDA’s ameliorate the
symptoms; CLOZAPINE is the drug of
choice for persons with severe tardive
dyskinesia.
 ADVERSE EFFECTS:
1. Olanzapine and Ziprasidone
decreases depressive
symptoms in persons with
schizophrenia

2. Decreases risk of suicide and water

intoxication

3. Treatment-resistant OCD

4. Borderline PD
 ADVERSE EFFECTS:

1. Orthostatic Hypotension, Syncope,

and Tachycardia

2. Cardiac changes – Ziprasidone

3. Agranulocytosis – Clozapine

4. Seizures – Clozapine
 ADVERSE EFFECTS:

1. Hyperprolactinemia – Risperidone
is most strongly associated;
Aripiprazole does not increase
prolactin

2. Cognitive and Motor impairment-

all cause sedation
3. Body Temperature Regulation
4. EPS
 ADVERSE EFFECTS:
1. Weight gain – Risperidone,
Olanzapine, Quetiapine and
Clozapine;
2. Anticholinergic symptoms –
Clozapine and Olanzapine
3. Sialorrhea (hypersalivation) –
Clozapine
4. Obsessive-Compulsive symptoms–
Clozapine, Risperidone and
Olanzapine;
 ADVERSE EFFECTS:

1. Priapism (prolonged erection)

2. Genitourinary symptoms
3. Dysphagia (painful swallowing)
4. Transaminase elevations and
hepatic dysfunction
5. Cholesterol and Triglyceride
elevation
6. Hypothyroidism
 USE IN PREGNANCY AND
LACTATION

*NO STUDY
II. Anxiolytics

-Clonidine
-Benzodiazepines
-Buspirone
ALPHA-ADRENERGIC RECEPTOR
AGONISTS
(Clonidine and Guanfacine)
1.Anti-hypertensive agents

2.Reduces firing rate of

noradrenergic neurons and reduces
plasma concentration of
norepinephrine

3.Resets the body’s sympathetic tone

at a lower level and decreases
arousal.
PHARMACOLOGY:
1.Well-absorbed in the GIT

2.Peak plasma levels: 1 – 3 hrs after

oral adm.

3.Half-life : 6 – 20 hrs (Clonidine)

10 – 30 hrs (Guanfacine)

4.No known laboratory interferences

THERAPEUTIC INDICATIONS:

1.Withdrawal from:
- Opioids
- Alcohol
- Benzodiazepines
- Nicotine
THERAPEUTIC INDICATIONS:
a.Symptoms of rapid opioid
withdrawal:
- hypertension
- tachycardia
- dilated pupils
- sweating
- lacrimation
- rhinorrhea
THERAPEUTIC INDICATIONS:
a.Dosage:
- Clonidine 0.1 to 0.2 mg PO qid

- hold for systolic BP <90 mm Hg

or bradycardia

- stabilize for 2 to 3 days, then

taper over 5 to 10 days
THERAPEUTIC INDICATIONS:
OR:
- Clonidine 0.1 to 0.2 mg PO q4h
to q6h as needed for
withdrawal signs or
symptoms

- stabilize for 2 to 3 days, then

taper over 5 to 10 days
THERAPEUTIC INDICATIONS:
a.Effects:
- Reduces symptoms of alcohol
and Benzodiazepine
withdrawal;

- Reduces craving, anxiety and

irritability of nicotine
withdrawal;

*Transdermal patch – better long

term compliance
THERAPEUTIC INDICATIONS:
1.Tourette’s Disorder

- Clonidine 0.05 mg/day – 0.3

mg /day in divided doses.

- 3 months needed before

beneficial effects are
seen

- reduces frequency of attacks

THERAPEUTIC INDICATIONS:
1.Post-Traumatic Stress Disorder
- hyperarousal
- exaggerated startle response
- insomnia
- vivid nightmares
- tachycardia
- agitation
- hypertension
- perspiration
PRECAUTIONS:

1.Should not be taken by adults with:

- BP below 90/60
- with cardiac arrythmias
- with bradycardia
PRECAUTIONS:

1.In case bradycardia develops

- gradual tapering discontinuation
PRECAUTIONS:

1.For patients with:

- cardiac disease
- vascular disease
- renal disease
- history of depression
PRECAUTIONS:

1.For patients with:

- Raynaud’s syndrome - excessively

reduced blood flow in response to
cold or emotional stress, causing
discoloration of the fingers, toes,
and occasionally other areas
PRECAUTIONS:

1.Avoid in:

- pregnant and nursing mothers

- elderly persons
- children
ADVERSE EFFECTS:

dry mouth and eyes nausea

fatigue hypotension
sedation constipation
dizziness sexual dysfunction
fluid retention skin irritation
vivid dreams hallucinations
nightmares
OVERDOSE:

coma

constricted pupils

decreased - BP
- pulse rate
- respiratory rate
WITHDRAWAL:
anxiety
restlessness
perspiration
tremors
abdominal pain
palpitations
headaches
dramatic increase in BP
WITHDRAWAL:

- 20 hours after last dose of

Clonidine

- 2 – 4 days after last dose of

Guanfacine
DRUG INTERACTIONS:
1.TCAC’s (tricitric acid cycle) -
reduces hypotensive effects of
Clonidine
2.Clonidine increases CNS depressive
effects of Barbiturates, alcohol,
trazodone
3.Unwanted synergistic hypotensive
effects with other antihypertensives;
4.Yohimbine blocks effects
 BENZODIAZEPINES
1.Acts by binding to GABA A receptors
which opens chloride channels and
reduces the rate of neuronal and muscle
firing.

2.Act as hypnotics in high doses and as

sedative in low doses

3.Drug of choice for management of

acute anxiety and agitation.

4.Risk for psychological dependence

EFFECTS:

1.CNS effects on anxiety and sleep

2.Inhibit spinal polysynaptic afferent

pathways making them effective
muscle relaxants.
EFFECTS:

1.Anticonvulsants

2.All BZD are completely absorbed

unchanged from the GIT except for
CLORAZEPATE.
EFFECTS:

1.Absorption, peak concentrations and

onset of action are quickest with the
following:
- Diazepam (Valium)
- Triazolam (Halcion)
- Lorazepam (Ativan)
- Estazolam (Esilgan)
- Alprazolam (Xanor)
EFFECTS:

* Rapid onset of action important for

single dose to calm an episodic
outburst or to fall asleep rapidly.
EFFECTS:

1.Only LORAZEPAM and MIDAZOLAM

have rapid and reliable absorption
following IM administration.
EFFECTS:
1.Longest-acting BZD:

- Diazepam - Chlordiazepoxide
- Clonazepam - Clorazepate
- Flurazepam - Prazepam
- Quazepam - Halazepam

*with plasma half-lives of 30 to >100

hours
EFFECTS:
1.Half-life of between 8 – 30 hours =
Lorazepam, Oxazepam, Temazepam and
Estazolam

2.Alparazolam has half-life of 10 – 15

hours

3. Triazolam has shortest half-life = 2 – 3

hours
 LONG HALF-LIFE BZD

A.ADVANTAGES

- less frequent dosing

- less variation in plasma concentration

- less severe withdrawal phenomena

 LONG HALF-LIFE BZD

A.DISADVANTAGES

- drug accumulation

- increased risk of daytime

psychomotor impairment

- increased daytime sedation

 SHORT HALF-LIFE BZD

A.ADVANTAGES

- no drug accumulation

- less daytime sedation

 SHORT HALF-LIFE BZD

A.DISADVANTAGES

- more frequent dosing

- earlier and more severe withdrawal

syndromes

- rebound insomnia and anterograde

amnesia more common
ZOLPIDEM AND ZALEPLON

1.Benzodiazepine agonists at BZ2 site

2.Rapidly and well-absorbed, although

can be delayed for as much as 1 hour
if taken with food
ZOLPIDEM AND ZALEPLON

1.Zolpidem t1/2= 2.6 hrs; Zaleplon

t1/2= 1 hour

2.No active metabolites; selective

sedative effects; no muscle relaxant
and anticonvulsive effects like BZD
THERAPEUTIC USES:

1.Status Epilepticus

- LORAZEPAM and DIAZEPAM are

the most commonly used BZD
for seizure disorder.
THERAPEUTIC USES:
1.Status Epilepticus

- Diazepam is longer-acting than

Lorazepam however very lipid-
soluble and highly-protein bound
and very large distribution of
unbound drug hence shorter
duration of action.

- Lorazepam has a more prolonged

duration of action
THERAPEUTIC USES:

1.Anxiety Disorders

- may be given orally for short-term

treatment of severe anxiety

- for panic attacks: may give IV

Lorazepam or Diazepam
THERAPEUTIC USES:

1.Mixed Anxiety-depressive Disorder

- Alprazolam is indicated; second-line
drug

1.Panic Disorder and Social Phobia

- Alprazolam and Clonazepam
THERAPEUTIC USES:

1.Obsessive-Compulsive Disorder and

PTSD

- Clonazepam has serotonergic effects

and is effective in treating the
anxiety component of OCD.
THERAPEUTIC USES:
1.Insomnia

Mild Insomnia - Flurazepam

Quazepam, Estazolam

Moderate - Midazolam

Severe - Triazolam, Temazepam

THERAPEUTIC USES:

1.Insomnia

Flurazepam – longest half-life;

minor cognitive
impairment

Triazolam – shortest half-life;

mild rebound anxiety
THERAPEUTIC USES:
1.Insomnia

Quazepam shares final metabolite

with Flurazepam.

Desalkylflurazepam- T1/2 100

hours

Quazepam is associated with

daytime impairment
when used for a long time.
THERAPEUTIC USES:

1.Insomnia

Zolpidem and Zaleplon are

solely indicated for insomnia.
THERAPEUTIC USES:

1.Depression

- Alprazolam 1 – 1.5 mg/day to be

raised by .5 mg a day every 3 or
4 days. Maximum of 4 mg/day.
THERAPEUTIC USES:
1.Bipolar 1 Disorder

-Clonazepam effective in acute

mania

- as adjuvant to Lithium – increased

time between cycles and fewer
than usual depressive episodes.

-Alprazolam also effective but is

second-line over Clonazepam
THERAPEUTIC USES:

1.Akathisia

2. Parkinson’s Disease

3. Premedication before procedures

4. Intensive care
THERAPEUTIC USES:

1. Alcohol Withdrawal
-Diazepam and Chlordiazepoxide

1. Muscular Disorders
-Tetanus, Restless leg syndrome,
Tourette’s syndrome
OTHER PSYCHIATRIC
INDICATIONS:
1.Clonazepam augmentation may
accelerate the antidepressant effects
of Fluoxetine.

2.IM Lorazepam used to manage

substance-induced (except
methamphetamine) and psychotic
agitation in ER.
OTHER PSYCHIATRIC
INDICATIONS:
1.Flumazenil is used to reverse BZD
Overdose

*Flumazenil 0.2mg (2 ml) IV

over 30 seconds; after 30
seconds, 0.3mg IV over
30 seconds; 0.5mg at 1
minute interval up to
cumulative dose of 3 mg.
ADVERSE EFFECTS:
1.Drowsiness – most common;
residual daytime sedation

2.Dizziness and ataxia

3.Most serious is when taken with

another CNS depressant such as
alcohol – marked drowsiness,
disinhibition, respiratory depression.
ADVERSE EFFECTS:

1.Anterograde amnesia - high-potency BZD

2.Triazolam – associated serious aggressive

behavior with doses greater than 1 mg.
PRECAUTIONS:

1.Hepatic disease

2.Elderly patients

3.COPD and Sleep Apnea

4.History of Substance Abuse

PRECAUTIONS:

1.Renal disease

2.Cognitive disorders

3.Porphyria
PRECAUTIONS:

1.Myasthenia Gravis

2.Breastfeeding

3.Pregnancy
DRUG INTERACTIONS:

1.Alcohol and other CNS depressants – cause

synergistic adverse effects with possible
increase in depression and suicide

2.Antacids and anticholinergics – may slow

down absorption of BZD

3.Clonazepam + Lithium + antipsychotics –

ataxia and dysarthria
DRUG INTERACTIONS:
1.BZD + Clozapine = delirium

2.Oral contraceptives and INH – increase

plasma conc.

3.Nefazodone and Fluvoxamine – inc. plasma

conc. of Triazolam and Alprazolam to
potentially toxic levels.

4.Smoking – increase metabolism of BZD

DRUG INTERACTIONS:
1.Rifampicin, Phenytoin, Carbamazepine and
Phenobarbital – increase metabolism of
Zaleplon

2.BZD increase plasma conc. of phenytoin

and digoxin.

3. SSRI’s may prolong and exacerbate the

severity of Zolpidem-induced
hallucinations.
 BUSPIRONE

1.Indicated for treatment of anxiety

disorder

2.Low potential for abuse; lacks

euphoric effect

3.Not associated with withdrawal

phenomena or cognitive impairment
 BUSPIRONE

1.Acts as an agonist or partial agonist

on 5HT1a receptors;

2.No significant effects on the

respiratory, cardiovascular, Muscular
and auntonomic nervous systems.
THERAPEUTIC INDICATIONS:

1.Safe and effective for the treatment

of anxiety disorders.

2.More effective for symptoms of

anger and hostility,; less effective for
somatic symptoms.

3.Full effect seen at dosages above 30

mg/day.
THERAPEUTIC INDICATIONS:

1.Full clinical response may take 2 – 3

weeks

2.Not effective in treatment of panic

disorder or social phobia

3.Reduces the increased arousal and

flashbacks of PTSD
THERAPEUTIC INDICATIONS:

1.Can effectively reduce aggression and

anxiety in persons with organic brain
disorders.

2.Opposition defiant symptoms, ADHD

3.Premenstrual dysphoric disorder

THERAPEUTIC INDICATIONS:

1. May ameliorate sexual inhibition of

SSRI’s

2. SSRI - induced bruxism

ADVERSE EFFECTS AND
PRECAUTIONS:
1.Most common adverse effects are
headache, nausea, dizziness, and
insomnia

2.Should be used with caution by

persons with hepatic and renal
impairment, pregnant women and
nursing mothers.

3.Can be used safely in the elderly

DRUG INTERACTIONS:

1.It increase blood concentration of

Haloperidol

2.With MAOI - hypertensive episodes

3.Erythromycin, Itraconazole,
Nefazodone, and grapefruit juice -
raise plasma concentration of
Buspirone.
DRUG INTERACTIONS:

1.Can cause transient elevations in

growth hormone, prolactin and
cortisol concentration.

2.Treatment is usually initiated 5 mg

TID or 7.5 mg BID, raised to 5 mg
every 2 to 4 days; up to 15 – 60
mg/day.
III. Treatment for Adverse
Effects of Psychotropics
-Amantadine -Dantrolene

-β-adrenergic receptor -Dopamine Receptor

antagonists Agonists

-Anticholinergics -Sildenafil

-Antihistamines -Yohimbine
MEDICATION-INDUCED
MOVEMENT DISORDERS:

1.Neuroleptic-induced Parkinsonism

- Resting tremor, rigidity (cogwheel or

leadpipe), bradykinesia (slowed
thinking), excessive salivation,
drooling, shuffling gait
dysphoria.
MEDICATION-INDUCED
MOVEMENT DISORDERS:
1.Neuroleptic Malignant Syndrome

- Muscular rigidity and dystonia,

akinesia, mutism,
obtundation, agitation;
autonomic symptoms: high fever,
sweating, and inc. BP/HR; elevated
CPK
MEDICATION-INDUCED
MOVEMENT DISORDERS:
1.Neroleptic-induced Acute Dystonia

- Brief or prolong contractions of

muscles that results in
abnormal movement.; oculogyric
crisis, tongue protrusion, trismus,
torticollis, laryngeal-pharyngeal
dystonias, dystonic postures
MEDICATION-INDUCED
MOVEMENT DISORDERS:

1.Neuroleptic-induced Acute Akathisia

- Subjective feelings of restlessness,
objective signs of restlessness

1.Neuroleptic-induced Tardive Dyskinesia

- Late-appearing disorder of
involuntary,
choreoathetoid movements.
MEDICATION-INDUCED
MOVEMENT DISORDERS:

1.Medication-induced Postural Tremor

- Rhytmical alteration in movement

that usually exceeds 1 beat per
second; Lithium Valproate,
antidepressants.
 β-ADRENERGIC RECEPTOR
ANTAGONISTS

1.Beta blockers; Beta antagonists

2.Peripheral effects in the treatment of

hypertension, angina, certain cardiac
arrhythmias, and migraine

3.Propanolol, Nadolol, Pindolol, Labetalol,

Metoprolol, Atenolol and Acebutolol
 β-ADRENERGIC RECEPTOR
ANTAGONISTS

1.Do not interfere with standard

laboratory tests.

2.Excreted in the breastmilk.

THERAPEUTIC INDICATIONS:

1.Anxiety Disorders

- Social phobia (PERFORMANCE

TYPE)

*Propanolol 10 – 40 mg 20 to
30 minutes before
performance
THERAPEUTIC INDICATIONS:

1.Anxiety Disorders

- less effective for the treatment

of panic disorder than are
benzodiazepines or
selective serotonin reuptake
inhibitors (SSRIs)
THERAPEUTIC INDICATIONS:
1.Lithium-induced Postural Tremor

- Initial approach:
lower dose of lithium
eliminate aggravating factors
administer lithium at HS

*Propanolol 20 -160 mg/day,

BID/TID
THERAPEUTIC INDICATIONS:

1.Neuroleptic-induced Akathisia

- more effective than

anticholinergics
and
benzodiazepines

- not effective in acute dystonia

and parkinsonism
THERAPEUTIC INDICATIONS:
1.Aggression and Violent Behavior

- Impulse Disorders,
Schizophrenia,
Aggression asso. with brain
injuries and degenerative
disorders.

*Propanolol 50 – 800 mg/day,

BID/TID
THERAPEUTIC INDICATIONS:
1.Alcohol Withdrawal

- adjuvant to benzodiazepines

- Suggested dosage schedule:

no propanolol for HR<50

50 mg for HR 50 – 80
100 mg for HR 80 and above
THERAPEUTIC INDICATIONS:

1.Antidepressant Augmentation

- Pindolol administered at the

onset of antidepressant
therapy may shorten and hasten
the by several days.

- may induce depression

EFFECTS ON SPECIFIC
ORGAN SYSTEM:

1.Antagonize the normal physiological

response to hypoglycemia

2.Worsen A-V conduction defects and

lead to complete A-V heart block – death
EFFECTS ON SPECIFIC
ORGAN SYSTEM:

1.Produce bradycardia

2.Blocks bronchodilating effects of

epinephrine
PRECAUTIONS:

1.Contraindications:
- asthma
- insulin-dependent diabetes
- congestive heart failure
- significant vascular disease
- persistent angina
- hyperthyroidism
ADVERSE REACTIONS:
1.hypotension and bradycardia most
common

2.depression asso. with propanolol

(rare)

3.nausea, vomiting, diarrhea and

constipation

4.agitation, confusion, hallucinations

(rare)
ADVERSE EFFECTS AND
TOXICITY:
1.Cardiovascular

-Hypotension
-Bradycardia
-Dizziness
-Congestive failure (in patients
with compromised myocardial
fxn)
ADVERSE EFFECTS AND
TOXICITY:
1.Respiratory
- asthma (less risk with B1-
selective drugs)

1.Metabolic
- worsened hypoglycemia in
diabetic patients on
insulin or oral agents
ADVERSE EFFECTS AND
TOXICITY:

1.Gastrointestinal
- nausea, diarrhea, abdominal
pain

1.Sexual
- impotence
ADVERSE EFFECTS AND
TOXICITY:

1.Neuropsychiatric

- lassitude - vivid nightmares

- fatigue - depression (rare)
- dysphoria - psychosis (rare)
- insomnia
ADVERSE EFFECTS AND
TOXICITY:
1.Other (rare)
- Raynaud’s phenomenon
- Peyronie’s disease

1.Withdrawal syndrome
- rebound worsening of angina
pectoris when discontinued
DRUG INTERACTIONS:
1.Increased plasma concentrations of
antipsychotics, anticonvulsants,
theophylline, and levothyroxine
(Propanolol)

2.Barbiturates, Phenytoin and cigarette

smoking increase the elimination of β-
antagonists that are metabolized by the
liver
DRUG INTERACTIONS:

1.Co-administration with MAOI’s =

hypertensive crisis and bradycardia

2.Co-administration with Calcium channel

inhibitors = depressed myocardial
contractility and A-V nodal cond
CLINICAL GUIDELINES:

1.Pulse and BP should be taken

regularly.

2.Drug use should be temporarily

discontinued if it produces severe
dizziness, ataxia or wheezing.
CLINICAL GUIDELINES:

1.Treatment should never be

discontinued abruptly.

*Propanolol tapered by 60
mg/day until dose of
60 mg/day is reached,
then tapered 10-20
mg/day every 3 to 4 days.
 AMANTADINE

1.Used primarily for treatment of

medication-induced movement disorders

2.Antiviral agent for Influenza A infection

3.Augments dopaminergic
neurotransmission in the CNS

4.Well-absorbed from GIT; t1/2 12-18

hrs; excreted unmetabolized in the urine
 AMANTADINE
1.Primary indications: Parkinsonism,
Akinesia, Rabbit Syndrome (focal perioral
tremor of choreoathetoid type)

2.Not generally considered as effective in

acute dystonic reactions and not effective
in tardive dyskinesia and akathisia.

3.Beneficial to elderly persons prone to

anticholinergic side effects
ADVERSE EFFECTS:

1.CNS:

- mild dizziness, insomnia, and

impaired concentration (5 -
10%)
- irritability, depression, anxiety,
dysarthria and ataxia (1-5%)
- seizures, and psychotic
symptoms
ADVERSE EFFECTS:
1.PNS:

- nausea (most common),

headache, loss of
appetite, blotchy skin
spots
- Livedo reticularis (purple
discoloration of the
skin caused by dilation
of BV)
PRECAUTIONS:
1.Relative contraindication: Renal
disease and seizure d/o

2.Should be used with caution in

persons with edema and
cardiovascular disease

3.May be teratogenic
PRECAUTIONS:

1.Excreted in milk

2.Overdosage: toxic psychoses

(confusion, hallucinations,
aggressiveness), cardiopulmonary
arrest.
DRUG INTERACTIONS:
1.Amantadine + MAOI = increase in
resting BP

2.Amantadine + CNS stimulants =

insomnia, irritability, nervousness,
possible seizures, and irregular
heartbeat.

3.Should not be co-administered with

anticholinergics because adverse
effects may be exacerbated.
GUIDELINES:
1.The usual starting dosage is 100 mg
p.o. BID; may increase up to 200 mg
BID.

2.Should be used in persons with

renal impairment only in consultation
with the physician treating the renal
condition.

3.If successful, should be continued

for 4 – 6 weeks.
GUIDELINES:

1.Should be tapered over 1 – 2 weeks

once a decision has been made to
discontinue use.

2.Persons taking amantadine should

not drink alcoholic beverages.
 ANTICHOLINERGICS
1.Anti-muscarinics because specific
for muscarinic receptors.

2.Anticholinergics:

-Benztropine (Cogentin) -Orphenadrine (Norflex)

-Biperiden (Akineton) -Procyclidine (Kemadrin)

-Ethopropazine (Parsidol) - Trihexyphenidyl (Artane)

 ANTICHOLINERGICS

1.Well absorbed in GIT; lipophilic

2.IM administration is preferred

because of low risk for adverse effects
 ANTICHOLINERGICS

1.Trihexyphenidyl is the most

stimulating; Benztropine is the least
stimulating.

2.No known laboratory interferences.

THERAPEUTIC INDICATIONS:

1.Neuroleptic-induced Parkinsonism -
most common in the elderly; occurs
after 2-3 weeks of treatment

2.Neuroleptic-induced acute dystonia-

most common in young men
THERAPEUTIC INDICATIONS:

1.Akathisia – not generally considered

as effective as the β-adrenergic
antagonists or benzodiazepines.
PRECAUTIONS AND
ADVERSE EFFECTS:

1.Prostatic hypertrophy, urinary

retention, and narrow-angle glaucoma
PRECAUTIONS AND
ADVERSE EFFECTS:
1.Adverse effects: anticholinergic intoxication
- delirium, coma, seizures, agitation,
hallucinations, severe hypotension,
supraventricular tachycardia,
peripheral manifestations
such as flushing, mydriasis, dry
skin, hyperthermia and
decreased bowel sounds.

*Tx: Physostigmine (Antilirium) 1-2 mg IV

or IM every 30 or 60 minutes.
DRUG INTERACTION:

1.Dopamine receptor antagonists,

tricyclic and tetracyclics, MAOI’s.

2.Anticholinergic Intoxication
Syndrome
DOSAGE AND GUIDELINES:
1.Neuroleptic-induced Parkinsonism

- Benztropine 1 – 4 mg OD to
QID; should be
administered for 4 – 8
weeks; tapered over 1–2
weeks.

- In young men, prophylaxis may

be indicated.
DOSAGE AND GUIDELINES:

1.Neuroleptic-induced Acute Dystonia

- Benztropine 1-2 mg IM
repeated 20-30 min if
needed

- Lorazepam 1 mg IM or IV
DOSAGE AND GUIDELINES:

1.Laryngeal Dystonia

- medical emergency

- Benztrophine 4 mg 10 min
period, followed by
Lorazepam 1-2 mg slow IV
DOSAGE AND GUIDELINES:

1. Prophylaxis is indicated in persons

who had 1 episode or in persons
who are at high risk; given for 4
-8 weeks and then gradually tapered
over 1 – 2 weeks.
 ANTIHISTAMINES

1.H1 Receptor Antagonists

2.Diphenhydramine – neuroleptic-
induced acute dystonia and
parkinsonism
 ANTIHISTAMINES

1.Hydroxyzine, Promethazine –
sedative, anxiolytics

2.Cyproheptadine – anorexia nervosa

and inhibited male and female orgasm
caused by serotonergic agents.
PRECAUTIONS AND
ADVERSE EFFECTS:
1.Use in the elderly because it is
associated with sedation, dizziness and
hypotension

2.Paradoxical excitement and agitation

3.Persons whould be warned about

driving and operating machinery because
of poor motor coordination.
PRECAUTIONS AND
ADVERSE EFFECTS:

1.Epigastric distress, nausea,

vomiting, diarrhea and constipation

2.Mild anticholinergic activity

3.Co-administration with opioids can

increase euphoria
PRECAUTIONS AND
ADVERSE EFFECTS:

1.Excreted in breastmilk

2.Potential for teratogenicity

DRUG INTERACTIONS:
1.Add to sedative property of CNS
depressant

2.Add to anticholinergic effects

resulting in severe anticholinergic
intoxication

3.Cyproheptadine may antagonize the

beneficial effects of SSRI’s.
LABORATORY INTERFERENCES:

1.May eliminate the wheal and

induration that form the basis of
allergy skin tests.

2.Promethazine may interfere with

pregnancy test and increase blood
glucose concentration.
LABORATORY INTERFERENCES:

1.Diphenhydramine may yield a false-

positive urine test for PCP.

2.Hydroxyzine can falsely elevate

certain tests for 17-
hydroxycorticosteroids.
DOSAGE AND GUIDELINES:

1.Diphenhydramine 25-50 mg IV
effective for acute dystonia.

2.Diphenhydramine 25 mg TID up to
50 mg QID for parkinsonism, akinesia
and buccal movements.
DOSAGE AND GUIDELINES:

1.Diphenhydramine 50 mg OD- mild

transient insomnia

2.Hydroxyzine 50-100mg QID for

long term treatment of anxiety; 50 -
100 mg IM every 4 – 6 hours for
short-term treatment of anxiety.
 DANTROLENE
1.Direct-acting skeletal muscle
relaxant; directly affects contractile
response of the muscles at the site
beyond the myoneural junction.

2.May cause muscle weakness,

slurring of speech and drooling,
diarrhea, headache and depression,
elevated liver function tests.
 DANTROLENE

1.Primary indication: muscle rigidity in

neuroleptic malignant syndrome
DOPAMINE RECEPTOR AGONISTS

1.Levodopa, Bromocriptine, Pergolide,

Pramipexole, Ropinirole

1.Parkinsonism, EPS, Akinesia, Focal

perioral tremors, Hyperprolactinemia,
Galactorrhea, Neuroleptic Malignant
Syndrome.
DOPAMINE RECEPTOR AGONISTS

1.Improve erectile dysfunction

2.Adverse effects: nausea, vomiting,

orthostatic hypotension, headache,
dizziness, and cardiac arrythmias.
DOPAMINE RECEPTOR AGONISTS
1.Patients may experience choreiform
and dystonic movements and
psychiatric disturbance after long term
use.

2.Long-term use of Bromocriptine and

Pergolide can produce retroperitoneal
and pulmonary fibrosis, pleural
effusions and pleural thickening.
DOPAMINE RECEPTOR AGONISTS

1.Pramipexole and ropinirole may cause

irresistible sleep attacks.

2.Contraindicated in pregnant women

and nursing mothers.
DOPAMINE RECEPTOR AGONISTS

1.With TCAC’s = neurotoxicity

2.With diuretics and Anti-HPN=

potentiate effects
DOPAMINE RECEPTOR AGONISTS

1. BZD, Phenytoin, Pyridoxine =

interfere with therapeutic effects

2. Bromocriptine + ergot alkaloids =

hypertension and myocardial
infarction
 SILDENAFIL

1.PDE5, which acts on arteriolar

smooth muscle of corpus cavernosum

2.Inhibits PDE5, allowing blood to fill

the corpus cavernosum and cause
erection

3.For erectile dysfunction

 SILDENAFIL

1.Most potential adverse effect in

Myocardial infarction

2.Contraindicated in patients taking

organic nitrates

3.No laboratory interferences

 YOHIMBINE

1.Alpha-2 adrenergic receptor

antagonist

2.For idiopathic and medication-

induced sexual disorders
 YOHIMBINE

1.A/E: anxiety, inc. BP/HR, inc.

psychomotor activity, irritability,
tremors, headache, flushing,
dizziness, urinary frequency, nausea ,
vomiting, sweating.

2.No known laboratory interferences

THANK YOU &
GOOD DAY!