The document discusses drugs acting on the central nervous system (CNS). It first introduces that CNS drugs are used for both medical and non-medical purposes to act on the brain and spinal cord. It then discusses the major neurotransmitters of the CNS including noradrenaline, dopamine, serotonin, and acetylcholine. For each neurotransmitter, it briefly describes their physiological functions. The document also provides information on drugs used for Parkinson's disease, epilepsy, and schizophrenia, outlining their mechanisms of action, therapeutic uses, and common medications employed to treat each condition.

1. DRUGS ACTING ON CNS
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2. Introduction
CNS drugs act on brain and spinal cord and used in;
•medical uses (treatment of mental illnesses, suppression of
seizures, relief of pain, and production of anesthesia) and
• non-medical uses (stimulants, depressants, euphoriants,
and other “mind-altering” uses).
Transmitters of the CNS;
More than a dozen neurotransmitters
physiological functions of major CNS NT are discussed
briefly as follows.
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3. •Noradrenaline:
Noradrenergic transmission is important in
•control of mood (functional deficiency resulting
depression)
•wakefulness, and alertness.
•Dopamine:
Dopamine is important in
motor control,
has behavioural effects (excessive dopamine activity
is implicated in schizophrenia),
important in hormone release (prolactin, GH) and
dopamine in chemoreceptor trigor zone causes
nausea and vomiting.
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4. Serotonin( 5-HT):
Physiological functions associated with 5-HT pathways include;
•feeding behaviour, behavioural response
(hallucinatory behaviour),
•control of mood and emotion,
•control of body temperature and
•vomiting.
Acetylcholine(Ach):
Ach has effects
•on arousal,
•on learning, and
•on short-term memory.
•Dementia and parkinsonism are associated with
abnormalities in cholinergic pathways.
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5. Summary of NT of the CNS.

6. 1. Drugs for Parkinson’s Disease
Parkinson’s disease is a neurodegenerative disorder characterized
by
tremor, rigidity, postural instability, and slowed movement.
Most cases involve people over the age of 65
Cause of Imbalance (DA, Ach)—Degeneration of neurons
supplying DA to striatum; therefore, excitatory influence of ACh is
unopposed leading to release of GABA
PD correlated with destruction of dopaminergic neurons in the
SN with a consequent reduction of dopamine actions in corpus
striatum of brain's basal ganglia that are involved in motor control.
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7. Parkinsonism (PD) – signs
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8. 8
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9. Overview of Drug Therapy
A. Therapeutic Goal—To improve ability for activities of daily
life (only symptom relief)
B. Treatment Strategy—Restore balance between DA and ACh
by activating DA receptors or blocking
ACh receptors
C. Overview of Drugs Employed—Two major categories
(dopaminergic drugs & anticholinergic drugs).
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10. Drug Mechanism of Action Therapeutic Role
DA Replacement
Levodopa
Levodopa/carbidopa
Levodopa undergoes conversion
to DA in the brain and then
activates DA receptors (carbidopa
just blocks destruction of
levodopa in the periphery)
First-line drug, or suppliment to a
dopamine agonist
DA receptor Agonists
Bromocriptine
Pergolide
Pramipexole
Ropirinole
Direct activation of DA receptors
First-line drug, or suppliment to
levodopa
(the nonergot agents-pramipexole and
ropirinole- are preferred)
COMT Inhibitors
Entacapone
Tolcapone
Inhibit breakdown of levodopa by
COMT
Adjunct to levodopa (to increase
‘’ontime ”and decrease “ wearing off
“)
DA Releaser
Amantadine
Promotes release of DA from
remaining DA neurons may also
block DA reuptake
Second line therapy for motor
fluctuations
MAO-B Inhibitor
Selegiline
Inhibits the breakdown of DA by
MAO-B
Used in newly diagnosed patients for
possible neuroprotection; second or
third-line agent as adjunct to levodopa
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11. Synthesis of dopamine from levodopa in absence and presence of carbidopa, an inhibitor of
dopamine decarboxylase in the peripheral tissues.
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12. Actions: Levodopa decreases rigidity, tremors, and other symptoms.
Therapeutic uses:
 Levodopa in combination with carbidopa is a potent and efficacious drug
In approximately two-thirds of patients , levodopa and carbidopa treatment
reduces severity of the disease for the first few years of treatment.
Patients then typically experience a decline in response at 3rd to 5th year.
Adverse effects of levodopa
1. Peripheral effects: Anorexia, nausea, and vomiting occur b/c of stimulation of
CTZ of the medulla. Tachycardia and ventricular extra systoles result from
dopaminergic action on the heart. May also cause orthostatic hypotension.
2. CNS effects: Visual and auditory hallucinations and abnormal involuntary
movements (dyskinesias) may occur. Levo-dopa can also cause mood changes,
depression, psychosis, and anxiety.
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13. Late complications of levodopa
Wearing Off and On-Off Phenomena
Within 4 -6 yrs of Rx with levodopa, effects last for shorter periods and the
following pattern may occur:
 Patients may first notice slowness (bradykinesia) or tremor in the
morning before the next dose is due.
Less commonly, some experience painful dystonia, muscle spasms
that can cause sustained contortions of various parts of the body,
particularly the neck, jaw, trunk, and eyes and possibly the feet.
May be caused by;
 disease progresses beyond ability of Ldopa to control it.
 tolerance
Strategies to manage:
Infusion, sustained release, or multiple short interval doses of L-Dopa
Add selegiline to prevent metabolism by MAO-B.
Use receptor agonists
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14. Centrally Acting Anticholinergic Drugs:
(Benzhexol, procyclidine)
First drugs used was drugs like atropine but caused
intense anticholinergic effects so now classic ones are
obsolete.
Mechanism of action help control symptoms by blocking
access of ACh to receptors.
Therapeutic use less effective than levodopa but less
serious adverse effects; good for mild disease in young
patients; avoid in elderly.
Adverse effects peripheral and CNS effects.
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15. Drugs for epilepsy
Epilepsy :
Refers to group of disorders characterized by excessive excitability of
neurons within the CNS.
Seizure Generation—initiated by synchronous, high-frequency discharge
from group of hyperexcitable neurons (focus); symptoms depend on
location of focus.
Types of Seizures—Two Broad Categories
A. Partial (Focal) Seizures
1. Simple partial—No effect on consciousness
and may involve single limb
2. Complex partial—Impairment of consciousness, which may
be seen as confused or bizarre behaviour.
B.Generalized Seizures—May be convulsive or nonconvulsive. As a
general rule, they produce immediate loss of consciousness.
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16. How Antiseizure Drugs Work
Suppress discharge of neurons within a seizure focus and
suppress propagation of seizure activity from focus to other areas.
Suppression of Sodium Influx—Phenytoin, carbamazepine,
valproic acid, and lamotrigine reversibly bind to sodium channels.
Suppression of Calcium Influx—Valproic acid and ethosuximide
used for absence seizures by inhibiting influx of calcium through T-
type calcium channels
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Table 7. Drugs for specific types of seizures
Seizure Type Drugs used for treatment
Effective and well
tolerated
Effective but less
tolerated
Newer Alternatives
Partial Seizures
Simple Partial
Complex partial
Carbamazepine
Phenytoin
Valproic acid
Clorazepate
Phenobarbitone
Primidone
Gabapentin
Lamotrigine
Topiramate
Tiagabine
Same as simple partial Same as simple partial Same as simple partial
Generalized seizures
Tonic-clonic (grand mal) Carbamazepine
Phenytoin
Valproic acid
Phenobarbitone
Primidone
Lamotrigine
Topiramate
Absence (petit mal) Ethosuximide
Valproic acid
Clonazepam Lamotrigine
Myoclonic Valproic acid
Clonazepam -
Lamotrigine
Topiramate
Atonic Same as myoclonic - Same as myoclonic

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Action on Ion
Channels
Enhance GABA
Transmission
Inhibit EAA
Transmission
Na+:
Phenytoin, Carbamazepine,
Lamotrigine
Topiramate
Valproic acid
Ca++:
Ethosuximide
Valproic acid
Benzodiazepines
(diazepam, clonazepam)
Barbiturates (phenobarbital)
Valproic acid
Gabapentin
Vigabatrin
Topiramate
Felbamate
Felbamate
Topiramate
Na+:
For general tonic-clonic and
partial seizures
Ca++:
For Absence seizures
Most effective in myoclonic but
also in tonic-clonic and partial
Clonazepam: for Absence
Classification of Anticonvulsants by mechanism of action

19. Summary of Drug Treatment
Tonic-clonic, partial focal, or partial Complex seizure with and without
Secondary Generalization:
First line
Phenobarbitone, 60-180 mg/day P.O. in divided doses
 Only barbiturate with selective anticonvulsant effect.
Bind at allosteric site on GABA receptor, ↑ duration of opening of Cl channel.
↓ Ca-dependent release of neurotransmitters at high doses.
Inducer of microsomal enzymes – drug interactions.
S/Es: sedation, skin rash, decreased libido, confusion, ataxia
C/Is: acute intermittent porphyria
P/Caution: impaired renal or hepatic function, during pregnancy and lactation,
in the elderly.
Dosage forms: Tablet, 15mg, 30mg, 100mg; elixir, 20mg/5ml;
Injection (sodium), 25mg/ml, 100mg/ml,
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20. Alternatives
Phenytoin (Diphenylhydantion) 5 mg/kg/day, P.O. in single or divided doses. Maximum
dose is 400 mg/day; the usual maintenance dosage is 200-300 mg/day.
S/Es: gum hyperplasia, hirsutism, lymphadenopathy, facial coarsening, ataxia,
incoordination, and confusion
P/Caution: pregnancy, liver dysfunction, and lactation.
Dosage forms: Tablet, 50mg, 100mg; capsule, 50mg, 100mg; suspension, 30 mg/5ml;
powder for injection (sodium) 250 mg in vial.
OR
Carbamazepine, 600-1,800 mg/day P.O.. in 2 divided doses
S/Es: GI irritation, aplastic anaemia, hepatotoxicity, ataxia, dizziness, diplopia, vertigo
C/Is: hypersensitivity to tri-cyclic compounds, AV block
P/C: pregnancy, hepatic or renal impairment, lactation, severe CV disease
Dosage forms: Tablet, 100mg, 200mg; syrup, 100mg/5ml.
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23. When to discontinue therapy?
About 60% of adults who have their seizures completely controlled
with antiepileptic drugs can eventually discontinue therapy.
The following patient profile yields the greatest chance of
remaining seizure-free after drug withdrawal:.
complete medical control of seizures for 1 to 5 years;
single seizure type, either partial or generalized;
In most cases it is preferable to reduce the dose of the drug
gradually over 2 to 3 months.
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24. Antipsychotic Agents
(Drugs for schizophrenia)
Clinical presentation
Schizophrenia is a chronic psychotic illness characterized by
• Disordered thinking and
• Reduced ability to comprehend reality.
Etiology
Although there is strong evidence that schizophrenia has a
biologic basis, the exact etiology is unknown.
•Genetic, perinatal, neurodevelopmental, and
neuroanatomic factors may all be involved.
Possible primary defects include;
excessive activation of CNS receptors for dopamine, and
insufficient activation of CNS receptors for glutamate.
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25. Main clinical features of the disease are as follow.
Positive symptoms:
delusions (often paranoid in nature)
hallucinations, usually in the form of voices
thought disorder, irrational conclusions, abnormal
behaviours, such as stereotyped movements and occasionally
aggressive behaviours.
Negative symptoms:
withdrawal from social contacts
flattening of emotional responses.
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26. Conventional Antipsychotic Agents I: Group properties
Classification
•Can be classified by potency, generation or chemical
structure.
•From a clinical view point, classification by potency is
more helpful.
Classification by potency
• Conventional antipsychotic agents can be classified
as low potency, medium potency, or high potency
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Antipsychotic Drugs: Relative Potency and Incidence of Side Effects
Incidence of Side Effects
Drug
Equivalent
oral dose
(mg)
Extrapyramidal
effects
Sedation Orthostatic
hypotension
Anticholinergic
effects
Conventional
agents
Low potency
Chlorpromazine
Thioridazine
Moderate
potency
Triflupromazine
Perphenazine
Loxapine
High potency
Haloperidol
Fluphenazine
100
100
25
10
10
2
2
Moderate
Low
Moderate
Moderate
Moderate
High
High
High
High
High
Moderate
Moderate
Low
Low
High
High
Moderate
Low
Low
Low
Low
Moderate
High
Moderate
Low
Low
Low
Low
Atypical Agents
Clozapine
Risperidone
quetiapine
50
4
Very low
Very low
High
Low
Moderate
Low
High
None

28. Classification of antipsychotic drugs based on generation;
first-generation ('typical') antipsychotics (pre- 90s).
 Chlorpromazine, haloperidol, fluphenazine, flupenthixol,
second-generation ('atypical') antipsychotics (post 90s)
 clozapine, risperidone, quetiapine.
Distinction between typical and atypical groups is not
clearly defined but rests on:
incidence of extrapyramidal side effects (less in atypical group)
efficacy (specifically of clozapine) in 'treatment-resistant' group
efficacy against negative symptoms (2nd generations are best).
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29. Mechanism of action
• Suppress symptoms of psychosis by blocking dopamine (D2)
receptors in the mesolimbic area of the brain.
Therapeutic Uses;
Schizophrenia primary reason for antipsychotic drugs to
suppress symptoms (not cure) and help prevent relapse, also
for treatment of bipolar disorder, prevention of emesis,
dementia, and other organic mental syndromes.
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30. Summary of drug therapy for schizophrenia
A. Emergency phase
First line
Haloperidol, 5-10 mg I.M./I.V. over 30-60 minutes. Daily dose
may go as high as 40 mg.
Alternative
Chlorpromazine hydrochloride, 25 mg, I.M. and raise to 200 mg QD for acute
attacks
B. Stabilization phase
First line
Haloperidol, 1-15 mg/day P.O.
Alternative
Chlorpromazine, 75- 300 mg/ P.O. QD in divided doses.
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31. C. Maintenance (chronic therapy)
First line
Haloperidol, 1-15 mg/day P.O.
Alternatives
Chlorpromazine, 75- 300 mg/day P.O. QD. in divided doses.
OR
Fluphenazine decanoate, 12.5-100 mg IM every 3-4 weeks
Dosage forms: Injection, (Depot, Oily), 25mg/ml in 1ml ampoules
N.B.
After 6 months in remission the drug can be withdrawn for a trial
period to see if relapse occurs, at which point therapy is
instituted.
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32. Antidepressants:
 Used primarily to relieve symptoms of depression.
Clinical Features:
The principal symptoms are depressed mood and loss of
pleasure or interest in all or nearly all of one’s activities.
Pathogenesis:
Neurotrophic Hypothesis;
 brain derived neurotrophic factor (BDNF)
monoamine hypothesis of the depression;
 depression is caused by a functional insufficiency
of monoamine NTs (noradrenaline, serotonin, or
both).
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33. Treatment Modalities:
•Pharmacotherapy
•depression-specific psychotherapy
•electroconvulsive therapy
1. Tricyclic Antidepressants (TCAs)
 Amitryptiline, nortryptiline
 Imipramine, desipramine
 First-choice drugs
 Mechanism of Action—Block monoamine reuptake
 Pharmacokinetics—Long and variable half-lives; given in
single daily dose
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34. Therapeutic Uses:
1. Depression—Takes 1–3 weeks for initial responses
2. Bipolar disorder, chronic insomnia, attention-
deficit/hyperactivity disorders
3. Other uses—Chronic insomnia, ADHD, and panic disorder
Adverse Effects—Orthostatic hypotension is most
common; anticholinergic effects; diaphoresis;
sedation; cardiac toxicity is most serious; seizures.
2. Selective Serotonin Reuptake Inhibitors (SSRIs)—Effective as
TCA without hypotension, sedation, or anticholinergic effects;
overdose doesn’t cause cardiotoxicity
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35. Fluoxetine:
The most widely prescribed antidepressant since it is as
effective as TCAs, has fewer side effects, and is less dangerous;
but should be avoided taking with MAOIs.
•Mechanism of action—Selective inhibition of serotonin
reuptake to intensify transmission at serotonergic synapses;
produces CNS excitation rather than sedation.
•Therapeutic uses—For major depression, obsessive compulsive
disorder, and is not approved but used for panic disorder and
premenstrual syndrome with investigations into bulimia, alcohol
abuse, obesity, etc.
Other SSRIs—Others available: sertraline , fluvoxamine ,
paroxetine , Citalopram ; none should be combined with MAOIs
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Dose
mg/day
Drug
interaction
Half life Steady state
(Days)
Fluoxetine 5-20 high 2-4 days 30-60
Sertraline 50 low 26 Hrs 7-14
Paroxetime 20 high 20 Hrs 10-14
Citalopram 20-40 low 35 Hrs 7

37. Sedative-Hypnotic Drugs
Introduction—Anxiety and insomnia common complaints;
we can use same drugs with different dosages.
A. Drugs used for anxiety called “antianxiety agents” or
“anxiolytics” (old term was “tranquilizers”).
B. Drugs used for sleep known as “hypnotics”.
C. Historical Perspective—Barbiturates were used before
benzodiazepines.
Benzodiazepines—First choice for treating anxiety and
insomnia as they have fewer side effects compared to
barbiturates; most produce identical effects (Diazepam,
alprazolam and others).
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38. Molecular Mechanism of Action—Potentiates the actions
of gamma-aminobutyric acid (GABA), which is an inhibitory
neurotransmitter.
Therapeutic uses—Three major uses: anxiety, insomnia,
and seizure disorders; also for muscle spasm, ethanol
withdrawal, panic disorder, and anesthesia induction.
Adverse effects—CNS depression, anterograde amnesia,
paradoxical effects, respiratory depression, and low
incidence of abuse.
Tolerance and physical dependence—Little or no tolerance
with anxiolytic and hypnotic effects but significant
tolerance to antiseizure effects; dependence low, but most
common one is alprazolam ; discontinue gradually.
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39. Benzodiazepine-Like Drugs—zolpidem and zaleplon
A. Zolpidem —For short-term management of insomnia; binds
to GABA; plasma level peaks in 2 hours after oral dose with side
effects of daytime drowsiness and dizziness.
B. Zaleplon —New class of hypnotics; rapid onset, short
duration; helps for falling asleep but not for staying asleep.
Barbiturates—(Phenobarbitone, secobarbital, thiopental)
Nonselective depression of CNS; can be used for daytime sedation,
induction of sleep, suppression of seizures, and general anesthesia
-are powerful respiratory depressants that can be fatal
with over dosage.
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40. Summary of Drug treatment for anxiety:
First line
Diazepam, 2.5 mg, P.O. TID for not more than 4 weeks, 2-
10 mg IV for acute agitation
Alternative
Oxazepam, 15-30 mg P.O. 3-4 times daily
S/Es: drowsiness, fatigue, hypotension
C/Is: acute pulmonary insufficiency
Dosage forms: tablet, 10 mg
OR
Bromazepam, 1.5-3 mg tablet P.O. TID
Dosage forms: Tablet, 1.5 mg, 3 mg, 6mg
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41. Opioid (Narcotic) Analgesics
is any drug, natural or synthetic, with actions like morphine;
narcotic refers to opioids, cocaine, marijuana, and LSD.
enkephalins, endorphins, and dynorphins serve as
neurotransmitters.
Opioid Receptors—Mu (the most important), kappa, and delta.
1. Mu receptor- activation includes analgesia, respiratory
depression, euphoria ,miosis and constipation.
2. Kappa receptor- activation produces analgesia,
sedation, and dysphoria.
3. Delta receptors- are responsible for producing
spinal/supraspinal analgesia
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42.  Classification of Drugs That Act at Opioid Receptors
1. Pure opioid agonists—Activate mu and kappa and divided
into strong opioid agonists (morphine) and moderate-to-
strong opioid agonists (codeine).
2. Agonist-antagonist opioids—Five are available
(pentazocine, nalbuphine, butorphanol, dezocine,
and buprenorphine); when administered alone,
produce analgesia, but given to a person taking
opioids, produce an antagonistic effect.
3. Pure opioid antagonists-Naloxone, naltrexone
Antagonize mu and kappa receptors and are used for
reversal of respiratory and CNS depression.
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43. Basic Pharmacology of the Opioids
Morphine:
Produces analgesia, sedation, euphoria, respiratory depression,
cough suppression, and decreased bowel motility.
Mechanism of analgesic action—Mimics endogenous opioid
peptides (mu and kappa receptors).
Therapeutic use—Relief of pain (moderate to severe) for labor and
delivery, MI pain and dyspnea associated with LVF and pulmonary
edema, and preoperatively for sedation and anti-anxiety.
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44. Adverse effects—Respiratory depression, constipation,
orthostatic hypotension, urinary retention, cough suppression,
biliary colic caused by morphine, emesis, increased intracranial
pressure (ICP), euphoria/dysphoria, sedation, and miosis.
Abuse liability
Toxicity—Triad of signs: coma, respiratory depression and
pinpoint pupils—provide support and give antagonist
(naloxone).
Other Strong Opioid Agonists-pethidine , methadone,
levomethadyl, heroin, fentanyl (can be given parenterally,
transdermally, transmucosally, or as lozenges or lozenges on
a stick).
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45. Morphine-dose-10-15mg oral
Codeine-10-30mg to suppress cough
Tramadol-50-100mg oral/im/iv-analgesic
Pethidine-50-100mg im.,s.c- prefered analgesic during
labor
Pure opioid antagonist:
Naloxone –at 4-10mg dose it also antagonizes the action
of morphine
Is a drug of choice for morphine poisoning
For reversing neonatal asphyxia due to opioid use during
labor
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