Chapter 9

Drugs affecting The Central Nervous system

Chapter learning objectives:

 List CNS acting drugs available in Ethiopia
 Discuss the uses, general drug actions, general adverse reactions, C/Is, precautions, &
interactions associated with the administration of the CNS acting drugs
 Apply important pre-administration & ongoing assessment activities the nurse should
perform on the pt taking CNS acting drugs
 Demonstrate ways to promote an optimal response to therapy, how to manage common
ADRs, & important points to keep in mind when educating pts about the use of CNS acting
drugs

Chapter Outline:
 Anesthetic drugs  Anti-anxiety drugs  Narcotic (opioid)
 Sedative hypnotic  Antipsychotics analgesics
drugs  Antiepileptic drugs  CNS stimulants
 Antidepressants  AntiParkinson’s drugs  Drug dependence &
abuse

11.1 Anesthetic Agents

 Anesthetic agents depress the nervous system, causing a loss of consciousness (except for
local & regional anesthetic agents) &relieving pain.
 Anesthetic agents are classified as:
o General Anesthetic:
 General anaesthetic agents are employed as an adjunct to surgical procedures.
 They achieve a state of complete & reversible loss of consciousness in which the pt
is unaware of & unresponsive to painful stimuli
 Unlike local anaesthetics, general anaesthetics are given systemically.

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  They produce their effects by acting on the CNS, whilst maintaining the functioning
of other body systems such as the CV & respiratory systems
o Local Anesthetic:
 Block specific nerve pathways in a region & result in temporary analgesia &
paralysis but no loss of consciousness.
 Local anaesthesia is the method of choice for many minor surgical procedures.
 It is especially useful in pts suffering from severe cardiorespiratory disease who are
more susceptible to the risks of general anaesthesia

11.1.1 General Anesthetic agents

A. Four Stages of Anesthesia
 There are 4 stages of anesthesia that occur rapidly. These stages are:
o Stage I- Analgesia:
 The pt initially experiences analgesia without amnesia.
 Later in stage I, both analgesia & amnesia are produced
o Stage II- Excitement:
 During this stage, the pt appears delirious, may vocalize but is completely amnesic.
 Respiration is rapid, & HR & BP. Duration & severity of this light stage of
anesthesia is shortened by rapidly increasing the conc of the agent.
o Stage III- Surgical Anesthesia:
 This stage begins with slowing of respiration & HR & extends to complete
cessation of spontaneous respiration (apnea).
 Four planes of stage III are described based on changes in ocular movements, eye
reflexes, & pupil size, indicating increasing depth of anesthesia
o Stage IV- Medullary Paralysis:
 This deep stage of anesthesia represents severe depression of the CNS, including
the vasomotor center in the medulla & respiratory center in the brainstem.
 Without circulatory & respiratory support, death would rapidly ensue

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B. Commonly used IV anesthetic agents
 IV anesthetics are often used for the rapid induction of anesthesia, which is then
maintained with an appropriate inhalation agent.
 They rapidly induce anesthesia and must therefore be injected slowly.
 Recovery from IV anesthetics is due to redistribution from sites in the CNS
1) Barbiturates: Thiopental
o Potent anesthetic but a weak analgesic ultrashort-acting barbiturate Because
thiopental is slowly metabolized by the liver, toxic accumulation can occur.
o Thiopental has minor effects on the CV system, but it may contribute to severe
hypotension in pts with hypovolemia or shock
o All barbiturates can cause apnea, coughing, chest wall spasm, laryngospasm, &
bronchospasm. [Note: The latter is of particular concern for asthmatic pts.]
2) Benzodiazepines: Midazolam
o They are used in conjunction with anesthetics to sedate the pt
o Facilitate amnesia while causing sedation
3) Opioids
o B/c of their analgesic property, opioids are frequently used together with anesthetics.
o The most frequently employed opioids are fentanyl, sufentanil, & alfentanil
o B/c opioids rarely affect the CVS; they are particularly useful for cardiac surgery &
other high-risk cases.
o They are administered either intravenously, epidurally, or intrathecally
o Opioids are not good amnesics, & they can all cause hypotension, respiratory
depression, & muscle rigidity as well as post-anesthetic N & V
4) Ketamine
o a short-acting, non-barbiturate anesthetic, induces a dissociated state in which the pt
is unconscious but appears to be awake & does not feel pain
 This dissociative anesthesia provides sedation, amnesia, & immobility
o It also stimulates the central sympathetic outflow, which, in turn, causes stimulation
of the heart & increased BP & CO.

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  This property is especially beneficial in pts with either hypovolemic or
cardiogenic shock as well as in pts with asthma
 Ketamine is therefore used when circulatory depression is undesirable
o Ketamine is employed mainly in children & young adults for short procedures.
 However, it is not widely used, b/c it increases cerebral blood flow & induces
postoperative hallucinations, particularly in adults
5) Propofol
o Used in the induction or maintenance of anesthesia
o Onset is smooth and occurs within about 40 seconds of administration.
o Supplementation with narcotics for analgesia is required.
o Whereas it facilitates depression in the CNS, it is occasionally accompanied by
excitatory phenomena, such as muscle twitching, spontaneous movement, or hiccups
o It is widely used & has replaced thiopental as the first choice for anesthesia induction
& sedation, b/c it produces a euphoric feeling in the pt & does not cause post-
anesthetic N & V
o It very useful for such surgeries as resection of spinal tumors, in which
somatosensory evoked potentials are monitored to assess spinal cord functions
o Adverse effects
 Common: bradycardia, apnoea, hypotension, pain on injection
 Rare: anaphylaxis, convulsions, pulmonary oedema
6) Etomidate
o It is a hypnotic agent but lacks analgesic activity & used to induce anesthesia
o Induction is rapid, & the drug is short-acting
o It is only used for pts with coronary artery disease or CV dysfunction, such as shock
o Its adverse effects include a ↓in plasma cortisol & aldosterone levels, which can
persist for up to 8 hrs
C. Commonly used Inhalation anesthetics
 Types of inhalational anesthetics
o Volatile anesthetics: halothane, enflurane, isoflurane, desflurane, sevoflurane

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  Have low vapor pressures & thus high boiling points so that they are liquids at
room temperature (20 o C).
o Gaseous anesthetics: nitrous oxide, xenon
 Have high vapor pressures & low boiling points such that they are in gas form at
room temperature.
 Specific drugs inhalational anesthetics:
o Halothane:
 The 1st of the halogenated volatile anesthetics to be developed & halothane has
been largely replaced by more modern agents
 It is still used in pediatric population b/c of its pleasant odor & lack of
hepatotoxicity
 Like other halogenated hydrocarbons, halothane is vagomimetic & causes
atropine-sensitive bradycardia; produces concentration-dependent hypotension &
may cause malignant hyperthermia
o Enflurane:
 Less potent than halothane, but it produces rapid induction and recovery
 C/I in pts with kidney failure
 Enflurane anesthesia exhibits the following differences from halothane
anesthesia:
 Fewer arrhythmias, less sensitization of the heart to catecholamines, &
greater potentiation of muscle relaxants due to a more potent curare-like
effect
 A disadvantage of enflurane is that it causes CNS excitation, for this reason, it is
not used in pts with seizure disorders.
o Isoflurane:
 It is not tissue toxic
 Unlike the other halogenated anesthetic gases, isoflurane does not induce cardiac
arrhythmias and does not sensitize the heart to the action of catecholamines.
 However, it produces concentration-dependent hypotension due to peripheral
vasodilation

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  It also dilates the coronary vasculature, increasing coronary blood flow and
oxygen consumption by the myocardium.
 This property may make it beneficial in patients with ischemic heart disease
 All halogenated inhalation anesthetics have been reported to cause hepatitis, but
at a much lower incidence than with halothane
o Sevoflurane
 Has low pungency, allowing rapid uptake without irritating the airway during
induction, thus making it suitable for induction in children.
 It is replacing halothane for this purpose.
 Recovery is faster than with other anesthetics.
 It is metabolized by the liver, releasing fluoride ions; thus, like enflurane, it may
prove to be nephrotoxic.
o Nitrous oxide
 Potent analgesic but a weak general anesthetic, for example, nitrous oxide is
frequently employed at concentrations of 30 percent in combination with oxygen
for analgesia, particularly in dental surgery
 However, nitrous oxide at 80 percent (without adjunct agents) cannot produce
surgical anesthesia.
 It is therefore frequently combined with other, more potent agents to attain
pain-free anesthesia
 This anesthetic does not depress respiration, nor does it produce muscle
relaxation.
 Under the usual circumstances of co-administration with other anesthetics, it also
has moderate to no effect on the CVS or on increasing cerebral blood flow, & it
is the least hepatotoxic of the inhalation anesthetics.
 It is therefore probably the safest of these anesthetics, provided that at least
20 percent oxygen is always administered simultaneously
D. Clinical use of general anesthetics
 The neurophysiologic state produced by general anesthetics is characterized by five
primary effects: unconsciousness, amnesia, analgesia, inhibition of autonomic
reflexes, & skeletal muscle relaxation

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  None of the currently available anesthetic agents when used alone can achieve all five of
these desired effects. In addition, an ideal anesthetic drug should induce rapid, smooth
loss of consciousness, be rapidly reversible upon discontinuation, and possess a wide
margin of safety.
 The modern practice of anesthesiology relies on the use of combinations of intravenous
& inhaled drugs (balanced anesthesia techniques) to take advantage of the favorable
properties of each agent while minimizing their adverse effects.
 Anesthesia can be divided into three stages: induction, maintenance, and recovery.
o Induction is defined as the period of time from the onset of administration of the
anesthetic to the development of effective surgical anesthesia in the pt.
 Induction of anesthesia depends on how fast effective concentrations of the
anesthetic drug reach the brain
o Maintenance provides a sustained surgical anesthesia
o Recovery is the time from discontinuation of administration of the anesthesia until
consciousness & protective physiologic reflexes are regained.
 Recovery is the reverse of induction and depends on how fast the anesthetic drug
diffuses from the brain.
 The choice of anesthetic technique is determined by the type of diagnostic, therapeutic, or
surgical intervention to be performed
 For minor superficial surgery or for invasive diagnostic procedures, oral or parenteral
sedatives can be used in combination with local anesthetics, so called monitored
anesthesia care techniques
o These techniques provide profound analgesia, with retention of the pt’s ability to
maintain a patent airway & to respond to verbal commands
 For more extensive surgical procedures, anesthesia may begin with preoperative
benzodiazepines, be induced with an intravenous agent (eg, thiopental or propofol), & be
maintained with a combination of inhaled (eg, volatile agents, nitrous oxide) or IV (eg,
propofol, opioid analgesics) drugs, or both

11.1.2 Local Anesthesia

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  A local anesthetic agent blocks pain at the site where the medication is administered
 Used to render a specific portion of the body insensitive to pain
 Interfere with nerve impulse transmission to specific areas of the body
 Do not cause loss of consciousness
 It is used for: Suturing lacerations, Short-term localized surgery, Spinal anesthesia,
Diagnostic producers
 Local anesthetics includes: Procaine, Tetracaine, Bupivacaine, Lidocaine
a) Lidocaine
o Moderate-acting local anesthetic agent
o Systemically it is also indicated for cardiac arrhythmia management
o Side effects:
 CNS depression, convulsion & respiratory depression
 CV effects. Main toxic actions are in the heart.
 These may cause arrhythmias, ↓ed contraction, hypotension, CV collapse
o C/Is:
 Do not use a vasoconstrictor on appendages such as fingers, toes, earlobes, & penis
 Use with caution with cardiac pts
 Hypersensitivity to amide-type local anesthetics, arrhythmias,
o Caution: Dosage should be reduced for elderly, debilitated, acutely ill; safety in
children has not been established. Severe renal/hepatic disease, hypovolemia, CHF,
shock, heart block, marked hypoxia, severe respiratory depression, bradycardia,
incomplete heart block.
o Anesthetic solutions containing epinephrine should be used with caution in peripheral
or hypertensive vascular disease and during or following potent general anesthesia.
11.1.3 Anesthetic Agents & Nursing implications
 Always assess past history of surgeries and response to anesthesia
 Assess past history, allergies, medications
 Assess use of alcohol, illicit drugs, opioids
 Assessment is vital during pre-, intra-, and postoperative phases

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 o Vital signs, Baseline lab work, ECG, Pulse oximeter (PO2), ABCs (airway,
breathing, circulation), Monitor all body systems
 Close and frequent observation of the patient and all body systems
 During a procedure, monitor vital signs, ABCs
 Watch for sudden elevations in body temperature, which may indicate malignant
hyperthermia
 During recovery, monitor for CV depression, respiratory depression, and complications
of anesthesia
 Implement safety measures during recovery, especially if motor/sensory loss occurs due
to local anesthesia
 Reorient patient to his/her surroundings
 Provide preoperative teaching about the surgical procedure and anesthesia
 Teach the patient about postoperative turning, coughing, deep breathing
 If an Neuromuscular blocking agent is to be used for a procedure when the patient is to
be awake, teach the patient that he/she may be paralyzed but still able to hear and feel

11.2 Sedative hypnotic drugs

 Sedative versus Hypnotic
o Sedative:
 Depress the CNS to sedate or relax, producing a calming effect
 Referred to as tranquilizers
o Hypnotic:
 Depress the CNS enough to cause sleep
o Sedative-Hypnotic:
 Produce calming effect at lower dose & sleep at higher dose
A. Barbiturates:
 MOA: potentiate γ amino butric acid (GABA) action on chloride entry into the neuron by
prolonging the duration of the chloride channel openings
 Classification: Barbiturates are classified by duration of action. These are:
o Ultra short-acting barbiturates (e.g. thiopental Na)

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  Single doses have a duration of 20 minutes or less
o Short-acting barbiturates (e.g. Secobarbital, pentobarbital)
 The average duration of action of the short-acting barbiturates is 3 - 4 hrs
o Intermediate-acting barbiturates (e.g. amobarbital, aprobarbital & butabarbital
 The average duration of action of the intermediate-acting barbiturates is 6- 8 hrs
o Long-acting barbiturates (e.g. Phenobarbital, mephobarbital)
 The average duration of action of the long-acting barbiturates is 10 - 16 hrs
 Barbiturates action:
o Depression of CNS: At low doses, the barbiturates produce sedation (calming effect,
reducing excitement). At higher doses, the drugs cause hypnosis, followed by
anesthesia (loss of feeling or sensation), & finally, coma & death.
o Respiratory depression: Barbiturates suppress the hypoxic & chemoreceptor
response to CO2 & overdosage is followed by respiratory depression & death.
o Enzyme induction: Barbiturates induce P450 microsomal enzymes in the liver.
 Therapeutic uses of Barbiturates:
o Anesthesia: The ultra-short-acting barbiturates, such as thiopental, are used IV to
induce anesthesia.
o Anticonvulsant: Phenobarbital is used in long-term management of tonic-clonic
seizures, status epilepticus, & eclampsia. Phenobarbital has been regarded as the
DOC for treatment of young children with recurrent febrile seizures. However,
phenobarbital can depress cognitive performance in children, & the drug should be
used cautiously.
 Adverse effects:
o CNS: Barbiturates cause drowsiness, impaired concentration, & mental & physical
sluggishness. The CNS depressant effects of barbiturates synergize with those of
ethanol
o Drug hangover: Hypnotic doses of barbiturates produce a feeling of tiredness well
after the pt wakes. This drug hangover may lead to impaired ability to function
normally for many hours after waking. Occasionally, nausea & dizziness occur

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 o Physical dependence: Abrupt withdrawal from barbiturates may cause tremors,
anxiety, weakness, restlessness, N & V, seizures, delirium, & cardiac arrest.
Withdrawal is much more severe than that associated with opiates & can result in
death
B. Benzodiazepines:
 MOA: Potentate the effect of GABA by increasing the frequency of Cl channel opening
 Classifications:
o Short acting agents: e.g Triazolam
o Intermediate acting agents: e.g Alprazolam, Lorazepam, Oxazepam, Temazepam,
Chlordiazepoxide
o Long acting agents: e.g. Diazepam, Flurazepam
 Benzodiazepines actions:
o Reduction of anxiety: At low doses, they are anxiolytic
o Sedative & hypnotic actions: They are used to treat anxiety have some sedative
properties, & some can produce hypnosis at higher doses
o Anterograde amnesia: temporary impairment of memory. This also impairs a
person's ability to learn & form new memories.
o Anticonvulsant: Have anticonvulsant activity & some are used to treat epilepsy
(status epilepticus) & other seizure disorders.
o Muscle relaxant: At high doses, they relax the spasticity of skeletal muscle.
 Therapeutic uses of Benzodiazepines:
o Anxiety disorders: They are effective for the Tx of the anxiety symptoms secondary
to panic disorder, generalized anxiety disorder, social anxiety disorder, performance
anxiety, posttraumatic stress disorder, obsessive-compulsive disorder, & the extreme
anxiety sometimes encountered with specific phobias, such as fear of flying. They are
also useful in treating the anxiety that accompanies some forms of depression &
schizophrenia
o Muscular disorders: Diazepam is useful in the Tx of skeletal muscle spasms, such as
occur in muscle strain, & in treating spasticity from degenerative disorders, such as
multiple sclerosis & cerebral palsy

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 o Amnesia: The shorter-acting agents are often employed as premedication for anxiety-
provoking & unpleasant procedures, such as endoscopic, bronchoscopic, & certain
dental procedures as well as angioplasty. They also cause a form of conscious
sedation, allowing the person to be receptive to instructions during these procedures.
Midazolam is an injectable-only benzodiazepine also used for the induction of
anesthesia.
o Seizures: Clonazepam is occasionally used in the Tx of certain types of epilepsy,
whereas diazepam & lorazepam are the DOC in terminating grand mal epileptic
seizures & status epilepticus.
o Sleep disorders:. Commonly prescribed benzodiazepines for sleep disorders include
long-acting flurazepam , intermediate-acting temazepam , & short-acting triazolam
 Adverse effects of Benzodiazepines
o Drowsiness & confusion: most common adverse effects
o Dependence: Psychological & physical dependence on benzodiazepines can develop
if high doses of the drugs are given over a prolonged period. Abrupt discontinuation
of the benzodiazepines results in withdrawal symptoms, including confusion, anxiety,
agitation, restlessness, insomnia, tension, & rarely, seizures.
 Precautions:
o Benzodiazepines should be used cautiously in treating pts with liver disease.
o They should be avoided in pts with acute narrow-angle glaucoma.
o Alcohol & other CNS depressants enhance the sedative-hypnotic effects of the
benzodiazepines.
o Benzodiazepines are, however, considerably less dangerous than the older anxiolytic
& hypnotic drugs. As a result, a drug overdose is seldom lethal unless other central
depressants, such as alcohol, are taken concurrently.
C. Sedative hypnotic drugs: General Nursing Implications:
 Avoid alcohol consumption (CNS depressant)
 Avoid 1st generation antihistamines & other CNS depressants
 Avoid Caffeine & caffeinated foods (CNS stimulant)
 C/I in pregnancy & lactation

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  Avoid dangerous activities & driving until effects have been established
 Avoid abrupt withdrawal (can cause withdrawal symptoms after prolonged use)
 Follow Liver & Renal Function tests
 Watch for CNS effects including increased sedation, dizziness, confusion, hallucinations
 Can suppress respiratory center in brain
 Death can result from overdose
 Keep medication out of reach of children

11.3 Antidepressants
 Depression is one of the most common psychiatric disorders. It is characterized by
feelings of intense sadness, helplessness, worthlessness, and impaired functioning.
Those experiencing a major depressive episode exhibit physical and psychological
symptom, such as appetite disturbances, sleep disturbances, and loss of interest in job,
family, and other activities usually enjoyed.
 Antidepressant drugs are used to manage depressive episodes such as major depression
or depression accompanied by anxiety
 Classification of antidepressants
o Tricyclic antidepressants (TCAs):
 Sedating: amitriptyline, clomipramine, doxepin, etc
 Less-sedating: imipramine, nortriptyline etc
o Selective serotonin reuptake inhibitors (SSRIs): citalopram, fluoxetine,
fluvoxamine, paroxetine, sertraline
o Others:
 Monoamine oxidase inhibitors (MAOIs): isocarboxazid, phenelzine
 Mirtazipine, nefazadone, venlafaxine
 Indications:
o SSRIs: Major depressive disorder, Anxiety disorders, Bulimia nervosa
o TCAs: Depression , Chronic pain (as an adjunct)
 Adverse effects of SSRIs & TCAs:

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 a) SSRIs:
 Non-Serious: Sexual dysfunction, GI distress, Agitation, insomnia
 Serious: Serotonin syndrome (SS) is a rare but potentially life-threatening
elevation in serotonin, most commonly caused by concomitant use of SSRIs &
MAOIs. Symptoms include: Hyperthermia, Muscle rigidity, Myoclonus , Rapid
fluctuations in vital signs (because of autonomic instability) , Rapid fluctuations
in mental status (confusion, irritability, extreme agitation, delirium, coma)
b) TCAs:
 Anticholinergic: Dry mouth, Confusion, Urinary retention, Constipation ,
Blurred vision, Increased intraocular pressure (IOP)
 Sedation: via blockade of histamine (H1) receptors
 Serious: CV toxicities are typically only seen when high doses are administered.
In high doses TCAs impair cardiac conduction, leading to a widening of the QRS
complex and heart block, often accompanied by hypotension
 Orthostatic hypotension: related to blockade of α1 receptors
 Antidepressant drugs: Nursing implication
o Caution client to rise slowly to reduce the effects of orthostatic hypotension
o Take antidepressant with food to enhance absorption
o Explain to client that full response may take several weeks (4 weeks)
o Antidepressants should be withdrawn gradually. Sudden withdrawal may preciptate
GI symptoms, insomnia, headaches or restlessness. SSRIs in particular have been
associated with withdrawal symptoms
o Assess client for constipation resulting from tricyclic antidepressant use
o Client taking MAO inhibitors should avoid tyramine-rich foods to avoid hypertensive
crisis
 Aged cheese, sour cream, yogurt, beer, wine, chocolate, soy sauce and yeast
o Inform physician and withhold fluoxetine if client develop rashes.

11.4 Anti-anxiety Agents

 Anxiety is a feeling of apprehension, worry, or uneasiness that may or may not be
based on reality.

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  Anxiety may be seen in many types of situations, ranging from the anxiety that may
accompany one’s employment to the acute anxiety that may be seen during withdrawal
from alcohol.
 Although a certain amount of anxiety is normal, excess anxiety interferes with day-to-
day functioning & can cause undue stress in the lives of certain individuals.
 Drugs used to treat anxiety are called antianxiety drugs.
 Another term that refers to the antianxiety drugs is anxiolytics.
 Types of antianxiety agents
o Antidepressants
 The most widely used antidepressants with anxiolytic properties are the SSRIs
o Benzodiazepines: eg. diazepam
o β -adrenoceptor antagonists (e.g. propranolol):
 They are used to treat some forms of anxiety, where physical symptoms
(sweating, tremor, and tachycardia), are troublesome

11.5 Antipsychotic Agents

 Psychotic illness is characterized by delusion, hallucinations, thought disorder, social
withdrawal and flattering of emotional response.
 Antipsychotics are a group of drugs used mainly for treating schizophrenia.
 Antipsychotic agents are classified into:
o Typical neuroleptics/ First-Generation Antipsychotics (chlorpromazine, thioridazine,
haloperidol, etc)
o Atypical neurolopitics/Second-Generation Antipsychotics (clozapine, Risperidone,
olanazapine etc).
 Most antipsychotic drugs are readily but incompletely absorbed.
 Many of these drugs undergo significant first-pass metabolism.
 Very little of any of these drugs is excreted unchanged, as they are almost
completely metabolized to more polar substances.
 The phenothiazine antipsychotic drugs, with chlorpromazine as the prototype, have
a wide variety of central nervous system, autonomic, and endocrine effects.

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  It blocks receptors including; dopamine and alpha-adrenoceptor, muscarinic, H1
histaminic, and serotonin (5-HT2) receptors.
 Clinical uses
 Schizophrenia, Mania, Vomiting
 Adverse Reactions
 Extrapyramidal reactions
 Autonomic nervous system effects (antimuscarinic effects, orthostatic hypotension)
 Metabolic and Endocrine Effects (weight gain, hyperprolactinemia, infertility, loss
of libido and impotence)
 Nursing considerations
 Teach family members the signs of EPS and NMS, and report to physician
immediately
 Normalization of symptoms may not occur for several weeks after beginning of
therapy
 Watch out for orthostatic hypotension and photosensitivity with phenothiazine like
CPZ
 Be sure that oral doses are swallowed, and not hoarded.
6. 1. Antiepileptic Drugs
 Seizure is associated with the episodic high frequency discharge of impulses by a
group of neurons in the brain.
 Seizure may be partial or generalized depending on the location and the spread of the
abnormal neuronal discharge. The attack mainly involves motor, sensory or behavioral
phenomena.
 Partial seizures are often associated with damage to the brain, whereas generalized
seizure occurs without obvious cause. Two common forms of generalized seizures are
grand mal and petit mal.
 Mechanism of action
 Anticonvulsant drugs act by two mechanisms: by reducing electrical excitability of
cell membrane and by enhancing GABA mediated synaptic transmission.

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  The main drugs used in the treatment of epilepsy are phenytoin, carbamazepine,
valproate, ethosuximide and phenobarbitone.
A. Phenytoin
 It is commonly used antiepileptic drug.
 It is effective against different forms of partial and generalized seizures; however it is
not effective in absence seizures.
 Well absorbed when given orally.
 It is metabolised by the liver. It is liver enzyme inducer and therefore, increases the
rate of metabolism of other drugs.
 Main side effects are sedation, confusion, gum hyperplasia, skin rash, anaemia,
nystagmus, and diplopia.
B. Carbamazepine
 It is derived from tricyclic antidepressant.
 Its pharmacological action resembles those of phenytoin, however, it is chiefly
effective in the treatment of partial seizure.
 It is also used in the treatment of trigeminal neuralgia and manic-depressive illness.
 It is powerful inducer of liver microsomal enzymes, thus accelerates the metabolism of
phenytoin, warfarin, oral contraceptives and corticosteroids.
 Carbamazepine causes sedation, mental disturbances and water retention.
C. Valproate
 Valproate is chemically unrelated to the other antiepileptic drugs.
 It is used in grand mal, partial, petit mal and myoclonic seizure.
 Relatively has few side effects, however, it is potentially hepatotoxic. It is non
sedating.
D. Ethosuximide
 Has fewer side effects and used in the treatment of absence seizures.
E. Phenobarbitone
 The clinical use of phenobarbitone is nearly the same as that of phenytoin. The most
important unwanted effect is sedation.
F. Benzodiazepines

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  Clonazepam and related compounds are claimed to be relatively selective as
antiepileptic drugs.
 Sedation is the main side effect of these compounds, and an added problem may be
the withdrawal syndrome, which results in an exacerbation of seizures if the drug is
stopped.
 Nursing considerations & antiepileptic drugs
 Advise female clients to use contraceptives
 Inform clients taking phenytoin that harmless urine discoloration is common
 Warn clients with diabetes that phenytoin may increase blood sugar level
 Reassure that barbiturates are not addictive at a low dosage
 Avoid taking alcohol with barbiturates
 Administer paranteral Fosphenytoin slowly to avoid cardiotoxicity
 Avoid mixing other drugs in same syringe with Fosphenytoin.
6. 2. AntiParkinson’s drugs
 Parkinsonism: Parkinsonism is characterized by a combination of rigidity, bradykinesia,
tremor, and postural instability.
 It is due to the imbalance between the cholinergic and dopaminergic influences on the
basal ganglia.
 Thus, the aim of the treatment is either to increase dopaminergic activity (by dopamine
agonist) or to decrease cholinegic (antimuscarinic drugs) influence on the basal ganglia.
A. Levodopa
 Levodopa, the immediate metabolic precursor of dopamine, does penetrate the blood
brain barrier, where it is decarboxylated to dopamine.
 Levodopa is rapidly absorbed from the small intestine. Food will delay the appearance
of levodopa in the plasma.
 It is extensively metabolized by peripheral dopa decarboxylase, hence given in
combination with carbidopa, a peripheral dopa decarboxylase inhibitor.
 When levodopa is given without carbidopa it causes vomiting (which is due to
stimulation of emetic center to dopamine) and CVS disorder (tachycardia, ventricular

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 extrasystoles, atrial fibrillation and due to increased catecholamine formation
peripherally).
 Nursing considerations:
 Give dopaminergic agents after meals to reduce GI symptoms
 Reassure client that levodopa may cause harmless darkening of urine and sweat.
 Change positions slowly to avoid orthostatic hypotension
 Elevate leg to reduce ankle edema.
B. Dopamine agonists
 The enzymes responsible for synthesizing dopamine are depleted in the brains of
Parkinsonism patients, and drugs acting directly on dopamine receptors may therefore
have a beneficial effect additional to that of levodopa.
 There are a number of dopamine agonists with antiparkinsonism activity.
 e.g: Bromocryptine
C. Monoamine Oxidase Inhibitors
 Selegiline is a selective inhibitor of monoamine oxidase B, hinders the breakdown of
dopamine; as a result, it prolongs the antiparkinsonism effect of levodopa.
 Selegiline has only a minor therapeutic effect on parkinsonism when given alone. It
may reduce disease progression.
D. Amantadine
 Amantadine, an antiviral agent, was by chance found to have antiparkinsonism
properties.
 Its mode of action in parkinsonism is unclear, but it may potentiate dopaminergic
function by influencing the synthesis, release, or reuptake of dopamine.
E. Acetylcholine Blocking Drugs (Benztropine, Trihexyphenidyl)
 A number of centrally acting antimuscarinic preparations are available that differ in
their potency and in their efficacy in different patients.
 Treatment is started with a low dose of one of the drugs in this category, the level of
medication gradually being increased until benefit occurs or adverse effects limit
further increments.
 Antimuscarinic drugs may improve the tremor and rigidity of Parkinsonism but have
little effect on bradykinesia.
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6. 3. Narcotic (opioid) analgesics
 Opioid is any substance that can produce morphine like effects.
 Opium is an extract of the juice of the poppy Papaver somniferum.
 Opium contains many alkaloids related to morphine.
 Morphine analogues
 Compounds closely related in structure to morphine.
 They may be agonist (codeine and heroin), partial agonists (nalorphine) or
antagonists (naloxone).
 Synthetic derivatives
 Pethidine, fentanyl, methadone, pentazocine, etc
 Opioid receptors
 Three receptors mediate the main pharmacological effects of opiates.
 Mu receptors are responsible for the analgesic and major unwanted effects
(respiratory depression, sedation and dependance).
 Delta for analgesia and peripheral effects of opiates and kappa contribute to
analgesia at spinal level and dysphoria.
 Agonists and antagonists of opioid receptors
 Pure agonists
o They all have high affinity to mu receptors and varying affinity to delta and
kappa receptors (codeine, methadone, dextropropoxyphene).
 Partial antagonists and mixed agonist-antagonists: Nalorphine, &
pentazocine.
 Clinical use of opioid analgesics
 Opioids are used in severe, constant pain, acute pulmonary edema (pulmonary
edema associated with left ventricular failure), cough suppression, diarrhea, and
preanaesthetic medication.

6. 4. CNS stimulants
 As compared to CNS depressants the stimulants of the CNS are therapeutically not so
useful as they lack selectivity of action.

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  Further, excessive stimulation of CNS is followed by its depression
 CNS stimulant can be classified into
 Convulsants and respiratory stimulants eg. Srychnine picrotoxin, nikethaimide
 Psychomotor stimulants Eg. Amphetamine, cocaine, caffeine
 Psychotomimetic drug Eg. Lysergic and diethylamide (LSD) psilocybin,
phencyclidine.
a) Convlsants and respiratory stimulants
 These are diverse group or drugs and have little clinical use.
 Certain short acting respiratory stimulants like doxapram, amiphenazole can be
used in respiratory failure.
 Strychnine, picrotoxin and leptazole are used as chemical tools in experimental
pharmacology in various animal models.
b) Psychomotor stimulants
 Drugs like amphetamine cause increased motor activity, euphoria, excitement and
anorexia due to release of noradrerline and dopamine.
 Clinical uses
o Amphaetamine is useful in the treatment of narcolepsy and attention deficit
in children.
o Cocaine is occasionally used as a local aneasthetic, mainly in
ophthalmology and minor nose and throat surgery.
 Khat is another drug that belongs to this group and it is a major drug of abuse in
Ethiopia.
 As drugs of abuse amphetamine khat and cocaine produce strong psychological
dependence and carry a high risk of adverse reactions.
c) Psycho mimetic drugs
 Drugs like LSD, phencyclidine and psilocybin cause sensory changes,
hallucinations and delusions, resembling symptoms of acute schizophrenia. They
are not used clinically but are important as drugs of abuse.
6. 5. Drug dependence and drug abuse
 There are many drugs that human beings consume because they choose to, and not
because they are advised to by physicians.

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 Society in general disapproves, because in most cases there is a social cost; for certain
drugs, this is judged to out-weigh the individual benefit and their use is banned in many
countries.
:The main drugs of abuse are given the following table
Type Example Dependence liability
Narcotic analgesics Morphine very strong
CNS depressants Ethanol strong
Barbiturates strong
Anxiolytic drugs Benzodiazepines moderate
Psychomotor stimulants Amphetamine strong
Cocaine very strong
Nicotine very strong
Caffeine weak

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