CNS STIMULANTS

AND DEPRESSANTS

karen icamina, m.d.

Cns stimulants

INTRODUCTION
Increases overall activity of the CNS
Physiologic effects: inc HR, BP, Temp, RR
Psychologic effects: dec fatigue,inc alertness,
irritability, paranoia, hallucinations
May also interfere with sleep patterns,
suppress appetite, interfere with motor
control
Effects similar to SYMPATHETIC NS activation

stimulants
Analeptic Respiratory stimulants
Amphetamine
Xanthine derivatives
Anorectic Agents
Stimulants for ADD

AMPHETAMINES
Stimulate the release of norepinephrine and
dopamine
Causes euphoria and allertness, sleeplessness,
tremors and irritability
Cardiovascular problem: inc HR, palpitation,
dysrhythmias, inc BP
T = 4 to 30 hours
Dec the urine pH aids in the excretion

AMPHETAMINES
Uses:
Narcolepsy, ADHD
Asthma and nasal decongestion
Weight loss aid

Amphethamine-like
drugs
Methylphenidate
Dexmethylphendate
Pemoline
Modafinil
Atomoxetine

ANOREXIANTS
Appetite suppressants
Primarily indicated for temporary adjunctive
management of obesity
Irritability, nervousness, palpitations, insomnia
Not recommended because of tolerance,
psychologic dependence, abuse
Phenylpropanolamine has been removed form OTC wt
loss drugs and cold remedies

ANORECTIC AGENTS
Benzphetamine HCL
Dextroamphetamine sulfate
Diethylpropion HCl
Phentermine HCl

ANALEPTICS
Cns stimulants affecting the brainstem and spinal
cord and cerebral cortex
Primary use is to stimulate respiration
antagonizes respiratory depression
Example:
Doxapram HCH
xanthines and methylxanthine

Caffeine
Theophylline

RESPIRATORY STIMULANT
DOXAPRAM use/reversal of post anesthetic
repiratory depression or apnea
Also stimulate other centers causing CV stimulation,
vomiting, hyperreflexia
Has a narrow safety margin
Close monitoring and observation

CNS
DEPRESSANTS

Sedative hypnotics
The mildest form of CNS depression is sedation
Increasing the drug dose produces hypnotic
effect
With very high dose of sedative hypnotics,
anesthesia may be achieved
Categories:
BARBITURATES
BENZODIAZEPINE
NONBENZODIAZEPINE
PIPERIDINEDIONES

BARBITURATES
LONG ACTING: phenobarbital and mephobarbital
used to control seizures in epilepsy
INTERMEDIATE ACTING: amobarbital, aprobarbital,
butabarbital used to maintain long periods of sleep
SHORT ACTING: secobarbital, pentobarbital used to
induce sleep

BARBITURATES
ULTRASHORT ACTING: thiopental sodium is used as
anesthetics
barbiturates should be restricted to short term use
(2 weeks) because of side effects and tolerance

BENZODIAZEPINES
Minor tranquilizer or anxiolytic
Marketed as hypnotics: flurazepam, temazepam,
triazolam, estazolam, quazepam
Anxiolytics: lorazepam, diazepam

BENZODIAZEPINES
Increase the action of the inhibitory
neurotransmitter gamma-aminobutyric acid (GABA)
to the GABA receptors
Can suppress stage 4 of NREM sleep vivid dream
or nightmares, can delay REM sleep
Effective for sleep disorder but should not be used
for > 3 to 4 weeks

BENZODIAZEPINES
Well-absorbed in the GI mucosa
Has a rapid onset of action and intermediate to
long acting effects
Half the dose is recommended for older adults
Aclohol or narcotics may cause additive CNS
response

NONBENZODIAZEPINES
ZOLPIDEM
Used for short term treatment of insomnia (less than
10 days)
Duration of action is 6 to 8 hours with a short half life
of 2-2.5 hours
Metabolized in the liver to 3 inactive metabolites
Excreted in the bile, urine, feces

PIPERIDINEDIONES
GLUTETHIMIDE
Resemble barbiturates
Marketed to be nonaddictive but can be addictive
and cause severe adverse reactions such as
vasomotor colllapse, serious blood dyscrasia and
allergies
Rarely used nowadays

anesthetics
Local
Lidocaine, Xylocaine

General depress the CNS, alleviate pain and cause

loss of consciousness
First anesthetics:
Nitrious Oxide laughing gas
Chloroform

BALANCED ANESTHESIA
Combination of drugs
hypnotic given the night before
Premedication: narcotic analgesic or benzodiazepine
and an anticholinergic
Short-acting barbiturate: thiopental
Inhaled gas: nitrous oxide and oxygen
Muscle relaxant as needed

Inhalation anesthetics
Nitrous oxide
Cyclopropane
Methoxyflurane
Enflurane
Isoflurane
Desflurane
Sevoflurane
Absorbed quickly, rapid action, eliminated rapidly
Side fx: respi depression, hypotension, dysrhythmias, hepatic
dysfunction

INTRAVENOUS
ANESTHETICS
Thiopental Sodium
Droperidol
Etomidate
Ketamine HCl
Propofol
Rapid onset, short duration of action
Adverse Fx: repiratory and cardiovascular
depression

TOPICAL
ANESTHETICS
Limited to mucous membrane, broken or unbroken
skin surfaces, burns
Forms: solution, liquid spray, ointment, cream, gel
These agents decrease the sensitive nerve ending
of the affected area

LOCAL ANESTHETICS
Block pain at the site where the drug is
administered, allowing consciousness to be
maintained
Dental procedures, suturing of skin
and other minorprocedures, prior
anesthesia insertion
Cocaine HCl
Procaine HCl
Lidocaine HCl

laceration
to spinal

SPINAL ANESTHESIA
Local anesthesia that is injected in the
subarachnoid space at the L3 or L4 space
Side Fx: respiraotry distress, respiratory failure,
hypotension, spinal headache
Other sites in the spinal column can be used: spinal
block, epidural block, saddle block, caudal block

ANTICONVULSANTS

Anti convulsants
Drugs used for epileptic seizures
Suppress the abnormal electric impulses from the
seizure focus to other cortical areas thus
preventing seizure but not eliminating the cause of
seizure
Classified as CNS depressants

action of anticonvulsants
By suppressing Na influx thru the drug binding to the
Na channel when it is inactivated, thus prolonging
the channel inactivation and preventing neuron firing
Phenytoin
Fosphenytoin
Carbamazepine
Oxcarbazepine
Valproic acid
Topiramate
Zonisamide
Lamotrigine

action of anticonvulsants
By suppressing the Ca influx thus preventing the
electric current generated by the Ca ions to the T
calcium channel
Valproic acid
Ethosuximide

action of anticonvulsants
By increasing the action of GABA which inhibits
neurotransmitter throughout the brain
Barbiturates
Benzodiazepine
Tiagabine
Newer agents:
Gabapentin- promote GABA release
Vigabatrin- inhibits degradation of GABA

HYDANTOINS
o the 1st anticonvulsant used is PHENYTOIN (Dilantin)
o Less toxic effects, small effect on general sedation,
non addicting
o Teratogenic
o Pharmacokinetics:slowly absorbed from the small
intestines, highly protein bound, t = 22 hours,
excreted in the kidneys

HYDANTOINSPhenytoin

Pharmacodynamics: onset of action in 30 min to 2

hours, peak serum concentration in 1.5 to 3 hours,
steady state of serum concentration in 7 to 10 days
Side effects: gingival hyperplasia, slurred speech,
confusion, depression, thrombocytopenia, leukopenia
Others: nausea, vomiting, constipation, drowsiness,
headache, alopecia, hirsutism, nystagmus

BARBITURATES
Phenobarbital
Long acting barbiturate
Used to treat Grand Mal Seizures and acute episodes
of status epilepticus, meningitis, toxic reaction and
eclampsia
Side effect: general sedation and tolerance
Discontinuance should be gradual to avoid recurrence
of seizure

SUCCINIMIDES
Used to treat petit mal seizures
May be used in combination with other anticonvulsants
EXAMPLE

Ethosuximide
Methsuximide
Pensuximide

OXAZOLIDONES/
OXAZOLIDINEDIONE
Used to treat petit mal seizure
Used alone or
anticonvulsants
EXAMPLE

Trimethadione
Paramethadione

in

combination

with

other

BENZODIAZEPINES
Clonazepam
Effective in controlling petit mal or absence seizures

Clorazepate dipotassium
Anjunct therapy in treating partial seizure

Diazepam
Used for treating acute status epilepticus

IMINOSTILBENES
CARBAMAZEPINE used in treating refractory
seizure d/o that have not responded to other
anticonvulsant therapies
Used to control grand mal and partial seizures and a
combination of these seizures
Also used for bipolar d/o, trigeminal neuralgia and
alcohol withdrawal

VALPROATE
Valproic acid used for petit mal, grand mal and
mixed types of seizure
Hepatotoxic
Start at low dosage and gradually increase over a
period of weeks until the serum drug level is within
therapeutic range

READ ON:
DRUGS USED TO TREAT THE FFPARKONSINISM, ALZHEIMERS DSE,
MYASTHENIA GRAVIS,
MULTIPLE SCLEROSIS, MUSCLE SPASMS

Antipsychotics/
anxiolytics

ANTIPSYCHOTICS
Typical
Phenothiazines
Nonphenothiazines
Butyrophenones
Dibenzoxazepine
Dihydroindolones
thioxanthenes

Atypical
clozapine

ANTIPSYCHOTICS
MOA:
Block the actions of dopamine dopaminergic
antagonists
Block the D2 receptor as well causing the EPS
causing pseudoparkinsonism
Atypical antipsychotics exhibit weak affinity for D2
receptors and stronger affinity to D4 receptors thus
blocking the serotonin receptor
Fewer EPS than typical antipsychotic

EXTRAPYRAMIDAL SYMPTOMS
Pseudoparkinsonism

Stooped posture
Masklike facies
Rigidity
Tremors at rest
Shuffling gait
Pill-rollin motion of the hand
bradykinesia

PHENOTHIAZINES
3 GROUPS
Aliphatic phenothiazines
Produces strong sedative effect, dec BP, cause moderate
EPS
Chlorpromazine (Thorazine)

Piperazine phenothiazine
Low sedative and strong antiemetic effect, little effect on
BP, cause more EPS
Fluphenazine and Perphenazine

Piperidine phenothiazine
More sedative effect, few EPS, low to moderate effect on
BP
Thioridazine and Mesoridazine

NONPHENOTHIAZINES
Butyrophenones
Dibenzoxazepines
Dihydroindolone
thioxanthene

Butyrophenones
Haloperidol (Haldol)

Very potent
Absorbed well through the GI mucosa
Has a long T
Highly protein bound
Metabolized in the liver, excreted in the kidneys
Alters the effects of dopamine receptors sedation
and EPS
Used for psychoses and dec signs of agitation

Dibenzoxazepines
Is a moderate potent agent
Moderate sedative and orthostatic hypotensive
effects
Strong EPS effects

Dihydroindolone
Molindone Hydrochloric acid
Has a low sedative and orthostatic hypotensive
effects
Stong EPS effects

thioxanthene
Thiothixene
Highly potent
Low sedative and othostatic hypotensive effects
Strong EPS effects

Atypical antipsychotics
Are effective in treating both the positive and
negative symptoms of schizoprenia
Are not likely to cause EPS or tardive dyskinesia
DRUGS:

Clozapine
Risperidone
Olanzapine
Quetiapine

anxiolytics
Antianxiety drugs treats anxiety and insomnia
Benzodiazepine
more effective than barbiturates bec they enhance
the action of GABA, an inhibitory neurotransmitter
within the CNS
Fewer side effects, less dangerous in overdosing
Long term use causes drug tolerance and dependence

anxiolytics
Certain amount of anxiety may make one more
alert and energetic but when excessive an
anxiolytic may be prescribed
Action resembles that of the sedative hypnotics but
not that of the antipsychotics

BENZODIAZEPINES
Multiple uses: anticonvulsants, sedative-hypnotics,
preoperative drugs, anxiolytics
Example:

Chlordiazepoxide
Diazepam
Clorazepate dipotassium
Lorazepam
Alprazolam
Prazepam
Halazepam

BENZODIAZEPINES
Lipid soluble and absorbed readily from the GI
tract
Highly protein bound
Metabolized in the liver
Excreted in the urine
Side fxs: sedation, dizziness, headaches, dry
mouth, blurred vision, rare urinary incontinence,
constipation
Adverse Rxn:
dependency

leukopenia,

tolerance,

drug

BENZODIAZEPINES
Should not be abruptly discontinued because
withdrawal symptoms are likely to occur
Agitation, nervousness, insomnia, tremor, anorexia,
muscular cramps, sweating
Slow to develop ~ 2 to 10 days
Gradually decreased over a period of days
Withdrawal symptoms from long term use:
paranoia, delirium, panic, hypertension, convulsion

MOOD
STABILIZERS/
ANTI
DEPRESSANTS

ANTIDEPRESSANTS
4 GROUPS

Tricyclics (TCAs)
Selective Serotonin Reuptake
Inhibitors(SSRIs)
Atypical antidepressants that affects
neurotransmitters
Monoamine oxidase inhibitors (MAOIs)

TCA
Used to treat major depression
IMIPRAMINE- 1st drug
Block the uptake of the neurotransmitters
Norepinephrine and Serotonin in the brain
Clinical response after 2 to 4 weeks
Elevates mood, increases interest in daily living
and activity, decrease insomnia

TCA
Amitriptyline
Doxepin
Trimipramine
Given at night to minimize the problems caused
by their sedative action
Side fx: orthostatic hypotension, sedation,
anticholinergic effects, cardiac toxicity and
seizures
Others: allergic rxn, sexual dysfunction, blood
dyscrasia

TCA
Drug interaction:
Alcohol, sedatives and barbiturates potentiates
CNS depression
Concurrent use of MAOIs with amitryptiline may
lead to cardiovascular instability and toxic
psychosis
Antianthyroid meds may increase the risk of
dysrhythmia

SELECTIVE SEROTONIN REUPTAKE

INHIBITORS
Block the reuptake of serotonin into the nerve
terminal of the CNS thereby enhancing its
transmission at the serotonergic synapse
Do not block the uptake of dopamine or NE
Do not block cholinergic and alpha adrenergic
receptors

SELECTIVE SEROTONIN REUPTAKE

INHIBITORS
Primary use is for major depressive d/o
Effective for treating anxiety d/o such as
obsessive-compulsive,
panic,
phobia,
post
traumatic stress d/o and other forms of anxiety
Side Fx: dry mouth, blurred vision, insomina,
headache, nervousness, anorexia, nausea, diarrhea
and suicidal ideation

SELECTIVE SEROTONIN REUPTAKE

INHIBITORS
Fluoxetine (Prozac)
Fluvoxamine
Sertraline (Zoloft) most commonly prescribed
Paroxetine
Citalopram
Escitalopram

ATYPICAL
ANTIDEPRESSANTS
2ND gen antidepressants
Affect 1 or 2 of the 3 neurotransmitters: serotonin, NE

Amoxapine

Bupropion

Maprotiline

Nefazodone

Trazodone

Mirtazapine

Venlafaxine

Reboxetine

ATYPICAL
ANTIDEPRESSANTS
Not taken with MAOIs and should not be used within
14 days after discontinuing MAOIs

MONOAMINE OXIDASE INHIBITORS

(MAOI)
This enzyme (MAO) inactivates NE, dopamine,
epinephrine and serotonin inhibition of MAO = inc
levels of these neurotransmitters
Tranylcypromine sulfate
Isocarboxazid
Phenelzine sulfate

MONOAMINE OXIDASE INHIBITORS

(MAOI)
Effective in treating depression but limited use bec
of adverse rxns
Prescribed only when the client does not respond to
TCAs or 2nd gen antidepressants
Side Fx: CNS stimulation (agitation, restlessness),
orthostatic hypotension and anticholinergic effects

MOOD STABILIZER
Lithium for Bipolar d/o (manic phase)
Narrow therapeutic range
(> 1.5 to 2 mEq/L are toxic) serum levels
monitored biweekly,including serum Na
95% is absorbed in the GI tract;metabolized in the
liver, excreted unchanged in the urine
T = 24-36 hrs

MOOD STABILIZER
Onset of axn is fast but the desired effect may be
observed after 5 to 6 days
Side Fx: dry mouth, thirst, inc urination, wt gain,
bloated feeling, metallic taste, edema of hands and
ankles
Not given together with NSAIDS
Serum Na and thyroid function must be closely
monitored