Download 02_CLINICAL PHARM_ DRUGS_CNS

CLINICAL PHARMACOLOGY OF
DRUGS AFFECTING THE
NERVOUS SYSTEM
Central Nervous System Stimulants
• Stimulants are drugs that exert their action through
excitation of the central nervous system. Psychic
stimulants include caffeine, cocaine, and various
amphetamines.
CNS Stimulants (cont’d)
AMPHETAMINE
Levoamphetamine, dextroamphetamine, and
methamphetamine (Methedrine)
• Amphetamine is a
noncatecholaminergic
sympathetic amine
that shows neurologic
and clinical effects
quite similar to those
of cocaine.
CNS Stimulants (cont’d)
AMPHETAMINE
Clinical Therapeutics of CNS
Stimulants
Depression
• The symptoms of
depression are intense
feelings of sadness,
hopelessness, and despair,
as well as the inability to
experience pleasure in
usual activities, changes in
sleep patterns and
appetite, loss of energy,
and suicidal thoughts.
ANTIDEPRESSANTS
Tricyclic antidepressants Inhibitors of the reuptake of noradrenaline (norepinephrine)
and serotonin (5-HT) in central monoaminergic neurons
1. Sedative
• Amitriptyline
• Clomipramine
• Dosulepin (dothiepin)
• Doxepin*
• Maprotiline
• Mianserin*
• Trazodone*
• Trimipramine
Tricyclic antidepressants (TCAs )
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2. Less sedative
Amoxapine
Imipramine
Lofepramine*
Nortriptyline
Selective serotonin reuptake
inhibitors (SSRIs)
• Inhibitors of the reuptake of serotonin (5HT) in central monoaminergic neurons
• Fluoxetine
• Paroxetine
• Fluvoxamine
• Sertraline
• Citalopram
Monoamine oxidase inhibitors (MAOIs)
• Inhibitors of the enzyme monoamine oxidase
– Selegiline
Tricyclic antidepressants. Adverse
effects
Monoamine oxidase inhibitors
Monoamine oxidase inhibitors
Monoamine oxidase inhibitors
Adverse effects from these drugs are very
common
• The tyramine reaction is
characterized by severe
hypertension, headache,
palpitation, sweating, nausea,
and vomiting. It can be fatal.
• It occurs as a result of ingestion
of tyramine-rich foods or coadministration of other drugs
that potentiate aminergic
neurotransmission.
• This reaction makes these drugs
potentially hazardous and limits
their clinical use.
Drugs and foods that can precipitate the
tyramine reaction in patients taking MAOIs
(not selegiline or moclobemide)
Tyramine-rich foods
• Cheese (especially cheddar)
– Not cottage or cream cheeses
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Meat and yeast extracts
Some red wines
Hung game and poultry
Pickled herring
Broad beans
Alcoholic and dealcoholized beverages
Psychoses and bipolar disorder
Antipsychotic/neuroleptic drugs
Dopamine receptor antagonists
• Phenothiazines
– Chlorpromazine
– Prochlorperazine
– Thioridizine
• Thioxanthenes
– Flupenthixol
– Clopentixol
• Butyrophenones
– Haloperidol
• Atypical antipsychoticdrugs
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Risperidone
Clozapine
Olanzapine
Quetiapine
Sertindole
Antipsychotic/neuroleptic drugs
Antipsychotic/neuroleptic drugs
Tranquilizers
• phenothiazines, indoles,
thioxanthenes,
butyrophenones, piperazine
compounds, and piperidine
compounds.
• Benzodiazepines, known by
trade names such as Valium,
Xanax, Serax, Ativan,
Klonopin, Librium and
Tranxene. There are also
combination drugs such as
Librax.
SEDATIVE - HYPNOTIC AGENTS
Drug Classes of Sedative-Hypnotics
• Barbiturates
• Benzodiazepines
• Alcohols/Imidazopyridine
SEDATIVE - HYPNOTIC AGENTS
SEDATIVE - HYPNOTIC AGENTS
3. CNS effects:
Dose-dependent progression: (lower margin of
safety)
Sedation → ‘Hypnosis’ → Anesthesia →
Coma → Death
Anticonvulsant/antiepileptic effect
Benzodiazepines (Hypnotics and
anxiolytics )
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Long-acting
Diazepam 5 mg
Lorazepam 0.5 mg
Nitrazepam 5 mg
Chlordiazepoxide 15 mg
Short-acting
Oxazepam 15 mg
Temazepam 10 mg
Lormetazepam 0.5-1.0 mg
Loprazolam 0.5-1.0 mg
Used for epilepsy
Clobazam
Clonazepam
INDICATIONS
• Treatment of anxiety, and
premedication before
operations and procedures.
• Short-term use for night
sedation.
• Sedation for procedures.
• Treatment of seizures.
• Skeletal muscle relaxant to
relieve muscle spasm.
• Adjunct to the treatment of
alcohol withdrawal.
Effects and uses:
- drugs of choice for sedation and ‘hypnosis’ (higher margin
of safety)
flurazepam: long-acting pro-drug
temazepam: slowly absorbed, intermediate acting drug with no
active metabolites; most highly prescribed hypnotic
triazolam: rapid but short-acting drug
diazepam (Valium®): long-acting drug; may be useful as adjunct
in animal surgery
at sedative doses may cause euphoria and ‘disinhibition’
anticonvulsant (primary drug for initial treatment of status
epilepticus)
anxiolytic
muscle relaxation (used in spasticity; largely via effect in
spinal cord)
ethanol withdrawal
Adverse reactions:
- ‘hangover’ (esp. with benzodiazepines with
long half-lives: diazepam)
- early morning awakening for benzodiazepines
with short half-lives: triazolam
- impaired motor and cognitive skills
- anterograde amnesia
Alcohols/Imidazopyridine:
- Chloral Hydrate
Long (6-10h)
[pro-drug]
short-acting
• Zaleplon
• Zolpidem
• Zopiclone
Short-term treatment of insomnia.
Zaleplon, Zolpidem, Zopiclone
• Chronic insomnia is rarely helped
by treatment with hypnotics.
They are more effective for:
– Transient insomnia in those who
normally sleep well but are subject
to a disrupting event (e.g. an
operation or jet lag). Give 1 or 2
doses.
– Short-term insomnia associated with
a specific event (e.g. illness or
bereavement). Keep treatment to
less than 1 week.
• These drugs are not licensed for
long-term treatment.