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◦ Sympathomimetics
Ephedrine, epinephrine, pseudoephedrine phenylpropanolamine
◦ Anticholinergics\Antihistaminergics
Trihexyphenidyl, benztropine, meperidine, diphenhydramine,
oxybutinin
◦ Dopaminergics
Amantadine, bromocriptine, L-Dopa, carbidopa/levodopa.
◦ Miscellaneous:
Baclofen, cycloserine, hallucinogens, indomethacin
Verbal complaints: The patient says he/she is anxious,
nervous, edgy
Duration of action
Benzodiazepines e.g. Diazepam
Barbiturates e.g Phenobarbital
Azaspirodecanedione e.g. Buspirone
Imidazopyridine e.g zolpidem
Pyrazolopyrimidine e.g . Zaleplon
Propanediol carbamate e.g. meprobamate
Melatonin receptor agonist e.g. Ramelteon
Alcohols e.g. Ethanol, chloral hydrate
Beta-adrenergic blocking agents e.g, propranolol
Antipsychotic tranquilizers e.g. Ziprasidone
Antihistamines e.g. diphenhydramine, hydroxyzine
Tricyclic antidepressants, SSRIs
Benzodiazepine:
They are the most important class, used for treating both
anxiety states and insomnia.
> Decrease in renal plasma flow and in cerebral blood flow with a
marked fall in CSF pressure
Liver
> Combine with cytochrome 450 & competitively interfere with
the biotransformation of a number of drugs
Paradoxical Excitement:
- Common among geriatric & debilitated patients
- Phenobarbital & N-methylbarbiturates
Dependence: including psychologic and
physiologic dependence. Withdrawal symptoms:
excitation, insomnia, tremor, anxiety, hallucinations
and sometimes convulsions.
Pharmacokinetics
Flumazenil is absorbed orally; oral bioavailability is app.16%,
but it is not used orally.
On i.v. injection, action of flumazenil starts in seconds
and lasts for 1-2 hr; elimination half life is 1 hr, due to
rapid metabolism.
To reverse BZD anaesthesia:
Patients anaesthetized/sedated with a BZD wakeup, get
oriented and regain motor control within 1 min of an i.v.
injection of 0.3-1 mg of flumazenil
BZD overdose:
Majority of patients of BZD overdose require only supportive
measures like patent airway, maintenance of BP, cardiac and
renal function, etc.
In addition, flumazenil 0.2 mg/min may be injected i.v.
till the patient regains consciousness.
N.B: It cannot reverse the CNS depression of alcohol or
barbiturate overdose.
Flumazenil is safe and well tolerated.
Agitation, discomfort, tearfulness, anxiety, coldness
and withdrawal seizures are the occasional side effects.
• These include: Zopiclone, zolpidem and zaleplon (so
called Z-drugs)
• They have shorter half-lives than the BDZs.
• They all have reduced propensity to tolerance and
have less abuse liability.
Zopiclone
This newer cyclopyrrolone hypnotic is an agonist at a
subtype of BZD receptor.
It is reported not to disturb sleep architecture or
produce hangover or withdrawal phenomena on
discontinuation
Zopiclone has been used to weanoff insomniacs taking
regular BZD medication.
Its half life is 5-6 hours.
Zopiclone is indicated for short term (< 2 weeks)
treatment of insomnia.
Side effects
Metallic or bitter after-taste
Impaired judgement and alertness
Psychological disturbances
Dry mouth and rarely dependence.
Zolpidem
An imidazopyridine derivative with hypnotic actions
Precautions
Patients with hepatic dysfunction, elderly
Drug interaction
Rifampicin — decreases half-life of zolpidem
Resembles zolpidem
Mechanism of action: binds selectively to BZ, receptor subtype and
facilitates inhibitory actions of GABA
Decreases sleep latency: Little effect on total sleep time or on sleep
structure.
Pharmacokinetics
Rapidly absorbed from GIT, rapid onset & short duration of action
Elimination half-life is about 1 hour.
Metabolized mainly by hepatic aldehyde oxidase & partly by
cytochrome P450
NOTE: Amnesic effects & next-day psychomotor impairment may
occur
AZAPIRONES
Buspirone is the first example of a class of anxiolytic
agents that can relieve some symptoms of anxiety in
doses that do not cause sedation.
Buspirone is well absorbed from the gastrointestinal tract
Peak blood levels are achieved in 1 to 1.5 hours
The drug is more than 95% bound to plasma proteins.
It is extensively metabolized, with less than 1% of the parent
drug is excreted into the urine unchanged.
It has an elimination half-life of 4 to 6 hours.
It effects are mediated through interactions at the
serotonin (5-hydroxytryptamine, 5-HT) 5-HT1A
receptor, where it acts as a partial agonist.
It acts as an antagonist at postsynaptic 5HT1A sites in
the hippocampus (where there is little receptor reserve).
It has anxiolytic actions in humans.
In therapeutic doses, buspirone has little or no sedative effect
and lacks the muscle relaxant and anticonvulsant properties of
the benzodiazepines.
Side effects
Dizziness
Light-headedness
Headache
• Buspirone has been reported to increase blood pressure
in patients taking monoamine oxidase inhibitors
- Side effects:
Irritating to skin & mucous membrane unpleasant taste,
epigastric distress, nausea, occ. vomiting
CNS: lightheadedness, malaise, ataxia, nightmares
"Hangover"
idiosyncratic - disoriented, incoherent, paranoid
behavior
Icterus -acute poisoning Delirium & seizures
Hypnotic-sedative with rapid onset & short duration of action
> has anti-convulsant & muscle relaxant property
acts within 15-30 minutes
> distribution half-life is 1-3 hours > elimination half life is
10-25 hrs.
Side effects:
mint-like aftertaste dizziness, nausea & vomiting hypotension,
facial numbness mild "hangover“
Hypersensitivity - urticaria, fatal thrombocytopenia,
cholestatic jaundice
Acute intoxication - severe respiratory depression,
bradycardia
Idiosyncratic - mild stimulation to marked excitement &
hysteria
Contraindicated in patients with porphyria
Drug interaction: enhance metabolism of oral anticoagulants
Gluthetimide
Rarely recommended for continued use because of its
addiction liability, severity of withdrawal symptoms & certain
features of acute intoxication
Exhibits pronounced anticholinergic activity
Absorbed from GIT, 50% bound to plasma proteins, 95%
metabolized in the liver
Half-life is 5-22 hours
"hangover" excitement blurred vision, gastric irritation,
headache, skin rashes thrombocytopenia, aplastic anemia,
leukopenia
Side effects:
"hangover“, nausea, vomiting, diarrhea, esophagitis and
headache, idiosyncratic excitement
Side effects:
Nausea, occasional vomiting, rash
Idiosyncratic excitement, fever, thrombocytopenia
Etomidate