1.4 CNS Drugs - Sedatives and Hypnotics - Dr. Rani Qasem 2014-2015

5/8/2016
Dr. Rani Qasem

Susan Posky
Special topics in CNS Pharmacology-
Sedatives, Hypnotics & Antianxiety Drugs
Dr. Rani Qasem
Objectives
At the end of the lecture, the students should be able to:
1. Describe the differences in the categories of sedative hypnotic drugs

2. Discuss the mechanisms of action and physiological effects of sedative hypnotics
3. Describe the effects of sedative hypnotics on sleep architecture
4. Discuss the side effects and drug interactions of sedative hypnotics
5. Describe the management of insomnia
6. Know the classifications and pathophysiological causes of anxiety
7. Know the mechanism of action of the major classes of anti-anxiety drugs
8. Recognize pharmacological rationale for the clinical use of particular anti-anxiety
drugs
PHBS – 302 LECTURE: Sedative Hypnotics and

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Antianxiety Drugs EMMS Program Dr. Rani Qasem
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Introduction
• Sedatives-hypnotics produce sedation (with concomitant
relief of anxiety) and encourage sleep.
• Drugs have considerable variation in chemical structure.
– Drug classification is based on clinical uses rather than on similarities
in chemical structure.
• Anxiety states and sleep disorders are common problems
that are treated with sedative hypnotics.
PHBS – 302 LECTURE: Sedative Hypnotics and 3

BASIC PHARMACOLOGY OF
SEDATIVE-HYPNOTICS
• Sedative-hypnotics produce graded dose-dependent
depression of CNS function.
• Sedatives (anxiolytics): reduce anxiety and exert a calming
effect.
– The degree of central nervous system depression should be
the minimum consistent with therapeutic efficacy.
• Hypnotics: produce drowsiness and encourage the onset
and maintenance of sleep.
– Produce more pronounced depression of the CNS than
sedation, and this is achieved by increasing the dose.
• Individual drugs differ in the relationship between the
dose and the degree of CNS depression……. See next slide!
PHBS – 302 LECTURE: Sedative Hypnotics and Antianxiety

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Drugs EMMS Program Dr. Rani Qasem
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5/8/2016
Dose-response curves for two hypothetical

sedative-hypnotics
Drug A: Linear slope- Drug B- deviation

An increase in dose from a linear
may lead to a state dose-response
of general relationship.
anesthesia.
Require
At higher doses, proportionately
drugs depress greater dosage
respiratory and increments to
vasomotor centers in achieve central
the medulla, leading nervous system
to coma and death. depression.
Typical of older Examples:

sedative-hypnotics- benzodiazepines
(Barbiturates and and certain newer
alcohols) hypnotics.
Antianxiety Drugs EMMS Program Dr. Rani Qasem 5
Chemical Classification-
Benzodiazepines
• Benzodiazepines are widely used sedative-hypnotics.
• Core chemical structure is the fusion of a benzene ring and a 1,4 diazepine ring.
• Most contain a carboxamide group in the 7-membered heterocyclic ring.
• An electronegative substituent (halogen, nitro group) in position 7 is required
for sedative-hypnotic activity.
• Triazolam and alprazolam have a triazole ring at 1,2-position.
Carboxamide group
1,4-benzodiazepine
An
electronegative
substituent

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Chemical Classification-
Benzodiazepines
Triazole ring

Other Hypnotics: Barbiturates,

Glutethimide and Meprobamate
• Rarely used as sedatives.

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General Pharmacokinetic
Principles of Sedatives- Hypnotics
A. Absorption and Distribution
• Rate of oral absorption of sedatives hypnotics varies-
depends on a number of factors, including lipophilicity.
• Lipid solubility plays a major role in determining the rate at
which a particular sedative-hypnotic enters the CNS.
• All sedative-hypnotics cross the placenta during pregnancy.
• If sedative-hypnotics are given during the predelivery
period, they may depress neonatal vital functions.
• Sedative-hypnotics are detectable in breast milk and may
exert depressant effects in the nursing infant.

9
General Pharmacokinetic
Principles of Sedatives- Hypnotics
B. Biotransformation
• Metabolic transformation to water-soluble metabolites is
necessary for clearance of sedative-hypnotics from the body.
• Microsomal drug-metabolizing enzyme systems of the liver
are most important for metabolism.
• t1/2 depends on rate of metabolic transformation.
C. Excretion
• The water-soluble metabolites of sedative-hypnotics are
excreted mainly via the kidney.

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Factors Affecting Biodisposition

of Sedatives-hypnotics
• Altered hepatic function due to disease or drug-induced increases or
decreases in microsomal enzyme activities.
• Very old patients and patients with severe liver disease, the t 1/2 of these
drugs is significantly increased- Multiple normal doses can result in
excessive CNS effects.
• The activity of hepatic microsomal drug-metabolizing enzymes may be
increased in patients exposed to certain older sedative - hypnotics on a
long-term basis.
– Barbiturates (especially phenobarbital) and meprobamate increase
their own hepatic metabolism as well as that of other drugs.
• Increased biotransformation of other pharmacologic agents as a result of
enzyme induction by barbiturates is one mechanism of drug interactions.
• Benzodiazepines and newer hypnotics do not change hepatic drug-
metabolizing enzyme activity with continuous use.
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Classes of Sedatives- Hypnotics

• Benzodiazepines- most widely used anxiolytic drugs.
• Barbiturates
• Ethanol
• Chloral hydrate
• Z drugs (zolpidem, zaleplon, eszopiclone)
• Buspirone
• Ramelteon
• Antidepressants
• Antihistamines
• Antipsychotics
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Anxiolytics-
Tranquilizers-
BENZODIAZEPINES

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Pharmacodynamic Principles- GABA Receptor

• GABA (γ-aminobutyric acid) receptor is a Cl- ion channel
• Activated by GABA, the major
inhibitory neurotransmitter in the CNS.
• GABA-A receptor is a pentameric
structure - five subunits (α, β, and γ
subunit families).
• Sedatives-hypnotics bind GABA-A
receptors in the CNS.
• One major “GABA-A” isoform consists
of two α1, two β2, and one γ2 subunits.
• GABA binds at two locations between
adjacent α1 and β2 subunits.
• Benzodiazepine’s binding pocket (the
BZ site) is between an α1 & γ2 subunit.
• Barbiturates bind to GABA-A but a different site from benzodiazepines.
• Benzodiazepines and other sedative-hypnotics have low affinity for GABA B
receptors, which are activated by the spasmolytic drug baclofen.
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Benzodiazepines potentiate
GABAergic inhibition!!!
• Binding of GABA to its receptor triggers an opening of a chloride channel,
which leads to an increase in chloride conductance.
• The influx of chloride ions causes a small hyperpolarization.
• Benzodiazepine binding to GABA receptor increases the affinity of GABA
for the GABA-binding site-
– Benzodiazepines do not substitute for GABA- they enhance GABA’s
effects allosterically and without directly activating GABA A
receptors or opening the associated chloride channels.
– The enhancement in Cl- conductance takes the form of an increase in
the frequency of channel-opening events.
• The clinical effects of benzodiazepines correlate with the binding affinity
for the GABA receptor.

15
Schematic diagram of benzodiazepine–GABA–chloride

ion channel complex.
GABA = γ-aminobutyric acid.

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Benzodiazepines-
Pharmacological Effects
• Have neither antipsychotic activity nor analgesic action, and they do not
affect the autonomic nervous system.
• Individual benzodiazepines show small differences in their relative
anxiolytic, anticonvulsant, and sedative properties.
Benzodiazepines exhibit the following actions:
1. Reduction of anxiety: At low doses, benzodiazepines are anxiolytic at the
GABA-A receptors.
2. Sedative and hypnotic actions: Benzodiazepines have sedative properties
and some at high doses produce hypnosis (artificial sleep) by acting on α1-
GABA-A receptors.
3. Anterograde amnesia: Mediated through α1-GABA-A
4. Anticonvulsant: Several benzodiazepines have anticonvulsant activity and
some used to treat epilepsy. Partially mediated by α1-GABA-A receptors.
5. Muscle relaxant: At high doses, benzodiazepines relax spastic skeletal
muscles by increasing presynaptic inhibition through α2-GABAA receptors.
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Pharmacokinetics of
Benzodiazepines
• The duration of action varies widely among this group, and
pharmacokinetic considerations are important in favoring one
benzodiazepine over another.
Intermediate acting
Long acting
Long acting
Long acting
Long acting
Intermediate acting
Short-intermediate-acting
Intermediate acting
Short acting
Z-drugs PHBS – 302 LECTURE: Sedative Hypnotics and

Antianxiety Drugs EMMS Program Dr. Rani Qasem 18
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Categorization of Benzodiazepines
According to Duration of Action
• Short-acting compounds:
– Half-life of 1–12 hours- Have few residual effects if taken before bedtime,
– Upon discontinuation- Rebound insomnia and daytime withdrawal
symptoms- next day rebound anxiety.
– Brotizolam, midazolam, and triazolam.
• Intermediate-acting compounds:
– Half-life of 12–40 hours- Have some residual effects in the first half of the
day if used as a hypnotic.
– Upon discontinuation- Rebound insomnia is more common than longer-
acting benzodiazepines.
– Alprazolam, estazolam, flunitrazepam, clonazepam, lormetazepam,
lorazepam, nitrazepam, and temazepam.
• Long-acting compounds:
– Half-life of 40–250 hours- may accumulate in the elderly and patients with
severely impaired liver function.
– Reduced severity of rebound and withdrawal effects.
– Diazepam, clorazepate, chlordiazepoxide , and flurazepam.
Pharmacokinetics of
Benzodiazepines
• Benzodiazepines are lipophilic- are rapidly and completely absorbed orally.
• All benzodiazepines subject to hepatic metabolism.
– Most undergo microsomal oxidation (phase I reactions)- catalyzed by
cytochrome P450 - especially CYP3A4.
– Metabolites are then conjugated (phase II reactions) to form glucuronides
that are excreted in the urine.
• Many phase I metabolites are pharmacologically active with long half-lives.
– Example: Desmethyldiazepam has an elimination half-life > 40 hours is the
active metabolite of chlordiazepoxide, diazepam, prazepam, and
clorazepate.
• Alprazolam and triazolam undergo hydroxylation and the resulting
metabolites exert short-lived pharmacologic effects because they are rapidly
conjugated to inactive glucuronides.
• The short elimination half-life of triazolam (2–3 hours) favors its use as a
hypnotic rather than as a sedative drug.
• Metabolism is affected by inhibitors and inducers of hepatic P450 isozyme.
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Biotransformation of Benzodiazepines
-Active metabolites labelled with an asterisk-
Prodrug
“Half-life of
36–200 hours”
“Half-life of
40–250 hours”
Microsomal oxidation – • Glucuronide conjugation –
1. Slow and metabolic 1. Rapid and metabolic
products may be active. products are inactive.
2. Significant changes with 2. Little change with aging.
aging. 3. Lorazepam, oxazepam
Therapeutic Uses
1. Anxiety disorders: Treatment of anxiety symptoms that accompany:
– Panic disorder
– Generalized anxiety disorder (GAD)
– Social anxiety disorder
– Performance anxiety
– Posttraumatic stress disorder
– Obsessive-compulsive disorder
– Extreme anxiety encountered with specific phobias such as fear of flying.
– Anxiety that accompanies some forms of depression and schizophrenia.
• Drugs should not be used to alleviate normal stress of everyday life and
should be reserved for continued severe anxiety- only used for short periods
of time because of their addiction potential.
• Clonazepam, lorazepam and diazepam are preferred for anxiety that may
require treatment for prolonged periods of time.
• Anti-anxiety effects are less subject to tolerance than sedative & hypnotic
effects – Tolerance is decreased responsiveness to repeated drug doses.
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Therapeutic Uses… continued

2. Muscular disorders: Diazepam is useful
– In skeletal muscle spasms- muscle strain
– Spasticity from degenerative disorders- multiple sclerosis and cerebral
palsy. Tolerance develops- Baclofen & Tizanidine are good alternatives.
3. Amnesia:
– Short-acting agents used as premedication for anxiety-provoking and
unpleasant procedures.
– Induce conscious sedation- the person remains receptive to instructions
during procedures.
– Midazolam used for the induction of anesthesia.
4. Seizures:
– Clonazepam- for certain types of epilepsy.
– Diazepam and lorazepam - drugs of choice in grand mal epileptic seizures
and status epilepticus.
– Chlordiazepoxide, clorazepate, diazepam, and oxazepam - useful in acute
alcohol withdrawal to reduce the risk of withdrawal-related seizures!
Therapeutic Uses… continued

5. Sleep disorders:
– Not all benzodiazepines are useful
hypnotics but all have sedative
effects.
– In treating insomnia one should
balance the sedative effects needed
at bedtime with the residual
sedation (“hangover”) upon
awakening.
– Hypnotics are given for only a
limited time, usually less than 2 to 4
weeks.
– Rebound insomnia is a major
problem upon discontinuation-
espcially with short acting
compounds like triazolam.
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Therapeutic Uses- Commonly prescribed

benzodiazepines for sleep disorders:
1. Flurazepam:
– Long-acting benzodiazepine- significantly reduces both sleep-induction time
and the number of awakenings- it increases the duration of sleep.
– Little rebound insomnia- effectiveness for up to 4 weeks.
– Flurazepam and its active metabolites t1/2 ≈85hrs- daytime sedation.
2. Temazepam:
– Patients who experience frequent wakening- difficulty maintaining sleep.
– Peak sedation occurs 1-3 hrs after oral dose- given 1-2 hrs before bedtime.
3. Triazolam:
– Short duration of action
– Used to induce sleep- difficulty getting asleep!
– Tolerance frequently develops within a few days
– Withdrawal results in rebound insomnia- patient demands another
prescription or higher dose- Drug is best used intermittently instead of daily.
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Benzodiazepines are Safe!!
Drug B- deviation from a linear dose-response relationship.

Require proportionately greater dosage increments to achieve central
nervous system depression.
Examples: benzodiazepines and certain newer hypnotics.
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Adverse effects
1. Drowsiness and confusion- very common.
2. Ataxia occurs at high doses- interferes with fine motor activities.
3. Cognitive impairment (decreased long-term recall and retention of new
knowledge- especially problematic in the elderly- may worsen
dementia)
– Triazolam shows rapid development of tolerance, early morning
insomnia, and daytime anxiety, amnesia and confusion.
4. Precautions: liver disease- acute narrow-angle glaucoma-alcohol and
other CNS depressants.

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Dependence- Recreational use

• Benzodiazepines are considered to be major drugs of abuse.
• Benzodiazepines are categorized as Schedule IV
• Psychological and physical dependence can develop if high doses are given
over a prolonged period.
• Benzodiazepines mortality is higher among poly-drug misusers .
• Heavy alcohol use also increases mortality among poly-drug users.
• Abrupt discontinuation results in withdrawal symptoms, that include:
– Confusion, anxiety, agitation, restlessness, insomnia, tension, and
(rarely) seizures.
• Long half-live benzodiazepines- such as flurazepam, withdrawal symptoms
occur slowly and last several days after discontinuation of therapy.
• Short half-life benzodiazepines, such as triazolam, induce more abrupt and
severe withdrawal reactions.
• Temazepam may be the most psychologically habit-forming (addictive)
benzodiazepine.
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Drug Scheduling- Controlled Substance

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Contraindications
1. Pregnancy- Benzodiazepines are pregnancy category D or X.
– If used, benzodiazepines with longer safety record
like diazepam or chlordiazepoxide are recommended over potentially
harmful temazepam or triazolam.
– Use lowest effective dose for shortest period to minimizes risks to the
unborn child.
2. Elderly - benzodiazepine benefits are least and risks are greatest in elderly.
– Have increased risk of dependence and more sensitive to adverse effects.
– Long-term effects resemble dementia, depression, or anxiety syndromes, and
progressively worsen over time- adverse effects on cognition can be mistaken
for the effects of old age.
– Benzodiazepines should be prescribed with caution and for a short period at
low doses in the elderly.
– Short to intermediate-acting benzodiazepines are preferred such
as oxazepam and temazepam.
– Nonbenzodiazepines such as zaleplon and zolpidem and low doses of sedating
antidepressants are preferred alternatives.
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Benzodiazepine antagonist-
Flumazenil
• Flumazenil has high affinity for the benzodiazepine binding site on GABA-A
receptor and acts as a competitive antagonist.
• Flumazenil blocks the actions of benzodiazepines and Z-drugs but does NOT
antagonize ethanol, barbiturates, meprobamate, opioids, or general anesthetics.
• Clinical uses: Reversal of CNS depressant effects of benzodiazepine overdose
and to speed recovery in anesthetic and diagnostic procedures using BZDs.
• For intravenous (IV) use only.
• Onset is rapid, but duration is short- t1/2≈1 hour- rapid hepatic clearance.
• Frequent administration may be needed to revere long-acting benzodiazepines.
Adverse effects:
• Dizziness, nausea, vomiting, and agitation are the most common side effects.
• Reversal of the benzodiazepine may precipitate withdrawal in dependent
patients or cause seizures if used to control seizures.
• Seizures and cardiac arrhythmias may result if the patient ingests tricyclic
antidepressants (TCAs).
OTHER ANXIOLYTIC AGENTS

Antidepressants-
– Selective serotonin reuptake inhibitors (SSRIs, such a escitalopram).
– Selective serotonin & norepinephrine reuptake inhibitors (venlafaxine).
– Lower potential for physical dependence than benzodiazepines- became
first-line treatment for generalized anxiety disorders.
– First-line agents in patients with concerns for addiction or dependence or
a history of addiction or dependence to other substances.
– Used alone, or prescribed in combination with low dose of
benzodiazepine during first weeks of treatment.

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OTHER ANXIOLYTIC AGENTS

Buspirone-
– Useful for the chronic generalized anxiety disorder -efficacy comparable
to benzodiazepines.
• Mechanism of action differs from benzodiazepines-
• Acts as a partial agonist of serotonin (5-HT1A) receptors and has affinity for
brain dopamine D2 receptors & 5-HT2A serotonin receptors.
• Advantages of buspirone:
– The frequency of adverse effects is low, with the most common effects
being headaches, dizziness, nervousness, and light-headedness.
– Has NO anticonvulsant and muscle-relaxant properties
– Causes minimal sedation, psychomotor and cognitive dysfunction
– No withdrawal symptoms & dependence is unlikely.
– It does not potentiate the CNS depression of alcohol.
• Buspirone has the disadvantage of a slow onset of action.
– Not effective for short-term or “as-needed” treatment of acute anxiety.
• Can cause hypothermia and increase prolactin and growth hormone levels.
Barbiturates
• Largely replaced by benzodiazepines because of the following negative
properties of barbiturates:
1. Induce tolerance
2. Induce Drug-metabolizing enzymes
3. Induce physical dependence,
4. Cause very severe withdrawal symptoms and coma in toxic doses.
Mechanism of action of Barbiturates
1. Barbiturates interact with GABA-A receptors enhancing GABAergic
inhibitory transmission- produces sedation and hypnosis!
• The binding site is distinct from that of the benzodiazepines.
• Barbiturates prolong the duration of the chloride channel openings.
2. At high doses, may act as a GABA-mimetic, directly activating chloride
channels.
3. Barbiturates block excitatory glutamate AMPA receptors.
4. Anesthetic concentrations block high-frequency sodium channels.
PHBS – 302 LECTURE: Sedative Hypnotics and Antianxiety 34
Drugs EMMS Program Dr. Rani Qasem
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Classification of Barbiturates
Classified according to their duration of
action:
• Thiopental – Ultra-short acting – Given IV
for induction of anesthesia.
• Pentobarbital, Secobarbital, Amobarbital
– Short-acting barbiturates that are
effective as sedatives and hypnotics (but
not antianxiety).
• Phenobarbital –Long-acting – duration of
action > 1 day- used to treat seizures.

35
Therapeutic uses of Barbiturates

1. Anesthesia:
– Ultra-short acting thiopental used I.V. to induce anesthesia.
2. Anticonvulsant:
– Phenobarbital used in long-term management of tonic-clonic seizures,
status epilepticus, and eclampsia
– Considered the drug of choice for treatment of recurrent febrile
seizures in young children- drug can depress cognitive performance in
children!
3. Anxiety:
– Used as mild sedatives to relieve anxiety, nervous tension & insomnia.
– Largely replaced by safer benzodiazepines.

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Adverse effects of Barbiturates

• CNS: Drowsiness, impaired concentration, mental and physical sluggishness
• Drug hangover!
• Precautions: Barbiturates induce P450 system- this increases metabolism of
other drugs.
• Increase porphyrin synthesis- contraindicated in acute intermittent porphyria.
• Physical dependence: Abrupt withdrawal cause tremors, anxiety, weakness,
restlessness, nausea, vomiting, seizures, delirium, and cardiac arrest.
Withdrawal is much more severe than with opiates and can result in death.
• Poisoning: A leading cause of death resulting from drug overdose – cause
severe depression of cardiovascular and respiratory centers-
– Treatment
• Artificial respiration
• Purging the stomach of its contents
• Hemodialysis with large quantities.
• Urine alkalinization- sodium bicarbonate.
Other Hypnotic Agents

1. Z-drugs
2. Ramelteon
3. Chloral Hydrate
4. Antihistamines
5. Ethanol (Ethyl alcohol)

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Z-drugs
• Zolpidem, Zaleplon, Eszopiclone
Pharmacological properties:
• Act on a subset of the benzodiazepine receptor family, BZ1.
• Have no muscle-relaxing properties and no anticonvulsant effects.
• Few withdrawal effects, minimal rebound insomnia, little or no tolerance.
• General adverse effects of the group: CNS effects like nightmares, agitation,
headache, dizziness, daytime drowsiness and somnolence. Gastrointestinal
upset.
39
Ramelteon
• Selective agonist at melatonin receptors MT1 & MT2.
• Light hitting the retina → signal the hypothamlamic suprachiasmatic nucleus

(SCN → signals the pineal gland & inhibits melatonin release.
• As darkness falls → no light, melatonin is released from the pineal gland.
• Melatonin stimulates MT1 and MT2 receptors induces and promotes sleep -
thought to maintain the circadian rhythm of sleep-wake cycle.
• Ramelteon - treatment of insomnia in which falling asleep is the primary
complaint.
• Can be administered long-term- potential for abuse is minimal- no evidence of
dependence or withdrawal effects
• Adverse effects: Dizziness, fatigue, somnolence- may increase prolactin levels.
PHBS – 302 LECTURE: Sedative Hyp notics and
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Chloral Hydrate
• A trichlorinated derivative of acetaldehyde
• Converted to an active metabolite- Trichloroethanol.
• Used for the short-term treatment of insomnia and as a sedative before
minor medical or dental treatment.
• Induces sleep in 30 minutes and lasts for 6 hours.
• Has a very narrow therapeutic window. High doses depress respiration & BP.
• Has unpleasant taste & is irritating to GI tract and causes epigastric distress.
Inactive
Active
PHBS – 302 LECTURE: Sedative Hypnotics

and Antianxiety Drugs EMMS Program
Dr. Rani Qasem
Inactive Inactive
“Trichloroacetic acid” “Dichloroacetic acid” 41
Antihistamines
• 1st generation antihistamines have sedating properties.
• Diphenhydramine, hydroxyzine and doxylamine, are
effective in treating mild types of situational
insomnia.
• Have numerous undesirable side effects (such as
anticholinergic effects) that make them less useful
than the benzodiazepines.

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Ethanol (Ethyl alcohol)

• A CNS depressant- Anxiolytic and sedative effects-
its toxic potential outweighs its benefits.
• Ethanol is metabolized in the liver to acetaldehyde
by alcohol dehydrogenase (ADH) and acetaldehyde
to acetate by aldehyde dehydrogenase (ALDH).
• Elimination: Mainly kidney- a fraction through the lungs.

• Ethanol synergizes with many other sedative agents producing severe CNS
depression - benzodiazepines, antihistamines, or barbiturates.
• Chronic consumption: Severe liver disease, gastritis, nutritional deficiencies
and cardiomyopathy.
• Alcohol withdrawal is treated with benzodiazepines.
• Carbamazepine used to control convulsive episodes during withdrawal.
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Drugs to Treat Alcohol Dependence
• Disulfiram:
– Inhibits aldehyde dehydrogenase & blocks the oxidation of
acetaldehyde to acetic acid.
– Causes the accumulation of acetaldehyde in the blood that in
unpleasant reactions- flushing, tachycardia, hyperventilation, and
nausea.
– This is considered a “conditioned avoidance response” to quit drinking.
• Naltrexone:
– Long-acting opiate antagonist used in conjunction with supportive
psychotherapy.
• Acamprosate:
– Used in alcohol dependence treatment programs- unknown
mechanism of action.

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Summary of Sedatives- Hypnotics

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5/8/2016

Dr. Rani Qasem

Dr. Rani Qasem

1. Describe the differences in the categories of sedative hypnotic drugs

PHBS – 302 LECTURE: Sedative Hypnotics and

PHBS – 302 LECTURE: Sedative Hypnotics and 3

PHBS – 302 LECTURE: Sedative Hypnotics and Antianxiety

Dose-response curves for two hypothetical

Drug A: Linear slope- Drug B- deviation

Typical of older Examples:

PHBS – 302 LECTURE: Sedative Hypnotics and 6

PHBS – 302 LECTURE: Sedative Hypnotics and 7

Other Hypnotics: Barbiturates,

PHBS – 302 LECTURE: Sedative Hypnotics and

PHBS – 302 LECTURE: Sedative Hypnotics and

PHBS – 302 LECTURE: Sedative Hypnotics and

Factors Affecting Biodisposition

Classes of Sedatives- Hypnotics

PHBS – 302 LECTURE: Sedative Hypnotics and

Pharmacodynamic Principles- GABA Receptor

PHBS – 302 LECTURE: Sedative Hypnotics and

Schematic diagram of benzodiazepine–GABA–chloride

PHBS – 302 LECTURE: Sedative Hypnotics and

Z-drugs PHBS – 302 LECTURE: Sedative Hypnotics and

Therapeutic Uses… continued

Therapeutic Uses… continued

Therapeutic Uses- Commonly prescribed

Benzodiazepines are Safe!!

Drug B- deviation from a linear dose-response relationship.

PHBS – 302 LECTURE: Sedative Hypnotics and

Dependence- Recreational use

Drug Scheduling- Controlled Substance

PHBS – 302 LECTURE: Sedative Hypnotics and

OTHER ANXIOLYTIC AGENTS

PHBS – 302 LECTURE: Sedative Hypnotics and 32

OTHER ANXIOLYTIC AGENTS

PHBS – 302 LECTURE: Sedative Hypnotics and

Therapeutic uses of Barbiturates

PHBS – 302 LECTURE: Sedative Hypnotics and

Adverse effects of Barbiturates

Other Hypnotic Agents

PHBS – 302 LECTURE: Sedative Hypnotics and

• Light hitting the retina → signal the hypothamlamic suprachiasmatic nucleus

PHBS – 302 LECTURE: Sedative Hypnotics

PHBS – 302 LECTURE: Sedative Hypnotics and

Ethanol (Ethyl alcohol)

• Elimination: Mainly kidney- a fraction through the lungs.

Drugs to Treat Alcohol Dependence

PHBS – 302 LECTURE: Sedative Hypnotics and

Summary of Sedatives- Hypnotics

PHBS – 302 LECTURE: Sedative Hypnotics and

PHBS – 302 LECTURE: Sedative Hypnotics and

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