PHARMACOLOGY

Sedative-Hypnotic-Anxiolytic Drugs Transcriber: Cj 

Editor: MGB
Lecturer: Deo L. Panganiban, MD, FPSECP Number of pages: 9

I. Sedative-Hypnotic IV. Newer Sedative Hypnotics a. Phenobarbital

II. The Drugs a. Zolpidem VI. Ethanol
III. Benzodiazepines b. Buspirone VII. Pharmacotherapy of Alcoholism
a. Diazepam V. Barbiturates a. Disulfiram

Sedative 5. Chloral dervatives** (older sedative-hypnotic)

• Decreases activity • Chloral hydrate
• Moderates excitement 6. Carbamates** (older sedative-hypnotic)
• Calming or tranquilizing effect • Meprobamate
• Used as pre-medication for surgical procedures 7. Piperidinediones
• Glutethimide
Hypnotic
• Thalidomide: (kakasawa na to haha; initially
• Produces drowsiness
prescribed as a sedative for pregnant women,
• Facilitates the onset and maintenance of sleep
until they eventually realized that it was a
that resembles natural sleep and from which the
teratogenic; now it can be used as an
person can be aroused easily
immunosuppressant/anti-cancer drug)
8. Antihistamines: the older antihistamines; because
I. SEDATIVE-HYPNOTIC
SEDATIVE-HYPNOTIC DRUGS
the newer ones were developed para hindi
• CNS depressants st
antukin (Finals review! 1 generation
• depress the CNS in a dose dependent manner,
Antihistamines make you drowsy, eg.
progressively producing sedation, sleep, nd rd
Diphenhydramine; while 2 and 3 generation
unconsciousness, surgical anesthesia, coma and nd
Antihistamines do not, eg. Loratadine (2 ),
ultimately fatal depression of respiratory and nd rd
Cetirizine(2 ), Desloratadine (3 ))
cardiovascular function
• Diphenhydramine
• Hydroxyzine

III. BENZODIAZEPINES
→Potentiate GABA effects
-
→Increase FREQEUNCY of Cl Channel opening
→Have no GABA mimetic properties
→Act through Benzodiazepine receptors
→These receptors are part of GABA A complex
Bz1 – mediates sedation
Bz2 –mediates anti-anxiety and cognitive functions
**Shows that the effects of sedative-hypnotics are dose-
dependent; the greater the dose, the “wilder” the effect  • Benzodiazepines
Benzodiazepines were first introduced in 1960’s
st
with the synthesis of the 1 benzodiazepine,
II. THE DRUGS Chlordiazepoxide
1. Benzodiazepines • As a class, they all have similar CNS effects and
• Diazepam adverse effects; while they only differ in their
• Midazolam: more water soluble than onset and duration of action.
Diazepam; less painful when injected IV • Composition: a benzene ring fused to a 7-
2. Non-Benzodiazepines membered diazepine ring structure.
• Zolpidem
• Buspirone • A halogen or nitrogen
3. Barbiturates substituent in the 7
• Phenobarbital position – sedative-
• Amobarbital hypnotic effect
• Thiopental
4. Alcohol
• Ethanol
Pharmacology: Sedative-Hypnotic-Anxiolytic
Sedative-Hypnotic-Anxiolytic Drugs | 1
 • Relatively wide margin of safety
• Prolonged, daily use may produce dependence
• Have little effect on respiratory or cardiovascular
function compared to the Barbiturates
• Fatality from overdose is rare except when taken
with alcohol or other CNS depressants
• Exert qualitatively similar clinical effects
• Low capacity to produce fatal CNS depression
• Coma may occur at very large doses
• Has displaced other agents as first line Sedative
hypnotics.
Classification according to duration of action:
1. Short-acting (T½ <6 hours): makes good pre-
anesthetic drugs due to short action
• Triazolam
• Midazolam
 Zolpidem (2hrs) and zopiclone (5-6 hrs) –
non benzodiazepines but are active at the
benzodiazepine receptor
2. Intermediate acting (T½ 6-24 hours)
• Lorazepam: The “date-rape” drug :> **24
hours of anterograde amnesia :>
• Chlordiazepoxide
• Alprazolam
• Estazolam
• Flunitrazepam
• Temazepam
3. Long acting (>24 hours): usually used for longer
sedation periods
• Flurazepam
• Quazepam
• Diazepam** ( prototype)
Benzodiazepine Receptors
1. Bz1 or Omega 1
• mediate sedative, hypnotic action
2. Bz2 or Omega 2
• mediate cognition, memory, motor control
3. Bz3
• outside CNS; abundant in the kidneys
Characteristics of Benzodiazepine Receptors:
• Benzodiazepine receptor is a part of the GABA A
receptor
• Upon binding, this will cause an allosteric change
in the GABAA receptor
• GABAA receptors are responsible for most
inhibitory neurotransmission in the CNS
• Benzodiazepine binding enhances coupling of  2.
GABA to its receptor
• High affinity
• Saturable and stereospecific; a certain dose will
occupy all the receptors
GABAA receptor:
• An Oligomeric glycoprotein (α, β, δ, γ, ε,π, ρ etc)
• Major player in inhibitory synapses
-
• A Cl channel
• Binding of GABA causes the channel to open and
-
Cl to flow into the cell with the resultant
membrane hyperpolarization
• Various receptors are actually part of the GABAA
receptor, with each receptor accommodating a
specific ligand
A. DIAZEPAM
Mechanism of Action:
• Interaction of Benzodiazepine with
Benzodiazepine receptor in the Chloride
ionophore (ionophore: substance that is able to
transport particular ions across a lipid membrane
in a cell.)
• This leads to an allosteric change in t he GABAA
receptor, causing enhanced binding of GABA
• This enhanced binding of GABA leads to an
-
increase in Cl conductance
• Hyperpolarization of neuronal membrane
(increases the FREQUENCY of channel opening)
Pharmacologic actions and effects:
1. CNS
• Sedation – calming effect
• Hypnosis – facilitate onset and maintenance
of sleep
• Anticonvulsant
• Muscle relaxation; not as marked as when
neuromuscular blockers are used
• Anterograde amnesia
Respiratory system
• hypnotic dose has no effect in normal
individuals
• caution in children, elderly and patients with
impaired hepatic function (I.e. alcoholics)
Pharmacology: Sedative-Hypnotic-Anxiolytic Drugs | 2
 • hypnotic doses worsen sleep-related
breathing disorders by decreasing muscle
tone in the upper airway muscles or by
decreasing the ventilator response to CO 2
Eg. Obstructive sleep apnea (OSA)
**OSA - a contraindication to the use of alcohol or any
sedative-hypnotic agent, including a benzodiazepine;
**Partial airway obstruction of those who snore regularly
may be converted to OSA under the influence of these drugs.
• exaggerated effects in patients with
pulmonary disease
Eg. COPD
**As dose is increased, effects are also increased in
progression. Benzodiazepines however, don’t reach the peak
of this curve. They cannot produce respiratory depression,
but can still induce coma. They are safer compared to
barbiturates, pero not really that safe, kasi nakakapagcause
din ng coma. Lesser evil lang.
**Ethanol can cause respiratory depression. A friendly  •
 post-evals encouragement/reminder :D
3. CVS
• negative inotropic effect
• Coronary vasodilatation on IV administration
• decrease BP and increase heart rate
4. GIT
• Decrease nocturnal gastric secretion
• Relieves anxiety-related GI disorders
Pharmacokinetics:
• completely absorbed from the GIT
o All the benzodiazepines are absorbed
completely, except clorazepate
• very high lipid solubility → high rate of entry into
CNS → rapid onset, short duration
o ~99% lipid solubility: conc’n in the CSF is
approx equal to the conc’n of free drug in
plasma
• Peak plasma concentration in 30-90 minutes after
oral intake
• onset after IM administration is variable, but
faster than oral
• Biphasic plasma concentration time curve:
o An initial rapid and extensive
distribution phase (half-life 3 hrs.)
o Prolonged elimination phase (half-life 20-
48 hrs.)
• Elimination half-life may be prolonged in the
newborn, elderly, patients with hepatic or renal
disease
• High protein binding (99%)
• readily crosses the blood brain barrier
• CNS concentration approximates plasma
concentration
• crosses the placenta and secreted in breast milk
**Diazepam IV reaches therapeutic concentration at a faster
time + less dose compared to PO, since PO route goes
through hepatic first-pass effect
Benzodiazepines are metabolized by CYP3A4 and
CYP2C19 to active metabolites, Nordazepam and
Temazepam; then both metabolites are further
metabolized to Oxazepam (see the following
diagram)
• Temazepam and Oxazepam subsequently
undergoes glucuronidation
• do not induce activity of hepatic microsomal
enzymes
• Drug and its metabolites are excreted in urine.
**Diagram of the text 
Pharmacology: Sedative-Hypnotic-Anxiolytic Drugs | 3
Therapeutic uses of Diazepam:
1. Anxiety
2. Insomnia
3. Seizure disorders
• Status epilepticus and spasms due to tetanus
• Lorazepam as alternative
4. Anesthesia
• Pre-anesthetic medication (Lorazepam as
alternative)
• Induction agent – Midazolam
5. Muscle spasticity
• Reflex muscle spasm due to trauma to
muscles, bones and joints
• Spasticity due to upper motor neuron lesions
6. Control signs and symptoms of withdrawal from
alcohol
• acute agitation
• tremors
• impending or acute delirium tremens
• hallucinosis
Adverse Effects:
• Sedation and impairment of performance
o motor incoordination
o impairment of mental and motor function
o increased reaction time
o residual daytime sedation
• Memory impairment
o anterograde amnesia – may be associated
with inappropriate behaviour
o dose-related
o tolerance may develop
• Increase risk of respiratory depression in patients
with chronic respiratory insufficiency
• Increase arterial carbon dioxide tension and
decrease oxygen tension in patients with chronic
obstructive pulmonary disease
• Increase frequency of seizures in patients with
epilepsy
• Disinhibition (paradoxical) reactions (dose realted):
o restlessness, agitation, irritability
o Aggressive, inappropriate behavior
o delusions, hallucinations
o hostility, acute rage
• Pregnancy and Lactation
o Teratogenic
o Fetal respiratory depression
o “Floppy infant syndrome”
 hypothermia
 hypotonia, poor sucking
 respiratory depression
Abuse and Dependence:
• Abuse potential decreased when properly
prescribed and supervised BUT CAN STILL HAPPEN
• dependence may occur at therapeutic doses taken
on regular basis for prolonged periods
• Shorter acting Benzodiazepines produce the
greatest dependence ; since they’re short acting,
they have a shorter effect, and after the short
effect you want more, so you take multiple short
effect drugs.
Withdrawal syndrome:
• similar in character with those of barbiturates and
alcohol
• occurs after abrupt discontinuation of drug
• withdrawal symptoms may include temporary
intensification of the problems that originally
prompted their use (e.g. insomnia, anxiety)
• other symptoms include dysphoria, palpitations,
panic attacks, hypersensitivity to light, sound and
touch
• major syndrome includes convulsions, confusional
state, hyperthermia; death can occur
• can be prevented by gradually tapering the dose
before stopping treatment
• abuse by the pregnant mother can result in
withdrawal syndrome in the newborn
IV. THE NEWER SEDATIVE HYPNOTICS
A. ZOLPIDEM
• an imidazopyridine
• structurally unrelated to Benzodiazepines but
binds to the Bz1 receptor
• shortens sleep latency and prolongs total sleep time
• currently approved for short term treatment of 
insomnia (7-10 days)
• rarely produce residual daytime sedation or
amnesia
• do not produce respiratory depression even at
large doses
Mechanism of Action:
• binds selectively to Bz1 receptors
• Facilitates GABA-mediated neuronal inhibition
• Actions can be antagonized by Flumazenil
Pharmacokinetics:
• readily absorbed from the GIT
• first pass hepatic metabolism results in an oral
bioavailability of about 70%. (lower when the drug
is ingested with food)
Pharmacology: Sedative-Hypnotic-Anxiolytic Drugs | 4
 • Peak plasma concentration in 2-3 hrs (may be
increased n those with cirrhosis and in older
patients; adjustment of dose is necessary)
• plasma half-life is approx. 2 hours
• rapidly metabolized by liver enzymes into inactive
metabolites
• dosage should be reduced in the elderly, in
patients with hepatic dysfunction, patients taking
Cimetidine and other drugs that inhibit drug
metabolizing enzymes
B. BUSPIRONE
Mechanism of Action:
• Acts as partial agonists at the serotonin (5-HT1-A)
receptor, thereby reducing release of 5-HT &
other mediators
***(More serotonin mas happy; Buspirone
acts as a substitute for serotonin, so by 
negative feedback, decreased yung release ng
serotonin, kasi yung Buspirone, acts like
serotonin aka partial agonist 
 )
• Clinically, partial agonists (in this case, Buspirone)
can activate receptors to give a desired
submaximal response when inadequate amounts
of the endogenous ligand (Serotonin) are present
• Has affinity for brain Dopamine (DA2) receptors:
o Ipsapirone, Gepirone - related a nxiolytics
o Anxiolytic effects of buspirone takes more
than a week to become established
o Not anticonvulsant or muscle relaxant
• Used to treat generalized anxiety disorders (GAD)
• Relieves anxiety without causing marked
sedative, hypnotic or euphoric effects
• Minimal sedation
• Cognitive and psychomotor dysfunction is low
• Ineffective in control of panic attacks
• Adverse effects :
o headaches, nervousness, dizziness but
not sedation or loss of consciousness
Classification according to duration of action:
C. FLUMENAZIL : Benzodiazepine antagonist
• Structure similar with benzodiazepines but with
replacement of keto function at position 5 and a
methyl substituent at position 4
• Management of suspected Benzodiazepine
overdose
o Cumulative dose of 5 mg should produce
response
• Reversal of sedative effects of Benzodiazepine
during either general anesthesia, or diagnostic or
therapeutic procedures
• Antagonism of benzodiazepine-induced
respiratory depression is less predictable
Pharmacology: Sedative-Hypnotic-Anxiolytic Drugs | 5
• Available only for IV administration with short t½
of (0.7 – 1.3 hours)  because benzodiazepines
have a longer duration of action, there is a need
to repeat administration of flumanezil
• Adverse effects: agitation, confusion, dizziness,
and nausea. Seizure and cardiac arrhythmias on
px with tricyclic antidepressant
V. BARBITURATES
→Prolong GABA activity
-
→Increase DURATION of Cl channel opening
→Have GABA mimetic property at high doses
→Do not act through Benzodiazepine receptors
→Have their own binding sites on the GABA complex
→Also inhibit complex 1 of electron transport chain
• most commonly used drug for sedation and
hypnosis before the advent of Benzodiazepines
• toxic and highly addictive
• abrupt withdrawal can cause death
• poisoning accounted for a great number of deaths
from sedative hypnotics
• low degree of selectivity (whether you give it for
anxiety, it may still produce sedation or coma)
• Low therapeutic index ( finals review. Haha
therapeutic index is a measure of how safe a drug
is. TI = . LD = lethal dose, ED = effective dose.
The lower the therapeutic index, the more
dangerous the drug is.)
• less selective than Benzodiazepines
• produce strong physiological dependence on long
term use
• depresses the medullary respiratory center
• also produce loss of brainstem vasomotor c ontrol
and myocardial depression
1. Long acting
• Phenobarbital** (prototype)
2. Intermediate acting
• Amobarbital
3. Short acting
• Pentobarbital
• Secobarbital
4. Ultrashort acting
• Thiopental: used for induction of 
anesthesia
 A. PHENOBARBITAL 6. Cardiovascular system
• hypnotic dose produce slight decrease in BP
Mechanism of Action:
and heart rate
• Binds to Barbiturate receptor in the GABA A
• Myocardial depression at toxic doses
receptors
• Enhance binding of GABA to GABA A Receptor 7. Uterus
• Increase Chloride conductance • Decrease tone and frequency of contractions
• Hyperpolarization of neuronal membrane 8. Abuse and dependence potential
(increases the DURATION of channel opening) • the barbiturates may have euphoriant effects

Pharmacologic actions and effects:

Pharmacokinetics:
1. Central nervous system
• weak acid
• Mild sedation to deep coma
• rapid absorption following oral administration
• Hypnotic doses decrease sleep latency and
• Sodium salts are more rapidly absorbed from GIT
increase total sleep time
• available in tablet, liquid, parenteral and rectal
• Over dosage can produce death due to
formulations
respiratory depression
• onset of action: 10 mins to 60 mins
• mood alteration
• presence of food decreases rate of absorption
• anticonvulsant at low doses
• distributed rapidly to all tissues and body fluids
• Sub-anesthetic doses may increase reaction
• low lipid solubility
to painful stimuli aka paradoxical excitement 
• low plasma protein binding
2. Peripheral Nervous structures • Long duration of action; plasma half-life is 53-118
• selectively depress transmission in autonomic hrs.
ganglia and reduce nicotinic excitation by • metabolized primarily in the liver by glucuronide
choline esters conjugation
• metabolic products are excreted in the urine
3. Respiratory system
Depress both the respiratory drive and the • 25% of Phenobarbital is excreted unchanged in
•

mechanisms responsible for the rhythmic the kidneys

character of respiration. • Phenobarbital excretion can be increased by

hypnotic doses produced same degree of 

alkalinization of the urine.
•

respiratory depression during physiologic • In the elderly and in those with limited hepatic

sleep function, dosages should be reduced.

• Phenobarbital causes auto metabolism by
• Degree of respiratory depression is dose
dependent induction of liver enzymes

• Hypostatic pneumonia
Adverse Effects:
• Coughing, sneezing, hiccoughing and
1. Hypersensitivity reaction
laryngospasm esp. for very acute use of 
• Stevens – Johnson syndrome
Thiopental
2. Central nervous system
4. Gastrointestinal tract
• drowsiness, residual CNS depression
• decrease tone and amplitude of intestinal
• paradoxical excitement
contraction→ constipation
• paradoxical dysphoria
• Hypnotic doses does not significantly delay
• hyperreactivity
gastric emptying time
• The relief of various GI symptoms by sedative 3. Respiratory system
doses is probably largely due to the central- • Hypoventilation, manifested as apnea
depressant action. • Hypostatic pneumonia
• Cough, hiccough/hiccup
5. Liver
• Laryngospasm
• does not impair normal hepatic function
• Induction of liver enzymes at high doses 4. Cardiovascular system
(CYP450, delta aminolevulinic acid synthetase, • bradycardia
aldehyde dehydrogenase, etc.) • Hypotension, syncope
• Acutely, it may inhibit the biotransformation 5. Gastrointestinal
of some drugs and endogenous substrates, • Nausea, vomiting
such as steroids • Constipation

Pharmacology: Sedative-Hypnotic-Anxiolytic Drugs | 6

 6. Enhance porphyrin synthesis
• may be fatal in patients with acute
intermittent porphyria (disorders of certain
enzymes in the heme bio-synthetic pathway)
7. Toxicity
• acute – unsteady gait, slurred speech,
sustained nystagmus
• chronic – confusion, poor judgment,
irritability, insomnia, somatic complaints
8. Drug Interaction
• Additive CNS depression with ethanol
Dependence:
• Similar to chronic alcoholism
• Arises from repeated administration on a
continuous basis in amounts exceeding usual
therapeutic doses
Withdrawal syndrome:
• Minor withdrawal symptoms appear 8-12 hrs.
after the last dose
o Symptoms appear in the following order:
anxiety, muscle twitching, tremors in
hands and fingers, progressive weakness,
distortion in visual perception, nausea,
vomiting, insomnia, orthostatic
hypotension
• Major withdrawal symptoms such as convulsions
and delirium occur within 16 hrs. and last up to 5
days after abrupt cessation of drug use.
• Symptoms of withdrawal can be very severe and
cause death
• Alcoholics, opiate, sedative-hypnotic and
amphetamine abusers are susceptible to
Phenobarbital abuse and dependence
• Intensity of withdrawal symptoms gradually
declines over a period of approximately 15 days
Tolerance:
• develops with prolonged use
• Amount needed to maintain the same level of  and liver by alcohol dehydrogenase (ADH)
intoxication increases
• Mechanisms:
o Pharmacodynamics
o Pharmacokinetics
• Tolerance to the effects on mood, sedation, a nd
hypnosis occurs more readily and is greater than
that to the anticonvulsant and lethal effects; thus,
as tolerance increases, the therapeutic index
decreases.
Therapeutic uses of Barbiturates:
1. Seizure disorders
• Grand mal seizures aka Tonic-Clonic seizures
• Benign febrile convulsion
2. Anesthesia
• Pre-anesthetic medication
3. Kernicterus and Hyperbilirubinemia: because
barbiturates induce protein (albumin) synthesis,
thereby increasing hepatic glucuronyl transferase
activity 
Contraindications:
• Pregnancy and lactation
• Acute intermittent porphyria or porphyria variegata
• Pulmonary disease
VI. ETHANOL
• widely used for its social value
• tolerance develops after chronic use
• Blood Alcohol Levels in human beings can be
estimated readily by the measurement of alcohol
levels in expired air
• Legally allowed Blood Alcohol Level is set at
below 80 mg % (80 mg ethanol per 100 ml blood;
0.08% w/v),
• Each of the following contains approximately 14 g
Ethanol which will produce a BAL of approximately
30mg% to 70-kg person:
o 12 oz. bottle of Beer
o 5 oz. glass of wine
o 1.5 oz. “shot” of 40% liquor
• BAL is determined by a number of factors,
including the rate of drinking, sex, body weight and
water percentage, and the rates of metabolism and
stomach emptying
Pharmacokinetics:
• Rapidly absorbed after oral administration
• Peak blood levels occur about 30 min after
ingestion when stomach is empty (Correlation:
Kumain kung gusto tumagal )
• Presence of food delays absorption
• undergoes first pass metabolism in the stomach
•  Aspirin increases ethanol bioavailability by
inhibiting gastric ADH.
• Ethanol is metabolized largely by sequential
hepatic oxidation, first to acetaldehyde by ADH
and then to acetic acid by aldehyde
dehydrogenase (ALDH)
• Hepatic cytochrome P450 (CYP2E1) and catalase
also contribute to ethanol metabolism
• Zero order kinetics
• 90-95% of ingested Ethanol undergoes hepatic
metabolism to acetate
• small amounts are excreted in urine, sweat and
breath
Pharmacology: Sedative-Hypnotic-Anxiolytic Drugs | 7
 • chronic alcohol consumption induces activity of  • Malabsorption
hepatic enzymes • Acute and chronic pancreatitis
• acute alcohol consumption inhibits activity of  • Fatty infiltration of the liver, hepatitis and
hepatic enzymes cirrhosis

7. Vitamin and Mineral Deficiencies

• Peripheral neuropathy
• Korsakoff’s psychosis (a neurological disorder 
caused by the lack of thiamine (vitamin B1 ) in
the brain. Its onset is linked to chronic alcohol 
abuse and/or severe malnutrition)
• Wernicke’s encephalopathy (syndrome
characterized by ataxia, ophthalmoplegia,
nystagmus, confusion, and impairment of 
short-term memory )
• Osteoporosis
• Hypomagnesemia

8. Sexual function
• Disinhibiting effects initially
• Excessive long term use can lead to
**Sequential hepatic metabolism of Ethanol  (also see figure
on the last page) deterioration of sexual function
o Gonadal atrophy, decrease fertility
o Impotence in men
Pharmacologic actions and effects:  Decrease sexual arousal
1. Central nervous system  Increased ejaculatory latency
• Depressant  Decreased orgasmic pleasure
• Mild depression to general a nesthesia 9. Hematologic and Immunologic
• Death can result due to respiratory • Anemia
depression • Thrombocytopenia
• Behavioral disinhibition • leukopenia
• Neurotoxic • Immunosuppression
2. Cardiovascular system
• “French paradox” (is the observation that  Acute Ethanol Intoxication:
French people suffer a relatively low incidence • Blood ethanol concentration of 20-30 mg/dL will
of coronary heart disease, despite having a produce
diet relatively rich in saturated fats.) o Increased reaction time
• Light to moderate amounts may be cardio- o Impulsive behavior
protective o Diminished fine motor control
o Increase HDL o Impaired judgment
o Anti-clotting mechanism • 50-80 mg/dL intoxicated
• Cardiac arrhythmias • 400 mg/dL can be fatal
• Cardiomyopathy
• Hypertension, Hemorrhagic stroke Tolerance and Dependence:
3. Skeletal muscle • reduced behavioral or physiological response to
• Decrease muscle strength the same dose of Ethanol
• Muscle atrophy • Withdrawal syndrome include sleep disruption,
sympathetic activation, tremors and in severe
4. Body temperature cases, seizures ( physical dependence)
0
• Hypothermia 2 to cutaneous vasodilatation • 2 or more days after withdrawal, delirium tremens
• increased sweating may occur characterized by hallucinations,
delirium, fever and tachycardia
5. Kidneys
• Delirium tremens can be fatal
• Inhibition of ADH release
•  psychological dependence - craving and drug-
6. Gastrointestinal tract seeking behaviour
• Esophageal dysfunction
• Peptic ulcer disease

Pharmacology: Sedative-Hypnotic-Anxiolytic Drugs | 8

Teratogenic Effect: Fetal Alcohol Syndrome
• Craniofacial abnormalities
o Microcephaly, long and smooth philtrum
o Shortened palpebral fissures, flat midface
o Epicanthal folds
• CNS dysfunction
o Hyperactivity, attention deficits
o Mental retardation
o Learning disabilities
• Pre and/or post natal stunting of growth

*** Disulfram - inhibits a cetaldehyde dehydrogenase

VII. PHARMACOTHERAPY OF ALCOHOLISM **Note: DIAZEPAM, ALPRAZOLAM, MIDAZOLAM,

• Disulfiram** ZOLPIDEM, (Benzodiazepines) PENTOBARBITAL SODIUM,
• Naltrexone PHENOBARBITAL SODIUM (Barbiturates) NEED S2
• Acamprosate NUMBER, NO REFILL PER Rx IN PRESCRIPTION WRITING.

A. DISULFIRAM

• Inhibits acetaldehyde dehydrogenase, therefore

-Nothing follows-
acetaldehyde accumulates
• Given alone, relatively non-toxic
• Given to persons who ingest alcohol will produce
signs and symptoms of Acetaldehyde poisoning
o Hot and flushed face
o Throbbing headache
o Respiratory difficulty
o Copious vomiting
o Hypotension, chest pains

Hepatic metabolism of 

Ethanol 

Pharmacology: Sedative-Hypnotic-Anxiolytic Drugs | 9