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PHARMACOLOGY Sedative-Hypnotic-Anxiolytic Drugs Lecturer: Deo L. Panganiban, MD, FPSECP I. Sedative-Hypnotic
Transcriber: Cj Editor: MGB Number of pages: 9
IV. Newer Sedative Hypnotics
a.
Phenobarbital
II. The Drugs
a.
Zolpidem
VI. Ethanol
III. Benzodiazepines
b.
Buspirone
VII. Pharmacotherapy of Alcoholism
a.
Diazepam
Sedative •
a. Disulfiram
V. Barbiturates
5.
Decreases activity Moderates excitement
•
•
Calming or tranquilizing effect
•
Used as pre-medication for surgical procedures
•
6. 7.
Produces drowsiness
•
Facilitates the onset and maintenance of sleep
•
Glutethimide
•
Thalidomide: (kakasawa na to haha; initially prescribed as a sedative for pregnant women, until they eventually realized that it was a teratogenic; now it can be used as an
person can be aroused easily
•
CNS depressants
•
depress the CNS in a dose dependent manner,
Meprobamate
Piperidinediones
that resembles natural sleep and from which the
I. SEDATIVE-HYPNOTIC SEDATIVE-HYPNOTIC DRUGS
Chloral hydrate
Carbamates** (older sedative-hypnotic) •
Hypnotic •
Chloral dervatives** (older sedative-hypnotic)
immunosuppressant/anti-cancer drug) 8.
Antihistamines: the older antihistamines; because the newer ones were developed para hindi st
antukin (Finals review! 1 generation Antihistamines make you drowsy, eg.
progressively producing sedation, sleep,
Diphenhydramine; while 2
unconsciousness, surgical anesthesia, coma and
nd
rd
and 3 generation 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 dosedependent; the greater the dose, the “wilder” the effect
•
Benzodiazepines Benzodiazepines were first introduced in 1960’s st
with the synthesis of the 1 benzodiazepine, Chlordiazepoxide
II. THE DRUGS 1.
Benzodiazepines
3.
4.
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 2.
•
•
membered diazepine ring structure.
Non-Benzodiazepines •
Zolpidem
•
Buspirone
Barbiturates
Composition: a benzene ring fused to a 7-
•
A halogen or nitrogen substituent in the 7
•
Phenobarbital
position – sedative-
•
Amobarbital
hypnotic effect
•
Thiopental
Alcohol •
Ethanol Pharmacology: Sedative-Hypnotic-Anxiolytic Sedative-Hypnotic-Anxiolytic Drugs | 1
•
Relatively wide margin of safety
•
Prolonged, daily use may produce dependence
•
An Oligomeric glycoprotein (α, β, δ, γ, ε,π, ρ etc)
•
Have little effect on respiratory or cardiovascular
•
Major player in inhibitory synapses
function compared to the Barbiturates
•
A Cl channel
Fatality from overdose is rare except when taken
•
Binding of GABA causes the channel to open and
•
GABAA receptor:
-
-
with alcohol or other CNS depressants
Cl to flow into the cell with the resultant
•
Exert qualitatively similar clinical effects
membrane hyperpolarization
•
Low capacity to produce fatal CNS depression
•
Coma may occur at very large doses
receptor, with each receptor accommodating a
•
Has displaced other agents as first line Sedative
specific ligand
•
Various receptors are actually part of the GABAA
hypnotics.
Classification according to duration of action: 1.
Short-acting (T½ **24 hours of anterograde amnesia :>
3.
•
Chlordiazepoxide
•
Alprazolam
•
Estazolam
•
Flunitrazepam
•
Temazepam
A. DIAZEPAM Mechanism of Action: •
Interaction of Benzodiazepine with
Long acting (>24 hours): usually used for longer
Benzodiazepine receptor in the Chloride
sedation periods
ionophore (ionophore: substance that is able to
•
Flurazepam
transport particular ions across a lipid membrane
•
Quazepam
in a cell.)
•
Diazepam** ( prototype)
•
This leads to an allosteric change in t he GABAA receptor, causing enhanced binding of GABA
Benzodiazepine Receptors 1.
-
•
mediate cognition, memory, motor control
Pharmacologic actions and effects:
Bz3 •
outside CNS; abundant in the kidneys
1.
Characteristics of Benzodiazepine Receptors: •
•
Hyperpolarization of neuronal membrane (increases the FREQUENCY of channel opening)
Bz2 or Omega 2 •
3.
mediate sedative, hypnotic action
This enhanced binding of GABA leads to an increase in Cl conductance
Bz1 or Omega 1 •
2.
•
CNS •
Sedation – calming effect
•
Hypnosis – facilitate onset and maintenance of sleep
Benzodiazepine receptor is a part of the GABA A receptor
•
Anticonvulsant
Upon binding, this will cause an allosteric change
•
Muscle relaxation; not as marked as when neuromuscular blockers are used
in the GABAA receptor •
GABAA receptors are responsible for most
•
Anterograde amnesia
inhibitory neurotransmission in the CNS •
Benzodiazepine binding enhances coupling of GABA to its receptor
•
High affinity
•
Saturable and stereospecific; a certain dose will occupy all the receptors
2.
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
Biphasic plasma concentration time curve: o
distribution phase (half-life 3 hrs.)
tone in the upper airway muscles or by decreasing the ventilator response to CO 2
o
•
**Partial airway obstruction of those who snore regularly
exaggerated effects in patients with
•
pulmonary disease Eg. COPD
Elimination half-life may be prolonged in the newborn, elderly, patients with hepatic or renal
sedative-hypnotic agent, including a benzodiazepine; may be converted to OSA under the influence of these drugs.
Prolonged elimination phase (half-life 2048 hrs.)
Eg. Obstructive sleep apnea (OSA) **OSA - a contraindication to the use of alcohol or any
An initial rapid and extensive
disease •
High protein binding (99%)
•
readily crosses the blood brain barrier
•
CNS concentration approximates plasma concentration
•
crosses the placenta and secreted in breast milk
**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,
**Diazepam IV reaches therapeutic concentration at a faster
but can still induce coma. They are safer compared to
time + less dose compared to PO, since PO route goes
barbiturates, pero not really that safe, kasi nakakapagcause
through hepatic first-pass effect
din ng coma. Lesser evil lang. **Ethanol can cause respiratory depression. A friendly
•
post-evals encouragement/reminder :D
Benzodiazepines are metabolized by CYP3A4 and
CYP2C19 to active metabolites, Nordazepam and Temazepam; then both metabolites are further
3.
4.
CVS
metabolized to Oxazepam (see the following
•
negative inotropic effect
•
Coronary vasodilatation on IV administration
•
decrease BP and increase heart rate
GIT
diagram) •
undergoes glucuronidation •
•
Decrease nocturnal gastric secretion
•
Relieves anxiety-related GI disorders
Temazepam and Oxazepam subsequently do not induce activity of hepatic microsomal enzymes
•
Drug and its metabolites are excreted in urine.
Pharmacokinetics: •
completely absorbed from the GIT All the benzodiazepines are absorbed
o
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
**Diagram of the text Pharmacology: Sedative-Hypnotic-Anxiolytic Drugs | 3
Therapeutic uses of Diazepam: 1.
Anxiety
2.
Insomnia
3.
Seizure disorders
4.
•
Status epilepticus and spasms due to tetanus
•
Lorazepam as alternative
on regular basis for prolonged periods •
they have a shorter effect, and after the short
alternative)
effect you want more, so you take multiple short
Induction agent – Midazolam
effect drugs.
Reflex muscle spasm due to trauma to
Withdrawal syndrome: •
Control signs and symptoms of withdrawal from
•
occurs after abrupt discontinuation of drug
•
withdrawal symptoms may include temporary
intensification of the problems that originally
•
acute agitation
•
tremors
•
impending or acute delirium tremens
panic attacks, hypersensitivity to light, sound and
•
hallucinosis
touch
prompted their use (e.g. insomnia, anxiety) •
•
Adverse Effects:
•
o
motor incoordination
o
impairment of mental and motor function
o
increased reaction time
o
residual daytime sedation
•
•
•
can be prevented by gradually tapering the dose
•
abuse by the pregnant mother can result in
withdrawal syndrome in the newborn
Memory impairment anterograde amnesia – may be associated
o
dose-related
o
tolerance may develop
IV. THE NEWER SEDATIVE HYPNOTICS A. ZOLPIDEM
Increase risk of respiratory depression in patients
•
an imidazopyridine
with chronic respiratory insufficiency
•
structurally unrelated to Benzodiazepines but binds to the Bz1 receptor
Increase arterial carbon dioxide tension and decrease oxygen tension in patients with chronic
•
shortens sleep latency and prolongs total sleep time
obstructive pulmonary disease
•
currently approved for short term treatment of
insomnia (7-10 days)
Increase frequency of seizures in patients with •
epilepsy •
major syndrome includes convulsions, confusional
before stopping treatment
with inappropriate behaviour
•
other symptoms include dysphoria, palpitations,
state, hyperthermia; death can occur
Sedation and impairment of performance
o
•
similar in character with those of barbiturates and alcohol
Spasticity due to upper motor neuron lesions
alcohol
•
Shorter acting Benzodiazepines produce the
Pre-anesthetic medication (Lorazepam as
muscles, bones and joints •
dependence may occur at therapeutic doses taken
greatest dependence ; since they’re short acting,
Muscle spasticity •
6.
•
Anesthesia
•
Abuse potential decreased when properly prescribed and supervised BUT CAN STILL HAPPEN
•
•
5.
Abuse and Dependence:
amnesia
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
rarely produce residual daytime sedation or
•
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
•
Available only for IV administration with short t½
increased n those with cirrhosis and in older
of (0.7 – 1.3 hours) because benzodiazepines
patients; adjustment of dose is necessary)
have a longer duration of action, there is a need
•
plasma half-life is approx. 2 hours
to repeat administration of flumanezil
•
rapidly metabolized by liver enzymes into inactive
•
•
Adverse effects: agitation, confusion, dizziness,
metabolites
and nausea. Seizure and cardiac arrhythmias on
dosage should be reduced in the elderly, in
px with tricyclic antidepressant
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
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 •
serotonin aka partial agonist ) •
Clinically, partial agonists (in this case, Buspirone) can activate receptors to give a desired submaximal response when inadequate amounts
hypnosis before the advent of Benzodiazepines •
toxic and highly addictive
•
abrupt withdrawal can cause death
•
poisoning accounted for a great number of deaths
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
from sedative hypnotics •
•
Low therapeutic index ( finals review. Haha therapeutic index is a measure of how safe a drug
Not anticonvulsant or muscle relaxant
is. TI =
. LD = lethal dose, ED = effective dose.
•
Used to treat generalized anxiety disorders (GAD)
•
Relieves anxiety without causing marked
The lower the therapeutic index, the more
sedative, hypnotic or euphoric effects
dangerous the drug is.)
•
Minimal sedation
•
less selective than Benzodiazepines
•
Cognitive and psychomotor dysfunction is low
•
produce strong physiological dependence on long
•
Ineffective in control of panic attacks
•
Adverse effects : o
headaches, nervousness, dizziness but not sedation or loss of consciousness
C.
low degree of selectivity (whether you give it for anxiety, it may still produce sedation or coma)
than a week to become established o
most commonly used drug for sedation and
FLUMENAZIL : Benzodiazepine antagonist •
term use •
depresses the medullary respiratory center
•
also produce loss of brainstem vasomotor c ontrol and myocardial depression
Classification according to duration of action: 1.
Structure similar with benzodiazepines but with replacement of keto function at position 5 and a
•
2.
methyl substituent at position 4 •
Management of suspected Benzodiazepine
3.
Cumulative dose of 5 mg should produce response
•
Reversal of sedative effects of Benzodiazepine during either general anesthesia, or diagnostic or
4.
Phenobarbital** (prototype)
Intermediate acting •
overdose o
Long acting
Amobarbital
Short acting •
Pentobarbital
•
Secobarbital
Ultrashort acting •
Thiopental: used for induction of anesthesia
therapeutic procedures •
Antagonism of benzodiazepine-induced respiratory depression is less predictable Pharmacology: Sedative-Hypnotic-Anxiolytic Drugs | 5
A. PHENOBARBITAL
6.
•
Mechanism of Action: •
•
receptors Enhance binding of GABA to GABA A Receptor
•
Increase Chloride conductance
•
Hyperpolarization of neuronal membrane
7.
8.
1.
Central nervous system •
Mild sedation to deep coma
•
Hypnotic doses decrease sleep latency and increase total sleep time
•
•
mood alteration
•
anticonvulsant at low doses
•
Sub-anesthetic doses may increase reaction to painful stimuli aka paradoxical excitement
2.
Peripheral Nervous structures •
•
weak acid
•
rapid absorption following oral administration
•
Sodium salts are more rapidly absorbed from GIT
•
available in tablet, liquid, parenteral and rectal formulations
•
onset of action: 10 mins to 60 mins
•
presence of food decreases rate of absorption
•
distributed rapidly to all tissues and body fluids
•
low lipid solubility
•
low plasma protein binding
•
Long duration of action; plasma half-life is 53-118 hrs.
•
choline esters 3.
Respiratory system •
Depress both the respiratory drive and the
•
•
metabolic products are excreted in the urine
•
25% of Phenobarbital is excreted unchanged in the kidneys
•
•
Degree of respiratory depression is dose
•
Hypostatic pneumonia
•
Coughing, sneezing, hiccoughing and laryngospasm esp. for very acute use of
Adverse Effects: 1.
Gastrointestinal tract •
2.
decrease tone and amplitude of intestinal contraction→ constipation
•
Hypnotic doses does not significantly delay gastric emptying time
•
5.
The relief of various GI symptoms by sedative
3.
Stevens – Johnson syndrome
Central nervous system •
drowsiness, residual CNS depression
•
paradoxical excitement
•
paradoxical dysphoria
•
hyperreactivity
Respiratory system
doses is probably largely due to the central-
•
Hypoventilation, manifested as apnea
depressant action.
•
Hypostatic pneumonia
•
Cough, hiccough/hiccup
•
Laryngospasm
Liver •
does not impair normal hepatic function
•
Induction of liver enzymes at high doses
•
Hypersensitivity reaction •
Thiopental 4.
Phenobarbital causes auto metabolism by induction of liver enzymes
dependent •
In the elderly and in those with limited hepatic function, dosages should be reduced.
sleep •
Phenobarbital excretion can be increased by alkalinization of the urine.
hypnotic doses produced same degree of respiratory depression during physiologic
metabolized primarily in the liver by glucuronide
conjugation
mechanisms responsible for the rhythmic character of respiration.
the barbiturates may have euphoriant effects
Pharmacokinetics:
selectively depress transmission in autonomic ganglia and reduce nicotinic excitation by
Decrease tone and frequency of contractions
Abuse and dependence potential •
Over dosage can produce death due to respiratory depression
Myocardial depression at toxic doses
Uterus •
(increases the DURATION of channel opening)
Pharmacologic actions and effects:
hypnotic dose produce slight decrease in BP and heart rate
Binds to Barbiturate receptor in the GABA A
•
Cardiovascular system
4.
Cardiovascular system
(CYP450, delta aminolevulinic acid synthetase,
•
bradycardia
aldehyde dehydrogenase, etc.)
•
Hypotension, syncope
Acutely, it may inhibit the biotransformation of some drugs and endogenous substrates, such as steroids
5.
Gastrointestinal •
Nausea, vomiting
•
Constipation
Pharmacology: Sedative-Hypnotic-Anxiolytic Drugs | 6
6.
Enhance porphyrin synthesis •
2.
may be fatal in patients with acute intermittent porphyria (disorders of certain
•
3.
enzymes in the heme bio-synthetic pathway) 7.
Pre-anesthetic medication
Kernicterus and Hyperbilirubinemia: because barbiturates induce protein (albumin) synthesis,
Toxicity •
Anesthesia
thereby increasing hepatic glucuronyl transferase
acute – unsteady gait, slurred speech,
activity
sustained nystagmus •
chronic – confusion, poor judgment, irritability, insomnia, somatic complaints
8.
Drug Interaction •
Contraindications: •
Pregnancy and lactation
•
Acute intermittent porphyria or porphyria variegata
•
Pulmonary disease
Additive CNS depression with ethanol
Dependence: •
Similar to chronic alcoholism
•
Arises from repeated administration on a
continuous basis in amounts exceeding usual therapeutic doses
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
Withdrawal syndrome: •
levels in expired air
Minor withdrawal symptoms appear 8-12 hrs. after the last dose o
•
Symptoms appear in the following order:
below 80 mg % (80 mg ethanol per 100 ml blood;
anxiety, muscle twitching, tremors in
0.08% w/v),
hands and fingers, progressive weakness,
•
Ethanol which will produce a BAL of approximately
vomiting, insomnia, orthostatic
30mg% to 70-kg person: o
12 oz. bottle of Beer
Major withdrawal symptoms such as convulsions
o
5 oz. glass of wine
and delirium occur within 16 hrs. and last up to 5
o
1.5 oz. “shot” of 40% liquor
days after abrupt cessation of drug use. •
•
•
BAL is determined by a number of factors,
Symptoms of withdrawal can be very severe and
including the rate of drinking, sex, body weight and
cause death
water percentage, and the rates of metabolism and
Alcoholics, opiate, sedative-hypnotic and
stomach emptying
amphetamine abusers are susceptible to •
Each of the following contains approximately 14 g
distortion in visual perception, nausea, hypotension •
Legally allowed Blood Alcohol Level is set at
Pharmacokinetics:
Phenobarbital abuse and dependence
•
Rapidly absorbed after oral administration
Intensity of withdrawal symptoms gradually
•
Peak blood levels occur about 30 min after
declines over a period of approximately 15 days
ingestion when stomach is empty (Correlation: Kumain kung gusto tumagal )
Tolerance: •
develops with prolonged use
•
Amount needed to maintain the same level of intoxication increases
•
•
•
Presence of food delays absorption
•
undergoes first pass metabolism in the stomach and liver by alcohol dehydrogenase (ADH)
•
Mechanisms: o
Pharmacodynamics
o
Pharmacokinetics
inhibiting gastric ADH. •
Ethanol is metabolized largely by sequential hepatic oxidation, first to acetaldehyde by ADH
Tolerance to the effects on mood, sedation, a nd
and then to acetic acid by aldehyde
hypnosis occurs more readily and is greater than
dehydrogenase (ALDH)
that to the anticonvulsant and lethal effects; thus,
•
as tolerance increases, the therapeutic index decreases.
Seizure disorders •
Grand mal seizures aka Tonic-Clonic seizures
•
Benign febrile convulsion
Hepatic cytochrome P450 (CYP2E1) and catalase also contribute to ethanol metabolism
•
Zero order kinetics
•
90-95% of ingested Ethanol undergoes hepatic
Therapeutic uses of Barbiturates: 1.
Aspirin increases ethanol bioavailability by
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 )
8.
**Sequential hepatic metabolism of Ethanol (also see figure
•
Osteoporosis
•
Hypomagnesemia
Sexual function •
Disinhibiting effects initially
•
Excessive long term use can lead to deterioration of sexual function
on the last page)
o
Gonadal atrophy, decrease fertility
o
Impotence in men
Pharmacologic actions and effects: 1.
Central nervous system •
Depressant
•
Mild depression to general a nesthesia
•
Death can result due to respiratory
9.
depression
2.
•
Behavioral disinhibition
•
Neurotoxic
Decrease sexual arousal
Increased ejaculatory latency
Decreased orgasmic pleasure
Hematologic and Immunologic •
Anemia
•
Thrombocytopenia
•
leukopenia
•
Immunosuppression
Cardiovascular system •
“French paradox” (is the observation that
French people suffer a relatively low incidence
Acute Ethanol Intoxication: •
•
Blood ethanol concentration of 20-30 mg/dL will produce
of coronary heart disease, despite having a
3.
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
Impaired judgment
o
Increase HDL
o
Anti-clotting mechanism
•
Cardiac arrhythmias
•
Cardiomyopathy
•
Hypertension, Hemorrhagic stroke
Skeletal muscle
•
50-80 mg/dL intoxicated
•
400 mg/dL can be fatal
Tolerance and Dependence: •
•
Decrease muscle strength
•
Muscle atrophy
reduced behavioral or physiological response to the same dose of Ethanol
•
Withdrawal syndrome include sleep disruption, sympathetic activation, tremors and in severe
4.
5.
cases, seizures ( physical dependence)
Body temperature 0
•
Hypothermia 2 to cutaneous vasodilatation
•
increased sweating
•
may occur characterized by hallucinations, delirium, fever and tachycardia
Kidneys •
Inhibition of ADH release
•
•
6.
Gastrointestinal tract •
Esophageal dysfunction
•
Peptic ulcer disease
2 or more days after withdrawal, delirium tremens
Delirium tremens can be fatal psychological dependence - craving and drugseeking behaviour
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 •
Disulfiram**
•
Naltrexone
•
Acamprosate
**Note: DIAZEPAM, ALPRAZOLAM, MIDAZOLAM, ZOLPIDEM, (Benzodiazepines) PENTOBARBITAL SODIUM, PHENOBARBITAL SODIUM (Barbiturates) NEED S2
NUMBER, NO REFILL PER Rx IN PRESCRIPTION WRITING. A. DISULFIRAM
•
Inhibits acetaldehyde dehydrogenase, therefore acetaldehyde accumulates
•
Given alone, relatively non-toxic
•
Given to persons who ingest alcohol will produce
-Nothing follows-
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
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