HYPNOTIC - SEDATIVE
DRUGS
Dra. Ma. Shiela C. Guiking
 Are drugs that belong to a group of agents that depress the
CNS in a relatively nonselective dose-dependent fashion,
producing progressively calming or drowsiness, sleep,
unconsiousness, surgical anesthesia, coma, fatal depression
of the respiration and cardiovascular regulation
 major therapeutic use is to cause sedation (with
concomitant relief of anxiety) or to encourage sleep
 SEDATIVES— drugs capable of producing
mild depression; decreased activity;
moderate excitement, and emotional
calmness
 - reduce anxiety (anxiolytic) and exert
a calming effect with little or no
effect on motor or mental functions,
 degree of CNS depression minimum
consistent with therapeutic efficacy
 HYPNOTICS — drugs that are used primarily
to
induce sleep
 - should produce drowsiness and encourage
the onset and maintenance of a state of
sleep
 - involves more pronounced depression of
the CNS
The Benzodiazepines are the most widely used
sedative hypnotics.
Structures- 1,4, Benzodiazepines-contain a
carboxamide group in the 7 – membered
heterocyclic ring structure.
A substituent in the 7 position, such as a
halogen or a nitro group, is required for
sedative-hypnotic activity
CLASSIFICATION:
BENZODIAZEPINES
Types:
A. Hypnotic Benzodiazepines
> Nitrazepam
> Flurazepam (Dalmane)
B. Anxiolytic Benzodiazepines
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Alprazolam ( Xanax)
Chlordiazepoxide ( Librium )
Chlorazepate ( Tranxene )
Clonazepam ( Klonopin )
Diazepam ( Valium )
Halazepam ( Paxipam )
Lorazepam ( Ativan )
Midazolam ( Versed )
Oxazepam ( Serax )
Prazepam ( Centrax )
Temazepam ( Restoril )
Triazolam ( Halcion )
Triazolam and Alprazolam : Triazolobenzodiazepines
Glutethimide, etc : Piperidinediones
> Meprobamate : Propanediol carbamates
> Barbiturates
> Alcohols : Ethanol, Chloral hydrate, Paraldehyde
> Cyclic esters
> Buspirone : azaspirodecanedione
> Zolpidem : Imidazopyridine
> Zaleplon : Pyrazolopyrimidine
> Beta – blocking drugs
> Clonidine
> Antipsychotic tranqulizers, tricyclic antidepressant drugs
> Antihistaminic agents (hydroxyzine, promethazine)
Since they commonly exert marked effects on the Peripheral autonomic nervous
system, they are sometimes referred to as “sedative
autonomic” drugs
PHARMACOKINETICS
A. Absorption
> to treat anxiety and sleep disorders: given orally
> oral absorption may depend on lipophilicity, with
plasma peak concentration ranging from 0.5 to 8 hours
rapid: triazolam, diazepam, clorazepate
slow : oxazepam, lorazepam temazepam
> with high lipid-water distribution coefficients in the
non-ionized form
> essentially completely absorbed
> Bioavailability : after intramuscular injection unreliable
(except lorazepam and midazolam )
B. Distribution
- some reach the systemic circulation only in the form of
active metabolite ( prazepam, flurazepam)
- rate of transport in blood depends on blood flow,
concentration gradients and permeability
- rate of entry into CNS depends on lipid solubility
- plasma protein binding 60% to over 95% cross the placental
barrier and secreted into breast milk
 PHARMACODYNAMICS:
 Mechanism of action
 appear to enhance GABA’s effects without directly
activating GABA receptors or opening the associated
chloride channels.
 The enhancement in chloride ion conductance induced by the
interaction of benzodiazepines with GABA takes the form
of an increase in the
 frequency of channel opening events
 Types of Benzodiazepine receptor interactions:
 1. AGONISTS
 facilitate GABA actions, and this occurs at multiple BZ receptor sites in the
case of benzodiazepines
 –> Zolpidem and Zaleplon – selective agonists at the BZ1 receptor subtype
 2. ANTAGONISTS
 – synthetic benzodiazepine derivative FLUMAZENIL, blocks the actions of
benzodiazepines and zolpidem but does not antagonize the actions of
barbiturates, meprobamate and ethanol
 3. INVERSE AGONISTS
 act as negative allosteric modulators of GABA receptor function ( B-
carbolines eg. N-butyl-B-carboline-3-carboxylate (B-CCB) )
 FLUMAZENIL
 > A specific benzodiazepine antagonist
> Available only for intravenous administration half-life is 1 hour
Duration - 30 to 60 mins.
Primary indication: management of benzodiazepine
overdose & reversal of its sedative
effects
 Dosage:
1 mg given over 1-3 minutes
cummulative dose of 1 to 5 mg given over 2 to 10
mins
additional course within 20-30 mins should sedation
reappear.
May cause seizures
 ORGAN LEVEL EFFECTS
 1. Sedation:
 defined as a suppression of responsiveness to a constant level of
stimulation, with decreased spontaneous activity and ideation
 2. Hypnosis:

- induction of sleep
 A. The latency of sleep onset is decreased
 B. The duration of stage 2 NREM sleep is increased
 C. The duration of REM sleep is decreased
 D. The duration of stage 4 NREM slow-wave sleep is
decreased
3.
Anesthesia
> diazepam and midazolam, are used IV but have not proved to be
fully successful as agents capable of producing surgical anesthesia
4. Anticonvulsant effects
> clonazepam, nitrazepam, lorazepam and diazepam have selective
actions that are clinically useful in the management of seizure
states
> they are capable of inhibiting the development and spread of
epileptiform activity in the CNS
5. Muscle relaxation
> they exert inhibitory effects on polysynaptic reflexes and
internuncial transmission
> high doses may also depress transmission at the skeletal
neuromuscular junction
6. Respiratory System:
- hypnotic dose -* slight depression of alveolar
ventilation similar to natural sleep changes
dose dependent depression of alveolar ventilation and
pO2 -p CO2 narcosis and respiratory acidosis
7. Cardiovascular System
- minimal decrease in blood pressure, cardiac output and
systemic vascular resistance
- increased coronary blood flow
decrease both cerebral blood flow and cerebral 02
utilization
8. Gastrointestinal Tract
- improve anxiety related GI disorders
decrease nocturnal gastric secretion
UNTOWARD EFFECTS:
tolerance
physiologic & psychologic dependence
drowsiness
impaired judgement
diminished motor skills
hypersensitivity reactions
impairment of sexual function
- lightheadedness
- ataxia
- chest pain
- incontinence
- nausea
- headache
- vertigo
DRUG INTERACTIONS:
- Additive effect - alcohol, opioid analgesics,
anticonvulsants, and phenothiazines
- Delays hepatic clearance & prolongs
elimination
half time of diazepam &
metabolites - cimetidine
- Enhanced CNS depression effects antihistamines, antihypertensives and tricyclic
antidepressants

Types:

A. Long Acting Barbiturates:
> Phenobarbital (Luminal sodium)
> Barbital (Veronal)
> Mephobarbital ( Mebaral)
> Metharbital (Gemonil)

B. Intermediate Acting Barbiturates:
> Amobarbital (Amytal)
> Butarbital (Butisol)


C. Short Acting Barbiturates:
> Pentobarbital (Nembutal sodium)
> Secobarbital (Seconal)


D. Ultra – Short Acting Barbiturates
> Thiopental (Penthotal)
> Hexobarbital (Sombulex)
> Methohexital ( Brevital )
> Thiamylal (Surital)
 PHARMACOKINETICS:
 A. Absorption - rapid & complete absorption after oral intake
Distribution - redistribution from brain to highly perfused tissues such as
skeletal muscle and subsequently to poorly perfused adipose tissue
 > crosses the placental barrier
 - thiobarbiturates very lipid soluble - rapid entry into CNS
- readily cross placental barrier
- intravenous route -+ for induction of anesthesia & management of status
epilepticus
- cummulative with repeated administration
 Biotransformation - complete metabolism or conjugation in the liver
Elimination half life : Seco- 18 hrs
Pento – 48 hrs
Pheno – 4-5 days
Excretion
- mainly unchanged in the urine
elimination rate significantly increased by alkalinization of the urine
 PHARMACODYNAMICS
Barbiturates depress neuronal activity at
the midbrain reticular formation, facilitating
and prolonging the inhibitory effects of
GABA and glycine
 >
 Barbiturates increase the
 duration of GABA-mediated chloride ion
channel opening
Organ Level Effects:
1. Sedation
> Barbiturates have euphoriant effects
2. Hypnosis
> Barbiturates alter the stages of sleep in the
dose-dependent manner > they decrease sleep
latency, decrease number of awakenings and decrease
body movements
3. Anesthesia
> Thiopental and methohexital are very lipid
soluble, penetrating brain tissue rapidly following IV
administration > which are therefore useful in
anesthesia practice
4. Anticonvulsant Effects:
> Phenobarbital and metharbital (converted to
phenobarbital in the body) are effective in the
treatment of generalized tonic-clonic seizures
5. Respiration:
> Depress both respiratory drive & the
mechanisms responsible for the rhythmic character
of respiration
> Diminish neurogenic drive & in higher doses,
suppress hypoxic & chemoreceptor drive
> Laryngospasm – chief complaint of
barbiturate anesthesia
6. Cardiovascular System
> Cardiovascular reflexes are obtunded by partial inhibition of
ganglionic transmission –slight fall or no change in BP
> Decrease in renal plasma flow and in cerebral blood flow with a
marked fall in CSF pressure
7. Liver
> Combine with cytochrome 450 & competitively interfere with the
biotransformation of a number of drugs
> Chronic administration causes a marked increase in the protein
and lipid content of the hepatic smooth endoplasmic reticulum
8. Kidney
> Severe oliguria or anuria in acute barbiturate poisoning, largely
as a result of the marked hypotension
UNTOWARD EFFECTS:
After-effects:
- drowsiness for only a few hours
- residual CNS depression up to 10-22 hrs.
- distortions of mood
- impairment of judgement & fine motor skills
- other residual effects: vertigo, nausea, vomiting,
diarrhea, over excitement - awakes slightly
intoxicated, euphoric & energetic
irritability and temper
Paradoxical Excitement:
- common among geriatric & debilitated patients
- phenobarbital & N-methylbarbiturates
Pain:
- prescribed for localized or diffuse myalgic,
neuralgic, or arthritic pain
- may cause restlessness, excitement &
delirium in presence of pain
Hypersensitivity:
- may occur in patients with asthma, urticaria,
angioedema
- localized swelling,erythematous dermatitis
exfoliative dermatitis -- phenobarbital
ABSOLUTE CONTRAINDICATION:
ACUTE INTERMITTENT PORPHYRIA –
barbiturates enhance porphyrin synthesis
 DRUG INTERACTIONS
 A. increased CNS-depressant effects:
 1. other CNS depressants (ethanol)
2. isoniazid
3. methylphenidate
4. monoamine oxidase inhibitors
B. induction of microsomal hepatic enzymes ->
accelerated disappearance of drugs & endogenous
substances
accelerated metabolism of vitamins D & K
hamper bone mineralization & lower Ca`+
absorption
(phenobarbital)
* coagulation defects in neonates whose mothers are
taking phenobarbital
> enhance metabolism of steroid hormones -*
endocrine disturbances
> enhance metabolism of oral contraceptives unwanted pregnancy
C. induce hepatic generation of toxic metabolites of
chlorocarbon anesthetics & carbon tetrachloride - ~
promote lipid peroxidation - facilitates the periportal
necrosis of the liver
 MISCELLANEOUS HYPNOTIC-SEDATIVE DRUGS:
 a.Buspirone
b.Zolpidem
c.Zaleplon
d.Carbamates
e. Alcohols:
i. Paraldehyde
ii. Chloral Hydrate
iii. Ethchlorvynol
i. Meprobamate f. Piperidinediones
ii.Ethinamate
i. Gluthetimide
ii. Methyprylon
g. Clomethiazole
h. etomidate
 Buspirone
 Relieves anxiety without marked sedative or euphoric effects
No hypnotic, anticonvulsant or muscle relaxant property
 Mechanism of action: partial agonist at 5-HT1A receptors
 less psychomotor impairment than diazepam
suitable for generalized anxiety states
 - > Pharmacokinetics:
 rapid oral absorption
- extensive first-pass metabolism & form active metabolites elimination halflife: 2-4 hrs -> prolong in liver dysfunction
 -—+ reduced with rifampicin (cytochrome P450 inducer)
increased plasma levels with erythromycin & ketoconazole ( inhibitors of
CYP3A4)
 untoward effects: tachycardia, palpitations, nervousness, GIT distress,
paresthesias,
dose-dependent pupillary constriction
BP elevations on patients taking MAO inhibitors
 Zolpidem
 An imidazopyridine derivative with hypnotic actions
 Mechanism of action: binds selectively to BZ, (omega, ) subtype of
benzodiazepine receptors and facilitates GABA-mediated neuronal inhibition
 Actions antagonized by flumazenil
 Minimal muscle relaxing and anticonvulsant effect
Short-term treatment of insomnia
Minor effects on sleep patterns but suppress REM sleep at higher doses.
Less tolerance & dependence with extended use than with benzodiazepines
 Pharmacokinetics: rapidly metabolized in the liver to inactive metabolites
elimination half-life ---> 1.5 – 3.5 hours
 Precautions: patients with hepatic dysfunction, elderlies & cimetidine
 Drug interaction: rifampicin — decreases half-life of zolpidem
Ethanol & other CNS depressants — respiratory depression
 Zaleplon
 Resembles zolpidem
 Mechanism of action: binds selectively to BZ, receptor subtype,
facilitating 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 of about 1 hour.
metabolized mainly by hepatic aldehyde oxidase & partly cytochrome
P450
> Amnesic effects & next-day psychomotor impairment may occur
Alcohols:
Paraldehyde
Rapid acting hypnotic —> sleep ensues in 10-15 min
Rapidly absorbed & widely distributed
70-80% metabolized in the liver
> elimination half-life is 4-10 hrs
> excreted in expired air & urine
untoward effects = acidosis,
bleeding gastritis
fatty changes in liver & kidney (toxic hepatitis
&
nephrosis)
toxic dose: 25-150 gm
Chloral Hydrate
Has little analgesic activity
Decreases sleep latency, awakenings & slow wave sleep
> Metabolized in the liver to trichloroethanol
>Excreted mostly in urine as urochoralic acid
Untoward 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
Ethchlorvynol
a 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.
untoward effects:
mintlike 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
> toxic dose: 10-25 gram
Piperidinediones
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
Untoward effects:
"hangover" excitement
blurring of vision, gastric irritation, headache, skin rashes
thrombocytopenia, aplastic anemia, leukopenia
acute intoxication - less severe respiratory depression
antimuscarinic actions - xerostomia, ileus, urinary bladder atony, long
lasting mydriasis, hyperpyrexia
abstinence syndrome - tremulousness, tachycardia, fever, tonic muscle
spasms &generalized convulsions
> Toxic dose: 10-20 gms
Methyprylon,
Hypnotic
Metabolized in the liver & eliminated almost entirely
by urinary excretion
Plasma half-life is 4 hrs > Should be avoided in
patients
with intermittent porphyria
Untoward effects:
"hangover" nausea, vomiting, diarrhea, esophagitis and
headache
idiosyncratic excitement
acute intoxication - hypotension, shock, pulmonary
edema
coma - may last up to 5 days
Toxic dose: 6 gm
Carbamates
Meprobamate
Introduced as antianxiety agent in 1955
Causes widespread depression of CNS but not anesthesia
> Also acts as anticonvulsant
> Well absorbed when administered orally
Metabolized in the liver & eliminated in the urine
Half-life is 6-17 hours
Untoward effects:
Major - Drowsiness & ataxia
Impairment of learning & motor coordination, prolonged
reaction time
Acute intoxication- severe or fatal respiratory depression,
hypotension, shock, heart failure Abrupt discontinuation withdrawal syndrome (anxiety, tremors, insomnia,
hallucinations, generalized seizures)
Toxic dose: 36 grams
 Ethinamate
 is a urethane
 Rapid onset & short duration of action
Inactivated in the liver & excreted as glucoronide
in the urine
Untoward effects:
Nausea, occasional vomiting, rash
Idiosyncratic excitement Fever, thrombocytopenia
Other Sedative-Hypnotics:
 Etomidate
 Used as an intravenous anesthetic
 Advantages: lacks pulmonary and vascular
depressant activity Negative inotropic effect
 Used as sedative-hypnotics in ICU's, during
intermittent positive-pressure breathing and in
epidural anesthesia
Clomethiazole
Has sedative, muscle relaxant and
anticonvulsant
properties
-
 - Used for hypnosis of elderly &
institutionalized patients, for preanesthetic
sedation, management
of ethanol
withdrawal
SEDATION
DRUG
DOSAGE
HYPNOSIS
DRUG
bedtime)
DOSAGE (at
Alprazolam
0.25-0.5mg
2-3x daily
Chloral hydrate 500-1000 mg
Buspirone
5-10 mg
2-3x daily
Estazolam
0.5-2 mg
Chlordiazepoxide 10-20 mg
2-3x/d
Flurazepam
15-30 mg
Clorazepate
Lorazepam
2-4 mg
5-7.5 mg 2x/d
Drug
Dosage
Halazepam
Lorazepam
20-40 mg
3-4x/d
Drug
Dosage(at bedtime
Secobarbital 100-200 mg
1-2 mg
Temazepam
once or twice/d
Triazolam
7.5-30 mg
Oxazepam
15-30 mg
3-4x/d
0.125-0.5 mg
Phenobarbital
15-30 mg Zaleplon
2-3x/d
5-20 mg
Prazepam
10-20 mg Zolpidem
2-3x/d
5-10 mg
 CLINICAL PHARMACOLOGY of SEDATIVE-
HYPNOTICS:
 1. Treatment of anxiety states
 Benzodiazepines -* most common anxiolytic drug
(generalized anxiety disorder)
 alprazolam = panic disorders & agoraphobia
 major depressive disorders
Phenobarbital, meprobamate, antihistamines
Beta-blockers
> clonidine
 2.Treatment of sleep disorders
 Benzodiazepines
Zolpidem
Zaleplon
3.Preoperative medication
4.anticonvulsant
5.treatment of delirium tremens
6.induction of anesthesia
7. skeletal muscle relaxation in specific N-M disorders
meprobamate
benzodiazepines
8.diagnostic aid or treatment in psychiatry
THANK YOU
VERY MUCH
AND
STUDY WELL!
THE ALCOHOLS
Ethanol
Pharmacokinetics
water soluble molecule that is absorbed rapidly from the
GIT.
After ingestion in the fasting state, peak blood
concerntrations are reached within 30 mins
Presence of food delay absorption
Rapid distribution with tissue levels approximating the
concentration in blood.
In the CNS, the concentration rises quickly since the
brain receives a large proportion of blood flow and
ethanol readily crosses biologic membranes
Over 90% of alcohol consumed is oxidized in the liver
Excreted through the lungs and in the urine
Two Major Pathways of Alcohol Metabolism to
Acetaldehyde:
Alcohol Dehydrogenase Pathway:
The primary pathway involves alcohol dehydrogenase
(ADH), a cytosolic enzyme that catalyzes the conversion
of alcohol to acetaldehyde.
Enzyme found in liver, brain and stomach
Microsomal Ethanol Oxidizing system (MEOS)
also known as the mixed function oxidase system uses
NADPH as a cofactor in the metabolism of ethanol
chronic alcohol consumption results in significant
increases not only in ethanol metabolism but also in the
clearance of other drugs eliminated by the MEOS
system
Acetaldehyde Metabolism *
The product of this reaction is acetate which can be further
metabolized to CO2 and water.
Oxidation is inhibited by disulfiram, a drug that has been used
to deter drinking by alcohol dependent patients undergoing
treatment
When ethanol is consumed in the presence of disulfiram,
acetaldehyde accumulates and causes an unpleasant reaction
of facial flushing, nausea, vomiting, dizziness, and headache.
Other drugs like metronidazole, cefotetan, trimethoprimm
inhibit aldehyde dehydrogenase and can cause a disulfiram like
reaction if combined with ethanol
Some people primarily of Asian descent, have a genetic
deficiency in the activity of the mitochondrial form of
aldehyde dehydrogenase.
Blood Alcohol Concentration (BAC) and clinical effects in
nontolerant individuals
BAC (mg/dl)
Clinical Effect
200-300
Sedation, subjective “high”
increased reaction times
Impaired motor function,
slurred speech, ataxia
Emesis, stupor
300-400
Coma
>500
Respiratory depression,
death
50-100
100-200
PHARMACODYNAMICS OF ACUTE ETHANOL CONSUMPTION:
Central Nervous System:
causes sedation, relief of anxiety and at higher concentrations
slurred speech, ataxia, impaired judgement and disinhibited
behavior- drunkenness
CNS depressant, at high blood concentrations, it induces coma,
respiratory depression and death
No specific receptor but has been shown to participate in signaling
pathways, including neurotransmitter receptors for amines, amino
acids, and opioids; enzymes such as Na+/K+ ATPase, adenylyl cyclase,
phosphoinositide specific phospholipase C and ion channels such as
those for Ca+
Acute ethanol exposure enhances the action of GABA
Also inhibits the ability of glutamate to open the cation channel
associated with NMDA subtype of glutamate receptors, which is
implicated in many aspects of cognitive function including learning
and memory.
Heart:
>significant depression of myocardial contractility has
been observed in individuals who acutely consume
moderate amounts of alcohol at blood concentration
above 100 mg/dL.
Acetaldehyde is implicated as a cause of cardiac
dysfunction by altering myocardial stores of
catecholamines.
Smooth Muscle
Ethanol is a vasodilator probably as a result of both CNS
effects (depression of the vasomotor center) and direct
smooth muscle relaxation caused by acetaldehyde.
Severe overdose may cause hypothermia
Also relaxes the uterus
CONSEQUENCES OF CHRONIC ALCOHOL
CONSUMPTION
Liver and Gastrointestinal Tract:
liver disease is the most common medical complication of
alcohol abuse
alcoholic fatty liver, a reversible condition may progress
to alcoholic hepatitis and finally to cirrhosis and liver
failure
most common cause of chronic pancreatitis in Western
world
also alters pancreatic epithelial permeability and
promotes the formation of protein plugs and calcium
carbonate containing stones
malnutrition and vitamin deficiencies due to
malabsorption
Nervous System
Tolerance and physical dependence
Alcohol withdrawal – hyperexcitability in mild cases and
seizures, toxic psychosis, and delirium tremens in severe
ones
Psychologic depencence – compulsive desire to experience
the rewarding effects of alcohol and for current
drinkers, a desire to avoid the negative consequences of
withdrawal
Up regulation of NMDA subtype of glutamate receptors
and voltage sensitive Ca2+ channels may underlie the
seizures that accompany the alcohol withdrawal
syndrome.
GABA neurotransmission –believes to play a central role
in tolerance and withdrawal
Neurotoxicity
generalized symmetric peripheral nerve injury that begins with distal
paresthesias of the hands and feet
gait disturbances and ataxia due to degenerative changes in the CNS
dementia and rarely demyelinating disease.
- Wernicke-Korsakoff syndrome – paralysis of the external eye
muscles, ataxia and a confused state that can progress to coma
and death
associated with thiamin deficiency and rarely seen in the absence of
alcoholism
Most patients are left with a chronic disabling memory disorder
known as Korsakoff’s psychosis
alcohol may also impair visual acuity, with painless blurring that
occurs over several weeks of heavy alcohol consumption
Cardiovascular System:
dilated cardiomyopathy with ventricular hypertrophy and
fibrosis
interference of ethanol with the beneficial effects of B
blockers and ACE inhibitors
heavy drinking, associated with both atrial and
ventricular arrhythmias
hypertension (more than three drinks per day)
A number of observational studies concluded that
moderate alcohol consumption actually prevents CHD and
even reduces mortality – ethanol’s ability to raise serum
levels of HDL cholesterol, the ability to inhibit some of
the inflammatory processes that underlie
atheroscelrosis and the presence in alcoholic beverages
(red wine) of antioxidants and other substances that
may protect against atherosclerosis.
Blood
indirectly affects hematopoiesis through metabolic and nutritional
effects ,directly inhibits the proliferation of all cellulalr elements in
bone marrow
most common is mild anemia resulting from alcohol related folic acid
deficiency.
Iron Deficiency Anemia may result from gastrointestinal bleeding
Endocrine System and Electrolyte balance
gynecomastia and testicular atrophy
ascites, edema and effusions – decreased protein synthesis and
portal hypertension
alterations of whole body potassium induced by vomiting and
diarrhea
severe secondary aldosteronism
hypoglycemia – impaired hepatic gluconeogenesis
ketosis caused by excessive lipolytic factors
Fetal Alcohol syndrome
chronic maternal alcohol abuse during pregnancy
intrauterine growth retardation
microcephaly
poor coordination
underdevelopment of midfacial region ( appearing as a flattened face
minor joint anomalies
the fetal liver has little or no alcohol dehydrogenase activity, so the
fetus must rely upon maternal and placental enzymes for elimination
of alcohol
Immune System
inhibited in the lungs, enhanced in the liver and pancreas
suppression of the function of alveolar macrophages, inhibition of
chemotaxis of granulocytes, and reduced number and function of T
cells
Increased Risk of Cancer
risk for cancer of the mouth, pharynx, larynx, esophagus and liver
small increase in the risk of breast Ca in women.
Alcohol Drug Interactions:
chronic ethanol consumption and acetaminophen-induced
hepatotoxicity
inhibits metabolism of Phenothiazines, tricyclic
antidepressants and sedative hypnotic drugs
potentiates the effects of vasodilatora and oral
hypoglycemic agents
enhances the antiplatelet action of aspirin
MANAGEMENT OF ACUTE ALCOHOL INTOXICATION:
most important goals in the treatment are to prevent
severe respiratory depression and aspiration of vomitus
treatment of hypoglycemia and ketosis by administration
of glucose
Thiamine – Wernicke-Korsakoff Syndrome
Severe vomiting – large amounts of potassium
MANAGEMENT OF ALCOHOL WITHDRAWAL
SYNDROME
The major objective of drug therapy is prevention of
seizures, delirium and arrhythmias
Potassium, magnesium and phosphate balance should be
restored as rapidly as is consistent with renal function
Thiamine therapy initiated
Substituting a long acting sedative hypnotic drug for
alcohol and then gradually reducing (“tapering”) the dose
of the long acting drug (benzodiazepines preferred)
PHARMACOTHERAPY OF ALCOHOLISM
Disulfiram – tetraethylthiuram
an inhibitor of aldehyde dehydrogenase is the drug most
commonly used
rapidly and completely absorbed from the GIT
inhibits the metabolism of phenytoin, oral anticoagulants
and isoniazid
management should be initiated only when the patient has
been free of alcohol for at least 24 hours
usual oral dose is 250 mg daily taken at bedtime
Naltrexone
orally available opioid receptor antagonist that blocks
the effects of exogenous and endogenous opioids
50 mgs taken once a day
Should be used with caution in alcoholic patients with
evidence of mild abnormalities in serum aninotransferase
activity
Combination with disulfiram should be avoided
(hepatotoxins)
Topiramate
drug used for partial and generalized tonic clonic
seizures may be effective in reducing craving in chronic
alcoholics
OTHER ALCOHOLS:
METHANOL (methyl alcohol, wood alcohol)
a constituent of many commercial solvents
in the home, found in the form of “canned heat” or in
windshield washing products
can be absorbed through the skin or from the
respiratory or GIT and is then distributed in body water.
Primary mechanism of elimination of methanol in humans
is by oxidation to formaldehyde, formic acid and CO2.
Methanol poisoning – visual disturbance described as “like
being in a snowstorm.”
ETHYLENE GLYCOL
used as heat exchangers in antifreeze formulations and
as industrial solvents
relatively harmless and eliminated by the kidney, it is
metabolized to toxic aldehydes and oxalate.
Three stages of ethylene glycol overdose
Within the first few hours after ingestion – transient
excitation followed by CNS depression
4-12 hours – severe metabolic acidosis
Finally – delayed renal insufficiency follows deposition of
oxalate in renal tubules
* Fomepizole * - an alcohol dehydrogenase inhibitor
used for the treatment of ethylene glycol poisoning and
methanol poisoning
THANK YOU VERY MUCH
AND
STUDY WELL!