CNS
Alcohol
Alcohols are hydroxy derivatives of aliphatic hydrocarbons. Pharmacology of alcohol is
important for its presence in beverages, alcoholism & for alcohol intoxication.
Alcohol is manufactured by fermentation of sugars. Fermentation proceeds till alcohol
content reaches ~ 15%. Major source of commercial alcohol is molasses
Alcoholic beverages:
I. Malted liquors: Obtained by fermentation of germinating cereals; are undistilled –
alcohol content is low (3-6%)
E.g.: Beer, stout - Strong beers (up to 10%) are also available
II. Wines: Produced by fermentation of natural sugars as present in grapes & other fruits.
These are also undistilled
Types: Light wines (Cider) → Alcohol content is 9-12% (max ≤ 15%)
Fortified wines (Port) → 16-22%
Effervescent wines (Champagne) → 12-16%
III. Spirits: These are distilled after fermentation E.g.: Rum, Gin, Whiskey, Brandy, Vodka,
etc. Alcohol content of these can vary from 40-55%, in India for all licensed brands it is
standardized to 42.8% v/v or 37% w/w
Other forms of alcohol:
Absolute alcohol: 99% w/w ethanol
Rectified spirit: 90% w/w ethyl alcohol produced from fermented from fermented
molasses, by distillation
Methylated spirit: Also called denaturated spirit is produced by adding 5 parts of
wood naphtha (methyl alcohol) to 95 parts of rectified spirit so as to render it unfit for
drinking
Alcoholism:
A person is generally considered an alcoholic → when his or her lifestyle is dominated by
the procurement and consumption of alcoholic beverages and when this behavior interferes
with personal, professional, social, or family relations.
A light drinker generally is defined as one who consumes an average of one drink or less per
day, usually with the evening meal
A moderate drinker is one who has approximately three drinks per day
A heavy drinker is one who has 5 or more drinks per day (or in the case of binge drinkers, at
least once per week with 5 or more drinks on each occasion).
Important points on its effect on human body:
Central Nervous System: Ethanol primarily is a CNS depressant.
It acts by altering the levels of following neurotransmitters:
Neurotransmitter Effects
System
GABAA GABA release, ↑ receptor density
NMDA Inhibition of postsynaptic NMDA receptors; with chronic use, up-
regulation
DA ↑ Synaptic DA, ↑ effects on ventral tegmentum/nucleus accumbens reward
ACTH ↑ CNS and blood levels of ACTH
Opioid Release of β-endorphins, activation of µ-receptors
5-HT ↑ in 5-HT synaptic space
Cannabinoid ↑ CB1 activity → changes in DA, GABA, glutamate activity
The CNS is markedly affected by acute alcohol consumption. Alcohol causes sedation,
relief of anxiety and, at higher concentrations, slurred speech, ataxia, impaired judgment, and
disinhibited behavior, a condition usually called intoxication
BAC Clinical Effect
(mg/dL)
50–100 Sedation, subjective“high”,
slower reaction times
100–200 Impaired motor function,
slurred speech, ataxia
200–300 Emesis, stupor
300–400 Coma
> 400 Respiratory depression, death
Many countries permit mild degrees of intoxication, but beyond a certain statutory BAC, it
becomes a culpable offence
E.g.: In India, the statuatory limit has been fixed at 30 mg%Q
CVS: Chronic alcoholism contributes to hypertension & can lead to cardiomyopathy (Dilated)Q
Atrial fibrillation & other cardiac arrhythmias may occur due to conduction defects & Q-T
prolongation
Blood: Regular intake of small to moderate amounts of alcohol (1-2 drinks) has been found to
↑ HDL & ↓ LDL oxidation → 15-35% lower incidence of CAD
Risk reduction is greatest in high risk subjects & protection is lost if ≥3 drinks are consumed
daily
Kidney: Diuresis is often noticed, i) Water ingested along with drinks
ii) Inhibition of ADH secretion
Pharmacokinetics: More than 90% of alcohol in the plasma is metabolized in the liver by
three enzyme systems that operate within the hepatocyte. The remainder is excreted by the
lungs and in urine and sweat
Metabolism of ethanol & methanol:
The metabolism of alcohol generally is said to follow zero-order pharmacokinetics. This can, in
fact, be an oversimplification because at very high or very low concentrations of alcohol the
metabolism can follow first-order pharmacokinetics
Drug interactions: Acute alcohol ingestion inhibits, while chronic intake induces CYP
enzymes (especially CYP2E1)
Formation of toxic metabolite of paracetamol (NAPQI) is increased in chronic alcoholics
Individuals taking a sulfonylurea, cefoperazone or metronidazole have experienced bizarre,
somewhat disulfiram-like reactions when they consume alcohol
Note: The CAGE questionnaireQ is a tool for detecting individuals more likely to be abusing
alcohol and therefore at greater risk for alcohol withdrawal
Treatment: Alcohol-Related Disorders
Alcohol Withdrawal:
Treatment Regimens: i) Symptom-Triggered Therapy
ii) Fixed-Schedule Therapy
Pharmacologic Agents Used in the Treatment of Alcohol Withdrawal:
Drug Dose per Day Indication
Multivitamin 1 tablet Malnutrition
Thiamine 50–100 mg Deficiency
Crystalloid fluids (typically 50–100 mL/hr Dehydration
D5-0.45 NS with 20 mEq of
KCl per liter)
Clonidine 0.05–0.3 mg PO Autonomic tone rebound &
Transdermal patch also hyperactivity
Labetalol 20 mg IV every 2 hours as Hypertensive urgencies and
needed above
Antipsychotics, haloperidol 2.5 mg to 5 mg every 4 hours Agitation unresponsive to
benzodiazepines,
hallucinations or delusions
Antipsychotics, atypical 5–200 mg Agitation unresponsive to
benzodiazepines,
Quetiapine 5–15 mg
Aripiprazole hallucinations, or delusions in
patients intolerant of
conventional antipsychotics
Benzodiazepines: 0.5–2 mg Tremor, anxiety, diaphoresis,
Lorazepam 5 mg–25 mg
tachypnea, dysphoria, seizures
Chlordiazepoxide 0.5–2 mg
Clonazepam 2.5–10 mg
Diazepam
Alcohol oral Prevent withdrawal
Alcohol IV Prevent withdrawal
Pharmacologic Agents Used in the Treatment of Alcohol Dependence:
Drug Dosage Range per Day Indication
Disulfiram 250 mg–500 mg Deterrence
Acamprosate 999 mg–1,998 mg and higher Craving
(333 mg tablets)
Naltrexone 50 mg–100 mg Craving
Mood stabilizers (e.g., Seizure disorder doses Craving
lamotrigine, topiramate,
carbamazepine, valproic
acid)
Antidepressants (e.g., Depression doses Craving, depression, anxiety
clomipramine, bupropion,
doxepin, maprotiline,
fluoxetine)
