Dr. RAGHU PRASADA M SMBBS,MDASSISTANT PROFESSOR DEPT. OF PHARMACOLOGYSSIMS & RC. 1

Absorption in stomach 20%

Absorption in small intestine 80%

Factors that influence absorption

▪ Concentration of the drink

▪ Amount consumed

▪ Food in the stomach

▪ Mood

▪ Pylorospasm (spasm of valve)

Uniformly distributed throughout tissues and body fluidsReadily crosses placenta, to exposure fetus

Decision making skills impaired

Alcohol lowers inhibitions, impairing ability to make wise decisions

Immediate effects of alcohol

Reduces frequency of nerve transmissions

Dehydration

Water is lost from cerebrospinal fluid

Alcohol irritates the gastrointestinal system

Hangovers

Effects on the Nervous System

Cardiovascular Effects

Liver disease

▪ Cirrhosis

▪ Alcoholic hepatitis

Cancer

Chronic inflammation of pancreas

Impairs ability to recognize and fight bacteria and viruses

GI tract/Liver: Fatty liver, hepatitis, cirrhosis, esophagitis, gastritispancreatitis, cancers

Nervous system: Brain: Hepatic encephalopathy, Wernicke-Korsakoff syndrome(thiamine deficiency), cerebellar degeneration, central pontinemyelinolysis, dementia

Nutrition: Deficiencies of Vitamins: Folate, thiamine, pyridoxine, niacin, riboflavinMinerals: Magnesium, zinc, calciumProtein

Metabolites and electrolytesHypoglycemia, ketoacidosis, hyperlipidemia, hyperuricemia, hypomagnesemia, hypophosphatemia

Neuromuscular: Neuropathy, myopathy

Cardiovascular: Arrhythmia, cardiomyopathy, Hypertension

Bone marrow: Macrocytosis, anemia, thrombocytopenia, leukopenia

Endocrine: Pseudo-Cushing's syndrome, testicular atrophy, amenorrhea, DM?, Osteopenia/osteoporosis

cancers (i.e., breast)

Traumatic injuryFetal alcohol syndrome

Brain neurotransmitter physiology is abnormal………..

Effective treatments lead to

2/3rds reduction in alcohol problems

50% reductions in consumption at one year (with 1/3rd abstinent or drinking moderately)

beneficial when given in addition to non pharmacological therapies

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• Tremor• Nausea• Irritability• Agitation• Tachycardia• Hypertension• Seizures• Hallucinations

Careful monitoring and supportive careAmple fluids (p/o or IV fluids if dehydrated)Correction of electrolyte imbalanceParenteral Thiamine(100 mg p.o or i.v or i.m) dailyRestrict access to addicting substances

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Cross tolerant medications with alcohol

Benzodiazepines

Diazepam and Chlordiazepoxide

Lorazepam and oxazepam - short acting patients

with liver problems, in elderly)

Others (more than 150 agents, carbamazepine;

valproate, ß adrenergic antagonists etc.,)

Emerging: Baclofen13

Ethanol AcetateAcetaldehyde•Flushing

•Headache

•Palpitations

•Dizziness

•Nausea

ADH ALDH

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DISULFIRAM

Causes antabuse reaction due to accumulation of acetaldehydeThe effect lasts for 7-14 daysMetronidazole, chlorpropamide, tolbutamide, griseofulvin, cephalosporins and phenylbutazole

Contra indication- liver disease

structure similar to GABA amino acid.

Restores the GABA activity.

reduce glutamate surges that excite

NMDA- Rs.

acts as a neuro-protectant and protect

neurons from damage caused by

alcohol withdrawal

Prevent relapse in heavy drinking

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Stabilizes activity in the glutamate system Affinity for GABA A and GABA B receptors Inhibits glutamate effect on NMDA receptors

BUT cannot be used in liver disease

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NMDA

receptor

ETHANOL

glutamate

GABAA Receptor

GABA

Cl-

Volpicelli, 1992

Opiate blocker Evidence for reduced cravings and relapse rates 23% relapsed vs. 54% placebo during 12 week study Definition of relapse

a 5-HT3 antagonist that exerts its antidrinking effectsthrough cortico-mesolimbic dopamine systemmodulation.

improve drinking outcomes in patients with early-onset alcoholism.

Adverse events are mild

starting dosage of 4 mcg/kg twice daily should bemaintained throughout treatment.

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GABA, glutamate receptors (?) Some efficacy in those not abstinent at start of

medication Used for other psych disorders

Single agent

Acamprosate

Naltrexone

Disulfiram

Aimed at complete abstinence , can be started at any time including withdrawal phase,

may be started immediately during first consultation

Early onset with family loading, helps in heavy drinking and may be choice in which acamprosate trial has failed, Liver function test is mandatory

Patient completely motivated and with good social support, still low acceptability

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Benzodiazepines Clonidine Baclofen

It is used to denature ethyl alcohol No therapeutic value Methanol formaldehyde formic acid Manifestations Vomiting headache, vertigo, sev abdominal pain,

hypotension, delurium, acidosis, coma

Correction of acidosis Protect eyes Gastric lavage Blood pressure maintainance Ventilation Ethyl alcohol Fomepezole hemodialysis

(National Geographic, George Steinmetz, Feb 1992)