A Textbook of Clinical Pharmacology and Therapeutics

respiratory depression. Chronic neurological accompaniments

of persistent alcoholabuse include various forms of central

and peripheral neurodegeneration, most commonly involving

the vermis of the cerebellum, and a peripheral neuropathy.

Nutritional deficiencies may contribute to the pathogensesis

of neurodegeneration. Wernicke’s encephalopathy (difficulty

in concentrating, confusion, coma, nystagmus and

ophthalmoplegia) and Korsakov’s psychosis (gross memory

defects with confabulation and disorientation in space and

time) are mainly due to the nutritional deficiency of thiamine

associated with alcoholism. Any evidence of Wernicke’s

encephalopathy should be immediately treated with

intravenous thiamine followed by oral thiamine for several

months. Psychiatric disorder is common and devastating, with

social and family breakdown.

Circulatory: Cutaneous vasodilatation causes the familiar

drunkard’s flush. Atrial fibrillation (embolization) is

important. Chronic abuse is an important cause of

cardiomyopathy. Withdrawal (see below) causes acute

hypertension and heavy intermittent alcoholconsumption

can cause variable hypertension by this mechanism which

can exacerbate or be mistaken for essential hypertension

(Chapter 28).

Gastrointestinal: Gastritis, peptic ulceration, haematemesis

(including the Mallory–Weiss syndrome, which is

haematemesis due to oesophageal tearing during forceful

vomiting, as well as from peptic ulcer or varices). Liver

pathology includes fatty infiltration, alcoholic hepatitis and

cirrhosis. Alcoholcan cause pancreatitis (acute, subacute and

chronic).

Metabolic: Alcohol suppresses ADH secretion and this is one of

the reasons why polyuria occurs following its ingestion.

Reduced gluconeogenesis leading to hypoglycaemia may cause

fits. The accumulation of lactate and/or keto acids produces

metabolic acidosis. Hyperuricaemia occurs (particularly, it is

said, in beer drinkers) and can cause acute gout.

Haematological effects: Bone marrow suppression occurs.

Folate deficiency with macrocytosis is common and chronic

GI blood loss causes iron deficiency. Sideroblastic anaemia is

less common but can occur. Mild thrombocytopenia is

common and can exacerbate haemorrhage. Neutrophil

dysfunction is common even when the neutrophil count is

normal, predisposing to bacterial infections (e.g.

pneumococcal pneumonia), which are more frequent and

serious in alcoholics.

In pregnancy: Infants of alcoholic mothers may exhibit

features of intra-uterine growth retardation and mental

deficiency, sometimes associated with motor deficits and

failure to thrive. There are characteristic facial features which

include microcephaly, micrognathia and a short upturned

nose. This so-called fetal alcohol syndrome is unlike that

reported in severely undernourished women. Some

obstetricians now recommend total abstinence during

pregnancy.

440 DRUGS AND ALCOHOL ABUSE

Acetaldehyde

Ethanol

Microsomal

oxidase

(NADPH)

Cytoplasmic

alcohol

dehydrogenase

(NAD)

Catalase

(H 2 O 2 )

Aldehyde

dehydrogenase

(NAD)

Acetate

Acetyl coenzyme A

Krebs tricarboxylic

acid cycle

CO 2  H 2 O

Figure 53.1:Pathways of ethanol oxidation. :, major pathway.

• – – , minor pathways; NAD, nicotinamide adenine dinucleotide;
  NADP, nicotinamide adenine dinucleotide phosphate.

50

45

40

35

30

25

20

15

10

5

0 20 40 60 80 100 120 140 160 180

Relative probability

Blood alcohol concentration (mg/100 mL)

Figure 53.2:Relative probability of causing a road accident at
various blood alcohol concentrations. (Redrawn with permission
from Harvard JDJ. Hospital Update1975; 1 : 253).