A-Textbook-of-Clinical-Pharmacology-and-Therapeutics-5th-edition

440 DRUGS AND ALCOHOL ABUSE
Catalase
(H 2 O 2 )
Ethanol
Acetaldehyde
Acetate
Cytoplasmic
alcohol
dehydrogenase
(NAD )
Aldehyde
dehydrogenase
(NAD )
Acetyl coenzyme A
CO 2 H 2 O
Krebs tricarboxylic
acid cycle
Microsomal
oxidase
(NADPH)
respiratory depression. Chronic neurological accompaniments
of persistent alcohol abuse 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 alcohol consumption
can cause variable hypertension by this mechanism which
can exacerbate or be mistaken for essential hypertension
(Chapter 28).
Figure 53.1: Pathways of ethanol oxidation. :, major pathway.
– – – , minor pathways; NAD, nicotinamide adenine dinucleotide;
NADP, nicotinamide adenine dinucleotide phosphate.
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. Alcohol can cause pancreatitis (acute, subacute and
chronic).
Relative probability
50
45
40
35
30
25
20
15
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.
10
5
0 20 40 60 80 100 120 140 160 180
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 Update 1975; 1: 253).
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.