Seminars for the 5th year international students
Prof. MUDr. Jiří Horák
DRUG ABUSE AND POISONING
Drug abuse – a maladaptive pattern in the use of any substance that persists
despite adverse social, psychological, or medical consequences.
Tolerance – the body‘s ability to adapt to repeated uses of the drug and thus
mitigate the drug‘s pharmacologic action. As tolerance increases, higher doses
and more frequent administration are required to achieve the desired effect.
Physical dependence – results in a physiologic withdrawal syndrome after
cessation of drug use.
Psychological dependence – can result in alcohol or drug craving and associated
behaviours to obtain the drug.
Screening
- infections (endocarditis, hepatitis B or C, tuberculosis, sexually transmitted
diseases, recurrent pneumonias, skin abscesses, HIV infection)
- insomnia, mood swings, chronic pain, repetitive trauma, behavioral or social
problems
Physical findings
nedle marks, upper extremity edema, chronic sinusitis, perforated nasal septum
from cocaine use
Tobacco smoking
- the most preventable cause of death in western countries
- ~ 420,000 deaths each year in the US
- causal link to lung cancer and other malignancies, cardiovascular disease,
chronic obstructive pulmonary disease, pregnancy complications,
gastrointestinal disorders etc.
- passive smoking - implicated in lung cancer, cardiovascular disease, and
chronic obstructive pulmonary disease
Alcoholism
~ 100,000 deaths per year in the US
Pharmacology - 90% metabolized by the liver, the remainder is excreted by the
kidneys, lungs, and skin. Its elimination is independent of concentration. Once
drinking ceases, blood levels fall ~ 10 to 25 mg/dl/hr.
The alcohol dehydrogenase pathway metabolizes alcohol to acetaldehyde,
which is then converted to acetate. In both these reactions, NAD is reduced to
NADH. Excess NADH → elevated lactic acid and uric acid levels,
hyperlipidemia, hypoglycemia, hypoproteinemia, and increased collagen
synthesis. Acetaldehyde can promote cellular death. It can block secretion of
proteins from hepatocytes → ballooning.
1/9
Seminars for the 5th year international students
Prof. MUDr. Jiří Horák
Long-term use of alcohol → induction of the MEOS and cytochrome P-4502E1
→ development of tolerance and an increase in the metabolism of drugs
(pentobarbital, propranolol, tolbutamide, warfarin, diazepam).
P-4502E1 converts many foreign substances (solvents, anesthetic agents,
cocaine, INH, acetaminophen) into highly toxic metabolites. It activates
carcinogens and, coupled with vitamin A deficiency and the increased
mutagenicity of tobacco caused by alcohol, may lead to increased incidence of
cancers of GIT, lung, and breast.
Alcohol-related medical disorders
affected organ or system
disorder
nutrition
deficiencies of: folate, B1, B2, B6, niacin, Mg, Zn,
Ca, protein
brain
hepatic
encephalopathy,
WernickeKorsakoff
syndrome, cerebral atrophy, amblyopia, central pontine
myelinolysis
nerve
neuropathy
muscle
myopathy
liver
fatty liver, hepatitis, cirrhosis, hepatoma
heart
hypertension, cardiomyopathy, arrhythmia
blood
anemia, leukopenia, thrombocytopenia, macrocytosis
gut
esophagitis and gastritis
pancreatitis
metabolite and
hypoglycemia, hyperlipidemia, hyperuricemia,
electrolytes
ketoacidosis, hypomagnesemia, hypophosphatemia
endocrine
pseudo-Cushing‘s syndrome, testicular atrophy,
amenorrhea
bone
osteopenia
Acute alcohol intoxication
uptake of alcohol into the brain is rapid
Blood alcohol levels and symptoms
level
(mg/dl)
sporadic drinkers
50
congenial euphoria
75
gregarious or garrulous
100
incoordinated
125 - 150 unrestrained behaviour
200 – 250 alertness lost, lethargic
300 – 350
chronic drinkers
no observable effect
often no effect
minimal signs
pleasurable euphoria
effort required to maintain
emotional and motor control
drowsy and slow
stupor or coma
2/9
Seminars for the 5th year international students
Prof. MUDr. Jiří Horák
> 500
some die
coma
Fatalities can occur from respiratory depression, hypotension, and acidosis.
DD: drowsiness and stupor – hypoglycemia, acidosis, meningitis, subdural
hematoma
suspected head trauma → CT
Th: intubation, hemodialysis if the blood alcohol level exceeds 600 mg/dl
Alcohol withdrawal syndrome
minor symptoms – tremor, sweating, anxiety, tachycardia, nausea, diarrhea, and
insomnia
more profound symptoms – tremulousness, hyperactivity, tachycardia,
insomnia, nightmares, visual hallucinations, and alcohol craving
withdrawal seizures may occur 12 to 48 hours after abstinence
delirium tremens – it typically occurs 72 to 120 hours after cessation after a
decade or more of fairly heavy drinking: acute delirium, confusion, fear,
agitation, gross tremor, insomnia, incontinence, hypertension, tachycardia,
profuse sweating, and fever. Delirium tremens may last several days and is
a medical emergency – mortality rate 20 to 40% for those not receiving
treatment
Management of alcohol withdrawal
observe and normalize vital signs
replace fluids and electrolytes
begin sedation with benzodiazepines or barbiturates
use haloperidol (1 – 2 mg orally q4h as needed) cautiously for hallucinations or
agitation together with benzodiazepines
replace folic acid and thiamine
measure and replace calcium and phosphate
give multivitamin with zinc daily
begin beta-blocker or clonidine to reduce adrenergic signs
Prescription drug abuse
Benzodiazepines
can produce both physical and psychological dependence and a potentially
dangerous withdrawal syndrome
withdrawal symptoms: intense anxiety, insomnia, irritability, weight loss,
muscle spasms, palpitations, diarrhoea, sensitivity to light and sound,
tremors, and seizures; panic attacks and disturbing nightmares
Th: propranolol to reduce tachycardia, hypertension, and anxiety
In acute overdose flumazenil
3/9
Seminars for the 5th year international students
Prof. MUDr. Jiří Horák
Barbiturates
acute intoxication: sluggishness, difficult thinking, slurred speech, poor memory
and judgment, nystagmus, diplopia, vertigo
Th: oral charcoal, alkalinization of the urine (pH > 7.5) with forced diuresis
Opioids
commonly abused drugs: heroin, morphine, codeine, oxycodone, meperidine,
fentanyl
Commonly prescribed opioids
Agonists
morphine
methadone
meperidine
oxycodone
propoxyphene
heroin
hydromorphone
fentanyl
codeine
Mixed agonists-antagonists
pentazocine
nalbuphine
buprenorphine
butorphanol
Antagonists
naloxone
naltrexone
Opioids act by inhibiting neurons that tonically inhibit dopaminergic neurons,
resulting in the increased release of dopamine.
Acute opioid overdose
usually from injected heroin
Clin: cyanosis, pulmonary edema, respiratory distress, coma;
also: increased intracranial pressure, seizures, fever, pinpoint pupils
The acute syndrome is thought to result mainly from adulterants in the mixture
rather than the opiate itself
Unsterile intravenous practices → skin abscesses, cellulitis, meningitis,
thrombophlebitis, endocarditis, hepatitis, and HIV infection
Th of acute overdose: naloxone i.v., repeat in 2 to 3-minute intervals (titrate
carefully – risk of acute withdrawal symptoms in dependent patients)
4/9
Seminars for the 5th year international students
Prof. MUDr. Jiří Horák
Response within minutes: increases in pupil size, respiratory rate, level of
alertness
Withdrawal symptoms develop 6 – 10 hours after the last injection of heroin:
drug craving, anxiety, restlessness, irritability, rhinorrhea, lacrimation,
sweating and yawning develop early. Later: dilated pupils, piloerection,
anorexia, nausea, vomiting, diarrhea, muscle spasms, abdominal cramps,
bone pain, myalgias, tremor, sleep disturbance. These symptoms peak at
about 36 to 48 hours and then subside over 5 - 10 days if untreated. There
can be a protracted abstinence syndrome up to 6 months (mild anxiety,
sleep disturbance, bradycardia, hypotension).
Withdrawal can be managed with methadone (a long-acting synthetic agonist
drug). Patients with repeated relapses can be maintained on methadone in
doses of 60 mg or more daily. It may be used for years.
Amphetamines
The most frequently abused amphetamines are:
dextroamphetamine,
methamphetamine, methylphenidate, ephedrine, and phenmetrazine. They
have been used for weight reduction, attention deficit disorder, and
narcolepsy. They inhibit dopamine reuptake and release dopamine from
intracellular stores.
Tolerance develops rapidly to the stimulant effects.
Toxic effects resemble acute paranoid schizophrenia with delusions and
hallucinations.
Withdrawal symptomes are similar to those seen with cocaine.
Acute amphetamine toxicity: excessive sympathomimetic effects – tachycardia,
tremors, hypertension, hyperthermia, arrhythmias. Chronic users may have
an increased incidence of schizophrenia.
Th: a quiet environment, benzodiazepines for anxiety. Urine acidification with
ammonium chloride may accelerate amphetamine excretion.
Illicit drug abuse
Cocaine
- a naturally occuring alkaloid derived from the coca plant. Its use has
increased dramatically over the past decade. The „crack“ form. It is highly
addictive.
Cocaine can be ingested orally or by snorting, injecting i.v., or smoking crack.
The blood half-life is ~ 1 hour. Its major metabolite benzoylecogonine can be
detected in the urine for 2 to 3 days after a single dose. Through smoking, high
brain levels are obtained within seconds.
An intense, pleasurable reaction lasting about 20 to 30 minutes is followed by
rebound depression, agitation, insomnia, and anorexia and later by fatigue,
hypersomnolence, and hyperphagia (the „crash“). This typically lasts 9 to 12
5/9
Seminars for the 5th year international students
Prof. MUDr. Jiří Horák
hours. Users repeat the sequence at short intervals to recapture the euphoric
state and avoid the crash.
Cocaine blocks the reuptake of dopamine by binding strongly to the dopamine
reuptake transporter at presynaptic nerve endings. Physiologic responses are
related to catecholamine excess: tachycardia, hypertension, hyperthermia,
agitation, peripheral vasoconstriction, seizures, tachypnea, pupillary dilatation,
and anorexia.
The most devastating medical complications relate to the cerebrovascular and
cardiovascular effects of cocaine: potent vasoconstriction of the cerebral arteries
may result in acute stroke, of the coronary arteries → myocardial ischemia and
arrhythmias (AIM rare).
Th of myocardial ischemia: benzodiazepines, nitrates, phentolamine (alphaantagonist). For cocaine-induced hypertension or tachycardia, metoprolol or
labetalol is effective.
Th of cocaine intoxication: obtain vascular and airway access; benzodiazepines
repeatedly i.v. to control CNS agitation.
Most patients suffer psychological dependence with intense craving for cocaine,
along with fatigue and depression. Relapse is common and very difficult to
treat.
Cannabis
The cannabinoid drugs include marijuana (the dried flowering tops and stems of
the resin-producing hemp plant) and hashish (a resinous extract of the hemp
plant). Main drug is delta-9-tetrahydrocannabinol. This drug is intensely
lipophilic and is absorbed by the lung. Metabolites can be detected in the urine
for 2 to 3 days following casual drug use and up to 4 weeks in chronic users.
The primary mode of ingestion is smoking.
Acute physiologic effects: increase in heart rate, conjunctival congestion,
decreased intraocular pressure, bronchodilation, peripheral vasodilation, dry
mouth, fine tremor, muscle weakness, and ataxia.
Psychoactive effects: euphoria, enhanced perception of colours and sounds,
drowsiness, inattentiveness. Motor vehicle driving is impaired. Tolerance and
physical dependence occur.
Th: supportive and reassuring. Benzodiazepines can be used in severely agitated
patients. Amotivational syndrome in some chronic users.
Psychedelics
LSD (lysergic acid diethylamide) is the most potent psychedelic drug known. It
interacts with several serotonine receptors in the brain but the actual
psychoactive mechanism is not known.
Within 20 minutes of oral ingestion, sympathomimetic effects occur (mydriasis,
hyperthermia, tachycardia, elevated blood pressure, increased alertness, tremors,
and occasional nausea and vomiting). Within 2 hours, psychoactive effects
6/9
Seminars for the 5th year international students
Prof. MUDr. Jiří Horák
occur with heightened perceptions, body distortions, variable mood, and
possible visual hallucinations. After 12 hours the syndrome starts to clear. An
acute psychotic or panic reaction may occur.
Phencyclidine is now the most widely abused of the group.
Prompt stimulant effect similar to that of amphetamines: feeling of euphoria,
power, and invincibility.
Physical examination: hypertension, tachycardia, bidirectional nystagmus,
hyperthermia, hallucinations, extreme agitation, ataxia, and slurred speech.
Patients can have hypertensive crises, seizures, and bizzare, often violent
behaviour. Overdosing can result in death. The major problem is drug craving.
Th: a quiet environment, sedation with benzodiazepines, hydration, and
haloperidol for terrifying hallucinations.
Inhalants
Organic solvents: toluene, kerosene, gasoline, acrylic paint spray, carbon
tetrachloride, degreasors. Solvents are inhaled by children or young adolescents
and can produce dizziness and intoxication within minutes. Prolonged exposure
can cause bone marrow depression, cardiac arrhythmias, cerebral degeneration,
and damage to the liver, kidney, and the peripheral nervous system.
Amyl nitrite is a volatile liquid that dilates smooth muscle and is used as a
sexual enhancer. It is usually sprayed into the nose and can produce flushing,
dizziness, and a feeling of a rush. No chronic toxicity has been reported.
Acute poisoning
General approach to the poisoned patient
1. Emergency management
2. Clinical evaluation
3. Elimination of the poison from the GIT etc.
7/9
Seminars for the 5th year international students
Prof. MUDr. Jiří Horák
4.
5.
6.
7.
Administration of an antidote
Elimination of any absoberd substance
Supportive therapy
Observation and disposition
Emergency antidotes
Poison
Acetaminophene
Atropine
Benzodiazepines
Beta-blockers
Calcium channel blockers
Carbon monoxide
Cyanide
Digitalis
Hydrofluoric acid
Iron
Lead
Mercury
Arsenic
Gold
Methyl alcohol
Ethylene glycol
Nitrites
Opiates
Organophosphates
Tricyclic antidepressants
antidote
N-acetylcysteine
physostigmine
flumazenil
glucagon
calcium
oxygen
amylnitrate
sodium thiosulfate
sodium nitrate
Digibind FAB antibodies
calcium
deferoxamine
dimercaptosuccinic acid
dimercaprol
ethyl alcohol
methylene blue
naloxone
atropine
pralidoxime
sodium bicarbonate
Methods for elimination of absorbed substance
Alkaline diuresis
Phenobarbital
Salicylate
Hemodialysis
Ethylene glycol
Lithium
Methanol
Salicylates
Theophylline
Hemoperfusion
Barbiturates
8/9
Seminars for the 5th year international students
Prof. MUDr. Jiří Horák
Theophylline
--------------------
9/9