There are many illicit and licit drugs that are abused worldwide; it is estimated that approximately 9% of the population above 12 years of age use some form of illicit substance in the United States. Drug addiction and dependence contribute to significant morbidity and reduced quality of life and should be treated appropriately with medications and psychological interventions. Acute poisoning is also common; timely diagnosis and appropriate management could be life-saving. In this chapter, we will study the important pharmacological and clinical characteristics of commonly abused drugs from examination perspective.
Image: “Pills” by Matt Browne. License:  CC BY-ND 2.0

Image: “Pills” by Matt Browne. License: CC BY-ND 2.0


Drug abuse may mean use of an illicit drug, excessive or nonmedical use of a licit drug or deliberate use of chemicals (may not be considered “drugs” in general) in a harmful manner. Substances are abused to experience pleasurable or other “elevating” psychological effects associated with their intake.

The term “dependence” (previously called physical dependence) is used to describe a state when termination of drug exposure (“withdrawal”) is associated with signs and symptoms, frequently opposite of those caused by the drug.

“Addiction” (previously called psychological dependence) is used to describe a compulsive use of drug despite its known negative consequences.

“Tolerance” means a decreased response to a drug requiring larger doses to produce the same effects. It can be metabolic, behavioural, or functional.

Classification of Substances

Schedule Criteria Examples
I No medical use, high addiction potential Flunitrazepam, heroin, LSD, mescaline, PCP, MDA, MDMA, STP
II Medical use, high addiction potential Amphetamines, cocaine, methylphenidate, short-acting barbiturates, strong opioids
III Medical use, mModerate abuse potential Anabolic steroids, barbiturates, dronabinol, ketamine, moderate opioid analgesics
IV Medical use, low abuse potential Benzodiazepines, chloral hydrate, mild stimulants (phentermine, sibutramine), most hypnotics (zaleplon, zolpidem), weak opioids


Important stimulants include caffeine, nicotine, amphetamines and its congeners, and cocaine.


Health effects of caffeine.

Image: “Health effects of caffeine.” by Mikael Häggström. License: Public Domain

Caffeine is a methylxanthine that is a non-selective antagonist at A1 and A2 adenosine receptors and induces intracellular calcium release. Caffeine content of selected drinks/beverages:

Drink/beverage Caffeine content (mg)
Cold brew coffee (20 oz) 2160
Starbucks grande coffee mocha  (16 oz) 175
Starbucks grande coffee (16 oz) 330
Jolt Cola (23.5 oz) 280
Rockstar energy drink (8 oz) 240
Tim Horton’s Large coffee  (20 oz) 200
Brewed coffee, 1 ounce 115–175
Red Bull energy (12 oz can)    114
Mountain Dew (USA) (12 oz can)    54
Chai tea 50
3 chocolate covered coffee beans    49
Diet Coke (12 oz can)    47
Arizona iced tea (20 oz) 36
Decaf coffee 3-4
Tea, green 15

Symptoms of caffeine toxicity are CNS stimulation, tremors, insomnia, and nervousness; it may not be as harmful to the heart as initially suspected. Caffeine withdrawal is characterized by lethargy, irritability, and headache. Many “caffeine-free” energy drinks often contain non-caffeine methylxanthines.

Main symptoms of Caffeine overdose

Image: “Main symptoms of Caffeine overdose” by Mikael Häggström. License: Public Domain


Nicotine exposure can occur through tobacco smoking, tobacco chewing, or snuffing tobacco. Nicotine is an agonist at nicotinic acetylcholine receptors (nAChR). Symptoms of withdrawal are lethargy, irritability, and headache. Nicotine replacement therapies are available in gum, patch, candies, and “e-cigarette” forms. Varenicline and cytisine are partial agonists of α4β2-containing AChRs which are used in nicotine addictionBupropion is a nicotinic antagonist and an antidepressant that is approved for nicotine cessation therapy. Rimonabant, an antagonist at cannabinoid receptors, is also used in smoking cessation, although is not approved by FDA for the purpose.

Main side effects of nicotine

Image: “Main side effects of nicotine” by Mikael Häggström. License: Public Domain


Acetaminophen (known as paracetamol in Europe) is available as plain acetaminophen (Anacin, Tylenol, Tempra) or in combination with codeine, oxycodone, and hydrocodone. Phenacetin is a toxic prodrug which is metabolized to acetaminophen. Paracetamol is the major cause of liver failure in Europe, USA, and Australia. It has been available as OTC drug in the USA since 1960.

It is not excreted by the kidneys but is metabolized in the liverThe toxicity may arise due to intentional (suicide) or unintentional overdose. In children, toxicity may arise when parents are not medically educated enough to calculate a safe dose for children. Due to self-medication, toxicity/overdose may also occur as patients are unaware that paracetamol is present in other formulation also such as cough syrup/nasal decongestant.

In phase I reaction, it is oxidized to toxic intermediates by CYP450. Alcoholics are more prone to acetaminophen toxicity because of induction of CYP450. Glucuronidation occurs during the phase II reaction. Hence, if the substrates are lacking, toxicity is more likely to occur. The toxic metabolite of paracetamol is NAPQI (N-acetyl-p-benzoquinone imine).

In an average person, the maximum dose of acetaminophen is 4 g/day. Ingestion of > 150–200 mg/kg in children and > 7 g in adults is potentially toxicIn acute poisoning, nausea, vomiting, anorexia, stomach pain, pallor, fatigue, and perspiration occur during the first 24 hours. During 24–72 hours, right upper quadrant pain, dark colored urine, oliguria, and jaundice appear. During 72–96 hours, symptoms like fever, lightheadedness, headache, somnolence, syncope, fatigue, blurred vision, hunger, tremors, confusion, coma, dyspnea, tachypnea, hematuria, etc appear. Due to hepatic injury caused by paracetamol, the AST and ALT levels may rise above 2000 U/L.

Rumack-Matthew nomogram is a plot of acetaminophen plasma concentration versus the number of hours after the ingestion of acetaminophen. Acetylcysteine is a glutathione substitute, used in the treatment of acute poisoning. Liver transplantation may be required in fulminant liver failure.


Steroids are abused as performance enhancers and muscle building enhancersImportant side effects are severe acne, hepatic dysfunction, increased risk of myocardial infarction, behavioral changes (increased libido and aggression, called “roid rage”) short stature (due to premature epiphyseal closure), masculinization of females, etc.



Nitrous oxide, chloroform, and diethyl ether affect judgment and may cause loss of consciousness. Nitrous oxide is used by dentists; its inhalation in pure form can cause asphyxia and death. Diethyl ether is highly volatile and is highly flammable; can cause euphoria and disinhibition.

Industrial solvents

They are present in readily available commercial products such as gasoline, glues, paint thinners, shoe polish, aerosol propellants, etc. They are frequently abused by children in 6th or 7th grade or early adolescence due to their easy availability.

Their important active ingredients include benzene, hexane, methylethylketone, toluene, and trichloroethylene. They may be toxic to the liver, kidneys, bone marrow, brain, peripheral nerves, and lungs.

Treatment includes hyperbaric chambers and psychosocial counseling. It may take weeks to get them out of the body; typically they need “28 day treatment”. Alberto V05 syndrome is caused by drinking of hairspray, which is characterized by delirium, foul smell, metabolic acidosis or respiratory alkalosis.

Organic nitrites

Referred to as “poppers”, they include amyl nitrite, isobutyl nitrite, and other organic nitrites that are used as anal sexual intercourse enhancers due to their smooth muscle relaxing action. Their inhalation is associated with dizziness, tachycardia, hypotension, and flushing. Rarely methemoglobinuria has been reported. Lipoid pneumonia and death can be caused by aspiration of the liquid form.

Air Pollutants

Important air pollutants are carbon monoxide (the most common; 50 % of total), sulfur oxides, hydrocarbons, particulate matter, and nitrogen oxides.

Carbon monoxide (CO)

Symptoms of carbon monoxide poisoning

Image: “Symptoms of carbon monoxide poisoning” by Intermedichbo. License: Public Domain

It is a colorless, odorless gas with > 200-fold affinity for hemoglobinhemoglobin compared to oxygen. CO binds with hemoglobin reversibly to form carboxyhemoglobin. It does not transport oxygen to tissues.

Its threshold limit for a human is 25 ppm in 8 hours; its concentration can be 100 ppm in heavy traffic, even 400–800 ppm in over polluted cities. Death may also occur due to irreversible damage to the heart and brain. Symptoms of CO toxicity are mainly attributed to tissue hypoxia. Common symptoms are headache (the first symptom), confusion, reduced visual acuity, tachycardia, syncope, seizures, coma, and death. “Rose cheeks” may be present. Treatment includes hyperbaric oxygen.

Sulfur dioxide (SO2)

It is an irritating gas that forms a sulfurous acid upon contact with moist mucous membranes. It causes irritation of conjunctivae and bronchi, especially in asthmatic patients. Severe bronchospasm can be caused by as low as 5–6 ppm concentration in air. Delayed pulmonary edema may be seen with heavy exposure. Chronic low exposure can aggravate cardiopulmonary diseases. Treatment includes supportive management and anti-inflammatory medications.

Nitrogen dioxide (NO2)

It is an irritant gas that can cause irritation of eyes, nose, throat, and lungs, and pulmonary edemaIt causes damage to type I and type II alveolar cells. Treatment is mainly supportive such as bronchodilators, sedatives, and antibiotics.

Level of NO2 (ppm) Effect
25 Irritability
50 Moderately irritating to the eyes and nose
100 Pulmonary edema and death

Ozone (O3)

It is an irritant gas that can cause irritation and dryness of mucous membrane at as low as 0.01–0.1 ppm. Chronic exposure can cause bronchitis, bronchiolitis, pulmonary fibrosis, and emphysemaTreatment is mainly supportive.

Environmental Pollutants

Important environmental pollutants include polychlorinated biphenyls, dioxins, asbestos, and heavy metals.

Polychlorinated biphenyls (PCBs)

They are mainly used in electrical industry and are highly stable, poorly metabolized, and lipophilic. Because they are highly persistent, they tend to accumulate in the food chain. Thus, food is a major source of PCBs. Their most common effects are dermatological are erythema, folliculitis, acne, hyperkeratosis, etc. Elevation of serum triglycerides and liver enzymes may be seen. There is no antidote for PCBs.


They are mainly used in chemical industry and are very stable, poorly metabolized, and highly persistent in the environment. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is the most important dioxinTCDD is known to cause hepatotoxicity, wasting syndrome, immune dysfunction, teratogenicity, and cancer in animals. Dermatitis and chloracne (cystic acneiform lesions on face and upper body) are seen in humans. Dioxins may have teratogenic and carcinogenic effects in humans.


asbestos effect

Image: “Figure A shows the location of the lungs, airways, pleura, and diaphragm in the body. Figure B shows lungs with asbestos-related diseases, including pleural plaque, lung cancer, asbestosis, plaque on the diaphragm, and mesothelioma.” by National Heart Lung and Blood Institute. License: Public Domain

It was widely used in construction industry and in manufacturing industry as an insulator and is banned in most countries. It is poorly metabolized, lipophilic, highly persistent in the environment and tends to accumulate in the food chain. Asbestosis, a fibrotic lung disease, can be caused by inhalation of its fibers. It is also associated with mesothelioma, lung cancer, and cancers of the gastrointestinal tractThere is no antidote for asbestosis, only supportive treatment is available.



Paraquat is a bipyridyl herbicide widely used by agricultural industry, construction industry, and municipal governments for killing weeds and maintaining highways. When ingested, it causes hematemesis and bloody stools; followed by progressive pulmonary fibrosis which may cause death. It is nontoxic by other routes.

Management includes gastric lavage, prevention of absorption (with charcoal or Fullers Earth), dialysis, and other supportive treatment. Even with the best management, the mortality rate remains < 50 % with an ingested dose of 50–500 mg/kg. However, there is no universally accepted treatment, which is successful.

Agent Orange (2,4,5-trichlorophenoxyacetic acid)

It is a potent herbicide used in Vietnam. It is often contaminated with dioxin and other polychlorines during manufacturing processes. Large doses can cause muscle hypotonia and comaIts long-term association with non-Hodgkin lymphoma is known.

Glyphosate (RoundUp)

It is extensively used household herbicide globally and targets aromatic amino acid biosynthesis in plants. It causes eye and skin irritationThere is no specific treatment; flushing should be done.


Pesticides are classified into 3 major classes: chlorinated hydrocarbons, acetylcholinesterase inhibitors, and botanical agents.

Chlorinated hydrocarbons (hydrochlorocarbons)

DDT (“Deet”, Muskol) is the prototype hydrochlorocarbon. DDT and its analogs block inactivation of sodium channels in nerve membranes, thus causing unchecked firing of action potentials.

The first sign of toxicity is a tremor, which may progress to seizures. Chronic exposure is tumorigenic in animals; carcinogenic potential is unknown in humans with inconclusive association with Hodgkin lymphoma, brain cancer, and testicular cancer. No specific treatment is available.

Acetylcholinesterase inhibitors

Carbamates (e.g., carbaryl) and organophosphates (e.g., malathion, parathion) are acetylcholinesterase inhibitors that act by increasing muscarinic and nicotinic cholinergic activity. Acute poisoning is characterized by pinpoint pupils, increased secretions (perspiration, salivation, diarrhea, etc.), vomiting, bronchospasm, muscular symptoms (weakness, fasciculations, paralysis), CNS stimulation followed by CNS depression. Atropine and pralidoxime (not for carbamates) are used in the treatment of acute poisoning.

Botanical insecticides

Botanical insecticides include nicotine (causes ganglionic, CNS, and neuromuscular stimulation followed by depression), rotenone (causes gastrointestinal symptoms upon ingestion; conjunctivitis and dermatitis upon contact), and pyrethrum (causes mainly contact dermatitis; seizures and peripheral neurotoxicity upon ingestion or inhalation). Treatment of acute poisoning is symptomatic and supportive.

Popular Exam Questions

The correct answers can be found below the references.

1. Which of the following cancers is associated with chronic exposure to asbestos?

  1. Malignant astrocytoma
  2. Cancer of gastrointestinal tract
  3. Testicular teratoma
  4. Malignant melanoma
  5. Prostate cancer

2. Rumack-Matthew nomogram has the application in the treatment of toxicity of which of the following drug?

  1. Acetaminophen
  2. Steroids
  3. Caffeine
  4. Aspirin
  5. Ampicillin

3. Pralidoxime is used for the treatment of which of the following agents?

  1. Carbamates
  2. Malathion
  3. DDT
  4. CO
  5. Polychlorinated biphenyls

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