Substance Dependence (Addiction), Withdrawal and Overdose

Substance Dependence (Addiction), Withdrawal and Overdose

Overview of addition medicine. This section is a brief introduction to substance abuse, followed by section that look at specific drugs of addiction.

Substance Misuse: Consumption above designated low risk levels
Substance Abuse: repetitive substance use resulting in social complications (financial, occupational and legal)
Substance Tolerance: Defined by either of the following: a need for markedly increased amounts of the substance to achieve intoxication or desired effect or markedly diminshed effect with continued use of the same amount of the substance.
Substance Dependence: Cluster of psychological, behavioural and cognitive syndromes that comprise an inner drive to repetitive substance use. Dependence is a clinical syndrome in which there is a prominent physiological drive to consume a substance
Withdrawal: Neurons adapt to the chronic presence of a substance. Cessation of substance results in abnormal neuronal function and therefore symptoms.
Hazardous substance use: Repetitive use at levels that place a person at risk of psychological or medical harm
Harmful substance use: Repetitive pattern of use that causes actual physical (e.g. liver disease) or psychological harm (e.g. depression, anxiety)

Risk Factors

  • Age
  • Gender
  • Personality
  • Family background
  • Recent or past stressors
  • Mental illness
  • External factors
    • surrounding culture
    • price
    • availability
    • advertising


  • FBC - Infection, dehydration?
  • LFTs - Heavy alcohol use, hepatitis
  • EUC - Hydration status, electrolyte balance, renal function, blood alcohol level
  • CRP- Infection and Inflammation
  • Serology - Hep B, Hep C, HIV
  • Urine toxicology screen
  • Echocardiogram - If signs of endocarditis or murmurs on auscultation
  • Chest X-ray - If signs of respiratory infection
  • MRI - To rule out abscess’s formation under the skin at the site of cellulitis
Drug and duration of detectability in urine
Amphetamine 2-3 days
Cocaine 2-3 days
Weed 1-7 days (light test) 1 month for chronic users
Opiates 1-3 days

Clinical Presentation

  • Acute intoxication: Follows administration of alcohol or other psychoactive substances resulting in disturbances of level of consciousness, cognition, perception, affect, or behaviour.
  • Harmful use: A pattern of psychoactive substance use that is causing actual damage to the mental or physical health of the user.
  • Dependence syndrome: 3 or more of the following:
    • Strong desire or sense of compulsion to take the substance(craving).
    • Diffculty in controlling substance use (onset, termination, level of use).
    • A physiological withdrawal state when reducing or ceasing substance use.
    • Tolerance: increased doses are required to produce the original e ect.
    • Progressive neglect of alternative pleasures or interests.
    • Persisting use despite clear evidence of harmful consequences.

Alcohol dependence

Overview Alcohol dependence is the clinical term used to describe a person who has become addicted to alcohol. Dependent drinkers have typically lost control of their drinking, may experience withdrawal symptoms on cessation of intake. Ethanol is the most widely used CNS depressant. It is rapidly absorbed from the stomach and small intestine and distributed in total body water

Alcohol Intoxication sign and symptoms becomes more dangerous as blood alcohol increases

  1. Euphoria, disinhibition, grandulouness, impaired attention, impaired judgement
  2. Increase risk or accidents, injuries, violence
  3. Dysarthria, ataxia, confusion. disorientation, increase risk of falls, fractures
  4. Inhalation of vomitus, asphixiation, coma, death

Complications of alcohol use

  • Acute complication of alcohol use
    • Coma and respiratory disease
    • Alcohol overdose
    • Other drug overdose
    • Aspiration pneumonia
    • Burns
    • Drowning
    • Sexual risk-taking
    • Acute pancreatitis
    • Arrhythmia (atrial fibrillation - holiday heart)
  • Chronic complication of alcohol use
    • Liver Disease (Cirrhosis or alcoholic fatty liver disease)
    • Gastro-oesophageal relux, gastritis
    • Oesophageal varices
    • Acute pancreatitis
    • Chronic pancreatitis
    • Hypertension
    • Anaemia
    • Macrocytosis (50%)
    • Myopathy
    • Pulmonary infections
    • Thrombocytopaenia
    • Wernikes's Encephalopathy (Vitamin B1 deficiency)
    • Korsakoff's Syndrome (Complication of Wernike's)
Wernicke's Triad: Confusion, Cerebellar ataxia, abnormal eye movements with opthalmoplegia.
Korsakoff's Syndrome is characterised by anterograde and retrograde amnesia
  • Psychiatric complication/comorbidites
    • Anxiety
    • Depression
  • Social Complication
    • Financial
    • Occupation
    • Family
    • Relationship
    • Legal
Stages Of Change

Management of alcohol dependence

  • Education and information
  • Management of withdrawal
    • Oral vitamins (especially thiamine)
    • Benzodiapine
  • Pharmacological treatment of dependence
    • Disulfiram
    • Naltrexone
    • Acamprosate
  • Non-pharmacological treatment of depence
    • Cognitive behavioural therapy
    • 12-step programs
  • Support from family/friends
  • Support groups - alcoholics anonymous, 12-step programs
  • Follow-up
  • Personal, life-style and environmental change
Side note Without pharmacotherapy, the majority (75%) will relapse within the first year.
Pharmacology Naltrexone inhibitis effects of endogenous opioids at mu receptor sites (anti-craving agent). Side effects: nausea, diarrhoea, fatigue, headache, hepatotoxicity. Contraindications: pregnancy, liver disease, advanced renal disease, chronic pain*
Pharmacology Acamprosate inhibits excitatory glutamates at NMDA receptor (anti-craving agent). Side effects: Diarrhoea, skin eruptions, mild sedation is occasionally reported. Contraindicated: pregnancy
Pharmacology Disulfiram inhibits aldehyde dehydrogenase at the liver. This causes the hangover feeling due to accumulation of aldehyde. Side effects: Drowziness, pschotic reactions, peripheral neuropathy, optic neuritis, hepatitis, impotence, dermatitis, cardiovascular events. Contraindications: advanced renal and liver disease, pregnancy, drinking in the last 24hrs.

Alcohol Overdose can be life-threatening and is a differential diagnosis with someone presenting with abnormal mental states, confusion and ataxia/coma. The person may also present with an underlying medical or surgical condition which is missed.


  • DRSABCD (if necessary)
  • Vitals
  • Glasgow coma scale
  • Breath or blood alcohol levels
  • Urine or plasma drug screen
  • Blood sugar levels
  • IV fluids
  • Correct electrolytes
  • +/- Thiamine
  • Follow up with alcohol withdrawal management +/- alcohol dependence assessment

Alcohol Withdrawal can occur within hours to days after heavy use and can include elevated vital signs, tremor, transient hallucinations, anxiety, and seizures. The criteria (and symptoms) of alcohol withdrawal are identical to those for sedative-hypnotic withdrawal.

The treatment of choice for alcohol withdrawal is benzodiazepines. Anticonvulsants can also be used. Should not use antipsychotics. Benzodiazepines not dependent on liver function, such as lorazepam, are often preferred in the treatment of alcohol withdrawal.

Delirium Tremens (severe alcohol withdrawal): a syndrome associated with the abrupt discontinuation of alcohol in a chronic abuser, carries a high mortality rate if not promptly identified and treated.

Delirium Tremens

Watch Alcohol Withdrawal (Delirium Tremens)

Nicotine dependence

Overview The World Health Organization recognises smoking as a major cause of many chronic disease. Smoking is a main risk factor for many pulmonary and cardiovascular disease and also cancers. Smoking contain nicotine, which is the actual addictive agent and quite harmless. The harmful effects of smoking comes from the other agents which are added into the cigarettes. nicotine is a fast-acting drug with a short activity.

Signs and Symptoms of Smoking

  • ↑Heart rate
  • ↑BP
  • Relaxed
  • Anxiolysis (not anxious)
  • Improved concentration

Complication of smoking 

  • Respiratory complications
    • COPD
    • Exacerbates other respiratory diseases
  • Cardiovascular complications
    • Hypertension
    • Hypercholesterolaemia
    • Cerebrovascular disease
    • Myocardial Infarction
  • Cancer
    • Adenocarincoma of the oesophagus
    • Pancreatic cancer
    • Lung cancer
    • Gastric cancer
  • Passive smoking complication (other people)
    • Asthma induced in children
    • Cancer
    • Cardiovascular disease
    • Respiratory disease
    • ENT disorders


5As for assessing intervention
Address The patients agenda
Assess The reason for quitting (current and past attempts)
Advice Personalised message-coping stratgies
Assist Tips or quitting, medication, therapy
Arrange Follow-up, review
  • Education (assess intervention)
  • Cold turkey
  • Nicotine replacement
  • Nicotine Patch
  • Nicotine gum
  • Nicotine inhaler
  • Nicotine lozenger
  • Nicotine nasal spray
  • Other medications
    • Varenicline - partial agonist for nicotinic cholinoreceptor
    • Bupropion
  • Non-pharmacological therapy
    • Group support
    • Quitline
    • Cognitive behavioural therapy
    • Acupuncture
    • Hypnotherapy
  • Follow up and prevent relapse
Pharmacology Bupropion is an antidepressant that affects norepinephrine and dopamine systems by increasing its release into the synaptic cleft. Its effectiveness in smoking cessation is independent of its antidepressant effects. Side effects include insomnia, agitation, and, rarely, seizures. Contraindication: seizure or history of seizure, central nervous system tumour, abrupt alcohol or benzo withdrawal, eating disorders, use of monoamine oxidase inhibitors in the last 14 days.

Nicotine withdrawal is defined as occurring where abrupt cessation of nicotine use, or reduction in the amount of nicotine use, is followed with the signs of withdrawal in 24hours:

  • Dysphoria
  • Insomnia
  • Irritability, frustration or anger
  • Anxiety
  • Difficulty concentrating
  • Restlessness
  • Decreased heart rate
  • Increased appetite

Opioid dependence

Overview Seeking the relief of pain is one of the most common reasons for patient visit. Prescription drug abuse is a growing problem, and accidental deaths from use of oxycodone, hydrocodone, and morphine, among others, are increasing. Seizures may occur in patients with renal failure because of the action of the morphine metabolite morphine-3-glucuronide. Treatment of chronic, noncancer pain using opioids remains controversial. However, treatment of acute pain, or pain in patients with a terminal illness, is generally medically necessary

Opioids are drugs that act on opioid receptors (Mu, kappa, lamba). Opioids can be:

  • Agonists - Morphine, Heroin
  • Antagoinsts - Naloxone, Naltrexone
  • Partial agonists - Buprenorphine

Opioid agonist drugs have a range of pharmacological actions:

  • Analgesia
  • Euphoria
  • Sedation
  • Central nervous system depression, particularly respiratory depression
  • Pupil constriction
  • Reduced pulse and blood pressure
  • Side effects in general: Nausea, vomiting, constipation, increased sweating, decreased sexual function (impotence)
Side note Patients who are opioid tolerant are likely to require higher than usual doses of analgesic drugs to achieve reasonable levels of pain relied

Treatment for dependence

  • Substitution therapy
    • Methadone
    • Buprenorphine
  • Opioid anatagonist
    • Naltrexone

Non-pharmacological treatment

  • Lifestyle and environmental change
  • Counseling
  • Motivational enhancement therapy
  • Cognitive behavioural therapy


Watch Opioid Overdose

Opioid Withdrawal Signs

  • Restlessness
  • Yawning
  • Perspiration
  • Rhinorrhoea
  • Dilated pupils
  • Pilorection
  • Muscle twitching
  • Vomiting
  • Diarrhea

Opioid Withdrawal Signs

  • Anorexia
  • Abdominal pain
  • Hot and cold flushes
  • Myalgia
  • Insomnia
  • Cramps
  • Intense craving for opioids

Benzodiazepine dependence

Overdose Benzodiazpines are effective anxiolytic medications. They are also effective amnestic agents, especially in high doses. Benzodiazepine users, in general, may be classified either as having therapeutic dependence" or as being polydrug users.

Benzo intoxication

  • Sedation - roused in response to stimulation, but with rapid relapse when not stimulated
  • Slurred speech and drooling
  • Loss of balance with stumbling (gait disturbance)
  • Coordination (ataxia)
  • Disinhibition

Management of Benzodiazepine dependence

  • Patient education
  • Long-acting benzodiazepine (Diazepam)
  • Cognitive behavioural therapy
  • Psychotherapy
  • Treat mental illness
  • Support groups


  • Drowsiness, confusion
  • Dysarthria, ataxia
  • Impaired coordination
  • Coma
  • Respiratory depression
  • Death

Management of Benzodiazepine Overdose

  • Primary survery
  •  Investigations
    • FBC
    • UEC
    • LFT
    • Blood sugars
    • Arterial blood gas
    • Blood alcohol concentrations
    • CT/MRI scan
  • Gastric lavage or acivated charcoal
  • Rare cases - flumazenil
  • +/- thiamine (if concurrent alcohol suspected)
  • +/- naloxone (if concurrent opioid suspeted)

Therapeutic dependence is best managed by very slow withdrawal supervised by the patients general practitioner. Benzodiazepine withdrawal is usually mild. Withdrawal onset occurs 2-5 days after stopping, reaching a maximum on 7-10, and usually abating by the end of the second or third week. The complications are the development of delirum and seizures.

Bezodiazepine Withdrawal

  • Anxiety
  • Insomnia
  • Restlessness
  • Agitation
  • Irritability
  • Poor concentration
  • Poor memory
  • Depression
  • Muscle tension, aches and twitching

Withdrawal management

  • Establishing a good therapeutic relationship with the patient
  • Initial stabilisation of dose (preferably with a long-acting benzodiapzine)
  • Gradual dose reduction

Prescription drug misuse and abuse

Overview Prescription shoppers go from doctor-to-doctor seeking prescriptions for drugs for nonmedical purposes where each doctor is unaware of supply by the others. The drugs are sought for a range of reasons. These include euphoria, and self medication of pain, anxiety and depression, but in some cases they are sought for amelioration of heroin withdrawal symptoms or purely for financial gain.

Prescription shopping is when a patient unknowingly or deliberately seeks/obtains more medicine than they need by visiting many doctors without telling them about their other consultations
Misuse (noncompliant use): The intentional or unintentional use of a prescribed medication in a manner that is contrary to directions, regardless of whether a harmful outcome occurs.
Physical dependence: A state of adaptation manifested by a drug class-specific withdrawal syndrome that occur by abrput cessation of a drug, rapid dose reduction, adminitration of an antagonist
Withdrawal: A variety of unpleasant symptoms (e.g., difficulty concentrating, irritability, anxiety, anger, depressed mood, sleep disturbance, and craving) that occur after use of an addictive drug is reduced or stopped

Reasons for seeking more medicines than they need

  • Stockpiling them for later use
  • Satisfying a drug dependency
  • Selling, exchanging or giving medicine to relatives
  • Illegally exporting them overseas

Drugs most commonly subject to misuse

  • Oxycodone
  • Morphine
  • Injectable opioids
  • Anabolic steroids
  • Benzodiazepines (esp. alprazolam)
  • Pseudoephedrine

Suspicion of prescription shopping

  • Arriving after regular hours or want an appointment toward the end of the office hours
  • Stating that he/she is travelling though visiting family/friends
  • Exaggerating or feigning medical problems
  • Providing a convincing (text-book like) description of symptoms
  • Providing an old clinical report or images to support request
  • Declining physical examination
  • Unwillingness of inability to provide the name of regular doctor (doctor is unavailable)
  • Claiming to have lost prescription
  • Showing an unusual knowledge about opioid medications
  • Pressuring the doctor by eliciting sympathy or guilt or by direct threats