Substance Use Disorders Flashcards
Acute Intoxication
Transient condition following administration of alcohol and other psychoactive substance, resulting in decrease in LOC, cognition, perception, affect or
behaviour, or other psychophysiological functions and responses
Addiction
Repeated use of psychoactive substance to the extent the user is periodically or
chronically intoxicated, shows a compulsion to take preferred substance, has great difficulty
ceasing, and exhibits determination to obtain by any means
Tolerance
Physical adaptation to consumption, leading to a need for increasing
dose to achieve the same effect; Often precedes Physical Dependence
Dependence
Need for repeated administration to feel good, or avoid feeling bad
▪ Psychological – Refers to experience of impaired control (craving,
compulsions); Physical – Refers to Tolerance and Withdrawal symptoms
Dependence Syndrome
Cluster of Behavioural, Cognitive and Physiological phenomena which might develop after repeated use
o Strong desire to take the drug, Impaired control over use, Persistent use despite
awareness of harmful consequences, Higher priority given to drug than other activities, Increased Tolerance, and a Withdrawal associated when use is
discontinued; >3/6 of criteria = ICD-10 def of Dependence Syndrome
Withdrawal
Cluster of symptoms which occur on cessation/reduction of use of psychoactive
substance which was previously taken repeatedly, typically for prolonged time/high doses
o Typically, features are opposite to Acute Intoxication
o E.g. ETOH Withdrawal – Tremor, Sweating, Anxiety, Agitation, Depression, Nausea
and Malaise; Can be complicated and progress to Delirium Tremens
Harmful Use
Pattern of Psychoactive substance use that causes damage to health
o Physical or Mental; Commonly but not invariably has harmful social consequences
o Replaces non-dependent use in the ICD-10
Alcohol Metabolism
Ethanol is oxidised to Acetaldehyde by Alcohol
Dehydrogenase primarily; Acetaldehyde is highly
unstable and forms free radicals which are
highly damaged and need to be quenched by
antioxidants (E.g. Ascorbic Acid, Thiamine)
o Acetaldehyde is then converted to Acetate by Aldehyde Dehydrogenase 2 (ALDH2),
which is then subsequently converted to Acetyl CoA which can be metabolised to
produce ATP, or other biomolecules
How does alcohol affect CNS
Ethanol affects brain function by interacting with multiple neurotransmitter systems; In the
short term, believed to increase inhibitory neurotransmission (GABAA) resulting in sedation
and reduced anxiety
Alcohol Limits
Current alcohol advice (2016) states that safe levels are 14 units per week regardless of sex
o If drinking as much as 14 units, spread evenly over three days or more
o Heavy drinking sessions increase risk of death from long-term illness and accidents
o In Pregnancy – No safe level known, hence best to remain abstinent
Presentation of Acute Alcohol Intoxication
Slurred speech, Impaired Coordination and Judgment, Labile Affect; Hypoglycaemia, Stupor and Coma
Presentation of Acute Withdrawal
Malaise, Nausea, Autonomic Hyperactivity, Tremor, Labile Mood, Insomnia and Transient Hallucinations (Typically visual)
Alcohol Dependence Syndrome
Compulsion, Awareness but Persistence, Neglect,
Tolerance, Withdrawal, Stereotyped Pattern, Time Pre-occupied, Out-of-control use, Persistent wish to cut down (albeit futile)
Alcoholic Psychotic Disorders
ETOH Hallucinosis (Threatening, Second-person auditory hallucinations) or Jealousy (Paranoid delusions about Infidelity)
Alcohol Amnesic Syndrome
Korsakoff’s Psychosis, Wernicke’s
Encephalopathy
ETOH Induced Hypoglycaemia
ETOH metabolism requires
NAD, hence reducing the NAD/NADH ratio;
Gluconeogenesis is reduced as it is dependent on this ratio; Ketosis occurs due to Hypoglycaemia,
Managing Alcohol Withdrawal
Can be quantified using
CIWA-Ar (N+V, Tremor, Paroxysmal Sweats, Tactile
Disturbance, Auditory and Visual Disturbances)
o Offer Pharmacotherapy – Benzodiazepine (E.g. Chlordiazepoxide) or Carbamazepine
for prevention of DT in Acute ETOH Withdrawal
Delirium Tremens
Rapid onset Confusion typically due to acute withdrawal about 3 days
after; Exaggerated symptoms of Acute Withdrawal plus Seizures and Fever
Management of Delirium Tremens
o Oral Lorazepam first line; If persistent or oral declined, Parenteral Lorazepam or
Haloperidol alternatively; Phenytoin not used to treat withdrawal seizure
o Rehydration, Correction or Electrolyte Disturbances, Oral or Parenteral Thiamine e.g.
Pabrinex; Especially if Malnourished, Decompensated Liver Disease
Consequences of Alcohol Excess
ETOHXS leads to inadequate Nutritional Intake, Decreased Thiamine absorption in GI tract, and Impaired Thiamine Utilisation
Wernicke’s Encephalopathy
Exhaustion of B-Vitamins esp Thiamine; Many will have partial triad of ophthalmoplegia, Ataxia and Confusion
o Body has 2 – 3 weeks of Thiamine reserves which is easily exhausted if no intake, or
rapid depletion e.g. Chronic inflammatory states
o Thiamine is a co-factor in the Kreb cycle and
PPP; Necessary for Glucose metabolism,
Neurotransmitter production (E.g. Glutamic
acid, GABA), Myelin production etc
o Thiamine Deficiency – Oxidative Damage,
Mitochondrial Injury and Pro-Apoptotic
stimulation leads to neurological injury
Promoting Alcohol Abstinence
Motivational Interviewing, Psychological Therapies, Self-Help (E.g. Alcoholics Anonymous; Reduce pro-drinking activities, improves social ties with abstinent groups)
Promoting Alcohol Abstinence: Pharmacotherapy
Pharmacotherapy for after successful withdrawal from Moderate-Severe ETOH dependence
o Baseline U/Es, LFTs with GGTs,
SSRIs, GHB or Benzodiazepines should not be used to maintain abstinence
Promoting Alcohol Abstinence: Pharmacotherapy-Acamprosate TDS
Acts on NMDA and GABAA to reduce Cravings, and risk of Relapse; Up to
6/12 initially; Stopped if drinking persists 4 – 6/52 after starting
Promoting Alcohol Abstinence: Pharmacotherapy-Naltrexone OD
Antagonism of μ-Opioid Receptor, modulating the Dopaminergic pathway;
Believed to reduce Cravings more than Acamprosate although less effective in terms of result
Promoting Alcohol Abstinence: Pharmacotherapy-Disulfiram
Inhibits Acetaldehyde Dehydrogenase leading to accumulation; Causes Flushing, Headache, Anxiety and Nausea
o Disulfiram for Acamprosate or Naltrexone, or Prefer Disulfiram
o CI: Pregnancy, Severe Mental Illness, Stroke, Heart Disease, HTN
o Ensure that patients are supervised, initially 2/52ly for 2/12 then monthly
Prognosis of Alcohol Dependence
Continued ETOH increases rate of early death by 3-4×; Most commonly due to Heart Disease, Stroke, Cancers, Liver Cirrhosis, Accidents and Suicide
Prognosis of Alcohol Dependence: Poorer Prognosis
Poorer Prognosis if: Do not seek treatment, Female (Likely higher incidence of Comorbid Depression and Anxiety), Lower SES, Other Drug Abuse (Esp Cocaine), Prolonged Use (>20yrs)
Smoking
Smoking is the biggest avoidable cause of death, disability and social inequality in health
o Decreasing; 22% of men and 21% of women; Highest rates in 20-24yrs Women, and 25-34yrs men; Increasing in Developing Countries
o Typically begins when in adolescents for Psychosocial reasons; Nicotine encourages persistence through effects on user’s mood
Nicotine
Additive component of cigarettes; About 10mg per cigarette; 1-2mg inhaled
o Stimulant effects – Hepatic glucose, Catecholamine release; Direct Stimulation of
Nicotonic AChR affects many neurotransmitter systems; Increases dopaminergic
transmission in Mesolimbic system
Cigarette Components
Tar, Polycyclic Aromatic Hydrocarbons, Carbon Monoxide,
Acetaldehyde, Nitrosamines
Health Effects of Smoking
Carcinogenic =Ca Lung, Oropharyngeal, Oesophagus etc; Inflammatory response from Neutrophil and Macrophages =Emphysema + Bronchitis =COPD, Heart Disease
Smoking Cessation
Evidence that smokers with family and friends support more likely to stop; Smokers with partners who smoke are less likely that non-smoking partners; Limited evidence of exercise and use of glucose with Nicotine patches; Good evidence for use of NRT, Bupropion and Varenicline compared to use without; NRT and Bupropion non-inferior; Varenicline seen to be more effective but still under review
• National Campaigns, Bans on Advertising, Taxation, Smoking Bans in Workplaces, Pubs and Public Spaces have been very effective
Smoking Cessation: Brief Interventions
Opportunistic Advice, Discussion, Negotiation or Encouragement;
Referral to more intensive treatment; Refer onto NHS SSS and Smoking Cessation Clinics
o Individual Behavioural Counselling (typically for 4/52, combined with Pharm)
Smoking Cessation: NRT
Gum, Sublingual, Inhalator, Lozenges, Spray, Patches; Enough for 2/52 after stop date
o SE: Headaches, Nausea, Palpitations; Higher risk if Unstable Cardiovascular Disease
o In pregnancy, risk of NRT < continued smoking; Consider if failed abstinence without
NRT; Patches might be more beneficial
Smoking Cessation: Varenicline
(Agonism of Nicotinic AChR subtypes),
Smoking Cessation: Bupropion
(Selective Inhibitor of
Noradrenaline and Dopamine)
Smoking Cessation: Pharmacotherapy
o SE: Reduced Seizure Threshold if Hx of Epilepsy; Headaches, Nausea, Dizziness, Sleep
o CI: Allergy, Seizure Disorder or Hx, CNS Tumour, ETOH Withdrawal, Eating Disorders;
Concomitant use with MAOIs
o Enough for 2/52 after stop date; Review 3-4/52 after stop date
Toxicology Screening
Random Urine (8ml) in monovette should be sent if uncertain or unknown agent of poisoning; Qualitative results only; available within the day
Cannabis
Most commonly used; THC exerts central effects through CB1 Cannabinoid
receptor; Receptor expressed highly by GABAnergic Interneurones in Hippocampus,
Amygdala and Cerebral Cortex
o Consumed by Smoking, Vapour, Edibles, Oils,
o Inhibition of Amino Acid and Monoamine Neurotransmitter release
o Disruption of Psychomotor Behaviour, STM Impairment, Intoxication, Appetite
Stimulation, Antinociceptor Action and Anti-Emetic effects
o Use of Cannabis associated with Depression, Anxiety and Psychotic disorders if taken
from a younger age (Disruption to the developing brain)
Cocaine
Inhibition of Monoamine Reuptake, especially Dopamine, resulting in accumulation
within synaptic cleft; Also has actions on 5-HT receptors, Sodium channels (Local Anaesthetic
effects) and NMDA receptor
o Consumed by Intranasal, Smoked, Oral, IV
o Addiction occurs following transcriptional changes in the Mesolimbic pathway,
specifically Nucleus Accumbens; Cocaine users often also misuse Cocaine and Opioids
o Acute Intoxication mimics Mania or Psychosis; Half have Cocaine-related Violence
Amphetamines
Inhibit of Dopamine, NA and 5-HT Reuptake
o Intoxication similar presentation to Hypomania; Elevated Mood, Over-talkativeness,
Increased Energy and Insomnia; Hypertension and Pupil Dilation
o Withdrawal may present as Agitated Depression, Lethargy, Suicidal thoughts and Cravings; Managed with Benzodiazepines, Antipsychotics and Depression with TCAs
Crystal Meth
Particularly addictive form reaching high brain concentrations when
smoked; Frequency and Severe Psychiatric Symptoms and Withdrawal Reaction
MDMA
(Ecstasy) – Synthetic Amphetamine Analogue with Mild Stimulatory and
Hallucinogenic effects; “Safer” than Cocaine or Amphetamines
o Hyperpyrexia, AKI due to dehydration; Water Intoxication if overcompensated
o Unknown prevalence of Acute Psychosis
Opioids
(E.g. Heroin, Fentanyl) – Opioid Agonism; Euphoria, Analgesia, Drowsiness, Resp
Depression, Bradycardia, Pupil Constriction, Constipation; “Chasing”, Snorting, IVDU
o Tolerance develops rapidly; Overdose is common and frequently fatal due to Resp
Depression; Tolerance makes pain management using opioids challenging
▪ High risk of overdose following detoxification due to reversal of tolerance
Opioid Withdrawal
Withdrawal occurs 8-12hrs after last dose; Subsides over 10/7; Rarely life threatening
although severe; Craving, Restlessness, Myalgia, Sweating, Abdo Pain, Pupil Dilation,
Tachycardia, Yawning, Goose Bumps
▪ Symptomatic relief with Alpha Agonists (e.g. Lofexidine); Reducing Doses of Substitute drug (E.g. Methadone, Buprenorphine) to reduce withdrawal
symptoms; Clonidine, Naltrexone also used
Opioid Overdose
Pinpoint Pupils, Bradycardia, Hypotension and Hypoventilation; Naloxone
titrated until adequate spontaneous ventilation
Ketamine
General Anaesthetic; Selective Antagonism of NMDAR; Anaesthetic, Amnestic,
Dissociative and Hallucinogenic effects
o Related to PCP; Typically Injected or Snorted, but can also be smoked or orally
o Can cause dependence; Physical symptoms of withdrawal not very intense, however,
may increase Suicidal tendencies especially if history of depression
Examples of Depressants
Benzodiazepines
Alcohol
GHB
Withdrawal from Depressant
Sleep Disturbance, Irritability,
Tension, Anxiety, Hallucinations,
Seizures, Psychosis
Management of Depressant Dependence
Chlordiazepoxide
Reducing Regimen
Antipsychotics
Examples of Stimulants
MDMA
Amphetamines
Cocaine
Withdrawal from Stimulants
‘Crash’ – Agitation, Depression,
Lethargy, Suicidal thoughts
Management of Stimulant Dependence
Similar Management to
Opioids; Antipsychotics
and Benzodiazepines
Examples of Opioids/ Narcotics
Heroin
Fentanyl
Withdrawal from Opioids
‘Cold Turkey’ – Restlessness,
Tachycardia Pupil Dilation,
Rhinorrhoea, Goosebumps
Management of Opioid Misuse
Methadone/
Buprenorphine
Reducing Regimen
IVDU
Highest risk of overdose and complications, Phlebitis, DVT, Sepsis, Infective Endocarditis
(Tricuspid disease more common; S aureus), Bleeding, Neuropathic Pain, Ischemia
• Increased risk of Blood-borne Viruses (HBV, HCV, HIV)
Harm Reduction
Aims to reduce injecting, stabilising drug use and lifestyle, reducing
criminal behaviour (avoid need to obtain drugs), and reduce death rate
o Needle exchanges, Safer Injecting Advice (Washing hands, New needles, never
sharing, Hygienic preparation area, Cleaning area etc)
Psychosocial Interventions
• Abstinence Oriented, Maintenance Oriented or Harm Reduction
• Support for families and carers: Personal, Social and Mental Health Needs Assessment
• Brief Opportunistic Interventions, Self-Help groups, Contingency Management, Behavioural
Couples Therapy, Inpatient, Residential Care, Care while Incarcerated
