Addiction

Question 1

Define tolerance

Answer 1

Tolerance = loss of effect when taking the same dose

• The person may keep increasing the dose to achieve the desired effects.
• Tolerance occurs with most psychoactive substances over time.

Question 2

Define dependence

Answer 2

Dependence = a physiological + psychological need to keep using a drug

Dependence may occue due to:
* Physiological changes (notable with alcohol, opiates, benzodiazepines)
* Psychological factors (e.g. cravings and compulsions to use the drug)

Question 3

Why do withdrawal symptoms occur?

Answer 3

Withdrawal symptoms = occur due to physiological adaptations to the drug

E.g.:
* Benzodiazepines = stimulate GABA receptors
* GABA = an inhibitory neurotransmitter - has a relaxing effect
* Long-term use of benzodiazepines = results in the body reducing its natural production of GABA to balance the stimulating effects of the drug
* When drug is withdrawn → under-activity of GABA system → withdrawal symptoms - anxiety, irritability, tremors, insomnia, seizures

Question 4

Define addiction

Answer 4

Drug addiction = the compulsive use of substances, often leading to harmful physical, psychological and social consequences

Question 5

Which pathway in the brain is the reward pathway?

Answer 5

Mesolimbic pathway
* Primary neurotransmitter = dopamine

Key areas:
* Ventral tegmental area
* Nucleus accumbens
* Amygdala
* Prefrontal

Question 6

Pathway of psyhcological addiction

Answer 6

Addictive substances or behaviours = release dopamine within the mesolimbic pathway → providing a pleasurable reward

Repeated exposure to this stimulus = reduces the number and sensitivity of the dopamine receptors in this pathway, requiring an increasingly strong stimulus (e.g., a higher dose or frequency) to produce the same reward. The response to everyday activities reduces (everyday life becomes less rewarding). As a result, the person increasingly seeks out the substance or behaviour to stimulate the reward pathway.

Question 7

Which part of the brain are the cues for the addictive substance or behaviour embedded into?

Answer 7

Amygdala

• People, events, places or objects = can act as cues, triggering cravings.
• Stress = a common trigger → prompting the substance or behaviour as a** coping mechanism**.

Question 8

What region of the brain that is responsible for executive functions (decision-making, assessing risk, controlling impulses) is also changed during addiction?

Answer 8

Prefrontal cortex

Question 9

Examples of opioids and basic mechanism of action

Answer 9

Heroin, morphine, oxycodone, codeine
Stimulates opioid receptors

Question 10

Examples of stimulants and basic mechanism of action

Answer 10

Cocaine, MDMA (ecstasy), methamphetamine
* Cocaine = blocks reuptake of dopamine by the presynaptic membrane
* MDMA = stimulates the release of serotonin + blocks its reuptake
* Meth = stimulates the release of dopamine + blocks its reuptake

Question 11

Examples of depressants and basic mechanism of action

Answer 11

Alcohol, benzodiazepines
Stimulates gamma-aminobutyric acid (GABA) receptors

Question 12

Examples of hallucinogens and basic mechanism of action

Answer 12

LSD, psilocybin
Stimulate serotonin receptors, particularly 5-HT2A receptors

Question 13

Name a cannabinoids and basic mechanism of action

Answer 13

Cannabis
Stimulates cannabinoid receptors (CB1 + CB2)

Question 14

Name some anticonvulsants and the basic mechanism of action

Answer 14

Pregabalin, gabapentin
Blocks voltage-gated calcium channels in the presynaptic membrane, reducing the release of excretory neurotransmitters

Question 15

Name some nicotine products and the basic mechanism of action

Answer 15

Cigarettes, vapes
Stimulates nicotinic acetylcholine receptors

Question 16

What is the management plan for drug and alcohol addiction?

Answer 16

• Detoxification (may be coordinated at home or as an inpatient)
• Medication to help maintain abstinence
• Psychological + behavioural therapies (e.g., cognitive behavioural therapy)
• Ongoing support (e.g., a recovery coordinator and support groups)

Question 17

Name some medication used for opioid dependence

Answer 17

• Methadone (binds to opioid receptors)
• Buprenorphine (binds to opioid receptors)
• Naltrexone (helps prevent relapse)

Question 18

Name some medication used for nicotine dependence (smoking)

Answer 18

• Nicotine replacement therapy (e.g., patches, gum or lozenges)
• Bupropion
• Varenicline

Question 19

Define alcohol dependence

Answer 19

Alcohol dependence = involves daily alcohol consumption, strong urges and cravings for alcohol, difficulty controlling consumption, tolerance to the effects of alcohol + withdrawal symptoms when stopping.

Question 20

Mechanism of action for alcohol

Answer 20

• Alcohol = a depressant
• Alcohol = stimulates GABA receptors (which have a relaxing effect on the brain)
• Alcohol = also **inhibits glutamate receptors (NMDA receptors) **→ causing further relaxing effct on the brain (glutamate = excitatory neurotransmitter)

Question 21

Mechanism of action for alcohol dependence

Answer 21

• Long-term alcohol use = down-regulates the GABA system + up-regulates the glutamate system (balancing the effects of alcohol)
• The patient must continue drinking alcohol, or they will experience unpleasant, uncomfortable and potentially dangerous withdrawal symptoms.

Question 22

Formula to calculate alcohol units

Answer 22

Volume (ml) x Alcohol Content (%) ÷ 1000 = Units of Alcohol

Question 23

Tom Tip: Calculating alcohol units

Answer 23

Calculating alcohol units is a very common exam question. The simplest way is to multiply the volume in litres by the percentage. For example:

• For 750 mls of 12% wine: 0.75 x 12 = 9 units
• For a 25 ml shot of 40% vodka: 0.025 x 40 = 1 unit
• For 500 mls of 5.2% lager: 0.5 x 5.2 = 2.6 units

Question 24

What are the recommended alcohol consumption

Answer 24

• Not more than 14 units per week
• Spread evenly over 3 or more days
• Not more than 5 units in a single day

Question 25

Define binge drinking

Answer 25

Single session involving: * Women: 6 or more units * Men: 8 or more units

Question 26

Name the complications of alcohol use during pregnancy

Answer 26

* Miscarriage * Small for dates * Preterm delivery * Fetal alcohol syndrome

Question 27

Name some complications of alcohol excess

Answer 27

* **Alcohol-related liver disease** * **Cirrhosis** and its complications (e.g., oesophageal varices, ascites and hepatocellular carcinoma) * **Alcohol dependence** and **withdrawal** * **Wernicke-Korsakoff syndrome (WKS)** * **Pancreatitis** * **Alcoholic cardiomyopathy** * **Alcoholic myopathy** - with proximal muscle wasting and weakness * Increased risk of **cardiovascular disease** (e.g., stroke or myocardial infarction) * Increased risk of **cancer**, particularly breast, mouth and throat cancer

Question 28

What **questionnaire** is used to screen for **harmful alcohol use**?

Answer 28

Alcohol Use Disorders Identification Test (AUDIT)

Question 29

What are the CAGE questions can be used to screen for harmful alcohol use quickly?

Answer 29

The CAGE questions can be used to screen for harmful alcohol use quickly: **C – CUT DOWN**? Do you ever think you should cut down? **A – ANNOYED**? Do you get annoyed at others commenting on your drinking? **G – GUILTY**? Do you ever feel guilty about drinking? **E – EYE OPENER**? Do you ever drink in the morning to help your hangover or nerves?

Question 30

Name some examinations findings with excess alcohol use

Answer 30

* Smelling of alcohol * Slurred speech * Bloodshot eyes * Dilated capillaries on the face (**telangiectasia**) * Tremor

Question 31

What would blood test look liek for someome using alcohol in excess?

Answer 31

* **Raised mean corpuscular volume (MCV)** * **Raised alanine transaminase (ALT) + aspartate transferase (AST)** * **AST:ALT ratio** **above 1.5 **particularly = suggests **alcohol-related liver disease** * **Raised gamma-glutamyl transferase (gamma-GT)** (particularly notable with alcohol-related liver disease) * **↑ MCV** * **↑ ALT + AST** * **AST:ALT above 1.5** → suggests **alcohol-related liver disease** *** ↑ GGT → alcohol-related liver disease**

Question 32

What is the time course for alcohol withdrawal?

Answer 32

* 6-12 hours: **tremor, sweating, headache, craving** and **anxiety** * 12-24 hours: **hallucinations** * 24-48 hours: **seizures** * 24-72 hours: **delirium tremens**

Question 33

What is the medical emergency associated with alcohol withdrawal?

Answer 33

Delirium tremens Untreated → mortality rate is 35%

Question 34

Why does delirium tremens occur?

Answer 34

* Long-term alcohol use = results in the **GABA system** becoming **down-regulated** → the **glutamate system** becomes **up-regulated** to **balance the effects of alcohol** * **Alcohol removed** → the **GABA system = under-functions + glutamate system over-functions** * Causes **extreme excitability + excessive adrenergic** (adrenaline-related) activity

Question 35

How does delirium tremens present?

Answer 35

starts after 2d and can last up to 14d. It consists of: Impaired mental status: * Profound confusion * Visual, auditory, tactile hallucinations (often insects under skin) * Delusions * Psychomotor agitation Autonomic instability: * Tachycardia + hypertension + arrhythmias * Tachypnoea * Hyperthermia * Anxiety Neurological impairment: * Tonic-clonic seizures * Coarse tremor * Hyperreflexia * Ataxia (difficulties with coordinated movements)

Question 36

What tool can be used to score a patient on their withdrawal symptoms from alcohol and guide their treatment?

Answer 36

The **CIWA-Ar** (Clinical Institute Withdrawal Assessment for Alcohol, revised)

Question 36

What benzodiazepine is used to combat the effects of alcohol withdrawal?

Answer 36

* **Chlordiazepoxide (Librium)** * Diazepam = less commonly used alternative * Orally given Given orally as a **reducing regime** titrated to the required dose based on the local alcohol withdrawal protocol (e.g., 10 – 40 mg every 1 – 4 hours). The dose is reduced over 5-7 days.

Question 37

Apart from benzodiazepines (chlordiazepoxide) what are the other medications used in alcohol withdrawal?

Answer 37

* **High-dose B vitamins (Pabrinex)** (IV and IM) * **Long term thiamine** (oral) → prevent **Wernicke-Korsakoff syndrome**

Question 38

What are the 3 medications given for acute alcohol withdrawal?

Answer 38

* Benzodiazepine (chlorodiazepoxide (Librium)) * High-dose B vitamins (Pabrinex) * Long-term oral thiamine

Question 39

What are long-term management options are available for alcohol withdrawal?

Answer 39

* **Specialist alcohol service** involvement * **Alcohol detoxification programme** * **Oral thiamine** to prevent **Wernicke-Korsakoff syndrome** * **Psychological therapy** (e.g., cognitive behavioural therapy) * **Acamprosate**, **naltrexone** or **disulfiram** are medications used to help maintain abstinence * **Informing the DVLA** (their driving licence will be revoked until an extended period of abstinence)

Question 40

What medications can be used to help maintain abstinence?

Answer 40

* **Naltrexone** * Disulfiram * Acamprosate

Question 41

What deficiency does alcohol excess lead to?

Answer 41

**Thiamine (vitamin B1) deficiency** * Thiamine = poorly absorbed in the presence of alcohol. * Alcoholics = often have poor diets + get many of their calories from alcohol

Question 42

What can **thiamine (vitamin B1) deficiency** lead to?

Answer 42

* Wernicke's encephalopathy * Korsakoff syndrome

Question 43

Features of Wernicke's encephalopathy

Answer 43

* **Confusion** * **Oculomotor disturbances** (disturbances of eye movements) * **Ataxia** (difficulties with coordinated movements)

Question 44

Features od Korsakoff syndrome ## Footnote * **W**ernicke's encephalopathy → **w**obbly * **K**orsakoff syndrome → **k**aught up in mind

Answer 44

* Memory impairment (retrograde + anterograde) * Behavioural changes ## Footnote * **W**ernicke's encephalopathy → **w**obbly * **K**orsakoff syndrome → **k**aught up in mind

Question 45

Why is Wernicke's encephalopathy and Korsakoff syndrome so important to prevent and involve thiamine supplementation from abstaining from alcohol?

Answer 45

* **Wernicke's encephalopathy** = medical emergency w/ a **high mortality rate** * **Korsakoff syndrome** = often **irreversible** + results in patients requiring full-time institutional care