Substance use disorder Flashcards
Describe the pharmacodynamics of alcohol use? [2]
What is the physiolofical effect of this? [+]
GABA
* Binds to GABA-A receptors – mediates synaptic inhibition by opening chloride channels
NMDA
* Inhibition of excitatory amino acid receptor
Effects:
* anxiolytic, sedating, anticonvulsant, amnesic, disinhibition, euphoria, loss of coordination
* Coma, respiratory depression, death
Describe the acute and chronic pharmacodynamic effects of alcohol exposure [+]
Acute exposure
* Dopamine release
* Mesolimbic pathway = reward pathway
* Acetaldehyde activates also
Chronic exposure
* Downregulation of dopaminergic neurons
* Promotes increased alcohol consumption to achieve reward
Which screening tests to recognise problematic alcohol use? [2]
Which scores would inidcate different risks? [+]
AUDIT -Alcohol use disorders identification test (AUDIT) AUDIT is a comprehensive 10 question alcohol harm screening tool (WHO).
* 0 to 7 indicates low risk.
* 8 to 15 indicates increasing risk.
* 16 to 19 indicates higher risk.
* 20 or more indicates possible dependence
SADQ ((Stockwell et al. 1979) -SADQ is a self-administered 20-item questionnaire that evaluates severity of alcohol dependence. Scores range from 0 to 60.
* 0 -7 Non-dependent.
* 8 -15 Mild dependence.
* 16 -30 Moderate dependence.
* 31 -60 Severe dependence.
What are the effects of alcohol on the:
CV system [1]
GI system [5]
CNS [3]
CV:
- Dilated cardiomyopathy
Gastrointestinal System:
* Mallory-Weiss syndrome
* Gastritis
* Pancreatitis
* Alcoholic liver disease
* Effect on nutrition
CNS
* Polyneuropathy (Thiamine)
* Cerebellar degeneration
* Myopathy
Describe the difference types of alcoholic liver disease [3+]
Alcoholic Fatty Liver
- About 20 percent of alcoholics and heavy drinkers develop fatty liver, or steatosis. In many cases there are no clinical symptoms except for an enlarged liver (hepatomegaly). Fatty liver can be reversed if alcohol consumption is stopped or significantly reduced, but the condition can lead to death if alcohol consumption is not reduced or stopped. Some biopsies from people with fatty liver show inflammatory changes, an early sign of more serious liver disease.
Alcoholic Hepatitis
- Alcoholic hepatitis usually is diagnosed when a liver biopsy indicates inflammatory changes, liver degeneration, fibrosis, and other changes to liver cells.
- swollen liver, nausea, vomiting, and abdominal pain. Patients also may experience fever, jaundice, liver failure, and bleeding
Alcoholic Cirrhosis
- In cirrhosis, scar tissue replaces normal liver tissue, disrupting blood flow through the liver and preventing it from working properly. Clinical signs of cirrhosis include redness of the palms caused by capillary dilation (palmar erythema); shortening of muscles in the fingers (contractures) caused by toxic effects or fibrous changes; white nails; thickening and widening of the fingers and nails(clubbing); liver enlargement or inflammation; and abnormal accumulation of fat in normal liver cells (fatty infiltration). Diagnosis of cirrhosis must be made with biopsies, although laboratory tests can be helpful as well.
Describe the alcohol withdrawl timeline of symptoms [4]
Withdrawal symptoms occur at different times after alcohol consumption ceases:
6-12 hours: tremor, sweating, headache, craving and anxiety
12-24 hours: hallucinations
24-48 hours: seizures
24-72 hours: delirium tremens
Describe what is meant by delirium tremens [+]
Delirium tremens is the most severe manifestation of the alcohol withdrawal syndrome and constitutes a medical emergency.
* It is characterized by acute or subacute confusional state with anxiety, insomnia, and tremor; vivid visual, auditory, or tactile hallucinations; and fluctuating levels of psychomotor activity.
* These manifestations are accompanied by sympathetic hyperactivity with tachycardia, fever, diaphoresis (sweating), flushing, and hypertension.
* In general, delirium appears after 2–3 days of cessation of drinking and usually lasts 48–72h, but occasionally lasts much longer.
* Mortality if untreated can be between 15-50%.
Wernicke-Korsakoffs can present with lesions in which part of the brain ? [1]
Symmetrical lesions around 3rd ventricle (mammillary bodies)
Key features of Korsakoffs? [2]
Anterograde amnesia, Confabulation
Describe the pathophysiologial changes to brain seen in Korskoffs [2]
Wernicke’s plus
Marked widening in frontal intratemporal fissure
Reduced blood flow to frontal lobes (fMRI)
State and describe the MoAs of the preventative medications for alcohol dependency [3]
Acamprosate
* stimulates GABAergic inhibitory neurotransmission and antagonisis excitatory amino-acids, particularly glutamate.
Disulfiram (Antabuse)
* Blocking liver enzyme aldehyde dehydrogenase, which leads to an accumulation of acetaldehyde
Naltrexone
* Blocking opioid receptor leads to lower levels of dopamine
Describe the treatment for alcohol withdrawal [+]
Patient either needs to continue drinking or be offered a detox.
Management is generally done as an inpatient, particularly if severe or history of seizures.
Monitor withdrawal with CIWA score.
Management is primarily with Benzodiazepines (usually chlordiazepoxide)
- This can be a fixed reducing withdrawal regimen (5 7 days)
IM/IV pabrinex or oral thiamine is given alongside this
Describe how you manage opioid dependence [+]
Stabilisation on Methadone
* Long half life opioid
* Risk of diversion
* Titration of dose
* Gradual reduction
Treatment with Buprenorphine
* Partial agonist with strong affinity
* Lower risk of diversion
* Must be in withdrawal before using
Treatment with Naltrexone
* Opioid receptor antagonist
* Long term prevention
Generally Opiate withdrawal would be managed with harm reduction methods
* This might include opiate substitution e.g. with methadone and buprenorphine
* Controlled detox over a period of time.
* Withdrawal can be monitored with a COWS score (Clinical Opiate Withdrawal Scale)
Overdose
* Overdose is a significant risk with opiates particularly those new or changing dose of opiates and IV drug users.
* Naloxone would generally be issued to those at risk
Describe how methadone can be used to treat opioid dependence [+]
What are possible side effects? [3]
Methadone:
- SLIGHT Increased risk of mortality in the first 4 weeks of treatment.
- Gradual titration
- Normally tapered down over months.
- Can be used in long term treatment.
- Longer withdrawal syndrome.
Interactions:
* QTc prolongation at high dose > 100mg, and in combination with other medications.
* Medication interactions (CYP3A4).
NB: Methadone = full agonist
Describe how buprenorphine can be used to treat opioid dependence [+]
What are possible side effects? [3]
- Not associated with increased mortality during titration.
- Client needs to be in mild to moderate withdrawals to prevent precipitated withdrawals from opiates.
- Rapid titration.
- Less sedative.
- Client needs to be in mild to moderate withdrawals to prevent precipitated withdrawals from opiates.
- Rapid titration.
Describe the pathophysiology of pyschological addiction [+]
The brain has a reward pathway called the mesolimbic pathway. The primary neurotransmitter involved in this pathway is dopamine.
- The key structures involved in this pathway are the ventral tegmental area, nucleus accumbens, amygdala, and prefrontal cortex.
- At a very basic level, activation of this pathway by a behaviour provides pleasure and reinforces that behaviour.
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.
Cues for the substance or behaviour are embedded into the amygdala. People, events, places or objects can act as cues, triggering cravings. Stress is a common trigger, prompting the substance or behaviour as a coping mechanism.
Additionally, changes in the prefrontal cortex occur, leading to impaired function. The prefrontal cortex is responsible for executive functions such as decision-making, assessing risk, and controlling impulses.
How do you manage cocaine toxicity? [2]
chest pain:
* benzodiazepines + glyceryl trinitrate
* if myocardial infarction develops then primary percutaneous coronary intervention
hypertension:
- benzodiazepines + sodium nitroprusside
What are clinical features of MDMA poisoning? [5]
Clinical features
* neurological: agitation, anxiety, confusion, ataxia
* cardiovascular: tachycardia, hypertension
* hyponatraemia - this may result from either syndrome of inappropriate ADH secretion or excessive water consumption whilst taking MDMA
* hyperthermia
* rhabdomyolysis
How do you mx MDMA toxicity? [2]
Management
* supportive
* dantrolene may be used for hyperthermia if simple measures fail
Management
* Management of the intoxicated patient is dependent on the specific behavioural manifestation elicited by the drug.
* Agitation, e.g. from a ‘bad trip’, should be first managed with supportive reassurance in a calm, stress-free environment. If ineffective, benzodiazepines are the medication of choice.
* LSD-induced psychosis may require antipsychotics.
* Massive ingestions of LSD should be treated with supportive care, including respiratory support and endotracheal intubation if needed. Hypertension, tachycardia, and hyperthermia should be treated symptomatically. Hypotension should be treated initially with fluids and subsequently with vasopressors if required.
* Because LSD is rapidly absorbed through the gastrointestinal tract, activated charcoal administration and gastric emptying are of little clinical value by the time a patient presents to the emergency department
State which drugs you would use to reverse the following causes of an overdose:
* Paracetamol
* Opioids
* Benzos
* Betablockers [2]
Paracetamol:
- Acetylcysteine
Opioids:
- Naloxone
Benzos
- Flumazenil
Betablockers:
* Glucagon for heart failure or cardiogenic shock
* Atropine for symptomatic bradycardia
State which drugs you would use to reverse the following causes of an overdose:
* CCBs
* Cocaine
* Cyanide [2]
* Methanol
* CO
CCBs: Calcium Chloride
Cocaine: Diazepam
Methanol: Fomepizol or ethanol
Cyanide: Dicobalt edetate
CO: 100% oxygen
Describe the presentation of opiate withdrawal [+]
Opiate withdrawal presents with diarrhoea, mydriasis, muscular aches, yawning, a runny nose and insomnia.
Patients show features of sympathetic stimulation with tachycardia, hypertension and piloerection (goosebumps).
Likely that there is difficult venous access; therefore, it is likely that this man injects IV heroin and thus has damaged his veins.
What can you use to tx opiate withdrawal? [3]
Opioid replacement in the form of methadone or buprenorphine can be given to reduce the symptoms of opioid withdrawal but this should only be started by a specialist.
In some centres, dihydrocodeine is given in the interim to help ease symptoms before starting opioid replacement therapy.
Opiate relapse can be prevented using [] once detox is complete.
Overdose can be managed with []
Relapse can be prevented using neltrexone once detox is complete.
Overdose can be managed with naloxone
