Finish the chain, from slow to fast: - Chewing tobacco, _____, ____ - _____ _____, paste, _______, ____ - ________, _________, snorted, __ ________

- snuff, cigarettes - cocoa leaves, cocaine, crack - methadone, morphine, IV heroin

- may occur within hours of the last 'fix' - may peak between 2 - 4 days - usually will not last beyond 7 days THE ONSET, INTENSITY AND DURATION IS MULTIFACTORIAL. (e.g. previous experiences of withdrawal may be an important variable)

Substance Misuse Flashcards by Nilusha Muraleetharan

Define drug

Any natural synthetic or natural chemical substance that is used in the treatment, prevention or diagnosis of disease.

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Why do people take drugs?

For pleasure, to get a ‘rush’, euphoria –> positive reinforcement/ reward
As anxiolytics or to overcome withdrawal –> negative reinforcement
Because people are addicted and cannot control their use –> overwhelming urge

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The ____ the onset of the drug effects, the better the ______

faster

rush

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Finish the chain, from slow to fast:

Chewing tobacco, _____, ____
_____ _____, paste, _______, ____
________, _________, snorted, __ ________

snuff, cigarettes
cocoa leaves, cocaine, crack
methadone, morphine, IV heroin

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Explain the science of addiction.

Drugs of abuse increase DA in the nucleus accumbens of the mesolimbus
Increase in DA is key to +ve reinforcement
DA increased by cocaine, amphetamines, alcohol, opiates, nicotine and cannabinoids.

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The nucleus accumbens has high levels of ____ receptors

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The nucleus accumbens:

high levels of D3 receptors
DA release here is involved in learning associations
Reduced DA is noted in withdrawal states and is likely to be associated with depression, irritability and dysphoria.
DA is modulated mu opioids

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Opiates are ______ substances ; e.g. ______, ______

Opioids are ____- _______; e.g __________, _______
or ______; e.g. ______

natural
morphine, codeine

semi synthetic
dihydrocodeine,heroin

synthetic
methadone

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What receptors do opioids act as agonists at?

delta
kappa
mu
nociceptin receptors

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What effects are seen when opioids bind to delta receptors?

antidepressant, physical dependence, analgesia

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What effects are seen when opioids bind to kappa receptors?

sedation, dysphoria, miosis, inhibition of ADH release

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What effects are seen when opioids bind to mu receptors?

analgesia, euphoria, +ve reinforcement, respiratory depression

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What effects are seen when opioids bind to nociceptin receptors?

anxiety, depression, appetite, tolerance to mu agonist

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What are some chronic effects of opioids?

depression, insomnia, constipation, dependence, ahedonia

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What are some acute affects of opioids?

itching, miosis, nausea, euphoria, drowsiness, tranquility

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Mechanism of tolerance is?

not well understood

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How are opioids taken?

smoked, swallowed, injected, inhaled

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Opioid withdrawal:

may occur within hours of the last ‘fix’
may peak between 2 - 4 days
usually will not last beyond 7 days

THE ONSET, INTENSITY AND DURATION IS MULTIFACTORIAL. (e.g. previous experiences of withdrawal may be an important variable)

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What are some symptoms of withdrawal?

Depression
Diarrhoea
Shivering
Restlessness
Insomnia
Dilated eyes
Myalgia
Tachycardia
Piloerection
Rhinorrhoea

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Opioid withdrawal is associated with

increased noradrenergic activity due to opioid affect on locus coeruleus… tachycardia, piloerection

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short term opioid detoxification takes

30 days

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long term opioid detoxification takes

180 days

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what are some pharmacological aids for opioid detoxification?

In order to suppress all aspects of withdrawal:
methadone - full mu agonist
buprenorphine - partial mu agonist

In order to suppress autonomic signs - not subjective discomfort
clonidine - a2 adrenoceptor agonist

rapid opioid detoxification takes

3-10 days

ultra rapid opioid detoxification takes

1-2days

ultra rapid opioid detoxification: | withdrawal is precipitated using?

``` naloxone naltrexone PLUS: - clonidine benzodiazepine general anaesthesia ```

What's the risk of rapid/ ultra rapid opioid detoxification

respiratory distress, renal complications

How does methadone work?

Attenuates withdrawal + craving but patient does not experience 'rush'

Why is methadone administration supervised?

to reduce risk of abuse (there is some evidence of a black market for methadone - addicts sell methadone to finance buying heroin)

Maintenance therapy of methadone. Talk about it's half life

It can be v. effective but there is risk of dependence. It has a long half life. One oral dose of methadone can suppress craving for heroin + withdrawal symptoms for 36 hours.

Acute action of opioid is to _____ cAMP and _______ NA neuronal firing.

inhibit | reduce

Chronic action of opioid is ________ __-_____ of cAMP. This results in an _______ in NA tone which is revealed on _________ symptoms

compensatory up-regulation increase withdrawal

Compare methadone and buprenorphine for maintenance/ detoxification

Methadone: - full mu opioid agonist - half life: 24hrs but on chronic dosing; 36hrs. Buprenorphine - partial mu opioid agonist therefore reduced risk of respiratory depression - Antagonist at kappa therefore less likely to cause dysphoria - half life: 24hrs therefore withdrawal syndrome less

If heroin is injected, buprenorphine is useful because it's ______ property will prevent relapse

antagonist

What is naltrexone?

- oral - non-selective opioid antagonist (blocks acute opioid effects) - used to prevent relapse in drug-free subjects - most common adr's are GI

Most common ADR for Naltrexone is?

GI disturbance

What are some acute affects of cocaine?

``` formication euphoria increase heart rate and bp confusion psychosis ```

What are some chronic affects of cocaine?

``` paranoia depression psychosis anorexia variable effects on D1 and D2 receptors ```

What happens when cocaine use stops?

'CRASH' - depression - anxiety - hypersomnia (sleepy throughout the day) - anergia (abnormal lack of energy)

What is the current therapy for cocaine use?

Partial D3 agonist

THC alters both ______ and ________ neuronal activity

hippocampal | cerebral

Acute effects of THC?

``` relaxation confusion distorted perceptions anxiety impaired memory, concentration and coordination ```

The most commonly abuse drug in the UK is?

alcohol

Alcohol misuse results in

``` Psychological Physiological Psychiatric and Societal damage ```

Alcohol misuse is when:

a patient drinks to the extent of causing harm to self or others

EQUATION FOR ALCOHOL UNITS

Alcohol by Volume (%) x Litres = units

IF <50 units/week;

May not be required

IF 50-100 units/week;

Consider detox

IF >100 units/week

Detox required

What are some risk factors that have an increased need for alcohol detox

- older patients - severe dependence - Hx of failed community detox - Psychiatric co-morbidities - Poor physical health e.g. Diabetes, Liver damage, HTN - Hx of DTs and alcohol withdrawal seizures - Poor social support - Cognitic impariment

What are some pharmacological agents for alcohol detox

- Benzodiazepines e.g. Diazepam - Thiamine; High Potency Parenteral; Pabrinex IV / IM; 1 pair ampoules daily for 3-5 days. - Then; long-term Vit B Co.Strong; One Tab PO; OD. ALSO BREAKTHROUGH DOSE OF: Diazepam 10mg PO Max TDS should be prescribed for ‘breakthrough’ withdrawal symptoms, WHEN REQUIRED ALSO, FOR SEIZURES: Diazepam 5 – 10mg PR; PRN for seizures should also be prescribed. WHEN REQUIRED

Alcohol: | Pharmacological ‘Tools’ to support continued abstinence include:

- Disulfiram ~ Antabuse - Acamprosate - Naltrexone - Nalmefene

MOA of Disulfiram

Irreversibly inhibits effects of ALDH. SO, acetaldehyde accumulates. Leads to: - N&V - Headache - Sweating - Palpitations/ Tachycardia - Flushing

Large doses of alcohol + disulfiram =

- hypotension - collapse - arrhythmias

Adverse effects of Disulfiram?

- N & V - Halitosis - Psychiatric reactions; paranoia , depression - Hepatic cell damage