Substance Misuse & Addictions Flashcards

1
Q

What 2 distinct mechanisms does the basic science of substance misuse suggest?

A

Tolerance (the basis of physical dependence)

Reward centre (the basis of psychological craving)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is tolerance?

A

“Reduced responsiveness to a drug caused by previous administration”

Develops in response to many types of drug
eg opioids, ethanol, barbiturates, benzodiazepines

An example of homeostasis-the body likes things the way they were

Mechanisms underlying tolerance can vary

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the mechanisms of tolerance and some examples?

A

Dispositional=less drug reaches the active site, eg
- decreased rate of absorption
- increased rate of metabolism to inactive metabolites
- decreased rate of metabolism to active metabolites
- increased rate of excretion

Pharmacodynamic (aka tissue or functional tolerance) = site of action is less affected by the drug
- down-regulation or internalisation of drug receptors
- reduced signalling down stream of drug
receptors
- some other compensatory mechanism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

When does tolerance become dependence?

A

Development of tolerance may also lead to withdrawal symptoms

Development of tolerance will in itself cause dependence – have to keep taking the drug to achieve a normal state-as if not will be imbalance between drug effect and adaptive response

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the withdrawal phenomena?

A

Withdrawal effect of a drug is usually the reverse of the acute effect

Tolerance & dependence are closely linked

Development of tolerance may lead to physical dependence in order to avoid the (unwelcome) withdrawal effects

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are the acute effects and withdrawal effects of:

  1. Opioid
  2. Barbiturate
  3. Cocaine?
A
  1. constipation-diarrhoea
  2. anticonvulsant-convulsions
  3. elevated mood-depressed mood
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the reward pathway and how has it evolved?

A

The reward pathway:
- Neurones project from the ventral tegmental area to the nucleus accumbens & prefrontal cortex
- When VTA neurones are stimulated they release dopamine is released
- This causes a sensation of pleasure/reward

Why has the reward pathway evolved?
The reward pathway is normally activated by eating, drinking and sex
It therefore encourages those “healthy” behaviours that lead to propagation of your genes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

How do some drugs of abuse affect reward centres?

A

Some drugs of abuse tap into the reward pathway and increase dopamine levels eg
- heroin increases firing rate of dopaminergic neurones
- amphetamine increases dopamine release
- cocaine inhibits dopamine uptake
- alcohol

This produces the psychological component of addiction - “craving”

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What 2 distinct components of drug dependence have been shown in animal studies?

A

Physical dependence which develops as a consequence of tolerance to the drug

Psychological craving which is a result of stimulation of the reward pathways in the brain

In humans it is almost certainly more complex
eg discriminative (cue) effects

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are some examples of stimulants that are abused?

A

Cocaine
Amphetamine
Methamphetamine
Methylphenidate (prescribed for ADHD-may misuse it if they are prescribed it)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is the most potent natural stimulant?

A

Cocaine-extracted from leaves of coca plant

Cocaine (powder) and crack cocaine (smoked)
Crack produced by mixing cocaine with a base (sodium bicarbonate) and purified

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How does cocaine work?

A

Monoamine reuptake inhibitor – dopamine,serotonin,noradrenaline increase

  • Makes dopamine more available in the presynaptic space-so have sensation of rush of dopamine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are the effects of cocaine and how long do different modes of taking it take effect?

A

Depends on dose and rate of entry to the brain
smoking - almost immediate
injecting - 15 to 30 secs
snorting - 3 to 5 mins
the effects of crack smoking are very intense but quickly over ( 15 mins)

EFFECTS
stimulant and euphoriant

Anaesthetic effect

Hypersensitive

increased alertness and energy

increased confidence and impaired judgement

lessens appetite and desire for sleep

If mixed with alcohol - cocaethylene-almost like cocaine with longer half life

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the serious effects of cocaine?

A

damage to nose and airways (consistent vasoconstriction damages nasal septum)

convulsions with respiratory failure

cardiac arrhythmia’s and MI

hypertension and CVA

toxic confusion

paranoid psychosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the cocaine withdrawal effects?

A

Depression
Irritability
Agitation
Craving
Hyperphagia
Hypersomnia

Broadly opposite of drug effect

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How is amphetamine taken and what are the effects of taking it?

A

Sniffed, swallowed or injected

Effects similar to cocaine but longer lasting

Toxic confusion occasionally with convulsions and death

Amphetamine psychosis in heavy chronic use

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are some examples of opiates?

A

Opium
Morphine
Heroin (diamorphine)
Methadone
Codeine and dihydrocodeine

They’re all broadly, opiate agonists, often changing by exactly what opiate receptors they are hitting and half life issues as well

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Heroine is available as what and what may it be presented as?

A

Available as diamorphine or as diamorphine hydrochloride

May be presented as powder or as an almost tar like substance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

How can heroin be taken?

A

Taken by:
- Snorting ( not common in UK)
- Smoking(chasing the dragon)
- Injection (cultural or tolerance reasons)

Smoking is safest, injecting the most dangerous method of use

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Via what receptors does heroin act and what is its half life?

A

Opiod agonist
Acts via mu (principally)
Acts principally via Mu ,Delta and Kappa receptors

Kappa and Delta – analgesia
Mu – mood effects, analgesia and euphoria

Half life of 30mins – multiple administrations needed if dependant ( increased risk) - subjective effect of approx. 4hrs

Sleep disturbed, acute withdrawals in the middle of the night etc

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What are the effects of heroin and what can happen in an overdose of it?

A

Analgesia
Emotional analgesia
Nausea initially
Euphoria
Pin point pupils
Itching/sweating
Constipation
Decreased libido/menstrual irregularities
Reduced cough reflex

OVERDOSE:
Respiratory depression
Snoring indicates risk
Bradycardia
Hypotension
Death

Risk increased if mixed with other respiratory depressants – alcohol, benzodiazepines etc

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What is used in a Heroin overdose?

A

Naloxone – opiate antagonist
National Naloxone Programme

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What are the side effects of opiates?

A

First time - nausea/vomiting and headache

Medium term – phlebitis
-endocarditis
-Injection injuries/consequences (BBVs)
- Anorexia
- Constipation

Longer term - tolerance
- Withdrawal
- Social and health problems

BBV-Hep C most common

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What are the signs of opiate withdrawal syndrome?

A

craving
insomnia
yawning
muscle pain and cramps
increased salivary, nasal and lacrimal secretions
dilated pupils
piloerection (hence ‘cold turkey’)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
What is the role of methadone maintenance and what is its downfall?
Decriminalises drug use & allows normalisation of lifestyle Reduces iv misuse Leakage on to the illicit market
26
What is another name for diazepam?
Valium
27
Xanax is also known as?
Alprazolam
28
Benzodiazepines: What kind of agonists are they?
GABA agonists Anxiolytics, sedatives
29
Ecstasy (MDMA): what are its effects?
Relaxed euphoric state without hallucinations Majority of all ‘ecstasy tabs.’ contain no MDMA
30
What are the side effects of ecstasy?
Nausea and dry mouth Increased blood pressure and temperature In clubs users risk dehydration Large doses can cause anxiety and panic Drug induced psychosis
31
What is the psychoactive component of cannabis?
THC
32
What are the effects of cannabis?
Relaxing or stimulating, euphoriant , increases sociability and hilarity, increases appetite, changes in time perception, synaesthesia In higher dose - anxiety , panic , persecutory ideation, hallucinatory activity respiratory problems as with tobacco toxic confusion exacerbation of major mental illness cannabis psychosis
33
What are examples of performance & image enhancing drugs?
Anabolic Steroids Growth Hormone Injectable Tanning agents eg Melotan Risk from drug effect, route of administration (IM/IV) and route of access
34
What are anabolic (androgenic) steroids and when are they legitimately prescribed?
Anabolic steroids or steroids for brevity Family of drugs comprising testosterone and many synthetic analogues Legitimately prescribed in hypogonadism, muscular dystrophy, various anaemias, wasting in AIDS Muscle hypertrophy from steroid use is particularly marked in the upper body in the pectoralis, deltoid, trapezius, and biceps
35
What are the side effects of steroids?
Skin – acne, stretch marks, baldness Feminisation in males with hypogonadism and gynaecomastia (occasioning use of anti-oestrogens) Virilisation in women including hirsutism, deep voice, clitoral enlargement, menstrual irregularities, hair thinning Cardiovascular – increased cholesterol and hypertension Growth deficits due to premature closure of epiphyses Liver Disease – cholestatic jaundice, liver tumours
36
What are the psychological side effects of steroids?
Irritability and anger – ‘roid rage’ Hypomania and mania Depression and suicidality on withdrawal
37
What are the treatment options for drug misuse?
What drug What combinations Harmful/hazardous use? Dependency? Risk Biopychosocial treatment packages Strong emphasis on risk reduction Abstinence vs Harm reduction debates Treatment is effective
38
What can be done to reduce drug related deaths?
National Public Health crisis Optimise treatment Reduce barriers to treatment Public Health rather than criminal justice response Research National Naloxone Programme
39
What are the most worrying trends in harm in relation to alcohol?
Men Older people Home drinking Long term health conditions
40
What were some actions put in place to tackle alcohol issues?
- Minimum unit pricing - Ban on milti buy discounts - Age checks
41
What are the stages of damage of alcohol abuse on the liver?
Abuse of alcohol can cause hepatic steatosis or alcoholic hepatitis (these can return to a healthy liver with abstinence) The continues abuse of alcohol then leads to hepatic cirrhosis Healthy liver----Fatty liver----Cirrhosis of liver
42
Most heavy drinkers will have fatty liver, what percentage of those with alcoholic fatty liver progresses to cirrhosis?
20% Alcohol Abstinence improves Fatty Liver to normal
43
What are the signs of acute alcoholic hepatitis?
Alcohol intake > 6u / day Jaundice with Bilirubin > 80mg/dl No other aetiology for Liver inflammation Very high Mortality / No specific treatment yet
44
What scoring system is used for Alcoholic Hepatitis?
GAHS score Looks at Age, urea, WCC, INR and bilirubin
45
What does it mean if GAHS ≥ 9?
There is a marked rise in mortality 30 day mortality Without steroids 48% With steroids 22% 84 day mortality Without steroids 62% With steroids 41%
46
Why are alcohol and malnutrition linked?
60 % of chronic abusers have malnutrition Most of the calories is from Alcohol Total energy intake is reduced: Nausea & Vomiting Abdo pain Diarrhoea
47
What are the reasons for mortality in alcoholic cirrhosis?
75% die of Liver decompensation 20-25% Hepatocellular cancer sequelae
48
What are the indications for Liver transplantation?
ARLD is the most common indication Resistant complications of Cirrhosis Jaundice Ascites Encephalopathy Coagulopathy Hepatocellular Cancer
49
Is cirrhosis rare in teenagers?
YES its rare Deranged LFTs are common especially in obese teenagers
50
What is exposure to alcohol <14 years strongly associated with?
Later alcohol abuse and dependence
51
When does alcoholic ketoacidosis tend to occur?
Tends to occur the day after a massive binge. Lipolysis tends to be increased because of the increased levels of cortisol and catecholamines, caused by the extra stress placed on the patient’s body from the alcohol. The Lipolysis contributes to an abundance of FFA, which in turn sees some diverted to ketone production (the three ketones you will see mentioned are acetoacetate, beta-hydroxybutyrate, and acetone – alcoholic ketoacidosis tends to involve excess beta-hydroxybutyrate) . The metabolism of ethanol raises NADH/NAD which in turn impairs hepatic gluconeogenesis and the metabolism of lactate. So the patient has impaired ability to make glucose, or metabolise lactate, driving the hypoglycaemia and acidosis.
52
How do you stabilise a patient with alcoholic ketoacidosis?
IV fluids Vit B1 THIAMINE (Pabrinex) You latterly give some glucose once they have had Pabrinex, and use a symptom triggered diazepam scoring chart to help manage alcohol withdrawal.
53
What are the signs of Wernicke's?
CONFUSION GATE ATAXIA OPTHALMOPLEGIA
54
What can Wernicke's progress to that is IRREVERSIBLE?
KORSAKOFF'S
55
What can a deficiency in thiamine cause?
Can cause a build up of lactic acid, amongst other things (chronic alcohol misusers are prone to be deficient in as alcohol blocks duodenal uptake of thiamine and interferes with thiamine storage and conversion).
56
Lack of activity of alpha ketoglutarate dehydrogenase in particular has been linked to what?
Mitochondrial damage causing cellular necrosis, and triggering apoptosis (cell death) – cells in the cerebellum are particularly sensitive to this (hence the motor control issues).
57
What should you do if you ever see an unexplained lactic acidosis?
Thiamine (or its I.V. formulation Pabrinex) has very little downside to administration (there is the very small chance of anaphylaxis) – if you ever see an unexplained lactic acidosis, give thiamine. If you do not, and give glucose without it in the malnourished or thiamine deficient patient, you risk driving Wernicke’s Encephalopathy.
58
The metabolite of ethanol, ..., is thought to be particularly toxic especially to hepatic proteins
Acetaldehyde
59
What are the presentations of fatty liver & alcoholic hepatitis (think bloods)?
With Fatty Liver (alcoholic steatosis) – there is often a subclinical hyperbilirubinaemia and mild elevation of transaminases (AST/ALT). Gamma GT is elevated in a majority of patients. With Alcoholic Hepatitis – a diversity of presentations from jaundice, anaemia, and leucocytosis. The hepatic enzymes tend to present in a ratio of AST: ALT >2 (should normally be <1).
60
What are some specific markers of intracellular damage of the liver?
ALT and AST are markers of intracellular damage; gGT is a sensitive but non-specific marker involved with oxidative stress on the liver.
61
What is harmful use of alcohol defined as?
Harmful Use – pattern of use causing damage to physical or mental health. Use >1 month or repeatedly over 12 months
62
What is alcohol dependance?
Dependence – 3 or more of the following for >1month or repeatedly over 12 months: Cravings/compulsions to take Difficulty controlling use Primacy Increased tolerance Physiological withdrawal on reduction/cessation Persistence despite harmful consequences
63
What is a withdrawel state?
Withdrawal State – Group of symptoms of variable clustering and severity on complete/relative withdrawal of a psychoactive substance, after persistent use of that substance
64
What can occur usually 48-72 hrs after alcohol is stopped and presents with Profound confusion, tremor, agitation, hallucinations, delusions, sleeplessness, autonomic over-activity?
DELIRIUM TREMENS
65
How does Wernicke's encephalopathy present?
Confusion, ataxia, opthalmoplegia, nystagmus
66
How does Korsakoff's psychosis present?
Prominent impairment of recent and remote memory, preservation of immediate recall, no general cognitive impairment, retrograde and anterograde memory, impaired learning and disorientation, may exhibit nystagmus and ataxia
67
Wernicke's & Korsakoff's are caused by what?
Caused by thiamine deficiency - Poor intake and absorption, poor hepatic function, increased requirement for alcohol metabolism
68
What screening tool is used for alcohol abuse?
CAGE (2 or more = likely alcohol problem) Have you tried to Cut down? Have you felt Annoyed by people criticising your drinking? Have you felt Guilty about drinking? Have you felt the need to have an Eye-opener?
69
Apart from CAGE what other screening tools are available in the context of alcohol?
AUDIT (Alcohol Use Disorders Identification Test) FAST (4 questions) PAT (Paddington Alcohol Test; used in A&Es)
70
How can prevention of Wernicke-Korsakoff Syndrome be done?
THIAMINE
71
What drugs are used to manage alcohol withdrawel?
Benzodiazepines, commonly Chlordiazepoxide
72
What drugs are available as aversion/deterrence?
Disulfiram (Antabuse)
73
What alcohol anti craving meds are available?
Acamprosate (Campral) Naltrexone Nalmefene (Baclofen)
74
What is intoxication?
The pathological state produced by a drug, serum, alcohol, or any toxic substance; poisoning - Impaired attention and judgement, unsteadiness, flushing, nystagmus, mood instability, disinhibition, slurring, stupor, unconsciousness