Drugs of Abuse Flashcards
(42 cards)
1
Q
What is the role of laboratory in screening for DOA?
A
- Clinical (including emergency) toxicology
- Drug Treatment programmes
- Workplace drug testing/employment screening
- Forensic (including post mortem) toxicology
- Training and Education
2
Q
What is the Drug Screen?
A
- An initial testing procedure indicating the presence or absence of a drug and /or metabolite.
- Positive screens must always be confirmed by second testing method (confirmatory methods like LCMS-MS, GCMS)
- Published cut-offs will determine whether a drug is positive or negative
3
Q
What are features of screening drugs?
A
- Lower Cost
- Quick
- Semi-Quantitative
- High Sensitivity
- Low Specificity
4
Q
What are features of drug confirmation tests?
A
- Higher Cost
- Slower
- Semi-Quantitative/Qualitative
- High Sensitivity
- High Specificity
5
Q
What constitutes a drug screen?
A
Initial screen: Immunoassay:
- Benzodiazepine group (e.g. Diazepam, Temazepam, Nitrazepam, Lorazepam)
- Cannabis metabolite and Alcohol (not required in every situation)
Confirmation: LCMSMS:
- Opiates and Opioids: Morphine, Codeine, Heroin Metabolites, Dihydrocodeine, Methadone, Methadone, Metabolite, Buprenorphine, Nor Buprenorphine
- Stimulants: Amphetamine, Cocaine metabolite
Confirmation by GCMS:
- Cannabis metabolite
6
Q
What are opiates and what do they do?
A
What are they?
- Opiates – derived from the opium poppy morphine and codeine
What do they do?
- Relieve pain, relaxes muscles, respiratory depression and causes drowsiness
7
Q
How fast do opiates work?
A
- Morphine peak plasma conc within 30 mins after injection, 90 minutes orally.
- There is poor oral availability (25%) as undergoes extensive hepatic first pass metabolism
- It has a short half life
8
Q
How do we measure opiates in the lab?
A
- Heroin (Diacetyl morphine) half-life – <10 minutes (unsuitable for urine testing)
- Heroin undergoes rapid deacetylation to 6-monoacetyl morphine (6 times more potent than morphine)
- Monoacetyl morphine half-life - <24 hours
9
Q
What is seen in heroin drug screens?
A
Mono acetyl morphine, Morphine, Acetylcodeine and Codeine
- Acetylcodeine is contaminate in street heroine
- Codeine is a contaminant in street heroine as well
10
Q
What are symptoms of opiate overdose and how is it treated?
A
Symptoms
- Pinpoint pupils
- Respiratory depression
- Bradycardia
- Hypotension
- Pulmonary oedema
Treatment for Overdose
- Naloxone antagonist acting on mu receptors works in 2 mins
11
Q
What are features of Methadone?
A
- Acts on same opioid receptors – longer duration of effect. Increased doses can block euphoric doses of heroin
- Good oral bioavailability (~80%), Approx. half-life is 8-59 hrs
- Metabolised via CYP450 34A via hepatic demethylation to inactive primary metabolite 2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP)
- Look for both the compound and the metabolite
12
Q
How can labs inteprate whther someone is complying with their methadone treatment programme?
A
Methadone Parent and Methadone metabolite: Metabolite shows that patient has taken the drug. Parent detection means recent use
Methadone Metabolite: Metabolite shows that patient has taken the drug.
Methadone Parent: No metabolite present. This would be unusual and is a finding in spiked samples
13
Q
What are features of Buprenorphine?
A
- Opioid partial agonist
- Poor oral bioavailability – better sublingual
- Highly bound to plasma proteins
- Metabolised via CYP450 34A to Nor Buprenorphine
- Approximate half-life 24-60 hrs
- Agonist effects increase linearly with increase dose until moderate dose then ‘ceiling effect’ thus safer in overdose
14
Q
How can the lab help in establishing whether someone is complying with their Diamorphine treatment programme?
A
Diacetyl Morphine (PURE)
- Forms Monoacetyl Morphine
- Can be used in substation programmes
- Used to decrease the criminality of it
Diacetyl Morphine (STREET)
- Forms Monoacetyl morphine which is converted into acetyl codeine and codeine.
- The 2 compounds are only found in street heroine assessments
15
Q
What are features of Amphetamine?
A
Include Amphetamine, Metamphetamine (crystal meth) and MDMA(Ecstasy)
Amphetamine exists as 2 isomers
- Levoamphetamine ‘L’) – the L variant is street (‘speed’),
- Dextroamphetamine ‘D’ - the D variant can be prescribed in UK in narcolepsy (adults) and ADHD (children).
16
Q
What are the effects of Amphetamine?
A
CNS Stimulants causes
- Euphoria
- Alertness
- Increased energy
- Appetite suppression by increasing dopamine
- Serotonin
- Noradrenaline.
Methamphetamine stronger effects, longer duration, more addictive
17
Q
What are the Pharmacokinetics of Amphetamine?
A
- Peak concentrations in blood 2-3 hrs and Half-life 6-15 hours
- Rate of excretion in urine heavily dependent on urine pH
- Appearance in urine likely suggests use over past 1-4 days
18
Q
What are symptoms of Amphetamine in Overdose?
A
- Arrhythmia’s/cardiac arrest
- Increase in HR, BP and Temp
- AKI
- Seizures
19
Q
What is the treatment for the Amphetamine overdoses?
A
- Supportive
- Fluids
- Seizure management
- Temperature management
20
Q
What are benzodiazepines?
A
- Benzodiazepines – GABA (Gaba Amino Butyric acid) receptor agonist to produce sedative effects
- Used to treat anxiety, sleep disorders, alcohol withdrawal
21
Q
What is the pharmacokinetics of Benzodiazepines?
A
Metabolised by CYP 450 3A4 /5 and CYP 450 2C19 – many drug interactions
Onset of action and Half-life dependent on which Benzodiazepine taken:
- Diazepam (long acting, half-life 20-100 hrs)
- Lorazapam (intermediate acting, half-life 6-12 hrs)
- Midazolam (short acting, half-life 1-4 hrs)
22
Q
What are the features of Cannabis?
A
Combination of flowering plants: Cannabis sativa, Cannabis indica and Cannabis Ruderalis. Resin or leaves used and come in a variety of strengths
- Primary psychoactive ingredient is Delta-9-tetrahydrocannibinol
- Metabolised to ~5 metabolites – inactive Carboxy Tetrahydrocannibinol (30%)
- Highly lipid soluble so its deposition in fatty tissue means long elimination half-life especially in chronic users (weeks)
23
Q
What are the effects of Cannabis?
A
- Relaxation
- Euphoria
- Analgesic
- Confusion, Hallucinations
- Paranoia.
24
Q
What is Cocaine?
A
- Stimulant alkaloid obtained from leaves of the coca plant (Benzoyl Methyl Ecgonine)
- Enhances action of Dopamine by blocking receptors. Also acts as voltage gated sodium channel blocker – sudden cardiac death
25
What are Pharmacokinetics of Cocaine?
* Peak plasma levels 5-10 min after injection, 60 min intra-nasally
* Short half-life of 1 h
* Metabolite Benzoyl Ecgonine can be detected in urine after 4hrs remaining detectable ~4 days
* Unable to detect parent cocaine due to short half life
26
What are Novel Psychoactive Substances?
* Drugs designed to replicate the effects of illegal substances whilst remaining legal
* Now controlled under Psychoactive Substances act 2016 but has wide online availability
27
What are the types of effects of Novel Psychoactive Substances?
* **Sedation** (Synthetic cannabinoids)
* **Stimulant** (Mephedrone, Ethylphenidate)
* **Hallucinogenic** (Methoxetamine (ketamine like)
28
What are harmful effects of Novel Psychoactive Substances?
* Paranoia
* Psychosis
* Seizures resulting in death
* Longer term mental health issues
29
What are the features of Gabapentinoids?
* Structural analogues of the neurotransmitter GABA. Gives feelings of euphoria, relaxation and calm. Have additive effects for other drugs (opiates) so potentiates their action
* Both drugs used for management of epilepsy and chronic neuropathic pain and anxiety (Pregabalin)
* Prescription rate (3%) in prison population is twice that of the wider community
* Assays in Drugs labs now under development
30
Describe Drug Pharmacokinetics
* Enteral (e.g. heroin, cocaine) or Parenteral (Methadone)
* ‘Phase 1’ reactions involve hydrolysis, oxidation or reduction of the drug.
* Many drugs metabolised by hepatic microsomal cytochrome P450 enzymes (CYP enzymes) but these show variable liver distribution and can be expressed in lower amounts in GI tract, lung, kidney and other tissues.
* Phase II reactions drugs / metabolites rendered more polar by addition of glucuronide, acetate or sulphate enabling final products of drug metabolism to be excreted by kidney/biliary system.
31
What are the physiological and pathological factors affecting the Length of Detection of Drugs?
**Demographic factors**
* Age, weight, genetic constitution
**Disease related factors**
* Hepatic or renal disease, Thyroid (hyper- or hypo-)
**Chemical/environmental factors**
* Absorption of drug e.g. food
* Distribution of drug e.g. co-administer drug
* Metabolism of drug e.g. phenobarbitone
* Excretion of drug e.g. food or bicarbonate
32
What are the sample related factors affecting the Length of Detection of Drugs?
**Adulteration**
1. **Dilution (most common)**
* dilution in-vivo (drinking liquids)
* dilution in-vitro (adding water / other diluents to sample)
2. **Chemical**
* Adulterants added to sample to interfere with assay e.g. EMIT - liquid soap, salt, bleach, etc. (work by altering pH)
* Spiking with drugs to conceal non compliance with medication (e.g. Methadone)
* Taking Over the Counter (OTC) medications to confuse.
3. **Substitution (false I.D.)**
* Water, tea, someone else sample.
33
What are the other factors affecting the Length of Detection of Drugs?
**How the drug is taken**
* Heroin (“mainlining” vs smoking)
* Injected or snorted
* Methadone “mixers” e.g. cimetidine, ranitidine and cyclizine
**Drug Detection**
* What is detected? Parent drug or metabolite?
**Purity and Cutting agents**
* ‘Cutting agents’ refers to means by which illicit drugs are diluted at each stage of the chain of distribution. Cited cutting agents include: flour, lactose, brick dust, caffeine, nettles, levamisol, lignocaine, paracetamol
* Large profits made by increasing volume of drug – may be at most 50% pure
34
What is the length of detection of some commonly bused drugs?
* Morphine - 1-2 days (may be 5-7 days if detected via morphine-3-glucouronide)
* MAM - 1 day
* Methadone - 2-3 days
* Cocaine - 12-24 hrs (up to 3 days as Benzoyl Ecgonine)
* Amphetamine - 1-3 days (very dependent on urinary pH)
* Benzo’s - 2-14 days (dependent on use)
* Cannabis - 2-90 days (very variable)
* Barbiturates - 1-14 days (dependent on class of barbiturates)
35
What are some sample types used for the drug screening?
* Blood / plasma / serum (especially for forensic toxicology)
* Oral fluid (saliva)
* Hair
* Nails
* Sweat
* Breath
* Meconium
36
What factors should be considered with alternative matrices?
* Ease of collection and volume of sample produced
* Non-invasive vs invasiveness of collection
* Different range of analytes (parent drug vs metabolites)
* Different detection windows (some analytes)
* Potential to adulterate
* Choice of technologies with known cut-offs that have been scientifically and technically validated in clinical studies
* Ease of automation
* Stability of sample
* Expense
37
What are features of Oral Fluid used for Drug Screening?
* Volume: 0.5 – 1.5 litres/day
* Composition: 99% water, 0.3% protein and 0.3% mucin, electrolytes, bacteria, pH range 5.6 – 7.0 (average 6.4, unstimulated)
* Salivary flow under control of parasympathetic/sympathetic nerve control
38
What are Advantages and diadvanatges of using oral fluid for drug screening?
**The Advantages**
* Ease of collection device, non-invasive
* Reduced risk of adulteration/directly observed (still possible!)
* Can detect residual drug in mouth and recent use
**The Disadvantages**
* Specimen volume may be inadequate
* Short window of detection
* Other drugs can reduce salivary flow (dry mouth with cigarette smoking or drugs reducing salivary flow e.g. anti-hypertensives, anti-psychotics)
* Increasing salivary flow increases bicarbonate making saliva pH neutral leading to decreased ionisation of basic drugs and decreased detection
* Cut-off levels lower so detection methods need to be more sensitive
39
What is the composition of hair?
* Complex matrix of cylindrical shafts of cells with cuticle forming outer protective layer. Composed of sulphur rich proteins. Cortical cells within the hair shaft contain melanin.
* 85% is growing. 0.4mm/day for scalp hair. Each head hair follicle active for 4-8 years, non-head hair \<12months.
40
What are the main routes of incorporation of drugs into hair?
* **Blood supply**
* **Sweat**
* **External contamination** (Passive smoking for example)
41
What are the features of hair used for Drug screening analysis?
* Hair cut as close to the scalp is recommended (pencil thickness)
* Can be cut into segments to provide more detailed historical profile
* Should be washed to remove gross environmental contamination
* Analysis involves drying hair sample, pre-treatment to release drugs and then analysis via chromatographic methods.
42
What are advanatges and disadvantages of using Hair for Drug screening?
**Advantages**
* Confirms long term exposure can do time profiling on segments
* Brief periods of abstinence will not alter test outcome
* Strong, stable tissue can be stored indefinitely
* Less invasive collection, easy to collect, handle and store
* Low adulteration potential
**Disadvantages**
* Recent use not detected
* Hair has different affinities / binding capacities for various drugs based on amount of melanin in hair
* Some drugs incorporate into hair more readily (amphet., cocaine) better than others (benzo’s, cannabis)
* Variable influence of sunlight, weathering, water, chemical and heat treatments
* More sensitive methods of detection required hence more expensive
* Few controlled studies to guide interpretation
