Substance misuse (spring) Flashcards
What is substance abuse?
A disorder characterised by the destructive pattern of using a substance which leads to problems or distress
why abuse drugs?
as a normal physiological function, engaging in (positive) rewarding behaviours lead to pleasurable feelings
drugs represent substitutes for such behaviours
positive feedback can lead to psychological and physiological addiction
define…
Addiction:
Reinforcing stimuli:
Rewarding stimuli:
Addictive drug:
Addictive behaviour:
Sensitisation:
Addiction: a state characterized by compulsive engagement in rewarding stimuli despite adverse consequences
Reinforcing stimuli: stimuli that increase the probability of repeating behaviours paired with them
Rewarding stimuli: stimuli that the brain interprets as intrinsically positive or as something to be approached
Addictive drug: a drug that is both rewarding and reinforcing
Addictive behaviour: a behaviour that is both rewarding and reinforcing
Sensitisation: an amplified response to a stimulus resulting from repeated exposure to it
define…
Tolerance:
Dependence:
Physical dependence:
Psychological dependence:
Tolerance: the diminishing effect of a drug resulting from repeated administration at a given dose
Dependence: an adaptive state associated with a withdrawal syndrome upon cessation of repeated exposure to a stimulus (e.g., drug intake)
Physical dependence: dependence that involves persistent physical–somatic withdrawal symptoms (e.g., fatigue and delirium tremens)
Psychological dependence: dependence that involves emotional–motivational withdrawal symptoms (e.g., dysphoria and anhedonia)
Factors affecting likelihood of drug abuse
Abuse: Sexual, psychological, emotional or physical abuse can influence drug use as a coping mechanism
Underlying emotional disorders: Individuals with anxiety, depression, bipolar disorder or post-traumatic stress disorder are at increased risk of substance abuse and addictive behaviours.
Family history: Children raised by alcoholic or drug-addicted parents are more likely to develop substance use problems.
Inherited factors: Genetic susceptibilities and biological traits play a role in addiction and abuse but development is shaped by a person’s environment
Low frustration tolerance: Addicts are highly susceptible to the negative effects of stress
The substance: Some substances are more addictive than others.
factors leading to addiction?
what are some categories of Abused substances?
- Alcohol
- Nicotine: E.g. cigarettes, e-cigarettes
- Euphorics: E.g. cannabis, ketamine, nitrous oxide, salvia
- Opiates E.g. heroin, morphine, codeine
- Benzodiazepines: E.g. diazepam
- Stimulants: E.g. cocaine, amphetamine, ethylphenidate
list anatomical and physiological biological systems that are involved in effects
Anatomical:
- Meso-cortico-limbic system
- Hypothalamus
Physiological:
- Acetylcholine: piracetam
- Adenosine: caffeine
- Dopamine: cocaine, phenidates, amphetamines
- GABA: benzodiazepines
- Norepinephrine: yohimbine
- AMPAR: piracetam
- CB1R: tetrahydrocannabinol (in cannabis), cannabinomimetic NPS
- NMDAR: ketamine
- Opioid receptors: buprenorphine, heroin
- Orexin receptor: modafinil
name and briefly describe Behavioural treatment
approaches
Cognitive-behavioural therapy: Based on behaviours being learned responses which, through learning different responses, can be altered.
Contingency Management Interventions: Rewards compliance with abstinence
Motivational Enhancement Therapy: Focusses on identifying the need to change behaviours
Family Behaviour Therapy: Therapy undertaken with at least one significant other at session
Principles of pharmacological therapies for substance misuse:
Abstinence: included as can include use of pharmacological treatments which deter misuse e.g. Disulfiram for alcohol abuse, naltrexone after detoxification is complete)
Detoxification: Pharmacological induction of withdrawal e.g. naltrexone to block opioid receptors plus lofexidine (a2A adrenoceptor agonist) to reduce withdrawal symptoms)
Replacement/substitution therapy: Replacement of abused substance with, typically, a longer acting but less euphoric substitute (e.g. buprenorphine to replace heroin). Encourages stability and routine
Formulation or distribution to reduce misuse potential of replacement therapies: E.g. sublingual buprenorphine and naloxone has poor naloxone (antagonist) bioavailability but, if injected, blocks effects of buprenorphine (and other opiates)
The role of the pharmacist in substance misuse
substance misuse services
- Primarily pharmacological therapies
- Reporting missed doses
- Needle exchange schemes
- Health promotion and harm reduction
Identifying interactions
Detecting misuse:
- Unusual patterns of OTC medicine purchase (e.g. of codeine-containing medicines)
- Altered prescriptions (quantity, strength)
- Diversion of medicines
give examples of Phytocannabinoids
Δ9-tetrahydrocannabinol
Cannabidiol
Cannabigeroland
describe the structure of Δ9-tetrahydrocannabinol (‘THC’)
phenol ring, 5-carbon alkyl chain, central pyranring and mono-unsaturated cyclohexylring
clinical uses of synthetic cannabinoids
pain management
anti-emetic
appetite stimulant
anti-spastic
what consequences do drug abusers experience?
most common abused forms of cannabis?
Dried flowering tops of the female plant (‘buds’)
- Leaves have little cannabinoid content and so are rarely used
Resins and oils
- traditionally made from compression of the dried trichomes(‘slate’, ‘black’ etc.)
- Now often made by butane-based extraction (‘bubble’)
Some advocates of juicing the fresh plant
- Non-psychoactive as cannabinoids are present in the acid form and decarboxylated by drying and/or heating
Routes of administration of unlicensed cannabis?
uses of licensed cannabis?
Long term toxic effects of cannabis?
- Addiction
- Altered brain development
- Poor educational outcome, with increased likelihood of dropping out of school
- Cognitive impairment, with lower IQ among those who were frequent users during adolescence
- Diminished life satisfaction and achievement (determined on the basis of subjective and objective measures as compared with such ratings in the general population)
- Symptoms of chronic bronchitis
- Increased risk of chronic psychosis disorders (including schizophrenia) in persons with a predisposition to such disorders
Clinical management of cannabis abuse?
withdrawal symptoms of cannabis?
withdrawal symptoms not serious:
Dysphoria, disturbed sleep, decreased appetite
Salvia divinorum…
family?
moa?
use?
Family: Lamiaceae. Mint, salvia, oregano, marjoram, lavender, thyme
Hallucinogenic (leaves)
Native of Mexican Sierra and used by Mazatecs for ritual purposes
Salvinorin A…
moa?
dose?
effects?
what are the effects of Salvinorin A at different doses?
low doses ameliorate pain and mood
high doses exacerbate these symptoms
Nitrous oxide moa?
uses of nitrous oxide?
why is the abuse of nitrous oxide increasing?
Effects of gas inhalation?
is it short or long acting?
Clinically used as an analgesic during dental surgery and childbirth
Abuse increasing due to widespread availability and current legality
Effects of gas inhalation:
- Dizziness
- Euphoria
- Bursts of laughing
- Dissociation
- Sexual performance enhancer
Short acting (minutes; dependent on dose)
what happens when High levels of nitrous oxide are inhaled?
(give the mechanism, physical symptoms and therapy)
Mechanism
- N2O makes VitB12 unavailable
- Homocysteine accumulates leading to over stimulation of NMDARs, hyper-acidification and apoptosis
Physical symptoms
- Nerve damage, demyelination and neuropathy
- Vomiting and nausea
Therapy: high doses of Vit B12
What is the aim of drug misuse services?
To reduce the harms and costs arising from alcohol, prescribed and non-prescribed drug use and other substances.
To ensure that all aspects of a service user’s life are considered holistically, including substance misuse, housing, education, training, employment, offending, healthcare, family life, relationships, community participation and support networks, religion and culture.
To enable service users to take personal responsibility for their own self care and recovery, their families, children and the community.
PERSON CENTRED CARE
Who manages the treatment of patients?
Local management, organisation and payment for services via Public Health England (commissioned by Local Councils)
Services provided by specialist charities and NHS mental health units
e.g. Turning Point, Addaction, KCA, WDP, Reach Out Recovery, Alcohol and Drug Abstinence Service,Iris
How do people get referred to services?
- Self referral
- Police
- Social workers
- GP and other HCPs including pharmacists
- Criminal justice service
what is involved in the Management of Drug Misuse (from the start)?
Initial review: interviews and testing for substance misuse-urine (e.g. Eco cups) and blood testing, use of Clinical Opiate Withdrawal Scale (COWS)
Psychosocial and Pharmacological interventions- provided in the community and criminal justice system: include inpatient, residential, day-patient and outpatient services.
Psychosocial treatment
- Cognitive behavioural/psychodynamic therapy
- Behavioural couples therapy
- Contingency management-key worker
- Treat comorbid depression and anxiety
Pharmacological treatment-opioids/benzodiazepines
- Detoxification
- Abstinence
- Maintenance (substitution/ harm reduction) therapy
Management of Opioid Misusers… what happens during detoxification?
methadone or buprenorphine substitution then withdrawal if previously in maintenance therapy or as a patient choice
lofexidine (Britloflex®200mcg tablets) alone for young people, mild or uncertain dependence, short history of illicit drug use, rapid detoxification. (for Management of symptoms of opioid withdrawal)
what class is lofexidine?
what does it do?
dose?
what time of day is it given?
side effects?
monitoring requirements?
alpha2-adrenergic agonist
alleviates physical symptoms of withdrawal (not reduce craving).
Can also be used with opioid substitute (methadone or buprenorphine)
800mcg daily increased up to max 2.4mg daily (divided doses). 7-10 days use for sole therapy
Give at bedtime to offset insomnia.
Side effects-dry mucous membranes, hypotension, bradycardia, dizziness, drowsiness, QT interval prolongation-caution for interacting drugs
Monitor BP, pulse at initiation and for first 72 hrs or until stable dose and also on gradual discontinuation over 2-4 days.
which drugs are used to manage different withdrawal symptoms?
loperamide - diarrhoea
mebeverine - stomach/intestinal cramps
paracetamol and NSAIDs - muscular pain and headaches
metoclopramide/prochlorperazine - vomiting
short-acting benzodiazepines or zopiclone - insomnia, anxiety
Muscular pain-sometimes use topical therapy-voltarol gel
(Benzodiazepines are used for a few days only as addictive in themselves.)
Management of Opioid Misuse… what happens during abstinence
Detoxification programme followed by relapse prevention support
Abstinence supported for at least 6 months with psychosocial and drug therapy (mildly dependent clients may only need drug therapy)
Naltrexone is support for opioid abstinence. Naltrexone (Nalorex®) competitively displaces opioid agonists, blocking euphoric effects and minimising positive rewards associated with opioid use.
- Licensed as an adjunctive prophylactic treatment for detoxified formerly opioid-dependent people who have remained opioid free for at least 7–10 days.
- Test for opioid use with naloxone prior to starting naltrexone
- 25 mg naltrexone on day 1 followed by 50 mg daily thereafter for an initial period of 3 months or 3 x a week dosing
Management of Opioid Misuse…
what is the aim of Maintenance (substitution/ harm reduction) therapy?
which drugs?
Aims to provide stability by reducing craving and preventing withdrawal, eliminating the hazards of injecting and freeing the person from preoccupation with obtaining illicit opioids, and to enhance overall function.
Methadone, buprenorphine or Suboxone®
Drugs are given as part of a programme of supportive care
Prescribing of diamorphine (also dipipanone and cocaine) to treat addiction only allowed if prescriber has a Home Office license
Role of Pharmacies in Maintenance Therapy
- Significant point of contact with the client
- Provide information and advice
- Monitor for ADRs, interactions
- Monitor for other health issues (mental health, onset of problems relating to drug misuse or unrelated health issues)
- Encourage participation in harm reduction strategies
- Refer back to drug misuse team or prescriber where necessary
- Service Specification from local council (PHE) describing contracted duties
Maintenance Therapy for Methadone… dose?
- Initially 10-40mg daily
- Increase by up to 10mg daily (max 30mg weekly titration) until no signs of withdrawal or intoxication
- Usual dosage range 60-120mg daily
- Usually single dose-large doses may be twice daily e.g. 80mg supervised, 40mg to take home.
- Long t½ (15-60 hours) so no ‘rush’ and withdrawal onset 1-3 days, peak 3-6 days unlike heroin (t½ 2-3 minutes, withdrawal onset 6-12 hours, peak at 36-72 hours)
what are the different dosage forms of methadone?
1mg/1ml oral solution sugar free (SF) and non SF (green liquid)
10mg/1ml oral liquid for dilution with diluent (Methadose)(blue)
Tablets 5mg (Physeptone) (unlicensed)
Injection:
- 10mg/ml 1ml amps
- 10mg/ml 2ml amps
- 50mg/2ml amps
- 50mg/1ml amps
side effects of methadone?
- Nausea and vomiting
- Urticaria, pruritis, rashes
- Vertigo
- Sweating
- Bradycardia or tachycardia
- Mood changes
- Constipation
- Drowsiness/dizziness
using which route of administration is nausea worse in, with methadone?
Nausea worse with oral than injected
can you drive whilst under the influence of methadone?
It is an offence to drive while under the influence of this medicine but patients would not be committing an offence if:
- The medicine has been prescribed to treat a medical problem and
- It was taken according to the instructions given by the prescriber and in the information provided with the medicine and
- It is not affecting the ability to drive safely
Maintenance Therapy with Buprenorphine…
dose?
moa?
- Initially 0.8-6mg daily
- Increased at intervals until no signs of withdrawal or intoxication
- Usual dosage range 8-24mg daily, maximum 32mg daily
- Once daily dosage. Placed under the tongue and allowed to dissolve-sometimes need glass of water before to get mouth moist enough to dissolve.
- t½ 12 hours, duration 12-72 hours.
- Partial opioid agonist
- Blocks effects of ‘top up’ heroin
what are the different dosage forms of Buprenorphine?
Sublingual tablets (Subutex and generic, 0.4, 2 and 8mg strengths)
Temgesic S/L tabs unlicensed for substance misuse (0.2 and 0.4mg)
Suboxone® is SL buprenorphine with naloxone (opioid antagonist to reduce iv misuse-precipitates withdrawal if injected but ineffective orally or SL) 8/2mg and 2/0.5mg strengths
Espranor oral lyophilisate (freeze-dried wafer that dissolves rapidly on the tongue)
2 and 8mg strengths-not interchangeable with S/L formulation
how would you decide which drug Maintenance Therapy?
Methadone
- first choice: works well for clients misusing multiple drugs/alcohol and better for clients with anxiety during withdrawal but depends on many factors e.g. :
- History of opioid dependence
- Engagement and motivation with therapy
- Risks (overdose, diversion, family and/or homelife situation i.e. lack of support)
- Patient preference
- Prescriber’s experience
Buprenorphine :
- Less sedating
- Safer in conjunction with other sedating drugs
- Fewer drug interactions
- Dose reductions easier as withdrawal symptoms are milder
- Faster titration to steady state for maintenance (minimum 1 week)
- Less risk of overdose
BUT-cannot be given if liver dysfunction (LFTs measured prior to use)
how to support those with alcohol problems?
Person-centred care - Treatment and care should take into account people’s needs and preferences
Supporting patients and carers
Identification (community good option) and assessment (specialist treatment centres for accurate assessment)
Interventions for:
- hazardous & harmful drinking
- mild, moderate & severe dependence alcohol dependence
Interventions after successful withdrawal for:
- moderate alcohol dependence
- severe alcohol dependence
what does the Hazardous and harmful drinking intervention involve?
Two components:
- Screening questions e.g. Alcohol Use Disorder Identification Test (AUDIT)
- Brief motivating discussion (approx. 10 mins)
How effective?
- BI reduced consumption compared to control group (-38 grams/week for 1 year or longer)
Where?
- GP practices
- A&E
- Emerging research in community pharmacies
what are Brief Intervention (BI) opportunities in the pharmacy?
Self referral
- View poster/read flyer
- Health query linked to alcohol use
Pharmacy services
- Smoking cessation
- Harm minimisation (needle exchange, supervised consumption, instalment dispensing)
- Medication review service
- Health check
- Emergency Hormonal Contraception
Counter Purchases
- Smoking cessation
- GIT remedies
- Sleep aids
- Other CNS depressants
Prescribed medications
- Gastric problems
- Cardiovascular or heart problems
- Mental Health (e.g. addiction, depression) Diabetes
Interventions for mild, moderate and severe alcohol dependence?
Assessed if consuming typically more than 15 units alcohol/day or score 20 or more on Alcohol Use Disorder Identification Test (AUDIT)
Treatment setting options:
- Outpatient assisted withdrawal or
- Specialist alcohol services if there are safety concerns about community-based withdrawal
Mild to moderate, 2–4 meetings per week over the first week
Mild to moderate dependence and complex needs, or severe dependence, offered a more intensive community programme following assisted withdrawal in which the patient may attend a day programme lasting between 4 and 7 days per week over a 3-week period
Complex needs and severe dependence, inpatient or residential assisted withdrawal
(Complex needs - For example, psychiatric comorbidity, poor social support or homelessness.)
what is a A symptom-triggered approach?
involves tailoring the drug regimen according to the severity of withdrawal and any complications. The patient is monitored on a regular basis and pharmacotherapy only continues as long as the patient is showing withdrawal symptoms.
Alcohol withdrawal treatment regimens?
Fixed dose or symptom-triggered medication regimens
Preferred medication for assisted withdrawal is a benzodiazepine (chlordiazepoxide or diazepam)
In a fixed-dose regimen, titrate the initial dose of medication to the severity of alcohol dependence and/or regular daily level of alcohol consumption
In severe alcohol dependence higher doses will be required to adequately control withdrawal and should be prescribed according to the Summary of Product Characteristics (SPC)
Should be adequate supervision if high doses are administered
Benzodiazepine gradually reduced over 7–10 days to avoid alcohol withdrawal recurring
what is the Relapse prevention after withdrawal (with doses)?
(Not responded to psychological interventions alone, or who have specifically requested a pharmacological intervention?
Pharmacological treatment to start after assisted withdrawal:
- Acamprosate (start soon as possible after withdrawal)
- 666 mg (2 tabs) three times a day up to 6 months, or longer with at least monthly supervision
- Stop if drinking persists 4–6 weeks after starting treatment
- Oral naltrexone
- Start at 25 mg per day (half-tab)
- Maintenance dose of 50 mg per day
- Highlight information card about opioid-based analgesics
- Supervised monthly up to 6 months, or longer for those benefiting
- Stop if drinking persists 4–6 weeks after starting treatment
- Disulfiram (not gold standard treatment)
- Start treatment at least 24 hours after last alcoholic drink
- Usually prescribe at a dose of 200 mg per day (1 tab)
- Test liver function, urea and electrolytes to assess for liver or renal impairment
- Check SPC for ‘disulfiram-alcohol reaction’ and contraindications in pregnancy and in the following conditions: a history of severe mental illness, stroke, heart disease or hypertension.
Combination with psychological intervention (cognitive behavioural therapies, behavioural therapies or social network and environment-based therapies)
How could pharmacists support drinkers?
Discuss possible interactions and contraindications of alcohol with their medicines (OTC, POM, food herbal remedies)
Highlight and explain UK Government Guidelines on alcohol limits and explore if they are exceeding this
Advise them to see their GP and/or access other services (alcohol treatment centre ‘drop-in’ service or online information e.g. AA, DownYourDrink)
Provide motivating psychosocial support:
- Explore how the patient feels about their drinking (positive and negative aspects)
- If they want to reduce, if so, how? What could be feasible?
- Have they tried to reduce before, what worked or did not work?
- What would they like to do now about their drinking or in the near future?
fill in the blanks…
Substance Misuse Clinics provide a holistic, P………..C…….……. service for patients.
A K…………….. forges a relationship with each patient to help them change their life.
Patients are offered P…………………..and P……….………………. interventions
The drug treatment of substance misuse includes programmes for D……..………….., A……………… and Maintenance (or S………………… or H…….. R………………) therapy.
For opioid maintenance therapy M……………..or B……………………. are supplied from community pharmacies convenient for the client
Medicine supplies are made against F………….. prescriptions which are mostly written by prescribers in drug and alcohol treatment clinics.
person centered
keyworker
psychosocial, pharmacological
detoxification, abstinence, substitution, harm reduction
methadone, buprenorphine
FP10MDA
where does cocaine come from?
what is it used for?
Found in leaves of Erythorxylon coca (Andes)
Alkaloid
Historical medical use as a ‘tonic’ but now licensed use limited to ophthalmic procedures (local anaesthetic/dilatant)
moa of cocaine?
CNS:
- Blocks Dopamine active transporter (DAT)
- Blocks Norepinephrine transporter (NET)
- Blocks Serotonin transporter (SERT)
- Increases synaptic levels of these three transmitters.
DAT: Nucleus accumbens – reward and reinforecment effects
SERT: cortex reward and reinforcement effects
NET: Activation of sympathetic system
- Increased arterial pressure
- Tachycardia
- Ventricular arrhythmias
Production of illicit cocaine
Cocaine is extracted by
- Mashing coca leaves in a gasoline and alkali mixture
- Gasoline containing the dissolved alkaloid is drained into a barrel and a dilute acid added (sulphuric) to create aqueously soluble cocaine suphate
- Gasoline layer is removed and NaHCO3 is added to neutralise the acid and cocaine hydrochloride precipitates out of solution
- Cocaine base is filtered though a cloth and dried
This produces powder cocaine
CocaineHCl can be mixed with baking soda and warmed to obtain “crack cocaine” (freebase)
Routes of administration of cocaine?
Transmucosal. Cocaine hydrochloride is absorbed through mucosal membranes
- intranasally via insufflation
- inhaled when free base is heated
Injected
- Typically i.v.
- Often mixed with other drugs (e.g. heroin = ‘speedball’)
Short term Side effects of cocaine?
duration of action?
- Increased sense of energy and alertness
- Extremely elevated mood
- Feeling of supremacy
- Irritability
- Paranoia
- Restlessness
- Anxiety
- Dilated pupils
- Excited, exuberant speech
Numerous peripheral effects (see image)
Duration of action: 0.5 to 2 hr
Long term Side effects of cocaine?
Cardiac:
- Increases heart rate and blood pressure
- Lethal arrhythmia
CNS:
- Central vasoconstriction
- Increased risk of stroke
- Seizures
- Bizarre or violent behaviour
Lungs:
- Caustic and can damage the nose and sinuses.
Gastrointestinal tract:
- Vasoconstriction in gut leading to ulcers or perforation
Sexual function:
- Impaired sexual function in men and women
what are the withdrawal symptoms of cocaine?
how long do these symptoms last?
Symptoms include:
- Depression and anxiety
- Fatigue
- Difficulty concentrating
- Inability to feel pleasure
- Increased craving for cocaine
- Physical symptoms including aches, pains, tremors, and chills
- Formication (feeling of insects under the skin)
Withdrawal is rarely medically serious but very difficult to resist
Can cause suicidal thoughts.
Withdrawal symptoms resolve within 1-2 weeks but intense craving can return even years after the last use.
what is the treatment for cocaine addiction?
No FDA/EMA-approved medications to treat cocaine addiction
Some treatments are used off licence to target withdrawal symptoms rather than the underlying dependence
Patients with substance abuse problems often have concurrent mental health disorders that require additional behavioural or pharmacological interventions
Treatment must be comprehensive:
- neurobiological
- social
- medical aspects
Psychotherapy: CBT, TCs
Several medications marketed for other diseases have been claimed to show promise:
- Antidepressant and tranquilizers: (e.g. desipramine or diazepam) to reduce anxiety and depression.
- Amantadine: Dopamine reuptake inhibitor used in Parkinson’s Disease may reduce cocaine craving.
- Bromocriptine: D2 receptor agonist to decrease the craving for cocaine during detoxification and to reduce mood disturbance
- Propanolol: A beta-blocker drug used to treat high blood pressure, may be useful for severe cocaine withdrawal symptoms, as it reduces peripheral effects of adrenaline, inhibiting the “fight or flight” response to stressful situations.
what are the most widely used club drugs?
Amphetamines,
methamphethamine,
phenidates
methylene-dioxymethamphetamine (MDMA)
what can Phenidates and Methyl phenidates be used for?
what class of drugs are these?
MPH (Ritalin) is generally recommended as the first choice medication for ADHD in Europe
It is classified as a Schedule II drug, it has high potential for abuse and is available only through a prescription that cannot be refilled
Within Europe, both MPH classes of stimulant are approved in the UK and are covered in national guidelines
Derivatives have recently caused major problems as NPS
i.v. use increasing
Mechanism of action similar to cocaine
- “amphetamine-like”drug, with regards to the pharmacological, dopamine-releasing properties
- Major effect in the basal ganglia
what happens when Phenidates and Methyl phenidates are abused?
Used intranasally, methyl- and ethyl-phenidate reportedly have receptor effects similar to those of cocaine
A rapid release of synaptic dopamine occurs, producing subjective effects of an instant “high” and an intensely gratifying euphoria
Thus, the clinical picture of abuse is often quite similar to that of cocaine
Localization of methylphenidate binding with dopaminergic pathways was “identical” with that of cocaine and a similar “high” was described by patients receiving both drugs intravenously
treatment for Phenidates and Methyl phenidates dependence?
Treatment of dependence is by behavioural approaches
give examples of Amphetamine-type stimulants
what is Dextro-amphetamine used for?
how do Amphetamines work?
methamphetamine and amphetamine
ADHD, narcolepsy, obesity
Synthetic – indirect acting – sympathomimetic drugs
Cause release of endogenous biogenic amines (dopamine and noradrenaline)
Reverse action of biogenic amine transporters
Amphetamines are substrate of the transporters
why is methamphetamine abused Recreationally?
to increase alertness, relieve fatigue, control weight, treat mild depression, and for its intense euphoric effects
are Amphetamines short or long lasting and what effect does this have?
Short lasting effect leads to binging and consequent risks of fatal toxicity
what are the Routes of administration of Amphetamines?
in which route is the half life longest?
Methamphetamine users often begin with intranasal or oral use and progress to intravenous use, and occasionally smoking.
Following oral administration, peak methamphetamine concentrations are seen in 2.6-3.6 hours and the mean elimination half-life is 10.1 hours (range 6.4-15 hours). The amphetamine metabolite peaks at 12 hours. Following intravenous injection, the mean elimination half-life is slightly longer (12.2 hours).
how long do the effects of Amphetamines last?
Onset of effects is rapid following intravenous use and smoking, while effects onset more slowly following oral use. Overall effects typically last 4-8 hours; residual effects can last up to 12 hours.
how are amphetamines eliminated?
Methamphetamine is metabolized to amphetamine (active), p-OH-amphetamine and norephedrine (both inactive)
Several other drugs are metabolised to amphetamine and methamphetamine and include benzphetamine, selegiline, and famprofazone
Side effects of Amphetamines?
effects of overdose?
Side Effect Profile:
- Light sensitivity
- Irritability
- Insomnia
- Nervousness
- Headache
- Tremors
- Anxiety
- Suspiciousness
- Paranoia
- Aggressiveness
- Delusions
- Hallucinations
- Irrational behaviour
- Violence
Overdose:
- Hyperthermia
- Tachycardia
- Severe hypertension
- Convulsions
- Chest pains
- Stroke
- Cardiovascular collapse
- Possible death
what effects can abrupt discontinuation of Methamphetamine use produce?
Abrupt discontinuation of use can produce extreme fatigue, mental depression, apathy, long periods of sleep, irritability, and disorientation
treatment for Methamphetamine dependence?
by withdrawal and behavioural approaches
what is Methylene- dioxymethamphethamine?
why do people take it?
MDMA (Ecstasy)
Synthetic, psychoactive drug that has similarities to both the stimulant amphetamine and the hallucinogen mescaline
Produces feelings of increased energy, euphoria, emotional warmth and empathy toward others, and distortions in sensory and time perception
what is MDMA used for clinically?
It is currently in very early clinical trials as a possible pharmacotherapy aid to treat post-traumatic stress disorder (PTSD) and anxiety in terminal cancer patients.
how is ecstasy taken illicitly?
Ecstasy tablets and capsules contain other drugs that may include ephedrine, dextromethorphan, ketamine, caffeine, cocaine, methamphetamine, synthetic cathinones (“bath salts”)
These substances are harmful alone and may be particularly dangerous mixed with MDMA
Most risks are associated with the use of the drug in the environment in which it is most often consumed
why was LSD (a hallucinogen) suspended from further testing?
Strong effects on the uterus. It also caused restlessness in experimental animals that lead to suspension of further testing
how is the structure of LSD similar to serotonin?
both have an indole ring (benzene ring fused to a five-membered nitrogen containing pyrrole ring.)
what is the moa of LSD?
LSD is believed to exert its pharmacologic properties primarily through its effects on the serotonin system
Binds to 5-HT1A/1B/1D, 5-HT2A/2C, 5-HT5A, 5-HT6, and 5-HT7 receptors
what are the perceptual side effects of LSD?
150–250 micrograms of LSD p.o. typically produces:
- Illusions; i.e., objects changing shape and color
- Stationary objects seeming to move
- Colors becoming brighter or more intense
- Synaesthesia (i.e., one type of sensory experience is translated into another; e.g., one “sees” sound),
- Emotional changes
- Value judgment may be suspended
- Time and spatial orientation are often affected
- Events experienced while under the influence of LSD are given increased meaning
- Memory is generally not affected
- Transcendental experiences (“Psychedelic” term was coined)
what are the somatic side effects of LSD?
Effects may result from stimulation of both the sympathetic and parasympathetic nervous systems and tend to occur only at higher doses:
- Changes in heart rate and blood pressure
- Dilation of the pupils
- Sweating
- Hypersalivation,
- Piloerection
- Nausea, diarrhoea, vomiting
- Fatigue
- Increased muscular tension
- Tremors
- Headache, heaviness of the extremities
- Analgesia may occur as well
Management of the symptoms of hallucinogen ingestion
Side effect management is mainly through talk therapy
Volunteers at the Haight Ashbury Free Medical Clinic (HAFMC) developed techniques to “talk them down” from their drug frenzy observing that the individual’s environment had a lot to do with how the effects of LSD were perceived by the user
These techniques have been used and refined by the clinic’s Rock Medicine program at concerts with thousands of “trippers” at Grateful Dead and other concerts for over 40 years
Use of benzodiazepines and anti-psychotics has been adopted in cases where individuals may harm themselves or others
what are opium derivatives generally used for?
All used medically for mild to severe pain management
how is opium extracted from the plant?
Seedpod is incised with a blade
Milky fluid seeps from cuts in the unripe poppy seed pod
Scraped off and air-dried to produce opium
Dried in open wooden boxes
Resin is placed in bags or rolled into balls for sale
give the composition of the Alkaloids in opium
how is natural opium transformation for illicit use?
raw opium added to Hot water/Ca2+ oxide (lime): Alkali pH dissolves morphine.
Ammonium chloride added after filtration to precipitate morphine
Crude morphine powder (~50% morphine)
Acetic anhydride/boiling to acetylate
Brown heroin precipitation
Hydrochloric acid Purification: 75% Diacetyl morphine
6% yield
how do the Euphoric effects of opiates arise|?
Euphoric effects of opiates arise from activation of opioid receptors on GABAergic neurons that inhibit dopaminergic neurons in the ventral tegmental area causing disinhibition and greater dopamine release from VTA presynapses terminating in the nucleus accumbens
which opioid has an immediate effect on the body?
Fentanyl
what are opioid side effects?
Respiratory depression: reduces sensitivity of respiratory centre; most common cause of death from overdose with street use of opioids.
Euphoria: action on the reward pathway in the brain to increase dopamine release
Cough suppression (anti-tussive)
Nausea: activate the chemoreceptor trigger zone (which in turn activates the vomiting centre). Aspiration of vomit when unconscious common.
Constipation: due to maintained contraction of smooth muscle
Short term (acute) effects of opioids?
how serious are these symptoms?
- Analgesia (feeling no pain)
- Sedation
- Euphoria (feeling high)
- Respiratory depression
- Small pupils
- Nausea, vomiting
- Itching or flushed skin
- Constipation
- Slurred speech
- Confusion or poor judgment
Most acute symptoms are not serious (unless in overdose!)
Long term (chronic) effects of opioids?
what are the withdrawal symptoms of opioids?
- Anxiety
- Irritability
- Craving for the drug
- Rapid breathing
- Yawning
- Runny nose
- Salivation
- Goosebumps
- Nasal stuffiness
- Muscle aches
- Vomiting
- Abdominal cramping
- Diarrhoea
- Sweating
- Confusion
- Enlarged pupils
- Tremors
- Loss of appetite
treatment and approaches for opioid overdose?
Assess patient to clear airway.
Provide support ventilation, if needed.
Assess and support cardiac function.
Provide IV fluids.
Frequently monitor the vital signs and cardiopulmonary status until the patient has cleared opioids from the system.
Give IV naloxone if necessary (opioid antagonist)
- Administered intravenously or subcutaneously
- Rapidly reverses the respiratory depression and sedation caused by heroin intoxication.
Naloxone (Evzio) as an autoinjector dosage form for home
- Since 2015 any worker in a commissioned drug service can provide naloxone without a prescription
what are the symptoms of opioid overdose?
what is the treatment and Rehabilitation for opioid dependence?
Detoxification or
Replacement/substitution therapy
Plus behavioural approaches
what compounds are commonly used for drug replacement therapy?
Opioid maintenance
Methadone maintenance (longer lasting effects, can be overdosed)
Buprenorphine/naloxone maintenance: 4/1 ratio (naloxone gives withdrawal symptom if used i.v.
Alpha-2 adrenoceptor agonists, such as clonidine and lofexidine
Diacetyl morphine
Cognitive behavioural, supportive, or analytical-oriented psychotherapies
where can opioid addiction be treated?
Controlled environment: No infection (needle exchange)
- Specialized addiction centre
- Community clinic
- Private sector hospital
- Psychiatric hospital
- Detoxification Camp
- Prison
what is doping?
artificially change bodily physiology to enhance performance (most commonly muscle mass or blood oxygenation)
how is dependency different in Performance enhancing drugs
(PEDs) in sport?
Motivation for use different from other drugs as euphoria not sought
‘Dependency’ may involve underlying psychological problems with self image
list the types of Performance enhancing drugs
are these legal to possess?
- Stimulants (such as amphetamines)
- Anabolic steroids (such as nandrolone)
- Diuretics (to help lower body weight)
- Blood doping agents (such as EPO)
Many not illiegal to possess
how can oxygen in the blood be boosted clinically?
Homologous transfusion
Autologous transfusion
EPO treatment: a hormone produced by the kidney to enhance oxygen during hypoxia 0 to 19 mU/ml
Artificial blood substitutes (introduced in the list of illegal substances)
what are the side effects/risks of boosting oxygen in the blood?
what is the benefit?
Proper use of EPO has an enormous therapeutic benefit in the treatment of anaemia related to kidney disease
Misuse can lead to thickening the blood
Heart disease, stroke, and cerebral or pulmonary embolism
May also lead to autoimmune diseases
what are IPEDS?
give an example
Image and Performance Enhancing Drugs
Several drugs are now available which do not necessarily affect performance but improve physical appearance or offset the adverse effects of PEDs
E.g. Melanotan: darkens skin tone (tanning) and improves sexual function
The majority are untested in humans or are being used for off license effects
what is alcohol used for (apart from drinking)?
what are the claimed benefits of alcohol?
- Solvent (alkaloids, glycosides, resins, and volatile oils but not polysaccharides, gums, sugars, or protein)
- Preserving
- Mild anaesthetic
- Disinfectant
Claimed benefits:
- central relaxant
- circulation and stroke
what is the recommended max limit of alcohol per week?
Both men and women are advised to not drink more than 14 Units alcohol/week
complete the table…
what are the health risks of heavy drinking?
what measures of detoxification are taken for…
- Mild dependence (<20 units):
- Heavy dependence (>20 units):
- Extreme cases:
what physical withdrawal symptoms will Detoxification induce?
what advice can we give?
- Mild dependence (<20 units): home with no drugs?
- Heavy dependence (>20 units): home with tranquilizers, chlordiaxepoxide?
- Extreme cases: hospitalisation and drug administration?
Withdrawal symptoms will be at their worst for the first 48 hours
This usually takes 3-7 days from the time of your last drink
Sleep is disturbed. Sleep patterns should return to normal within a month.
During detox, drink plenty of fluids (about three litres a day). Water, squash or fruit juice are better choices.
Risk of seizures during detox
what is available for Abstinence Maintenance and preventing relapses?
Drug support
- Acamprosate (MoA not fully understood; may be NMDAR related)
- Disulfiram (aldehyde dehydrogenase inhibitor)
- Naltrexone (opioid antagonist; prevents capacity to experience rewarding effects of alcohol)
Counselling support
- Self help groups
- Twelve steps facilitation therapy
- CBT
Coping strategies for alcohol dependence?
Social situation: maintain distance with people and situations that may impair recovery.
Develop healthy habits: e.g. good sleep, regular physical activity and eating well.
Activities that don’t involve alcohol: e.g. replace destructive habits with hobbies or pastimes that are not centered around alcohol
