Lecture 31 - Emerging Therapies for Drug Dependence Flashcards
Which is the biggest drug problem?
Alcohol
Define the following terms:
- Drug use
- Drug misuse
- Tolerance
- Substance dependence
- Substance addiction
-
Drug use:
- Use sanctioned by societ
-
Drug misuse
- Unsanctioned use
- Involves risk to individual
-
Tolerance
- Recquiring increased dose to elicit same effect
-
Substance dependence
- Neuroadaptatation,
- Daily physical need for the drug
-
Substance addiction
- Dependence + harm(s)
Define substance use disorder
Give some epidemiological stats on SUD
Use of a drug resulting in harm
Epidemiology:
- High prevalence, endemic
- Lifetime prevalence 15-20%
- Dependence 6-8%
- 16% nicotine dependence
- Endemic:
- Cannabis
- Methamphetamine
- Rising epidemic
- Synthetic cannabinoids
- Fly under the radar, because these compounds aren’t picked up by routine drug testing
- Most establish before the third decade of life
All drugs of abuse …
- Target the brain’s reward pathways
- Increase endogenous dopamine in the synapse in the nucleus accumbens
What is the normal role of the brain’s reward pathways
- Engender the ‘pleasure’ experienced with normal activities or experiences
- Food, music, art
Outline the reward pathway in the brain
- VTA
- Ventral tegmental area
- Located on the floor of the midbrain
- Dopaminergic projections to:
- Nucleus accumbens
- Frontal cortex
Outline the areas in the brainstem
- Midbrain
- Pons
- Medulla
Describe physical changes to neurons in neuroadaptation
- Spine growth
- Neurons sprout spines, become bushier
- Increases sensitivity to signals from VTA
- **Delta FosB **involved
- ⇒ drug sensitivity
- Receptor density
- Decreased dopamine receptor density in the brain
Outline the role of genetics in addiction
- A number of vulnerable genotypes exist
- Genetics does play a significant role in the aetiology of addiction
- Of course, the environment must be ‘right’ - ie the drug must be available
There has been much research into the genetics of drug addiction
COMT
- Genetic variation in COMT influences the harmful effects of drugs
- Homozygous individuals are 4-6 x more likely
to manifest the psychotic reaction after (even brief) exposure to cannabis
Therapeutic application
- Genotype can predict efficacy of response to treatment
- eg. Alcohol dependence treatment with Naltrexone
- Fewer relapses in individuals with Asp40, compared to Asn40
Describe the aetiology of drug dependence
Multifactorial
- Genotype + environment (psych-soc) = phenotype
- Addiction isn’t caused by a single event
- Analogous to other chronic conditions (CVD etc.)
Compare GP confidence to treat across various chronic diseases
Most confident to least confident
- Hypertension
- T2DM
- Depression
- Prescription drug abuse
- Alcoholism
- Illicit drug use
What is unusual about nicotine addiction?
- Most smokers are addicted
- Compared to other drugs, where the majority of drug users won’t become addicted (eg cannabis, methamphetamine)
- This is thought to be due to the frequent bolus dose taken per day
Describe therapy for nicotine dependence
- Rehabilitation
- Cognitive behavioural therapy (CBT)
- Relapse prevention strategies (RP)
- Nicotine replacement therapy (NRT)
- Triples quit rates
- First line therapy for nicotine dependence
- Gum, lozenge, spray, patches
- Relapse prevention pharmacotherapy
- “Anti-craving”
- Varenicline
- Bupropion (Champix)
- Immunotherapy
- Vaccine in trials
- Controversy
Describe the effects of Methoxsalen
- MOA
- Slows the metabolism of nicotine
- Nicotine remains in the blood longer
- Individuals can more easily cut down
- However, not used in Australia, as NRT is more effective
- With increasing dose:
- Decreasing desire to smoke
- Increasing blood nicotine concentration
What are the risks of cannabis use?
- Psychosis
- Liver risks
What are the addictive compounds in cannabis?
- THC
- Main psychoactive effects
- CBD: Cannabidiol
Describe treatment for cannabis addiction
- Similar to that for tobacco smoking
Describe the receptors in the endogneous cannabinoid system
- CB1 R
- CNS
- CB2 R
- Immune cells
Describe the use of CB1 R agonists and antagonists
Agonists:
- eg Sativex
- Anti-wasting
- Anti-nausea
Antagonists
- eg Rimonabant
- Anti-addictive
- Appetite supressant
- Anti-psychotic
What is the correlation between standard alcoholic drink consumption per day and lifetime risk of death from alcohol related disease
- With increasing alcohol consumption, there is increased lifetime risk of death
- Women have greater risk than men for a given alcohol consumption
- 10 SDs per day =
- Men: 6 per 100 people risk
- Women: 10 per 100 people risk
What is the recommended consumption of alcohol?
- 2 standard drinks per day
- However, it is not recommended to drink everyday, as this can lead to habituation, which can lead to escalation
- But 2-3 drinks per day is not intrinsically harmful
- Pregnant women and children should abstain
- Ethanol is embryotoxic
Describe Alcohol withdrawal syndrome
Why does this occur?
Effect of alcohol on the brain
- __Chronic alcohol consumption leads to **neuroadaptation: **physical changes in the brain:
- Glutamate:
- Upregulation
- GABA (inhibitory system):
- Down-regulation of this activity
- Glutamate:
When alcohol consumption is stopped:
- Balance that has established over time is thrown off
- Glutaminergic system is in a state of overdrive, leading to overstimulation:
- Hyperadreneric
- Hypertension
- Tachycardia
- Withdrawal seizures
- Delirium
Describe treatment for alcohol addiction
- Medical management of withdrawal syndrome
- Enhance GABA system
- Benzodiazepines
- ‘restoring the balance’
- Correction of fluid and electrolytes
- Fluids
- Electrolites
- Vitamin B (thiamine)
- Management of co-morbidity
- Liver, pancreas, brain, lung injury
- esp. Microaspiration
- Liver, pancreas, brain, lung injury
- Enhance GABA system
- Rehabilitation
- CBT
- RP: relapse prevention strategies
- AA
- Social interaction of some sort
- Relapse prevention pharmacotherapy
- Naltrexone
- Especially for those with the ‘Reward phenotype’
- Dampens the reward signalling from alcohol
-
Disulfiram “antabuse” program
- Makes the individual averse to the alcohol, elicits nausea when alcohol is consumed
- Naltrexone
What are the risks associated with Heroin?
The real medical risks with Heroin are to do with the injection:
- OD risk
- Infection spread via injection
- HepB/C
- HIV
- Sepsis
Heroin was still administered to children up until 1946
List some opiates, and the trends of prescription in Australia
- Codeine
- Low rates, steady
- Morphine
- Slowly increasing
- Oxycontin
- Marked increase in use since 2000
- Pethidine
- Decreasing use
- Methadone
Describe therapy for opioid addication
- ORT: opioid replacement therapy
- Agonists:
- Methadone syrup
- Suboxone: Buprenorphine-naloxone
- Subutex: Buprenorphine
- Antagonists
- Naltrexone
- Agonists:
- Harm minimisation
- Safe injecting rooms
- Needle exchange
- Support networks
- Naloxone
- Opioid antagonist
- Emergency overdose treatment
- Rehabilitation programmes
- CBT
- RP: relapse prevention strategies
What is Suboxone?
Describe the MOA
Buprenorphine + Naloxone
MOA:
- Buprenorpine:
- Opioid partial agonist
- Less toxicity risk
- Opioid partial agonist
- Naloxone:
- Opioid antagonist
- Blocks the effect of opioids
- Opioid antagonist
List some stimulants
Outline the MOA
- Cocaine
- Inhibits reuptake of Dopamine in the synaptic cleft
- Increased dopamine action in the nucleus accumbens
- Amphetamines
- eg Benzedrine, MDMA (ecstacy)
- Increases biogenic amine and excitatory neurotransmitter activity in the brain:
- NA
- Dopamine
Describe therapy for stimulant addiction
- Rehabilitation
- CBT, RP
- Relapse prevention pharmacotherapy
- Fluoxetine, SSRI
- Disulfiram
- Topiramate
- Immunotherapy
- Currently in phase 3 trials
