lecture 31: emerging treatments for drug dependence: clinical evaluation Flashcards
What are substance use definitions?
- substance/drug use = sanctioned by society
- substance/drug misuse = unsanctioned; involves risk without apparent harm
- substance use disorder (ICD; DSM V) = drug use resulting in [harm] problems
- substance dependence = daily physical need for the drug = homeostasis (neuroadaptation)
- substance addiction = as above + harm/s
- tolerance = more drug to get same effect
- withdrawal = illness after stopping dependent use (neuroadaptation reversal)
- intoxication = impairment associated with high dosage
What is the epidemiology of substance use disorders?
- lifetime prevalence substance use disorders ~15-20%; dependence ~6-8% population
- tobacco (nicotine dependence) ~16%
- increasing prevalence/epidemic opioid use disorders (dependence) and opioid related deaths (analgesics)
- alcohol use disorders:
- lifetime risk disorder !20%
- 25% seek medical help
- 15-20% GP patients
- dependence ~4% M and 2% F (~80% males, 60% females drink)
- endemic cannabis, ATS (methamphetamine), “synthetics”, prescription psychotropics
- overwhelming majority SUDs and addiction establish before third decade of life
What is the neurobiology of addiction?
- all drugs of abuse target the brain’s pleasure centre
- brain reward (dopamine) pathways
- these brain circuits are important for natural rewards such as food, music and art
- typically, dopamine increases in response to natural rewards such as food
- when cocaine is taken, dopamine increases are exaggerated, and communication is altered
What is seen in brain scans of a meth abuser at different time points of abstinence?
- is this a brain disease
- or an acquired condition
- or are these people just weak?
- changes in the brain’s signalling
- this shows the density of dopamine receptors
- reasonable recovery after 24 months
What is environmental neuroadaptation?
- micrographs of nucleus accumbens neurons in animals exposed to nonaddictive drugs display dendritic branches with normal numbers of signal-receiving projections called spines (left and centre)
- but those who become addicted to cocain sprout additional spines on the branches, which consequently look bushier (right)
- presumably, such remodelling makes neurons more sensitive to signals from the VTA and elsewhere and thus contibutes to drug sensitivity
- recent findings suggest that delta FosB plays a part in spine growth
What is the relationship between genes and addiction?
- Goodwin D: Alcoholism and Genetics
- Schickit M: sons of alcoholics
- Van den Bree: Genetic and environmental influences on drug use and abuse/dependence in male and female twins
- McClellan A: drug dependence, a chronic medical illness
- Gerra G: OPRK1 polymorphism
- Bevilacque L: genes and addictions
- Schuckit M: alcohol use disorders
- i.e. a lot of research
What is the bio-psycho-social model of drug dependence / addiction?
- genotype + environment (Psych-soc) = phenotype
- drugs as reinforcers of behaviour (prim/sec)
- addiction NOT caused by single agent/event
- addiction process analogous with other chronic diseases e.g. heart disease and diabetes
- treatment focus: reduce mortality and morbidity
On what does target organ damage depend?
- genes and environment
How do genes influence vulnerability?
- genetic variation in COMT influences the harmful effects of abused drugs
- met/met (low, equal cannabis/no cannabis use)
- met/val (low, more cannabis use than no)
- val/val (high cannabis use, low no use)
- val/val more likely to suffer the harmful effects of abused drugs e.g. psychosis
What is the relationship between genes and treatment response?
- genetics can help predict the outcome of treatment for alcohol dependence
What kind of disease is drug addiction?
- drug addiction is a chronic disease
What is a comparison of relapse rates between drug addiction and other chronic illnesses?
- drug addiction: 40-60%
- type I diabetesL 30-50%
- hypertension: 50-70%
- asthma: 50-70%
How GP “confidence” to treat illegal drug use or alcoholism compare to other chronic diseases?
- hypertension: 82.8
- diabetes: 82.3
- depression: 44.1
- prescription drug abuse: 30.2
- alcoholism: 19.9
- illegal drug use: 16.9
What is the treatment for nicotine addiction?
- most smokers are “addicted”
- QUIT strategy; CBT (relapse prevention); others including acupuncture, hypnosis, groups etc
- nicotine replacement therapy (NRT): gum, lozenge, puffer, transdermal patch
- relapse prevention pharmacotherapy (“anti-craving”) e.g. Varenicline, Bupropion, Cytisine
- immunotherapy: vaccine in phase 3 trials
What are the effects of methoxsalen on nicotine concentration and smoking desire?
- desire to smoke decreases with increasing concentration of methoxsalen (30 and 30mg, 35 at 10mg)
- increasing concentration of blood nicotine with increasing methoxsalen dosage
What is world alcohol consumption?
- we are equatable with russua and america
What is the lifetime risk of death from an alcohol related disease by number of standard drinks per day, per 100 people with that drinking pattern?
- 2 standard drinks recommended
- not daily to avoid habituating
- reasonably strong correllation with escalation of habits
What is seen with chronic groin injecting?
What is seen with chronic leg/skin injecting?
What is seen with temazepam IV and digital infarction?
What is the opioid supply in australia?
- oxycontin going up
- morphine going up
What is seen with iatrogenic addiction (pethidine)?
- multiple operations for abcesses for a drug that doctors were prescribing
What is opioid replacement therapy (ORT) by replacement medications in victoria from 2000 to 2011?
