Lecture 15: Drug of abuse Flashcards
What are the main definitions and concepts of Drug Abuse
1) Tolerance (and sensitization)- the reduction (or increase) in response to a drug after repeated administration.
2) Physical Dependence - The state that develops as a result of tolerance produced by resetting of homeostatic mechanisms in response to repeated drug abuse (e.g. pharmacodynamic- related to receptor density or coupling efficiency, and therefore the response to a drug)
3) Withdrawal syndrome- The presence of a withdrawal syndrome is the only evidence of physical dependence.
The withdrawal syndrome is caused by removal of the drug of dependence and characterized by CNS hyperarousal.
The syndrome is characteristic of the particular category of drug and tends to be opposite to the effects of drug (
(e.g. opioids cause meiosis and bradycardia, withdrawal may cause dilated pupils and tachycardia)
The syndrome is characteristic of the particular category of drug and tends to be _________ to the effects of drug
The syndrome is characteristic of the particular category of drug and tends to be opposite to the effects of drug
(e.g. opioids cause meiosis and bradycardia, withdrawal may cause dilated pupils and tachycardia)
Briefly describe the mesolimbic dopamine system *
The mesolimbic dopamine system is a pathway in the brain in which dopamine is carried from one area of the brain to another.
Dopamine is responsible for controlling the brain’s pleasure and reward centers.
Starting in the midbrain’s ventral tegmental area, it is linked by the amygdale, the nucleus accumbens, the medial prefrontal cortex, and the hippocampus parts of the brain to another set of brain structures known as the limbic system.
This is the most common system involved in drugs
How does DSM-5 define Substance dependence syndrome
1) Use continued despite substance-related problems
2) Tolerance
3) Withdrawal
4) Others
3 or more symptoms = dependence
1 or 2 symptoms = abuse
What the term “Compulsive drug” do?
Distinguishes behavioural probelms from physical dependence.
State the 3 origins of substance dependence
1) Agent (the drug)
2) Host (the user)
3) Environment (the setting)
Describe the “Agent” origin of substance abuse
(the drug)
Reinforcement is the property which makes the user want to use the drug again.
It is related to the abuse potential of the drug
It is associated with certain central neurotransmitters (e.g. dopamine in nucleus acumbens).
It is related to the rapidity of onset of the drug’s action.
Describe the “Host” origin of substance abuse
(the user)
People show wide variability in their
1) Pharmacokinetic response to drugs (distribution and metabolism, and hence blood levels)
2) Pharmacodynamic response to drugs
3) Learned or behavioural or personality or genetic response to drugs.
Genetic
- Polymorphic inheritance for predisposition for addiction (concordance for alcoholism is greater in identical than fraternal twins)
- Mitochonridal alcohol dehydrogenase converts alcohol to acetaldehyde; it may be increased in some Asian populations, who never become alcoholic.
Describe the “Environment” origin of substance abuse
Societal norms
Also peer pressure, low employment and low education levels.
What are some specific drugs of abuse
1) CNS depressants
e. g. alcohol and benzodiazepines
2) Opioids
3) Psychostimulants
e. g. cocaine, amphetamine, fenfluramine
Describe a CNS depressant
Alcohol
Properties:
- CNS depressant (but low doses often perceived as stimulant and exceptions don’t tend to drink)
- Recent memory impaired
- Blackouts occur in high doses
- Mild intoxication is associated with motor inco-ordination, sleepiness and then stimulation and garrulousness
- Increasing dose leads to sedation, coma and death
As tolerance develops, sedation is reduced but lethal dose is unchanged so therapeutic index is reduced (Beware of early morning drinking)
Withdrawal symptoms: (50% of regular takers)
- Alcohol cravings
- Tremor, irritability
- Nausea
- Sleep disturbance
Delirium Tremens (~5$ of regular takers) -Severe agitation, confusion, hallucinations, fever etc.
Chronic use of alcohol is associated with depression, an increased risk of suicide, cognitive deficits even when sober, nutirtional deficiency (which may lead to brain damage) and organ toxicity (e.g. cirrhosis and CVS myopathy and pancreas)
(see graph)- The decay time changes from 1st order to zero order kinetics if you have 6+ drinks. Therefore it can be dangerous to drive/drink the day after a night of drinking.
If you find someone unconscious and smelling of alcohol, what should you do?
Airway Breathing Circulation Disability (look for trauma!! Don't assume they're unconscious because of the alcohol) Exposure
What is the trend of opioid abuse and what may be the cause of the increase?
- HUGE increase in opioid abuse rates over the last 10 years
- This may be due to increase of rate of opioid prescribing and the ability to afford opioid decreaseing.
- Doctors have become lazy, and there is a huge push for prescription for opioids
Describe opioids
Opioids produce well-being and euphoria which leads to reinforcement (naïve users may experience nausea and dysphoria).
- These drugs are very useful in treatment of acute pain (NB angina) and analgesic use rarely leads to dependance so fear of addiction does not justify withholding morphine in cancer pain.
- Opioids for chronic pain of non-malignant origin may be justifiable with appropriate caveats and controls, but should be prescribed and monitored in liaison with specialist services (multidisciplinary chronic pain clinics) because there is substantial potential for abuse, efficacy is often poor and chronic use rapidly leads to tolerance
- Short acting rapid onset opioids for acute pain: morphine; fentanyl ; pethidine; oxycodone; diamorphine; codeine.
- Longer acting slower onset opioids for longer term analgesia: sustained release morphine (kapanol, MST); oxycontin; methadone.
Not all opioids are the same in terms of CNS effect. Abuse potential related to lipid solubility and euphoric “high”.
Diamorphine»_space; Fentanyl > Pethidine > Morphine > Codeine
Name some short acting and longer acting opioids
- Short acting rapid onset opioids for acute pain: morphine (intravenous or elixir (sevredol)); fentanyl (intravenous); pethidine (intravenous or orally); oxycodone; diamorphine; codeine.
- Longer acting slower onset opioids for longer term analgesia: sustained release morphine (kapanol, MST); oxycontin; methadone.
