Drugs of abuse (Prof Dickenson) Flashcards
How would you define drug dependence ?
A state, psychological and/or physical
resulting from an interaction between a drug and organism, characterized by a compulsion (periodic or continuous) to experience the psychic effects and/or avoid the discomfort of withdrawal.
What effects do all drugs have in common ?
Wish, need, desire and craving (all psychological).
Which drugs systematically lead to withdrawal symptoms ?
Depressent drugs: opioids, alcohol etc.
Which drugs can be classed as:
- depressants ?
- opiates ?
- stimulants ?
- hallucinogens ?
- inhalants ?
- cannabis ?
Depressants: alcohol, barbiturates Opiates: heroin, morphine Stimulants: amphetamines, cocaine, ecstasy Hallucinogens: LSD, magic mushrooms Inhalants: glue, solvents Cannabis: classed alone
Do opioids cause physical and/or psychological withdrawal symptoms ?
Physical and psychological symptoms.
Can all drugs trigger:
- phsycological dependance ?
- physical dependance ?
Psychological dependence: yes, all drugs can trigger reward and or reinforcement mechanisms
Physical dependence: only depressant drugs can trigger
adaptive mechanisms
How does the Ventral Tegmental Area (VTA) reward system work ?
GABAergic neurons naturally inhibit dopaminergic neurons that release dopamine in the cortex.
Where do opioids, alcohol and cannabis act on the VTA ?
These drugs inhibit the GABAergic neurons of the VTA, thus increasing the amount of DA released in the cortex.
Where does nicotine act on the VTA ?
It stimulates the dopaminergic neurons of the VTA.
How do cocaine and NMDA work ?
Cocaine inhibits the reuptake of DA in VTA dopaminergic neurons. while NMDA causes DA release.
What are the typical characteristics of withdrawal systems ?
Withdrawal symptoms are opposite to the acute effects of the drug: if the drug is a depressant (e.g. heroin or alcohol), it inhibits the NS, which adapts over time to increase overall excitation (receptor up-regulation, NT synthesis, depolarization up, 2nd messengers up, plasticity up). When the drugs is removed, the body is in a naturally over-excited state.
What are the acute effects of heroin ?
- Pain relief
- Reflexes down
- Secretions down
- Temperature down
- Constipation
- Cough down
- Anxiety down
What are the withdrawal effects of heroin ?
- Aches and pains
- Kick the habit
- Tears, runny nose
- Fever - cold turkey
- Diarrhea
- Coughing
- Panicky
What were the treatments in the past for heroin dependency ?
What about today ?
Past: aversion therapy
Today: substitution therapy –> methadone or naoloxone for opioids
What are the major problems of drug dependence and abuse ?
(1) overdose
(2) crime as a result of need to obtain drug
(3) withdrawal symptoms - may be life threatening
(4) retreat from society
(5) acute effects of a particular drug and the chronic pathological effects
(6) AIDS, hepatitis etc. as a result of injections. Injection of tablets.
(7) drug combinations
On what receptors does cannabis act on ?
What types are they and where are they located ?
- inhibitory CB1 and CB2 receptors
- They both work through slow 2nd messengers
- Sites of action: spinal and supraspinal
How does the receptor coupling for cannabis compare to that of opioids ?
It is very weak.
What do patients like when they take cannabis ?
Analgesia, mood, sedation, amnesia, muscle relaxation –> spinal, cortical and hyppocampal sites of action.
Also increased appetite .
What are the effects of stimulants at low doses ?
• Mood amplification • Increased energy • Insomnia • Restlessness - motor • Hyperactive ideation • Talkativeness • Mild anorexia • Increased sexual interest
What are the effects of stimulants at high doses ?
- Irritability, hostility
- Extreme energy
- Total insomnia
- Motor stereotypies
- Disjointed ideas
- Rambling
- Total anorexia
- Decreased sexual interest
Where does heroin comme from ?
How does it work ?
- Heroin commes from morphine (juice of the opium poppy).
- Heroin = diamorphine, enters the brains rapidly and is converted to morphine
- 4 opioid peptides and 4 ORs known
- morphine activates MORs, open K+ channels and inhibits NT release
How does cocaine work ?
By blocking the reuptake and NA and DA (by blocking a presynaptic transporter).
What are the consequences of repeated cocaine consumption ?
- Mood, confidence, alert…
- Dry mouth, palpitations
- Anxiety and panic
- Heart failure - bp and heart rate up
- Cerebral haemorrhage
How do amphetamines work ?
Amphetamines enter the nerve terminal through uptake and cause NT release (DA, NA, 5-HT).
What are the effects of amphetamines ?
- Alert, awake, confident
- Amphetamine psychosis (DA)
- Motor problems - chewing (DA)
- Fatigue
- Anorexia
What are the effects of MDMA/ecstacy ?
- 5HT + DA levels increase
- energy, calm, empathy, enhanced sense of surroundings/temperature changes
- 5HT may relate to visual changes etc.
But autoreceptors may then be activated: - reduced release + activity of neurons and synthesis
of 5HT
Short term depletion of 5HT..3-4 days of comedown
What are the various effects of morphine in:
- the cortex ?
- the brainstem ?
- the spinal chord ?
- the PNS ?
- Cortex: reward and reduced anxiety
- Brainstem: analgesia, respiratory depression, nausea and cough
- Spinal chord: analgesia
- PNS: constipation
Can patients under morphine treatment become dependant ?
No, because pain block reward.
What are the effects of excessive alcohol consumption ?
- One drug is legal
- Violence - 35%
- Criminal damage
- Brain damage
- Liver damage
- CV problems
- Gastric damage
- Major dependence
- 20,000 deaths
- No medical use
What are the effects of cannabis consumption ?
- Benign
- Apathy
- Bronchitis
- Amotivational syndrome
- Mental problems… ??
- Minor psych dependence
- 0 deaths
- Potential use in pain, cancer and AIDS
