Drugs of Abuse Flashcards
What is tolerence?
Over time, with repeated doses of the drug, you need more drug to achieve the same effect. Very common.
Classic example = pain relief; eg codeine.
Sensitization is rare and very rarely seen.
What actually causes tolerance at the molecular level?
- Receptor Down Regulation
- Reduced receptor senstivity
- Increased compensatory mechanisms
How do drugs modulate the mesolimbic system?
The mesolimbic system controls reward/pleasure, and DOA’s modulate this by controlling dopamine levels.
- Direct Dopamine release from the nerve terminal (amp)
- Bind at DAT to block dopamine reuptake (coc + amp)
- Increasing DAT activity from mesolimbic disinhibition.
What are the three most important Neurotransmitters to know?
- DA dopamine
- GA GABA
- GL Glutamate
What is “withdrawal syndrome”
Evidence of physical dependance to a drug. Caused by the removal of the drug → CNS hyperarousal.
This can happen with alcohol, smoking or even caffeine.
Opposite effect to the drug itself
What are the specific symptoms of Opiod withdrawal Sydrome?
Craving, restlessness, irritability, inc. sensitivity to pain, nausea, muscle aches, insomnia, anxiety.
Due to an autonomic dysfunction: sweating, tachycardia, hypertension, nausea, vomiting, poops, fever.
What are the 3 factors which contribute to drug abuse?
Agent- the drug
Host- the user
Environment- the setting
In terms of the ‘agent’, drug itself what can cause addiction?
- Level of reinforcement (property that makes the user want to do the drug again!)
- Rapidity of onset
- Presence of withdrawal symdrome
- Convenient and effective method of administration
In terms of the ‘Host’ what can increase the chance of addiction?
**Personality: genetics, development, upbringing, social situations
Pharmacokinetics: eg; due to asian flush (alcohol → acetaladehyde) there’s a lower prevalence of asian alcholism
Pharmacodynamics
What are the important Drugs of Abuse to know about?
Alcohol
Opioids
Cannabis
propofol
cocaine
Amphetamines “p”
Alcohol as a drug of abuse.
- Works by GABA enhancement
- 5-10% (men) and 3-5% (women) addiction
- 90% hepatic metabolism 10% renal elimination
- Very soluble so quicly absorbed.
Alcohol at a low dose: mild sedation, motor inco-ordination, disinhibiton
Higher dose: sedation/anaesthesia
Tolerance, physical independence and withdrawal symptoms associated with alcohol?
Tolerance: decreased sedation but lethal dose unchanged
Physical dependance → early morning drinking
Withdrawal Syndrome: in ~50% alcoholics post cessation. (5% to delerium tremens, with 15% mortality)
What’s affected by chronic alcohol abuse
Liver Cirrhosis: fulminant hepatic failure GI bleed
Cardiac Failure: dilated cardiomyopathy, heart failure
Cushings Syndrome
Malnutrition, GI ulceration, GI cancer,
CNS effects: peripheral neuropathy
Fetal ETOH syndrome
What do you do?
- Check for danger
- Do the ABCDEs
*Make sure she’s breathing and the airway is clear.
- Admit to ICU (NOT jail as they will likely die)
- Airways and ventilation
- Dialysis
- Tests; blood ethanol, drugs
- Check for trauma (don’t assume its a singular cause)
Why is the opioid epidemic increasing?
Mainly due to medical intervention, with an increase in opioid prescriptions and funding was recently cut in the US. Dependent patient then looked to the black market to fuel their addiction
What are the different types of opioids?
Full Agonist: full effect at opioid receptor (morphine)
Partial Agonist:
Antagonists: used for intoxication Naloxone
What are opioids used for and what else can they cause?
- Analgesia
- Sedation
- Cough suppression
- Respiratory depression
- Consti[ation, nausea and vomiting
- Hypotension, bradycardia, pupillary constriction
*each opioid has their own side effects that are mainly due to lipid solubility.
What does Heroin do and what is it used for?
- Euphoric rush + period of sedation and tranquility
- Widely used in the UK for analgesia
- Rapidly metabolised → morphine
**>50 mill addicts worldwide!
Why does Heroin have such high morbidity and mortality rates?
- Overdose
- Infection
- Transmission of HIV and Hep
- Drug interactions
- Impurities or contaminants
Not all opioids have the same CNS effect, so what is their differing abuse potential due to (and whats the worst ones)??
Abus potential seems most directly related to lipid solubility of the drug!
diamorphine >> fentanyl > morphine > codeine
Chronic pain + opioids = substantial potential for abuse
What is Methadone used for?
Due to its slow onset/longer action, it’s effectively used in weaning programs for drug abusers.
What 3 types of treatment is offered to opioid dependent patients.
- Methadone
- Clonidine: for opioid withdrawals
- Ultra-rapid detoxification: administering high doses of antagonists under general anaesthesia (controversial, probably doesn’t work)
Describe the WHO analgesic ladder
- Start with a non-opioid, less addictive (paracetamol)
- Start with an analgesic with some opioid properties (tramadol), or an adjuvent (strong but non-opioid)
- If you really need an opioid, start with a mild type, like codeine
Why is it that the number of meth labs have diminished post 2005?
Meth labs got smarter and split the lab into seperate locations
What are amphetamines and what types are there?
- Increases release and reduces re-uptake of CNS catecholamines; dopamine, noradrenaline, seratonin
- CNS stimulant and appetitie suppressant
Ritalin has properties of this, be careful of addicted parents!
Dopamine stays in the nerve terminals for extended periods, can last hours to days!
What are the effects of amphetamines
- Libido, energy, elf esteem, confidence, irritability, psychosis, aggression, hallicinations, stroke, death
- Highly addictive once you’ve had that first rush
What is cocaine used for medically, and what are its effects?
A topical anaesthetic and vasoconstricter
- Excitatory effects due to huge increase of catecholamines: DA, (inhibited reuptake)
- euphoria, libido, energy, confidence
- anxiety, paranoia, restlessness, tremor, fever
- Seizures and cardiotoxicity
- HIGHLY ADDICTIVE
What’s the main issue with propofol
Narrow therapeutic index so it can cause a lot of harm!!
