WK 6- PHARMACODYNAMICS- ADDICTION VS ACUTE INTOXICATION Flashcards
What is the definition of intoxication
condition that follows administration of a psychoactive substance and results in disturbances in the level of consciousness, judgement, behaviour or psychophysiological functions and responses
What is the definition of addiciton
Condition characterized by an overwhelming desire to continue taking a drug that a person has become habituated to, through repeated consumption- desire to take drug it to receive its affects - usually alteration of mental status
What are 3 CNS depressants
- Alcohol
- Benzodiazepines
- Opiates (heroin)
What are 2 CNS stimulants
- Cocaine
2. Amphetamines (Ice, Ecstasy)
What is the mechanism of action of alcohol- how does it alter mental status
Allosteric inhibition of NMDA receptors and facilitation of GABA (increase chloride influx)–> results in dopamine release into the synapses of the mesolimbic reward pathway causing a ‘relaxed’ feeling
What is the mechanism of withdrawal from alcohol (what happens to receptors)
- Internalisation and decreased surface expression of normal GABA-A receptors
- Increase in surface expression of ‘low alcohol sensitivity’ GABA-A receptors (don’t respond to alcohol)
- Increased phosphorylation of NMDA receptors containing high conductance subunits-> causes influx of Ca-> causes muscular contractions (delirium tremors)
What is the mechanism of action of benzodiazepines
1) Nerve impulse cause release of GABA from
storage sites on presynaptic neuron
2) GABA released into synaptic cleft and interacts with receptors on the posty-synaptic neuron
3) the reaction allows chloride ions (Cl-) to enter the neurons
4) This effect inhibits further progress of the nerve
impulse
5) Benzodiazepines react with booster site on GABA receptor and enhances the inhibitory effects of GABA
What is a schedule 8 drug
Schedule 8 (S8) drugs and poisons are substances and preparations for therapeutic use which have high potential for abuse and addiction→ making possession without authority illegal
True or false- the shorter the half life of a drug, the more addictive it is
True- this is why benzodiazepines are so addictive
What are examples of opiods
Codeine, Heroin, Methadone, Oxycodone
What is the mechanism of action of opiods
- Heroin reaches the brain and becomes morphine
- Morphine will interact with kappa, delta and mu receptors
- This causes decreased release of GABA
- The lower amount of GABA= less inhibition→ causes flood of dopamine to enter the cortex- relaxed feeling
What is the mechanism of withdrawal from opioids
1) Increased mu-opiod receptor internalization and degradation (can’t get relaxing feeling)
2) Decreased efficacy of mu-opiod signal transduction)
3) Hyperactivation of adenylyl cylase signalling, leading to enhanced GABA release and to increased gene transcription via activation of transcription factors
What is the MOA of methamphetamine
methamphetamine causes release of all stored dopamine→ dopamine transporters move dopamine into synaptic cleft→ interacts with all receptors
Does ecstasy cause release of dopamine
NO- ecstasy works by blocking serotonin re-uptake, causing high levels of serotonin in synaptic cleft→ causes a relaxed feeling of euphoria
What is the MOA of cocaine
blocks dopamine reuptake transporter and floods the synapse with dopamine
What is the mechanism of withdrawal from cocaine
- Dopamine amine transporter expression increases
- The number of postsynaptic dopamine receptors decreases
- Presynpatic dopamine is depleted
- over time, cocaine addicts require more and more levels due to dopamine release reducing
- cause of death is normally always cardiac→ dopamine goes to NA, causes reflex tachycardia
What are some ways of monitoring what drugs are being used in the community
- Sewage monitoring
- Needle/syringe program
- Hospitalisations/coronial inquest
What are some factors that drive people to drug use
Genetic= some people are more likely to feel the effects of certain drugs (eg. codeine metabolised to morphine-> predisposes to addiction) or some people are bad metabolisers (ie acetaldehyde deficiency)
Social and environment= SES, family history, exposure, education
Biomedical/neurochemical= drugs hijack the reward pathway and put it at the top of the ‘needs’ list
What are the 3 ‘reductions’ of the National Drug Strategy
- Supply reduction= police decreasing availability of drugs in the community
- Harm reduction= Harm minimisation through safe injecting rooms/syringe programs
- Demand reduction= School based education programs
What are the 4 different routes of administration- what are their slang terms
Oral= Drop it Inhalation= Chase it Injection= Boot it Rectal= Shaft it
If a patient presents to the ED after taking a drug, why is it important to know what route was taken
The route can affect the pharmacokinetics of the drugs-> change it’s peak time and the effects-> eg. Drugs that are inject have immediate action, whilst those ingested take longer to peak
What are the 5 patterns of drug use (pyramid)
- Dependent
- Regular
- Recreational
- Occasional
- Experimental
At what stage of the patterns of drug use is acute harm most likely to occur and why
Experimental phase- this is where people have less tolerance to a drug and less education- allows for easy overdose
With drug use, what are the 3 categories of acute harm
- Social- broken relationships, employment issues, child protection, issues with the law
- Physical- overdose, loss of consciousness, IV drug use harm
- Mental- psychosis, aggression, anxiety, depression
What kind of diseases can result due to IV drug use
Injection injury= vasospasm, embolic events, vessel rupture
Secondary disease= septicaemia, endocarditis, infection, organ failure, embolus
Blood borne disease= HIV, HEP C, HEP B
Rhabdomyolysis, MI, Stroke, renal failure and seizures are due to which type of drug class- stimulants or depressants
Stimulants
Respiratory failure, Aspiration, Hypoxix brain injury, Leukoencephalities and seizures are due to which type of drug class- stimulants or depressants
Depressants
What 5 types of harm are due to chronic drug use
- Social Harm= assaults, unplanned pregnancy, broken relationships, homelessness, incarceration
- Financial harm
- Mental harm= psychosis, dependence, depression, anxiety
- Physical harm= organ damage, rapid ageing, STI’s, malnutrition, BBV and other IVDU injuries
What are the 9 physiological steps of dependence
- Exposure to substance with abuse potential (can cross BBB, can activate reward pathway)
- Positive aspects of neurochemical activation outweigh negative aspects in the individual
- Environmental context is conducive to repeated use
- Repeated use results in receptor adaptation (function or number)
- Downstream neurological function alters to adjust for receptor adaptation (homeostasis)
- Same amount of drug produces less physiological response-more drug required for equal outcome-tolerance
- Tolerance fuels desire for more drugs to achieve same outcome
- ‘Normal’ function now requires increased levels of binding (presence of the drug)-dependence
- Removal of substance produces adverse effects-withdrawal
Why is it important to use psychotherapy in addiction treatment
Allows the person to deal with underlying trauma/things that drove them to using drugs and to then develop coping strategies and resilience
When quitting a drug, what are the 4 ways in which cessation of the drug can be achieved (4 S’s)
Stop= cold turkey- way most people do it Soothe= provide symptomatic relief to withdrawal symptoms Swap= substitute therapies Slow= controlled gradual reduction
What are some advantages and disadvantages of rehab- ‘detox’
Advantages= protected and supportive environment, peer support, monitoring Disadvantages= Expensive, limited places, not the 'real world' and some patients may relapse when they have to face the real world
What are the pharmacotherapies for alcohol
Withdrawal= thiamine with diazepam/oxazepam
Stopped but dependent= naltrexone (opiate antagonist), acamprosate (GABA agent, anti-craving) or disulfam (alcohol dehydrogenase antagonist)
Long term= thiamine
What are the pharmacotherapies for opiates
- Methadone= full acting angonist- stabilises behaviour and allows for ‘headpsace’-> but risk of resp depression and overdose, helps with withdrawal
- Buprenorphine= partial agonist= ow risk of resp depression, patient must be in withdrawal when starting buprenorphine
- Buprenorphine/naloxone= naloxone is an antagonist, buprenorphine is a partial agonist
- Naltrexone= oral form of naloxone
- Rapid detox= clear body of opiates whilst under sedation
Why is buprenorphine given with naloxone
If you inject the bup/nal combination, the naloxone is in its environment (the bup is optimised for oral use)- the naloxone wins, binds to the receptors, blocks them and the buprenorphine can’t bind and they get NO or MINIMAL EFFECT→ stops people injecting
What are the pharmacotherapies for nicotine
- Verenicline (champix): nicotinic acetylcholine-receptor partial agonist, not to be used in pregnancy, childhood or those with significant psychiatric distress, reduce dose in renal impairment-lack of serious adverse effects (only nausea in 30%)
- Buproprion: anti-depressant so has co-positive aspects. Is a non-competitive nicotine receptor antagonist and at high concentrations inhibits the firing of noradrenergic neurons in the locus caeruleus.
