WK 6- PHARMACODYNAMICS- ADDICTION VS ACUTE INTOXICATION

Question 1

What is the definition of intoxication

Answer 1

condition that follows administration of a psychoactive substance and results in disturbances in the level of consciousness, judgement, behaviour or psychophysiological functions and responses

Question 2

What is the definition of addiciton

Answer 2

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

Question 3

What are 3 CNS depressants

Answer 3

1. Alcohol
2. Benzodiazepines
3. Opiates (heroin)

Question 4

What are 2 CNS stimulants

Answer 4

1. Cocaine

2. Amphetamines (Ice, Ecstasy)

Question 5

What is the mechanism of action of alcohol- how does it alter mental status

Answer 5

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

Question 6

What is the mechanism of withdrawal from alcohol (what happens to receptors)

Answer 6

1. Internalisation and decreased surface expression of normal GABA-A receptors
2. Increase in surface expression of ‘low alcohol sensitivity’ GABA-A receptors (don’t respond to alcohol)
3. Increased phosphorylation of NMDA receptors containing high conductance subunits-> causes influx of Ca-> causes muscular contractions (delirium tremors)

Question 7

What is the mechanism of action of benzodiazepines

Answer 7

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

Question 8

What is a schedule 8 drug

Answer 8

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

Question 9

True or false- the shorter the half life of a drug, the more addictive it is

Answer 9

True- this is why benzodiazepines are so addictive

Question 10

What are examples of opiods

Answer 10

Codeine, Heroin, Methadone, Oxycodone

Question 11

What is the mechanism of action of opiods

Answer 11

1. Heroin reaches the brain and becomes morphine
2. Morphine will interact with kappa, delta and mu receptors
3. This causes decreased release of GABA
4. The lower amount of GABA= less inhibition→ causes flood of dopamine to enter the cortex- relaxed feeling

Question 12

What is the mechanism of withdrawal from opioids

Answer 12

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

Question 13

What is the MOA of methamphetamine

Answer 13

methamphetamine causes release of all stored dopamine→ dopamine transporters move dopamine into synaptic cleft→ interacts with all receptors

Question 14

Does ecstasy cause release of dopamine

Answer 14

NO- ecstasy works by blocking serotonin re-uptake, causing high levels of serotonin in synaptic cleft→ causes a relaxed feeling of euphoria

Question 15

What is the MOA of cocaine

Answer 15

blocks dopamine reuptake transporter and floods the synapse with dopamine

Question 16

What is the mechanism of withdrawal from cocaine

Answer 16

1. Dopamine amine transporter expression increases
2. The number of postsynaptic dopamine receptors decreases
3. 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

Question 17

What are some ways of monitoring what drugs are being used in the community

Answer 17

1. Sewage monitoring
2. Needle/syringe program
3. Hospitalisations/coronial inquest

Question 18

What are some factors that drive people to drug use

Answer 18

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

Question 19

What are the 3 ‘reductions’ of the National Drug Strategy

Answer 19

1. Supply reduction= police decreasing availability of drugs in the community
2. Harm reduction= Harm minimisation through safe injecting rooms/syringe programs
3. Demand reduction= School based education programs

Question 20

What are the 4 different routes of administration- what are their slang terms

Answer 20

Oral= Drop it
Inhalation= Chase it
Injection= Boot it
Rectal= Shaft it

Question 21

If a patient presents to the ED after taking a drug, why is it important to know what route was taken

Answer 21

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

Question 22

What are the 5 patterns of drug use (pyramid)

Answer 22

1. Dependent
2. Regular
3. Recreational
4. Occasional
5. Experimental

Question 23

At what stage of the patterns of drug use is acute harm most likely to occur and why

Answer 23

Experimental phase- this is where people have less tolerance to a drug and less education- allows for easy overdose

Question 24

With drug use, what are the 3 categories of acute harm

Answer 24

1. Social- broken relationships, employment issues, child protection, issues with the law
2. Physical- overdose, loss of consciousness, IV drug use harm
3. Mental- psychosis, aggression, anxiety, depression

Question 25

What kind of diseases can result due to IV drug use

Answer 25

Injection injury= vasospasm, embolic events, vessel rupture
Secondary disease= septicaemia, endocarditis, infection, organ failure, embolus
Blood borne disease= HIV, HEP C, HEP B

Question 26

Rhabdomyolysis, MI, Stroke, renal failure and seizures are due to which type of drug class- stimulants or depressants

Answer 26

Stimulants

Question 27

Respiratory failure, Aspiration, Hypoxix brain injury, Leukoencephalities and seizures are due to which type of drug class- stimulants or depressants

Answer 27

Depressants

Question 28

What 5 types of harm are due to chronic drug use

Answer 28

• 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

Question 29

What are the 9 physiological steps of dependence

Answer 29

1. Exposure to substance with abuse potential (can cross BBB, can activate reward pathway)
2. Positive aspects of neurochemical activation outweigh negative aspects in the individual
3. Environmental context is conducive to repeated use
4. Repeated use results in receptor adaptation (function or number)
5. Downstream neurological function alters to adjust for receptor adaptation (homeostasis)
6. Same amount of drug produces less physiological response-more drug required for equal outcome-tolerance
7. Tolerance fuels desire for more drugs to achieve same outcome
8. ‘Normal’ function now requires increased levels of binding (presence of the drug)-dependence
9. Removal of substance produces adverse effects-withdrawal

Question 30

Why is it important to use psychotherapy in addiction treatment

Answer 30

Allows the person to deal with underlying trauma/things that drove them to using drugs and to then develop coping strategies and resilience

Question 31

When quitting a drug, what are the 4 ways in which cessation of the drug can be achieved (4 S’s)

Answer 31

Stop= cold turkey- way most people do it
Soothe= provide symptomatic relief to withdrawal symptoms
Swap=  substitute therapies 
Slow= controlled gradual reduction

Question 32

What are some advantages and disadvantages of rehab- ‘detox’

Answer 32

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

Question 33

What are the pharmacotherapies for alcohol

Answer 33

Withdrawal= thiamine with diazepam/oxazepam
Stopped but dependent= naltrexone (opiate antagonist), acamprosate (GABA agent, anti-craving) or disulfam (alcohol dehydrogenase antagonist)
Long term= thiamine

Question 34

What are the pharmacotherapies for opiates

Answer 34

• 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

Question 35

Why is buprenorphine given with naloxone

Answer 35

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

Question 36

What are the pharmacotherapies for nicotine

Answer 36

• 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.