Opiates

Question 1

opium origin

Answer 1

• somniferum: somni = sleep
• poppy plant, papaver
• morphine, morpheus: god of dreams
• dreamy euphoria
• pain relief

Question 2

natural opiates

Answer 2

• codeine

- morphine

Question 3

semi-synthetic opiates

Answer 3

• heroin

- slightly altered in lab

Question 4

synthetic opiates

Answer 4

• fentanyl
• very powerful: used for anaesthesia
• “china white”: illegal version

Question 5

history of opiates and opium

Answer 5

• ancient times: joy plant
• sumarians and assyrians
• ancient egypt, greece, rome (medical use)
• islam: arab traders (substitute for alcohol)
• india and china: from arab traders (can’t tolerate alcohol, introduced smoking opiates)
• europe: war, trade, exploration

Question 6

drug use in the 1800’s

Answer 6

• widespread through europe and usa
• few restrictions on sale and supply
• no prescription needed
• cure many aliments: panacea
• high degree of addiction
• new methods of administration: smoking (chinese), injections (civil war, soldiers disease)
• opium wars (britain vs. china)
• opium did not produce aggression or violence: no urge to ban
• kept the poor quiescent
• late 1800’s: heroin = 2x potent in brain
• Harrison Narcotics act 1914
• controlled drugs act 1970

Question 7

modern medical use

Answer 7

• pain relief / analgesia: main medical use
• diarrhea: loperamide (oral rehydration therapy is more common)
• cough suppression: codeine linctus (suppresses coughing center in the brain: dry cough)

Question 8

abuse of prescription opiates

Answer 8

• oxytocin

- when doc stops prescribing, already addicted patients turn to illegal opioids

Question 9

Morphine standart

Answer 9

• standard by which others are measured
• analgesia value of 1
• more potent: heroin (2), oxycodone (1.5)
• equipotent: hydrocodone
• less potent: codeine (10x weaker)
• fentanyl: 100x more potent

Question 10

pain and pain relief

Answer 10

• important warning / survival mechanism

- stimilus (nociceptors) > pain pathways > spinal cord > perceived in the brain (cortex)

Question 11

brains response to pain

Answer 11

• release endorphins: endogenous opioid peptides (small protein)
• natural pain-killers
• analgesia and well-being

Question 12

endorphins

Answer 12

• natural pain-killers
• inhibitory neurotransmitters
• bind to post-synaptic opiate receptos via signal transdoction pathway
• open potassium channels, K+ exit the cell
  = hyperpolarization (very negative charge inside the cell, very unlikely to reach threshold)
  = post-synaptic inhibition
  = inhibit pain signal
  = inhibit the perception of pain in the cortex

Question 13

opiates and endorphines

Answer 13

• morphine and other opiates: structurally similar to endorphins (mimic natural endorphins)
• are agonists at the endorphin (opiate) receptor
• opiates inhibit pain transmission
• CNS depressants
• analgesia and sleepiness

Question 14

opiate receptors

Answer 14

• 3 main receptors: µ, κ, δ
• morphine and heroine: µ receptor
• µ- receptor associated with euphoria
• κ-receptor: dysphoric effects, thought to balance out euphoric effects of endorphins in vivo (otherwise one would become addicted to pain)
• κ-receptors: new target for pain-relief therapies, that are not addictive

Question 15

pharmacokinetics: absorption

Answer 15

• oral
• inhalation
• intranasal: not so much
• subcutaneous injection:
• intramuscular injection: slower than IV, but constant release, painful
• intravenous: veins get damaged over time (collapsed veins)

Question 16

Addicts: progression in injection

Answer 16

1. inject right under the skin: subcutaneous
2. intramuscular
3. IV: problem with sharing needles
   - life expectancy for IV addict: 1 year

Question 17

chasing the dragon

Answer 17

don’t want to heat heroin up too much: slang term for right heating

Question 18

distribution

Answer 18

• body organs, including brain
• morphine poorly penetrated BBB
• heroin (diacetylmorphine): more lipidic = penetrates BBB more easily, once in brain it is converted to morphine

Question 19

metabolism and excretion

Answer 19

• liver metabolism
• urine excretion
• 90% excreted within 1 day
• traces detectable for 2-4 days
• more or less 4 h action and 8 h to be removed

Question 20

opiates addictive

Answer 20

• euphoria, rush, well-being, dopamine release: limbic system
• GABA: inhibitory effect on dopamine release in parts of the mesolumbic system (opening of gaba receptors: Cl- flows in: hyperpolarization)
• opiates inhibit GABA release
• inhibit an inhibitory NT: enhance dopamine release
• morphine prevents release of GABA, therefore GABA can’t prevent dopamine release anymore
• µ- receptor associated with euphoria
• addictive effect because of euphoria from dopamine release

Question 21

acute effects: opiates

Answer 21

• euphoria (rush)
• drowsiness, heavy limbs, vivid dream-like experiences
• body warmth
• intense introversion and impaired social interaction
• choice of drug use can depend on personality type
• CNS depressant
• respiratory depression (less than 12 bpm, drug not administered in clinical setting)
• cognitive impairment
• cough suppression
• nausea, vomiting: built tolerance to this
• constipation: more water absorption, no tolerance to this
• pin-point pupils: very small pupils

Question 22

toxicity

Answer 22

• more or less 4000 † per year
• CNS depressant: severe respiratory depression: less than 12 bpm
• coma > death
• clinical manifestations: coma, respiratory depression, pinpoint pupils (toxic triad for opioid use)

Question 23

chronic effects: opiates

Answer 23

• abusers: short life span (overdose, infections)
• 100x more likely to die
• infection and disease: HIV (25% of IV users): virus attacks white blood cells
• drug overdose: narrow therapeutic index, mix of CNS depressants
• criminal activity
• opiate abuse during pregnancy: developmental delays
• higher risk for stroke, embolism: dirt that clogs the veins
• hepatitis: inflammation of liver: spread through needles
• dead skin: due to loss of blood vessels
• neumonias: due to cough suppression
• respiratory infection
• endocarditis: heart infections

Question 24

opioid interactions

Answer 24

• synergism with other CNS depressants
• anxiolytics (benzodiazepines), alcohol
• potentiation of CNS depression

Question 25

tolerance and withdrawal

Answer 25

- chronic users: steadily increase the dose - fast tolerance to increased respiratory depression - fast tolerance to pain, euphoria and nausea: dose has to keep increased - no tolerance to constipation - withdrawal: motivation for drug use switches from positive to negative reinforcement to avoid withdrawal symptoms

Question 26

opiate withdrawal symptoms: phase 1

Answer 26

- flu like symptoms - 8-12 h after last dose - runny nose and eyes - sweat, increased blood pressure - irritability, depression, anxiety, tremor - hypersensitivity: pain receptors were blocked for a long time that the body increased pain receptors

Question 27

opiate withdrawal symptoms: phase 2

Answer 27

- cold turkey - peaks after 48-72 hours - more severe early symptoms - pupil dilation, anorexia, piloerection, spasm - can be so severe that patients die - ease through with benzodiazepines

Question 28

treating withdrawal

Answer 28

- no treatment - any opiate drug - detoxification with methadone (another opioid, but does not produce a high) - high risk of relapse (90% within 6 months), especially when returning to the same environment

Question 29

abuse of opiates

Answer 29

- prescription opioids - heroin - fentanyl: 100x more powerful than morphine, schedule II

Question 30

opioid epidemic

Answer 30

- illegal opioids - prescription opiates - death: overdose - hepatitis c and bacterial endocarditis

Question 31

prescription opiates

Answer 31

- fuelling the opioid epidemic - vicodin: painkiler + opioid (particulary addictive) - oxycontin: oxycodone: purdue pharma (market that it was a safe drug, not creating addiction and working 12h instead of 8. doctors felt safe prescribing them but al turns out to be false and a bunch of patients were addicted)

Question 32

opioid epidemic and pharma industry

Answer 32

- slick marketing: no one should feel pain - lax regulations: FDA and legislators weren't as strict with them because they were financially benefiting by licensing them - doctors and patients - over-prescription - turn to the black market: cheaper, easier

Question 33

response to opioid epidemic

Answer 33

- addiction treatment: methadone - access to naltrexone - tamper-proof formulations: turn into gel when combined with water, impossible to inject - drug monitoring programs - lower prescriptions: try to only prescribe while hospitalized (3-8 days, after 8 days high risk of addiction)

Question 34

methadone

Answer 34

- equipotent to morphine - orally active: avoid needle problems - long acting: less doses a day needed - acute: cope with physical withdrawal - maintenance: wear patients off slowly (MMT: methadone maintenance therapy) - addicts don't like methadone because they don't get the rush and euphoria, less addictive - used to wear addicts off of opioids - when not enough opioids in the body

Question 35

opioid antagonist

Answer 35

- naltrexone - binds to the opioid receptors but do not activate them - compete with opioids for the receptors: blocking the effects - to reverse respiratory depression induced by opioid overdose - ADR's: reversal of analgesia, increased BP, tremors, hyperventilation, rapid pulse - when there is too much opioids in the system