Opioid abuse

• Opiate receptors - located in the CNS, in peripheral tissues
• Endogenous agonists (ligands): endorphins, enkephalins, dynorphin (peptides)

Opiate CNS Effects

Stimulation of opiate receptors

• μ – respiratory depression, supraspinal analgesia, physical dependence
• κ – spinal analgesia, miosis
• δ – spinal analgesia, euphoria, sometimes dysphoria
• ε – supraspinal analgesia
• σ – mydriasis, dysphoria

Agonists

• morphine, codeine, heroin,...
• methadone, pethidine, der. fentanyl, …

Antagonists

• naloxone, naltrexone, nalorphine, levalorphan, ….

Agonists/Antagonists

• buprenorphine, pentazocine, …

Opiate Peripheral Effects

• reduced mobility in the gastrointestinal tract (constipation)
• vascular hypotonia (hypotension)
• bladder hypertonia (urinary retention)

Chronic abuse

• Development of tolerance - adaptation of receptor density (?)
• Reduced tolerance to respiratory depression
• In a state of drug withdrawal:

– hypersensitivity of adapted neurons

– unpleasant peripheral vegetative effects

Therapy

• "Harm reduction" programs: exchange of syringes and needles
• "Substitution programs" - the ultimate goal should be abstinence
• Replacement of heroin addiction with another drug (methadone, buprenorphine),
• Suppression of withdrawal symptoms, reduction of euphoric feelings by administration p.o.

Opioid Agents

Opium

• dried juice from unripe poppies "Papaver somniferum"

Papaver somniferum

• is contained in:

- morphine 4-30%

- codeine 0.3-3%

- noscapine, narcotine 4–10%

- papaverine 1-1.5%

- thebaine 0.2-1%

Heroin

File:Heroin.jpg

Heroin

• diacetylmorphine – "pro-drug" of morphine

– morphine transporter to the brain

– easier to penetrate membranes

– labile, deacetylates easily

• 6-monoacetylmorphine' and morphine 6-glucosiduronate are active metabolites

Abuse

• Usual doses of heroin: 10-15 mg/day
• With tolerance up to 2 g/day
• Symptoms: euphoria, lethargy, miosis, respiratory depression, bradycardia, hypotension, depression to coma, possible death
• Addicts report 4 stages after a heroin high (i.v. injection):

1. High – kick
2. well-being, happiness,
3. composure,
4. "abstract".

Causes of Death

• respiratory depression
• aspiration of vomit
• pulmonary edema
• rarely anaphylactic shock (hypersensitivity)
• heroin leukoencephalopathy (inflammation of the white matter of the brain)

Links

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