Lecture 12 & 13: Opioid addiction: Case Study & Chemistry Flashcards
What is the definition of an opioid addiction?
- A cluster of physiological, behavioural and cognitive phenomena, when use of an opioid has higher priority than other behaviours
What is the difference between opioid and opiate?
- Opioid: Umbrella term. Either natural or man made. Binds to opioid receptors in the brain. Can be agonist, partial agonist or antagonist
- Opiate: Naturally ocurring derived from natural source only (morphine, codeine, heroin)
How many days limited use should OTC opioids have?
- Codeine should be limited to no more than 3 day use
What are some patient risk factors with prescription opioids that can indicate opioid dependence?
- Depression, anxiety
- Previous history of alcohol/ substance misuse
- Previous history of opioid misuse
What are some drug risk factors with prescription opioids that can indicate opioid dependence?
- High doses
- Multiple opioids
- Multiple formulations of opioids
- More potenjt opioids
- Concurrent benzodiazepines
What are 5 practical steps to reduce high dose opioids?
- Education
- Engagement: Give patient choice
- Effective weaning plan: need agreement
- Emotional impact: Manage anxiety and depression (offer antidepressant if nec/ signpost)
- Expectations: Is difficult and may need support
What are the potencies of codeine, dihydrocodeine, oxycodone and tramadol comapred to morphine?
- Codeine: 100mg of codeine = 10mg of morphine (0.1)
- Dihydrocodeine = 0.1
- Oxycodone = 6.6mg = 10 mg of Morp (1.5)
- Tramadol = 0.1
What are some other risk factors for opioid dependence?
- Long term prescribing for non camcer conditions
- Emotional trauma, reports of concern
- Refusal for other treatment, not attend appointments
- Repeated seeking of med
- Taking doses more than prescribed. Alcohol misuse
- Appearing sedated
What are some tapering or withdrawal tips?
- Consider other non-pharmacological options for pain management
- Encourage and prepare
- Incremental taper of existing drug
- Consider conversion to methadone or buprenorphine
- Consider drug/alcohol services
- Dose of drug can be tapered 10% weekly or 2 weeks
What are some opioid withdrawal signs?
- Shivers
- Diarrhoea
- Difficulty sleeping
- Sweating
- Widespread or increased pain
- Body aches
- Irritability
- N & V
What should happen when the patient is on opioid substitution therapy and they have acute pain?
- Ongoing reassurance
- OST doesnt provide analgesia, only manages withdrawal
- Opioids for analgesia need to be prescribed in addition to maintenance regimen
- Likely to tolerate effects so larger doses are required
- Should be prescribed more on top - careful of CNS depression
What should happen if the patient is on methadone and have acute pain?
- Split the dose and adminster 2 or 3 times daily
- Titrate additional analgesia to effect
What should happen if the patient is on buprenorphine (administered sublingually) and have acute pain?
- Split the dose and administer 2 or 3 times daily
- Titrate additional analgesia or discontinue and provide alternative analgesia or change to methadone
Which opioid is compared to in opioid tolerance?
- Morphine
How does supervised methandone work in practice?
- Only methadone mixture should be used
- Observe patient
- Be aware of avoidance tactics
- Offer water
- Designated area for supervision
- Identity confirmed
- Usually 3 months minimum
What are the risks of long term opioid use?
- Serious bodily harm, overdose or death
- Hormone changes (infertility)
- Drowsiness
- Increased risk of physical dependence
- Decreased immune function
- Poor muscle tone
- Increased risk of falls
- Depression & anxiety
- Dry mouth
What are the features of the blood brain barrier?
BBB is a specialized structure that protects the brain and allows essential nutrients to pass.
* Endothelial Cell Tight Junctions: Line the brain’s blood vessels are tightly packed, preventing substances from passing.
* Selective Permeability: Only certain molecules to cross, such as glucose and amino acids, while blocking others (toxins and pathogens).
* Transport Mechanisms: Specific transporters for essential nutrients (e.g., glucose transporter) and efflux pumps (e.g., P-glycoprotein) to remove potentially harmful substances.
* Astrocytic End-Feet: Have extensions that envelop the blood vessels, providing support and signaling.
* Basement Membrane: Extracellular matrix layer provides structural support and permeability.
What are the main mechanisms for BBB penetration?
- **Passive Diffusion: **Small, lipophilic molecules (gases) can diffuse across.
* Facilitated Diffusion: Some larger or polar molecules, like glucose and AA, use specific transporter proteins - Active Transport: Sodium-glucose transporter actively transports glucose into the brain.
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Receptor-Mediated Transcytosis: Specific molecules can bind to receptors on the surface of endothelial cells, triggers endocytosis. insulin and certain growth factors
* Paracellular Transport: Inflammation, the tight junctions between endothelial cells can become more permeable, allowing some substances to pass through.
What are the molecular attributes for CNS penetration?
- Higher Log P: lipophilicity
- Fewer H-bond donors
- Fewer rotatable bonds (more rigid)
- Most CNS drugs contain an amine
What are some analogues to morphine?
- Oxycodone
- Dihydrocodeine
- Diamorphine
- Hydrocodone
- Codeine
What is in the structure of morphine and what are their main effects on opioid receptors?
- 5 rings
- Tertiary amino group
- Activity: mu (analgesia), kappa (analgesia/sedation), delta (analgesia favoured by enkephalins)
What is the structure activity relationship of morphine to the receptor?
- Amine nitrogen: Protonated, charged and forms ionic bond. Negatively charged receptor and positive charge on amine
- Phenol: H bonded to receptor
- Aromatic ring: Van der waals interaction, defined interaction (pie-pie)
- Change substituents to get different analgesic activity
What are some physico chemical properties of morphine (both physical and chemical)
- Morphine and hydrate are sparingly soluble in water
- Morphine is a weak base it can produce salts with strong acids (HCL, H2SO4) produces hydrochloride and sulfate salts
- Salts are 300x more soluble
How is diamorphine synthesized from morphine?
- Treated with acetic anhydride or acetyl chloride. Adds 2 acetyl (ester) groups
