Opioids Flashcards
What is Pain?
Pain is a subjective symptom or an unpleasant sensory and/or emotional experience that is typically associated with actual or potential tissue damage from mechanical or thermal causes or disease
Which ascending tract sends information about pain and temperature
Spinothalamic tract
Where does the descending pain-inhibitory pathway originate
The midbrain
A-delta and C fibers terminate in the ______ ____ of the spinal cord and transmit _______ and ______ pain
Dorsal horn; somatic; visceral
Describe the descending pathways
- Originate in the periaqueductal gray region of the midbrain and nuclei of the rostro-ventral medulla
- Project to dorsal horn and release norepinephrine, serotonin and enkephalin
- Inhibit the activity of ascending pain pathways
What are the endogenous opioid peptides
Endorphins
Enkephalin
Dynorphins
Three major classes of opioid receptors (g-protein coupled receptors)
Mu receptor
Kappa receptor
Delta receptor
Mu receptor
Endogenous ligands:
Drugs:
Endogenous ligands: Enkephalins, β-endorphin
Drugs: Morphine, fentanyl, methadone, meperidine, oxycodone, buprenorphine,
Kappa receptor
Endogenous ligands:
Drugs:
Endogenous ligands: Dynorphins
Drugs: Nalbuphine, butorphanol and pentazocine
Delta receptor
Endogenous ligands:
Drugs:
Endogenous ligands: Enkephalins
Drugs: none
Localization of opioid receptors
Found in the periaqueductal gray, dorsal horns of spinal cord, medulla and hypothalamus - also peripheral organs such as GI system and heart
Mu and delta receptors in limbic areas may be involved in ______ _______
Drug dependence
Kappa receptors in limbic structures may be involved in ______ actions of kappa agents
dysphoric
Narcotic
A term used to refer to morphine like drugs and some other abused substances - drugs that produce a stuporous sleeplike state and may or may not be analgesic
Opiates
Drugs that are derived from opium or have a morphine like pharmacological profile
Opioid
Refers to all opiates, agonist-antagonists and endogenous peptides
Which drugs undergo extensive first pass metabolism
Morphine and naloxone
Which opioid drugs are activated by metabolism
Codeine and heroin
Duration of action is related to both _______ and _______ _____
Lipohilicity; elimination rate
Effects of Opioid agonists
1) Analgesia (alleviating pain)
2) Cough suppression
3) Antidiarrheal effect and constipation (mu receptors on GI nerves)
4) Euphoria
5) Sedation
6) Respiratory depression (side effect) - decrease in the sensitivity of chemoreceptors in brainstem to CO2
7) Nausea
8) Endocrine Effects
9) Miosis (Edinger Westphal nucleus)
Which drugs are less efficacious in alleviating pain
Codeine and propoxyphene
Which opioids are used for cough suppression
Codeine, hydrocodone and dextromethorphan
What are the endocrine effects of opioids
- Decreased release of LH - mu receptor
- ADH secretion is increased by mu stimulation and decreased by Kappa stimulation
Opioid agonists (8)
1) Oxycodone
2) Codeine
3) Morphine
4) Heroin
5) Hydrocodone
6) Methadone
7) Fentanyl
8) Meperidine
Morphine Receptor: Oral to Parenteral ratio: Administration: Duration of analgesia:
Receptor: mu agonist
Oral to Parenteral ratio: 3 or 4 to 1
Administration: Available in injectable, oral, oral sustained release and suppository forms - sustaine release preparation
Duration of analgesia: 4-5 hours
Heroin
More _____ than Morphine
Converted to ______ and ______
Abuse potential:
More lipophilic than Morphine
Converted to 6-mono-acetyl morphine and morphine
Abuse potential: High
Codeine, Hydrocodone and Oxycodone
Which of these does not reach morphine like efficacy?
These drugs are often used in combination with what?
Which of these drugs are available as sustained release preparations?
Codeine;
NSAIDS or acetaminophen;
Oxycodone and Hydrocodone
Methadone Receptor: Duration of action: Administration (most common): Use:
Receptor: mu agonist
Duration of action: longer than morphine
Administration (most common): has good oral availability
Use: treatment of opioid abuse and chronic pain
Meperidine - a phenylpiperidine
Duration of action:
What does this drug form:
Interactions:
Duration of action: shorter duration of analgesia than morphine
What does this drug form: forms toxic metabolite, normeperidine, that can accumulate with frequent use
Interactions: with MAO inhibitors
Fentanyl - structurally related to meperidine Receptor: Duration of action: Potency in comparison to morphine: Availability:
Receptor: mu agonist
Duration of action: short acting - 1-1.5 hours
Potency in comparison to morphine: 100 x as potent
Availability: injectable form and as transdermal patches
How potent is Hydromorphone compared to morphine
2-3 X as potent
Mixed-Action Agonist/Antagonist (2)
1) Nalbuphine
2) Buprenorphine
Nalbuphine Receptors: Efficacy: Abuse potential: Availability:
Receptors: mu antagonist and kappa agonist
Efficacy: similar to morphine
Abuse potential: low
Availability: only in injectable form
Buprenorphine
Receptors:
Use:
Administration:
Receptors: Partial mu agonist
Use: Treatment of moderate to severe pain
Administration: Oral or patch
Opioid Antagonists (2)
1) Naloxone
2) Naltrexone
Naloxone Receptors: Administration: Duration of action: Use:
Receptors: High affinity for mu receptors, less for kappa and delta
Administration: greater activity parenterally than orally
Duration of action: 1 to 2 hours (short)
Use: Treat opioid overdoses - decrease parenteral abuse liability
Naltrexone
Administration:
Use:
Administration: Orally active with long half life
Use: Treatment of alcoholism and opiate addiction
Dextromethorphan
dextro isomer of levorphanol. Antitussive, but not analgesic. Also is an NMDA antagonist
Tramadol
Weak mu agonist - also blocks NE and 5-HT uptake
- Used for mild to moderate pain
- Available for oral use including a sustained release preparation
Tolerance of Opioids
Tolerance develops to most of the effects of the opioids
- Rapid = emetic action
- Moderate Rate = analgesic, respiratory, euphoria and endocrine effects
- Little or no tolerance - constipation and miosis
Cross tolerance
Physical dependence on opioids
Continuous exposure to opioids results in development of physical dependence. When drug administration is stopped, the body functions abnormally
Symptoms of withdrawal based on time 6-12 hours: 12-24 hours: 24-27 hours: Later:
6-12 hours: Drugs seeking behavior; restlessness, lacrimation, rhinorrhea
12-24 hours: Restless sleep for several hours; irritability, tremor, dilated pupils, anorexia
24-27 hours: Increased intensity of above, plus weakness, depression, nausea - possible electrolyte imbalance
Later: Above symptoms alternate with restless sleep with gradual decrease in activity – Delayed growth and development in infants born to addicted mothers may be detected for up to 1 year
Signs of Opioid abuse
1) Euphoria
2) Craving
3) Drug-seeking behavior
4) Withdrawal
Treatment of opioid abuse:
1) Methadone
2) Suboxone
3) Naltrexone
