Exam #01b (Opiates & Opioids) Flashcards
A peripheral nerve for the reception and transmission of painful stimuli is called what?
Nociceptor
What is the difference between perception and modulation?
Perception is the brains INTERPRETATION of a stimulus
Modulation is the bodies or drugs EFFECT ON PERCEPTION
This type of drug reversibly depresses neuronal function, producing analgesia, amnesia, and akinesia (loss of power of voluntary movement)?
Anesthetics
This type of drug, in moderate doses, dulls the senses, relieves pain, and induces sleep but in excessive doses causes stupor, coma, or convulsion?
Narcotics
True or False - opioid analgesics reduce the perception of pain WITHOUT a loss of consciousness?
True
What is the principle alkaloid extracted from opium poppy? What is extracted to a lesser extent?
Morphine (and to a lesser extent codeine)
What was opium historically used for?
constipating action
What is the principle alkaloid in the other poppy plant where opioid drugs are derived from?
Thebaine
True or False - thebaine is a convulsant drug that produces NO ANALGESIA and NOT USED CLINICALLY?
True - it’s an important synthetic intermediate in the production of semi-synthetic opioids
True or False - morphine has a high addiction liability?
True
What therapeutic effect is common to opioids acting at both mu and kappa receptors?
analgesia
What major difference in side effects is noted between mu and kappa opioid receptors?
binding at MU - produces EUPHORIA
binding at KAPPA - produces DYSPHORIA
Binding at which opioid receptor subtype is responsible for the following SE: constipation, respiratory depression?
mu
Explain the MOA of morphine binding to a mu receptor?
- morphine binds to mu receptor (7TM-GPCR) on a presynaptic terminal
- activates INHIBITORY G-protein (Gi)
- decrease in adenylate cyclase activity
- decreased [cAMP]
- leads to decreased Ca2+ influx at presynaptic terminal
- which results in decreased NT release (glutamate, substance P, etc.) and hyperpolarized pain afferent
- decreased pain fiber activity
Morphine also binds to mu receptor (7TM-GPCR) on a postsynaptic terminal which goes through the same pathway above, except it increases K+ efflux rather than decreasing Ca2+ influx. It still results in decreased pain transmission
List the (6) indications for opioids?
- moderate to severe pain (analgesia)
- cough (antitussive)
- diarrhea (antidiarrheal)
- acute pulmonary edema
- anesthesia
- addiction (ex. methadone)
Name the (2) opioid agents used as antidiarrheals (generic and brand)?
- Loperamide (Imodium)
2. Diphenoxylate + atropine (Lomotil)
Why is atropine added to Diphenoxylate in the drug Lomotil for treatment of diarrhea?
Atropine is an antimuscarinic that is added in a low dose to limit abuse of the drug
Which antitussive is a mu receptor agonist, but is NOT considered an opioid?
Dextromethorphan
Name the (4) pharmacophoric requirements of most opioid analgesics (“Morphine Rule”)?
- tertiary N with small alkyl substituent
- quaternary carbon adjacent to aromatic ring
- phenyl group directly attached to quaternary carbon
- 2 carbon spacer between quaternary carbon and tertiary N
True or False - the tetrahydrofuran ring is optional for morphine and related drug activity?
True
True or False - full agonist opioids (morphine, hydromorphone, oxymorphone, & oxycodone) ALL do not have a ceiling effect so if you increase the dose, you increase the analgesic effect?
True - they’re dose is only limited to their SE
True or False - morphine is more potent parenterally than orally?
True
True or False - Phase II metabolism (conjugation) of morphine can lead to both more potent and inactive metabolites?
True - glucuronide on right is more potent AND glucuronide on left is inactive
Give indications for each of the following opioids:
- Codeine
- Hydrocodone
- Oxycodone
- antitussive
- moderate pain
- moderate - severe pain
Name the (2) Morphinans and their unique structural change compared with morphine?
- Levorphanol (Levo-Dromoran) - mu agonist
- Butorphanol (Stadol) - mixed kappa agonist/
mu antagonist
Ring “E” (epoxide bridge) is missing
Name the (1) Benzomorphan opioid that is missing ring E and C?
Pentazocine (Talwin Nx) –> added Naloxone to try and reduce abuse potential
Name (2) Oripavine opioids that are derived from Thebaine? Which one is too potent for humans and primarily used in veterinary setting?
- Buprenorphine
2. Etorphine (Veterinarian drug)
Name the (2) mu-antagonists structurally related to morphine that are used to reverse opioid OD?
- Naloxone
- Naltrexone
They look like morphine and even have features that increase potency but have no intrinsic activity at mu receptors
Name the (3) ultra-short duration analogs of fentanyl used in anesthesia?
- Sufentanyl
- Alfentanyl
- Remifentanyl
True or False - fentanyl is a short duration mu agonist?
True - but by using different dosage forms (ie patch) duration is much longer
Tapentadol, a weak mu agonist related to Tramadol is primarily an inhibitor of what?
NE reuptake
Tramadol produces analgesia from what (2) MOA? What is Tramadol’s indication?
- weak mu agonist
- weak inhibitor of 5-HT and NE reuptake
Used for mild to moderate pain
True or False - Tramadol has little constipation and respiratory depression effects?
True - b/c it is only a weak mu agonist
What (2) AE are associated with Tramadol?
- increase incidence of seizure
2. increase incidence of serotonin syndrome
True or False - the (+) enantiomer of Tramadol is more effective than the (-) enantiomer and therefore that is what is marketed and sold?
False - the racemic mixture of Tramadol is superior to any single enantiomer
Name the (7) AE associated with opioid use?
- Dysphoria (individual-situational dependent, from kappa receptor binding
- Sedation
- Respiratory depression
- Cough supression
- Miosis (pinpoint pupils)
- N&V - worse during ambulation
- Constipation
What type of drug is the recommended initial treatment of RA? What is added to control symptoms? What is the typical specific drug mentioned in the first question given to treat RA?
Diseaes-modifying anti-rheumatic drugs (DMARD)
NSAID with or without a corticosteroid to control symptoms
Methotrexate
What is the first line biological agent prescribed after inadequate response from a DMARD to treat RA?
Tumor necrosis factor (TNF) inhibitors
