opioid pharm
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- opiates
- agent derived from opium
- opioids
- all agents acting on morphine receptors, including antagonists
- opioid receptors
-
1) mu
2) delta
3) kappa
4) sigma
5) epsilon - opioid receptors all belong to what?
- G protein-coupled class of receptors
- What are endogenous ligands for opioid receptors?
- peptides (with varying affinities for each receptor type)
- opioid receptor activity
-
1) inhibitory
2) decreasing intracellular cAMP
3) excitatory (very low doses) - excitation of G stimulatory protein will cause what?
-
1) increase activity of AC (adenylyl cyclase) and cAMP
2) increase protein kinase A
3) decrease K conductance
4) increase Ca conductance
5) increase action potential
6) increase transmitter release
7) excitatory effects - inhibition of G(i)
- decrease the activity of adenylyl cyclase/cAMP
- inhibition of G(o)
-
1) increase K conductance
2) decrease Ca conductance
3) decrease action potential
4) decrease transmitter release
5) inhibitory effects - 1) mu receptor
-
1) analgesia
2) resp. depression
3) euphoria
4) miosis
5) physical dependence
6) decreased GI motility - 2) kappa receptor
-
1) supraspinal analgesia
2) sedation
3) dysphoria (psychoses) - 3) delta receptor
- analgesia (spinal?)
- 4) sigma receptor
-
1) dysphoria
2) hallucinations - 1) mu receptor locations
-
1) brainstem
2) medial thalamus
3) some in spinal cord - 2) kappa receptor locations
-
1) mainly in the dorsal horn of the SC
2) some in the brainstem medullary reticular formation - 3) delta receptor locations
- mainly in the limbic system
- 4) sigma receptor locations
- mainly in the hippocampus and amygdala of the limbic system
- endogenous opioids derived from what?
- precursor polypeptides
- polypeptides include:
-
1) endorphines
2) dynorphines
3) enkephalins - polypeptides deffer in chain length, but share:
- same first few AA's (61-65)
- Is endomorphine polypeptide?
-
No, it is TETRApeptide
newly discovered
mu receptor selective - endogenous opioids act as:
-
1) NTM
2) neuromodulators
3) neurohormones
4) body's pain modulators - ~65% of opioid receptor homology exists among:
-
1) mu
2) delta
3) kappa - analgesia mediated via receptors located in the:
-
1) dorsal horn of SC
2) periaqueductal gray matter
3) thalamus - ventral brainstem receptors mediate effects on:
-
1) coughing
2) vomiting
3) respiration
4) pupillary diameter - hypothalamus controls what?
- neuroendocrine functions
- limbic system controls what?
- mood and behavioral effects
- peripheral mu receptors associated with:
- GI tract
- 4 primary interaction of opioid ligands with opioid receptors:
-
1) agonist
2) antagonist
3) partial agonist
4) mixed agonist/antagonist - partial agonist
- binds to the receptor, but produces less than maximal response
- mixed agonist/antagonist
- binds to more than one type of opioid receptor, acting as an agonist at one, and an antagonist at others
- central opioid effects
-
1) neuronal activity - <
2) analgesia
3) resp. depression
4) mood alteration
5) sedation
6) miosis
7) N/V
8) antitussive
9) endocrine (inhibits LHRH secretion) - peripheral opioid effects
-
1) histamine release
2) venous dilation
3) smooth muscle contraction
4) inhibition of Ach release - common opioid uses:
-
1) analgesia
2) pre-op sedation
3) anesthesia
4) epidural
5) diarrhea
6) cough suppression
7) opioid addiction withdrawal
8) opioid overdose (antagonist) - major opioid SE
-
1) resp. depression
2) N/V
3) hypothermia
4) constipation
5) histamine release
6) muscular rigidity - muscular regidity is due to:
- inhibition of dopamine release in the striatum (Parkinson-like)
- ADME of the opioids
-
1) most are well absorbed from GI tract
2) large 1st-pass metabolism (PO)
3) most distributes well
4) most cross placenta well - excretion of the opioids mainly via:
- renal and biliary mechanisms of metabolized forms
- opioid agonists #1
-
1) morphine (MS contin)
2) hydromorphone (Dilaudid)
3) Oxymorphone (Numorphan)
4) Codeine (Tylenol with Codeine)
5) Hydrocodone (Vicodine)
6) Oxycodone (Oxycontin) - opioid agonists #2
-
1) Heroin
2) Levorphanol (Levo-Deomoran)
3) Dextromethophan (Dimetane)
4) Meperidine (Demerol)
5) Methadone (Dolophine)
6) Propoxyphene (Darvon) - opioid agonists #3
-
1) Fentanyl (Sublimaze)
2) Sufentanil (Sufenta)
3) Alfentanil (Alfenta) - morhine is natural alkaloid from:
- Papaver somniferum
- morphine acts primarily at:
- mu receptors (some kappa)
- morphine develop
- rapid tolerance
- heroin
-
1) diacetylmorohine
2) semisynthetic
3) easily prepared from morphine
4) twice as potent as morphine
5) enters CNS rapidly, cause euphoria
6) not approved for clinical use - Codeine
-
1) 1/10 potency of morphine
2) little risk of addiction or resp. depression
3) partially converted to morphine in the body
4) potent antitussive - Oxycodone (Oxycontin)
-
1) twice as potent as morphine
2) high euphoric liability
3) 160 mg, extended release tab. - widely abused (Hillbilly Heroin)
4) many deaths linked to chewing the extended release form - Levorphanol (Levo-Dromoran)
-
1) very potent synthetic morphine analgesic congener (5X)
2) less constipating
3) longer lasting - Dextromethorphan (Dimetane)
-
1) a dextro-rotary isomer
2) no analgesic activity
3) effective antitussive - Meperidine (Demerol)
-
1) most widely used synthetic congener
2) 1/10 as potent as MS
3) shorter duration - Why Meperidine frequently abused?
- because it does not cause miosis, hard to detect
- Meperidine are metabolized to :
-
Normeperidine
1) CNS stimulant
2) potential Sz with renal pt - Meperidine are contraindicated with:
- MAOI therapy
- Methadone (Dolophine)
-
1) same potency as MS
2) less sedation than MS
3) longer duration of action (slower elimination)
4) used to counter withdrawal symptoms - Propoxyphene (Darvon)
-
1) structurally r/t MS
2) less than 1/10 as potent as MS
3) properties similar to other opioid - concern for Propoxyohen (Darvon)
- questions have been raised concerning it's benefit in dose strengths found in most products
- Fentanyl (Sublimaze)
-
1) chemically r/t meperidine
2) ~80X as potent as MS
3) continuous epidural
4) transdermal analgesia - advantage of Fentanyl is:
- it's short half-life of redistribution (12.5 min)
- potency of Fentanyl
-
1) Sufentanil (800X)
2) Fentanyl (80X)
2) Remifentanil (80X)
4) Alfentanil (20X) - Remifentanil (Ultiva)
-
selective mu-receptor agonist
(almost 100 % at mu-receptor) - Remifentanil differs from other Fentamyl derivatives by having:
-
an ester-linkage
1) short duration due to hydrolysis by non-spe. esterases
2) rapid recovery - opioid antagonists act by blocking:
- mu receptors mainly (some kappa blockade)
- opioid antagonists block:
-
1) analgesic
2) respiratory
3) euphoric
4) miosis
5) hypotension
6) smooth muscle actions of opioids
7) endogenous beta-endorphine
8) enkephalins - clinical use of opioid antagonists:
- to reverse opioid-induced resp. depression and in the Tx of "addicts"
-
Naltrexone (Trexan)
Nalmefene (Revex) -
1) similar with Narcan
2) longer half-life
3) given orally - Buprenorphine (Buprenex)
-
1) partial opioid agonist
2) shares structural components of Codeine and Naltrexone
3) binds to mu receptors, and elicits a weaker maximal response - use of Buprenorphine
-
1) less abuse potential
2) to conteract Heroin and Morphine addiction without causeing fullblown withdrawal symptoms -
1) Nallorphine (Nalline)
2) Levallorphan (Lorfan) -
1)mixed opioid agonist/antagonists
2) mu receptor antagonists
3) kappa receptor weak agonists -
1) Nallorphine (Nalline)
2) Levallorphan (Lorfan)
block: - block mu receptor mediated analgesia and euphoria
-
1) Nallorphine (Nalline)
2) Levallorphan (Lorfan)
stimulate: - kappa induced analgesia and sedation
- large doses of Nallorphine and Levallorphan may cause:
- dysphoria and hallucinations
- Pentazocine (Talwin) and Nalbuphine (Nubain)
- have similar actions, but are stronger kappa mediated analgesics
- Tramadol (Ultram)
-
1) newer analgesices
2) structural similarities to opioids and NSAIDs
3) analgesic strength similar to Codeine-Acetaminophen agents - Tramadol (Ultram) acts to block re-uptake of:
- serotonin and NE in central synapses, which then decreases pain info transmission in the brain
- both the parent compound and an active metabolite of Tramadol have:
- weak affinity for mu receptors, but their analgesic effect is not entirely reversed by Naloxone
- Tramadol (Ultram) can cause:
-
1) dizziness
2) sedation
3) Sz
4) hallucinations - neuroleptic anesthesia: Butyrophenone
-
1) Droperidol - D2 blocker with antiemetic
2) Opioid (ex. Fentanyl)
3) N2O
4) used in dental office - New therapeutic possibilities
-
1) use of peptide-type receptor agonists for pain relief (designed to target specific receptor sub-types)
2) transplantation of adrenal medullary chromaffin cells into the spinal subarachnoid space - transplantation of adrenal medullary chromaffin cells
-
1) secrete opioid peptides
2) to provide long-term pain relief to chronic pain sufferes w/o exogenous opioid SE's