Opioids Flashcards
2 opioid structures
phenanthrene
benzylisoquinolines
Opiate
term used to designate drugs derived from opium
Opioid
all substances;
natural & synthetic
that bind to opioid receptors and produce agonist effect
Opioid classification
Natural occurring
–Morphine
Semisynthetic analogs of morphine
- –Heroine
- –codeine
- –Hydromorphone [[Dilaudid]]
Synthetic
–Exogenous [[4 groups]]
4 types of synthetic opioids
[[exogenous]]
Morphinan derivatives
Diphenyl derivative
Benzomorphans
**Phenylpiperdines
believed that synthetic opioids; [[exogenous]] mimic the activity of endogenous [[naturally occurring; enkephalins, endorphins and dynoprhins]] at the opioid receptors
Morphinan derivative
type of synthetic opioid [[exogenous]]
- Levorphenol
- Butorphenol
becoming popular to use for withdrawal
Diphenyl Derivative
type of synthetic opioid [[exogenous]]
- METHADONE
used for withdrawal; but can get addicted to methadone
Benzomorphans
type of synthetic opioid
[[exogenous]]
- Phenazocine
- Pentazocine
PHENYLPIPERDINES
type of synthetic opioid [[exogenous]]
OR DRUGS
- Meperidine [[demerol]]
- Fentanyl
- Alfentanil
- Sufentatil
- Remifentanyl
Opioid receptor activity classification
Agonist
Partial Agonist
Mixed agonist/ antagonist
Antagonist
Agonist
full mu receptor effects
partial agonist
Regardless of dose can not produce full mu receptor effects like morphine
Buprenorphine
mixed agonist/ antagonist
agonist at other opioid receptor [[kappa or delta]] but antagonist at mu receptor
ex. Nalbuphine ; reverses resp. depression
[[agonist at kappa; antagonist at mu]]
Antagonist
inhibits mu receptor activity
ex. Naloxone [[Narcan]]
reverses opioid
Opiate Receptors
mu [[mu1 and mu2]]
kappa
delta
3 endogenous agonists
[[naturally occurring]]
Enkephalins
endorphins
dynorphins
Opioid and pain modulating systems
- ANTInociceptive; down regulates pain receptors
- Inhibits excitatory neurotransmitters [[Substance P]]
Mu 1
Supraspinal [[BRAIN]] Analgesia
Euphoria
Miosis [[pupil constriction]]
Bradycardia [[DIRECT action on vagus nerve]]
Urinary Retention
ALL endogenous and exogenous [[synthetic]] opioids work on Mu1
Mu 2
SPINAL analgesia
Physical Dependence
hypoventilation
Constipation
All endogenous [[natural]] and exogenous [[synthetic]] agonists act on Mu2
Mu receptors
Primarily in the CNS;
Brain and Spinal cord
some periphery
Mu1
Mu2
ALL endogenous [[naturally occurring]] and exogenous [[synthetic]] agonists act on Mu receptors
Bradycardia
Mu1 effect
DIRECT effect on Vagus nerve
Kappa receptors
ONLY Dynorphins work on KAPPA
Supraspinal[[Brain]] and spinal Analgesia
Dsyphoria [[Dynorphins, kappa]]
Sedation
Miosis [[constricted pupils]]
Diuresis
Delta
ONLY Enkephalins work on DELTA
Supraspinal [[Brain]] and spinal Analgesia
hypoventilation
physical Dependance
constipation and urinary retention
Opioids on G coupled opioid receptors
-Suppression/ inhibition of neurotransmitter [[substance P]]
-decreases adenylyl cyclase; cAMP
presynaptic
postsynaptic
G alpha i; decreases cAMP
[[increased conductance of K –> hyperpolarizes; decreases Ca into cell]]
Fentanyl in your epidural
makes a denser block
2 mechs of action
LA; block transmission via VGNaC
opioid activity on Mu receptors but mostly Mu2 [[ spinal analgesia; M2]]
Explain the mechanism of action of Opioids
opioids work on G alpha i opioid receptors
G alpha i
decreased cAMP
increases K conductance
[[hyperpolarizes]]
increased K out of the cell
hyper polarizes the cell and inhibits VGCa and decreases Ca into the cell
*when you have pain Ca is sent into the cell and releases NT [[substance P]] signals pain
by increasing K conductance and hyperpolarizing the cell it decreasing Ca into cell and decrease the release of pain NT
decreasing nociceptive [[pain]] receptor activity
Activation of Receptors can be
Direct; directly decreases neurotransmission
[[decreases Ca into cell]]
inhibits the release of excitatory NT [[substance P]]
Opioids onset of action
higher % not protein bound
higher % unionized
^faster onset of action
all opioids are weak bases
B + B = nonionized!
B + A = ionized
[[pt is acidotic pH under 7.35; will need a larger dose; more ionized]]
only unionized and not protein bound can diffuse
Anomaly Opioid
Sufentanil
20% nonionized
93% protein bound
NOT Highly nonionized and highly protein bound
[[would think it would be a weaker; slow onset]]
BUT 1000x stronger than morphine
VERY diffuse-able [[partition coeff. 1727]]
*attributed to molecule size/ structure
Drugs in potency order
most potent to least
Sufentanil
Remifentanil
Fentanyl
Alfentanil
Dilaudid
Morphine
Demerol
more potent; smaller dose
Factors that alter pharmacokinetics of Opioids
Age
-neonates; give less [[decrease rate of elimination; bc immature CYP 450]]
-elderly; give less
[[weaker BBB]]
Weight
dose based on ideal body weight [[not actual]]
Renal Failure
decrease dose
Hepatic failure
decrease dose
^both kidney and liver failure will effect metabolism and elimination oof opioid
DECREASE DOSE
Spinal Analgesia
analgesia produces by receptor activation in the spinal cord and dorsal root ganglion
pain [[sensory; afferent; approaching; dorsal root ganglion to the dorsal horn of gray matter –> laminae II and III]]
pain signals synapses in the substantial gelatenosa [[laminae II & III]]
Direct stimulation of these receptors produces intense analgesia [[pain relief]]
how?
Gi; decrease cAMP; increase K conductance; decrease Ca into cell decrease/ inhibit release of substance P [[pain NT]]; decreases activity at nociceptive [[pain]] receptors
Mu2 and kappa and delta
Supraspinal [[BRAIN]] Analgesia
analgesia produced by receptor activation in the BRAIN [[periaquaductal/ periventricular gray matter]]
Mu1 and kappa and delta