Understanding Narcotic Analgesics and Opiates: History, Mechanisms, and Uses

 
NARCOTIC ANALGESICS- I
NARCOTIC ANALGESICS- I
 
Blanton
Blanton
Narcotic
Narcotic
- refers to narcosis-
- refers to narcosis-
stupor or somnolence
stupor or somnolence
 
Opiate/ Opioid-
Opiate/ Opioid-
 refers to
 refers to
analgesia
analgesia
 
Graphic Photos Of Overdosed Adults With Child In
Car Put Ohio Heroin Epidemic In Spotlight
 
HISTORY
HISTORY
 
Opium Poppy
Opium Poppy
 
Papaver somniferum
Papaver somniferum
 
 
-Opium = crude extract
-Opium = crude extract
 
-Morphine = purified constituent
-Morphine = purified constituent
from Morpheus-Greek god of dreams
from Morpheus-Greek god of dreams
 
Uses of Opiates
Uses of Opiates
 
 
-Analgesia
-Analgesia
-
-
Preanesthetic Medication (sedative)
Preanesthetic Medication (sedative)
-Pulmonary Edema
-Pulmonary Edema
-Anesthesia
-Anesthesia
-Spinal Analgesia
-Spinal Analgesia
-Cough
-Cough
-Diarrhea
-Diarrhea
-Recreation
-Recreation
 
 
 
Opioid Compounds
Opioid Compounds
 
 
-Extracts of Opium- 
-Extracts of Opium- 
morphine,
morphine,
codeine, papaverine, etc
codeine, papaverine, etc
 
-Synthetic Opioids-
-Synthetic Opioids-
 Agonists,
 Agonists,
Antagonists, Mixed Agonist/
Antagonists, Mixed Agonist/
Antagonists
Antagonists
 
-Opiopeptins
-Opiopeptins
- 
- 
-endorphin,
-endorphin,
Enkephalins, Dynorphin
Enkephalins, Dynorphin
 
 
 
 
Morphine Derivatives
Morphine Derivatives
Agonists
Agonists
- substitutions: at 3, 6, 17
- substitutions: at 3, 6, 17
positions.
positions.
Antagonists
Antagonists
- substitutions:
- substitutions:
At 17 position (or at 14)
At 17 position (or at 14)
 
Opiates- Phamarmacology
Opiates- Phamarmacology
 
Mechanism(s) of Action
Mechanism(s) of Action
 
-*mu receptor
-*mu receptor
-kappa receptor
-kappa receptor
-delta receptor
-delta receptor
-N/OFQ- nociceptin,
-N/OFQ- nociceptin,
-Orphanin FQ
-Orphanin FQ
 
Opiates- Mechanisms
Opiates- Mechanisms
 
 
-G-protein coupling
-G-protein coupling
 
-Inhibition of cAMP formation
-Inhibition of cAMP formation
 
(1) Activation of K
(1) Activation of K
+
+
 channels
 channels
            (postsynaptic)
            (postsynaptic)
 
-Hyperpolarization of Neuron
-Hyperpolarization of Neuron
 
 
Opiates- Mechanism
Opiates- Mechanism
 
(2) Inhibition of VG Ca++ channels
(2) Inhibition of VG Ca++ channels
                                  
                                  
(presynaptic)
(presynaptic)
-Depression of Neurotransmitter
-Depression of Neurotransmitter
Release:
Release:
 -NE, DA
 -NE, DA
 -5-HT
 -5-HT
 -ACh
 -ACh
 -Substance P
 -Substance P
 
Endogenous Ligands
Endogenous Ligands
 
Morphine and Related Ligands
Morphine and Related Ligands
 
Peptides:
Peptides:
    -Proopiomelanocortin-POMC:
    -Proopiomelanocortin-POMC:
     
     
endorphins
endorphins
    -Proenkephalin A:
    -Proenkephalin A:
enkephalins
enkephalins
    -Proenkephalin B:
    -Proenkephalin B:
dynorphins
dynorphins
 
Endogenous Ligands
Endogenous Ligands
 
CNS and Nonnervous Tissues
CNS and Nonnervous Tissues
 
POMC: CNS
POMC: CNS
- pain areas
- pain areas
Pituitary, and Pancreas
Pituitary, and Pancreas
 
Proenkephalin A, B
Proenkephalin A, B
: CNS-
: CNS-
Widespread: pain, behavior,
Widespread: pain, behavior,
motor, autonomic
motor, autonomic
 
Endogenous Peptides
Endogenous Peptides
 
 
Differential Processing of
Differential Processing of
Precursors = Different Peptide
Precursors = Different Peptide
Products in Tissues
Products in Tissues
 
Opiates- CNS Effects
Opiates- CNS Effects
 
Analgesia (mu receptors)
Analgesia (mu receptors)
 
 
-
-
change perception of pain
change perception of pain
 
 
-change reaction to pain
-change reaction to pain
 
 
-raise threshold for pain
-raise threshold for pain
-decrease nociceptive pain greater
-decrease nociceptive pain greater
 
 
than neuropathic pain
than neuropathic pain
 
Opiates- Analgesia
Opiates- Analgesia
 
-Dull pain
-Dull pain
-Severe pain
-Severe pain
 
-Drowsiness
-Drowsiness
-Impairment- variable
-Impairment- variable
-Antagonism of Opiate Side
-Antagonism of Opiate Side
 Effects
 Effects
 
 
Mechanisms of Analgesia
Mechanisms of Analgesia
 
Ascending Pathways-
Ascending Pathways-
 
 
spinothalamic tract
spinothalamic tract
 
Descending Pathways-
Descending Pathways-
 
 
bulbospinal pathways
bulbospinal pathways
 
Synergy of Two Pathways
Synergy of Two Pathways
 
Opiates- CNS Effects
Opiates- CNS Effects
 
Ventral Tegmentum
Ventral Tegmentum
 
 
Euphoria
Euphoria
-
-
 
 
 
 
mu and delta receptors
mu and delta receptors
Dysphoria
Dysphoria
-
-
 
 
kappa receptors
kappa receptors
 
Opiates- CNS Effects
Opiates- CNS Effects
 
Alter Hypothalamic Heat
Alter Hypothalamic Heat
Regulatory Mechanism
Regulatory Mechanism
 
Neuroendocrine (mu)-
Neuroendocrine (mu)-
Decrease LH, FSH, ACTH,
Decrease LH, FSH, ACTH,
-endorphin
-endorphin
Increase Prolactin, ADH
Increase Prolactin, ADH
 
Opiates- CNS Effects
Opiates- CNS Effects
 
Miosis-  (mu and kappa)-
Miosis-  (mu and kappa)-
Stimulation of PNS innervation
Stimulation of PNS innervation
of pupil
of pupil
 
Convulsions- (mu, kappa,delta)-
Convulsions- (mu, kappa,delta)-
High concentrations, inhibition
High concentrations, inhibition
of GABA release
of GABA release
 
Opiates- CNS Effects
Opiates- CNS Effects
 
Antitussive Effects-  Depression
Antitussive Effects-  Depression
of medullary cough centers
of medullary cough centers
 
Nausea and Vomiting-
Nausea and Vomiting-
Stimulation of CTZ
Stimulation of CTZ
 
Opiates- Respiration
Opiates- Respiration
 
Therapeutic Concentrations
Therapeutic Concentrations
-Concentration Dependent
-Concentration Dependent
-Reduction in rate, minute
-Reduction in rate, minute
 volume, and tidal exchange
 volume, and tidal exchange
 
Few Clinical Problems
Few Clinical Problems
* Exception: respiratory disease,
* Exception: respiratory disease,
coadministration of respiratory
coadministration of respiratory
depressants
depressants
 
 
Opiates- Respiration
Opiates- Respiration
 
Suppression of Brainstem
Suppression of Brainstem
1) Centers that control rhythm
1) Centers that control rhythm
2) Centers that sense pCO
2) Centers that sense pCO
2
2
 
Hypoxic Stimulation Intact-
Hypoxic Stimulation Intact-
O
O
2
2
 ---> apnea
 ---> apnea
 
Opiates- Bronchoconstriction
Opiates- Bronchoconstriction
 
Histamine release
Histamine release
-CNS depression of respiration
-CNS depression of respiration
-CNS suppression of cough reflex
-CNS suppression of cough reflex
 
Caution
Caution
: asthma, cor pulmonale
: asthma, cor pulmonale
COPD
COPD
 
Opiates- Cardiovascular
Opiates- Cardiovascular
 
Therapeutic Concentrations
Therapeutic Concentrations
-Supine Position
-Supine Position
-Little Effects on bp, rate, rhythm
-Little Effects on bp, rate, rhythm
 
-Supine --> Standing Position
-Supine --> Standing Position
 peripheral vasodilation
 peripheral vasodilation
 decreased peripheral resistance
 decreased peripheral resistance
 inhibition of baroreceptor reflex
 inhibition of baroreceptor reflex
 
Opiates- CSF
Opiates- CSF
 
May Increase CSF Pressure
May Increase CSF Pressure
 
Contraindicated in head injury,
Contraindicated in head injury,
intracranial lesions
intracranial lesions
 
Opiates- GI Effects
Opiates- GI Effects
 
Inhibitory actions
Inhibitory actions
-Delay gastric emptying
-Delay gastric emptying
-Delay passage through small
-Delay passage through small
 and large intestines
 and large intestines
-Increase anal sphincter tone
-Increase anal sphincter tone
-Decrease defecation reflex
-Decrease defecation reflex
-Constipation
-Constipation
 
Opiates- Miscellaneous
Opiates- Miscellaneous
 
-Contraction of the bile duct
-Contraction of the bile duct
and sphincter of Oddi
and sphincter of Oddi
 
-Renal/Bladder Function
-Renal/Bladder Function
Depressed
Depressed
 
-Labor Prolonged
-Labor Prolonged
 
Tolerance
Tolerance
 
 
High Degree
High Degree
   
   
None
None
Analgesia
Analgesia
   
   
Miosis
Miosis
Euphoria
Euphoria
   
   
Constipation
Constipation
Dysphoria
Dysphoria
   
   
Convulsions
Convulsions
Mental Clouding
Mental Clouding
  
  
Antagonist
Antagonist
Sedation
Sedation
     
     
Actions
Actions
Resp. Depression
Resp. Depression
N & V
N & V
Cough Supression  
Cough Supression  
Moderate
Moderate
 Bradycardia
 Bradycardia
 
Study Guide
Study Guide
 
Know:
Know:
1) Uses of Opioids
1) Uses of Opioids
 
2) Classes of Opioids- Agonists,
2) Classes of Opioids- Agonists,
   Antagonists, etc.
   Antagonists, etc.
 
3) Receptors associated with opiates-
3) Receptors associated with opiates-
    mu vs kappa vs delta-
    mu vs kappa vs delta-
   
   
What functions do they serve?
What functions do they serve?
 
Study Guide
Study Guide
 
4) Opiate analgesia- characteristics
4) Opiate analgesia- characteristics
 
5) Effects of opiates on GI tract
5) Effects of opiates on GI tract
    function, respiration,cardio-
    function, respiration,cardio-
    vascular function, cough
    vascular function, cough
 
 
NARCOTIC ANALGESICS- II
 
 
Opiates- Pharmacokinetics
Opiates- Pharmacokinetics
 
Routes:
Routes:
PO, SL, Nasal, Rectal, Dermal
PO, SL, Nasal, Rectal, Dermal
IV, IM
IV, IM
 
First Pass Effect- (PO)- High
First Pass Effect- (PO)- High
for  Morphine 
for  Morphine 
(25% of the oral dose
(25% of the oral dose
is bioavailable)
is bioavailable)
 
Opiates- Pharmacokinetics
Opiates- Pharmacokinetics
 
 
IV Route
IV Route
more lipophilic- more penetrance
more lipophilic- more penetrance
of BBB
of BBB
 
Morphine- poor penetrance
Morphine- poor penetrance
Fentanyl- redistribution
Fentanyl- redistribution
 
Opiates- Pharmacokinetics
Opiates- Pharmacokinetics
 
 
Metabolism of Morphine
Metabolism of Morphine
 
Glucuronidation of the 3 or 6- OH
Glucuronidation of the 3 or 6- OH
 
Morphine 6-Glucuronide is a
Morphine 6-Glucuronide is a
 potent analgesic
 potent analgesic
 
Patient Controlled Analgesia
Patient Controlled Analgesia
 
-Automated Device- delivery of opiate
-Automated Device- delivery of opiate
for postoperative pain, cancer pain, or
for postoperative pain, cancer pain, or
other conditions
other conditions
 
-Device programmed for dose and
-Device programmed for dose and
interval between doses
interval between doses
 
Opiate Use and Dyspnea
Opiate Use and Dyspnea
 
Pulmonary Edema-
Pulmonary Edema-
Left Ventricular Failure
Left Ventricular Failure
 
Reduction in fear/anxiety
Reduction in fear/anxiety
 
Reduction in peripheral
Reduction in peripheral
resistance
resistance
 
Strong Agonists
Strong Agonists
 
Phenanthrene Class
Phenanthrene Class
 
Morphine
Morphine
Oxycodone
Oxycodone
Heroin
Heroin
 -
 -
More Potent
More Potent
 -Better Access to BBB
 -Better Access to BBB
 
 
-
-
Does not bind to opiate receptor itself. Is
Does not bind to opiate receptor itself. Is
metabolized to morphine (the active agent)
metabolized to morphine (the active agent)


 
Strong Agonists
Strong Agonists
 
Phenylheptylamine Class
Phenylheptylamine Class
 
Methadone
Methadone
-similar analgesic action as morphine
-similar analgesic action as morphine
-better bioavailability than morphine
-better bioavailability than morphine
-analgesic and addiction therapy
-analgesic and addiction therapy
 
Strong Agonists
Strong Agonists
 
Phenylpiperidine Class
Phenylpiperidine Class
 
Meperidine 
Meperidine 
(meh-pehr-ih-deen)
(meh-pehr-ih-deen)
-less potent but higher availability
-less potent but higher availability
 than morphine
 than morphine
-antimuscarinic actions
-antimuscarinic actions
-less constipating
-less constipating
-not antitussive
-not antitussive
-no effects on labor
-no effects on labor
 
 
Strong Agonists
Strong Agonists
Phenylpiperidine Class
Phenylpiperidine Class
Fentanyl/Sufentanil 
Fentanyl/Sufentanil 
(sue-fen-tuh-nil)
(sue-fen-tuh-nil)
-analgesia >> morphine
-analgesia >> morphine
-short duration
-short duration
-useful in anesthesia
-useful in anesthesia
-postoperative analgesia
-postoperative analgesia
 
Moderate Agonists
Moderate Agonists
 
Phenanthrene Class
Phenanthrene Class
 
Codeine
Codeine
-less potent than morphine
-less potent than morphine
-10% metabolized to morphine-
-10% metabolized to morphine-
  accounts for analgesia!
  accounts for analgesia!
 
-oral- with aspirin or acetaminophen
-oral- with aspirin or acetaminophen
 
-antitussive in its own right
-antitussive in its own right
 
 
Moderate Agonists
Moderate Agonists
 
Phenylheptylamine Class
Phenylheptylamine Class
 
Propoxyphene (
Propoxyphene (
pro-pox-ee-feen; 
pro-pox-ee-feen; 
Darvon)
Darvon)
-related to methadone
-related to methadone
 
-potency between  aspirin and codeine
-potency between  aspirin and codeine
 
-no antitussive effect
-no antitussive effect
 
 
Mild Agonists
Mild Agonists
 
Phenylpiperidine Class
Phenylpiperidine Class
 
Diphenoxylate/Loperamide
Diphenoxylate/Loperamide
(die-fen-ox-ih-late/ low-pehr-uh-mide)
(die-fen-ox-ih-late/ low-pehr-uh-mide)
-not analgesic
-not analgesic
-low abuse potential
-low abuse potential
-antidiarrheal activity
-antidiarrheal activity
 
Agonist/Antagonists- Mixed
Agonist/Antagonists- Mixed
 
Developed for analgesia
Developed for analgesia
with less liability
with less liability
 
kappa agonists
kappa agonists
 
mu antagonists or
mu antagonists or
 
 
weak agonists
weak agonists
 
Pentazocine 
Pentazocine 
(Mixed)
(Mixed)
(pen-taz-oh-seen)
(pen-taz-oh-seen)
 
kappa agonist
kappa agonist
mu agonist/antagonist
mu agonist/antagonist
 
Comparison with
Comparison with
Morphine:
Morphine:
-Less potent, addictive liability
-Less potent, addictive liability
-Precipitates withdrawal
-Precipitates withdrawal
-Similar respiratory depression
-Similar respiratory depression
 
Butorphanol
Butorphanol
 (Mixed)
 (Mixed)
(byoo-tore-fan-ahl)
(byoo-tore-fan-ahl)
 
-Similar to Pentazocine
-Similar to Pentazocine
-kappa agonist
-kappa agonist
-mu antagonist
-mu antagonist
 
-More potent than morphine
-More potent than morphine
-Increases in cardiac workload
-Increases in cardiac workload
 
 
 
Buprenorphine
Buprenorphine
(byoo-pre-nore-feen)
(byoo-pre-nore-feen)
 
-Partial mu agonist
-Partial mu agonist
-kappa antagonist?
-kappa antagonist?
 
-More potent than morphine
-More potent than morphine
-Can precipitate withdrawals
-Can precipitate withdrawals
-
-
Addictive Liability, 
Addictive Liability, 
but good analgesic with reduced
but good analgesic with reduced
potential for abuse
potential for abuse
!
!
 
Uses of Opioid Antagonists
Uses of Opioid Antagonists
 
1)  narcotic poisoning
1)  narcotic poisoning
 
2)  reduce side effects in opioid
2)  reduce side effects in opioid
    anesthesia
    anesthesia
 
3)  reverse neonatal respiratory
3)  reverse neonatal respiratory
    depression
    depression
 
4)  opioid addiction treatment
4)  opioid addiction treatment
 
5)  alcoholism treatment
5)  alcoholism treatment
 
Naloxone
Naloxone
 
 
-Rapid Acting
-Rapid Acting
 
-Short Duration
-Short Duration
 
 
Multiple Doses
Multiple Doses
 
Naltrexone
Naltrexone
 
-Orally Effective
-Orally Effective
 
-Treatment for Alcoholism
-Treatment for Alcoholism
 
-Liver Dysfunction
-Liver Dysfunction
 
Naloxegol (Movantik)PEGylated-Naloxone
Naloxegol (Movantik)PEGylated-Naloxone
 
 
-
-
Peripherally acting mu receptor antagonist
Peripherally acting mu receptor antagonist
(PEGylated form of naloxone- does not penetrate
(PEGylated form of naloxone- does not penetrate
the  blood brain barrier)
the  blood brain barrier)
 
-
-
oral treatment for opioid-induced
oral treatment for opioid-induced
constipation in adults with chronic non-
constipation in adults with chronic non-
cancer pain (FDA approved 2014).
cancer pain (FDA approved 2014).
 
Opiate Toxicity
Opiate Toxicity
 
Triad
Triad
 
 
-
-
Pinpoint Pupils
Pinpoint Pupils
 
 
-LOW Respiratory Rate
-LOW Respiratory Rate
 
 
-Stuporous --> Comatose
-Stuporous --> Comatose
 
Death- Respiratory Failure
Death- Respiratory Failure
 
Treatment of Poisoning
Treatment of Poisoning
 
-Maintain airway
-Maintain airway
 
-Reverse the respiratory effects
-Reverse the respiratory effects
  with opiate antagonists
  with opiate antagonists
 
-Monitor carefully-  be aware
-Monitor carefully-  be aware
 of other sedatives on board
 of other sedatives on board
 
Misc.  
Misc.  
Dextromethorphan
Dextromethorphan
 
-Isomer of levorphanol
-Isomer of levorphanol
 
-NOT
-NOT
 active at opioid receptors
 active at opioid receptors
 
-Antitussive- Acts at central
-Antitussive- Acts at central
 cough receptors
 cough receptors
 
-OTC drug
-OTC drug
 
 
Study Guide
Study Guide
 
1)  Drug List- Know whether drug is
1)  Drug List- Know whether drug is
     agonist, mixed agonist/antagonist,
     agonist, mixed agonist/antagonist,
     antagonist (
     antagonist (
drugs listed in lecture
drugs listed in lecture
script and ppt
script and ppt
)
)
 
2)
Know uses and limitations of the
Know uses and limitations of the
   drugs 
   drugs 
NO
NO
 structures, chemical
 structures, chemical
classes
classes
 
Study Guide
Study Guide
 
3)
Know the signs of opiate poisoning
Know the signs of opiate poisoning
    and the treatment, including
    and the treatment, including
antagonists
antagonists
.
.
 
 
FIRST AID
FIRST AID
BASIC SCIENCES
BASIC SCIENCES
2
2
nd
nd
 Edition
 Edition
Chaper 5, pp 406-407; Chapter 6, pp 519-520;
Chaper 5, pp 406-407; Chapter 6, pp 519-520;
536
536
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Delve into the world of narcotic analgesics and opiates, exploring the history of opium poppy, morphine derivatives, opioid compounds, and the pharmacology mechanisms of action. Discover the uses of opiates in analgesia, preanesthetic medication, and more, alongside the endogenous ligands involved. Gain insights into the mechanisms of opiates and their impact on neurotransmitter release and neuronal hyperpolarization.


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  1. NARCOTIC ANALGESICS- I Blanton Narcotic- refers to narcosis- stupor or somnolence Opiate/ Opioid- refers to analgesia

  2. Graphic Photos Of Overdosed Adults With Child In Car Put Ohio Heroin Epidemic In Spotlight

  3. HISTORY Opium Poppy Papaver somniferum -Opium = crude extract -Morphine = purified constituent from Morpheus-Greek god of dreams

  4. Uses of Opiates -Analgesia -Preanesthetic Medication (sedative) -Pulmonary Edema -Anesthesia -Spinal Analgesia -Cough -Diarrhea -Recreation

  5. Opioid Compounds -Extracts of Opium- morphine, codeine, papaverine, etc -Synthetic Opioids- Agonists, Antagonists, Mixed Agonist/ Antagonists -Opiopeptins- -endorphin, Enkephalins, Dynorphin

  6. Morphine Derivatives Agonists- substitutions: at 3, 6, 17 positions. Antagonists- substitutions: At 17 position (or at 14)

  7. Opiates- Phamarmacology Mechanism(s) of Action -*mu receptor -kappa receptor -delta receptor -N/OFQ- nociceptin, -Orphanin FQ

  8. Opiates- Mechanisms -G-protein coupling -Inhibition of cAMP formation (1) Activation of K+ channels (postsynaptic) -Hyperpolarization of Neuron

  9. Opiates- Mechanism (2) Inhibition of VG Ca++ channels (presynaptic) -Depression of Neurotransmitter Release: -NE, DA -5-HT -ACh -Substance P

  10. Endogenous Ligands Morphine and Related Ligands Peptides: -Proopiomelanocortin-POMC: endorphins -Proenkephalin A:enkephalins -Proenkephalin B:dynorphins

  11. Endogenous Ligands CNS and Nonnervous Tissues POMC: CNS- pain areas Pituitary, and Pancreas Proenkephalin A, B: CNS- Widespread: pain, behavior, motor, autonomic

  12. Endogenous Peptides Differential Processing of Precursors = Different Peptide Products in Tissues

  13. Opiates- CNS Effects Analgesia (mu receptors) -change perception of pain -change reaction to pain -raise threshold for pain -decrease nociceptive pain greater than neuropathic pain

  14. Opiates- Analgesia -Dull pain -Severe pain -Drowsiness -Impairment- variable -Antagonism of Opiate Side Effects

  15. Mechanisms of Analgesia Ascending Pathways- spinothalamic tract Descending Pathways- bulbospinal pathways Synergy of Two Pathways

  16. Opiates- CNS Effects Ventral Tegmentum Euphoria- Dysphoria- mu and delta receptors kappa receptors

  17. Opiates- CNS Effects Alter Hypothalamic Heat Regulatory Mechanism Neuroendocrine (mu)- Decrease LH, FSH, ACTH, -endorphin Increase Prolactin, ADH

  18. Opiates- CNS Effects Miosis- (mu and kappa)- Stimulation of PNS innervation of pupil Convulsions- (mu, kappa,delta)- High concentrations, inhibition of GABA release

  19. Opiates- CNS Effects Antitussive Effects- Depression of medullary cough centers Nausea and Vomiting- Stimulation of CTZ

  20. Opiates- Respiration Therapeutic Concentrations -Concentration Dependent -Reduction in rate, minute volume, and tidal exchange Few Clinical Problems * Exception: respiratory disease, coadministration of respiratory depressants

  21. Opiates- Respiration Suppression of Brainstem 1) Centers that control rhythm 2) Centers that sense pCO2 Hypoxic Stimulation Intact- O2 ---> apnea

  22. Opiates- Bronchoconstriction Histamine release -CNS depression of respiration -CNS suppression of cough reflex Caution: asthma, cor pulmonale COPD

  23. Opiates- Cardiovascular Therapeutic Concentrations -Supine Position -Little Effects on bp, rate, rhythm -Supine --> Standing Position peripheral vasodilation decreased peripheral resistance inhibition of baroreceptor reflex

  24. Opiates- CSF May Increase CSF Pressure Contraindicated in head injury, intracranial lesions

  25. Opiates- GI Effects Inhibitory actions -Delay gastric emptying -Delay passage through small and large intestines -Increase anal sphincter tone -Decrease defecation reflex -Constipation

  26. Opiates- Miscellaneous -Contraction of the bile duct and sphincter of Oddi -Renal/Bladder Function Depressed -Labor Prolonged

  27. Tolerance High Degree Analgesia Euphoria Dysphoria Mental Clouding Sedation Resp. Depression N & V Cough Supression Moderate Bradycardia Miosis Constipation Convulsions Antagonist None Actions

  28. Study Guide Know: 1) Uses of Opioids 2) Classes of Opioids- Agonists, Antagonists, etc. 3) Receptors associated with opiates- mu vs kappa vs delta- What functions do they serve?

  29. Study Guide 4) Opiate analgesia- characteristics 5) Effects of opiates on GI tract function, respiration,cardio- vascular function, cough

  30. NARCOTIC ANALGESICS- II

  31. Opiates- Pharmacokinetics Routes: PO, SL, Nasal, Rectal, Dermal IV, IM First Pass Effect- (PO)- High for Morphine (25% of the oral dose is bioavailable)

  32. Opiates- Pharmacokinetics IV Route more lipophilic- more penetrance of BBB Morphine- poor penetrance Fentanyl- redistribution

  33. Opiates- Pharmacokinetics Metabolism of Morphine Glucuronidation of the 3 or 6- OH Morphine 6-Glucuronide is a potent analgesic

  34. Patient Controlled Analgesia -Automated Device- delivery of opiate for postoperative pain, cancer pain, or other conditions -Device programmed for dose and interval between doses

  35. Opiate Use and Dyspnea Pulmonary Edema- Left Ventricular Failure Reduction in fear/anxiety Reduction in peripheral resistance

  36. Strong Agonists Phenanthrene Class Morphine Oxycodone Heroin -More Potent -Better Access to BBB -Does not bind to opiate receptor itself. Is metabolized to morphine (the active agent)

  37. Strong Agonists Phenylheptylamine Class Methadone -similar analgesic action as morphine -better bioavailability than morphine -analgesic and addiction therapy

  38. Strong Agonists Phenylpiperidine Class Meperidine (meh-pehr-ih-deen) -less potent but higher availability than morphine -antimuscarinic actions -less constipating -not antitussive -no effects on labor

  39. Strong Agonists Phenylpiperidine Class Fentanyl/Sufentanil (sue-fen-tuh-nil) -analgesia >> morphine -short duration -useful in anesthesia -postoperative analgesia

  40. Moderate Agonists Phenanthrene Class Codeine -less potent than morphine -10% metabolized to morphine- accounts for analgesia! -oral- with aspirin or acetaminophen -antitussive in its own right

  41. Moderate Agonists Phenylheptylamine Class Propoxyphene (pro-pox-ee-feen; Darvon) -related to methadone -potency between aspirin and codeine -no antitussive effect

  42. Mild Agonists Phenylpiperidine Class Diphenoxylate/Loperamide (die-fen-ox-ih-late/ low-pehr-uh-mide) -not analgesic -low abuse potential -antidiarrheal activity

  43. Agonist/Antagonists- Mixed Developed for analgesia with less liability kappa agonists mu antagonists or weak agonists

  44. Pentazocine (Mixed) (pen-taz-oh-seen) kappa agonist mu agonist/antagonist Comparison with Morphine: -Less potent, addictive liability -Precipitates withdrawal -Similar respiratory depression

  45. Butorphanol (Mixed) (byoo-tore-fan-ahl) -Similar to Pentazocine -kappa agonist -mu antagonist -More potent than morphine -Increases in cardiac workload

  46. Buprenorphine (byoo-pre-nore-feen) -Partial mu agonist -kappa antagonist? -More potent than morphine -Can precipitate withdrawals -Addictive Liability, but good analgesic with reduced potential for abuse!

  47. Uses of Opioid Antagonists 1) narcotic poisoning 2) reduce side effects in opioid anesthesia 3) reverse neonatal respiratory depression 4) opioid addiction treatment 5) alcoholism treatment

  48. Naloxone -Rapid Acting -Short Duration Multiple Doses

  49. Naltrexone -Orally Effective -Treatment for Alcoholism -Liver Dysfunction

  50. Naloxegol (Movantik)PEGylated-Naloxone -Peripherally acting mu receptor antagonist (PEGylated form of naloxone- does not penetrate the blood brain barrier) -oral treatment for opioid-induced constipation in adults with chronic non- cancer pain (FDA approved 2014).

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