1. Opium comes from poppy seeds.
It consist of a mixture of opiates. (naturally occurring)
Morphine named after the Greek god of dreams Morpheus.
Ethylmorphine(3-ethyl ether) in 1898.
Diacetylmorphine (heroin) may be considered as the first prodrug
(1874) Marketed as non-addicting analgesic, antidiarrheal and
antitussive agent.
Tolerance and withdrawal is associated with upregulation of
adenylate cyclase (inhibition by protein) and internalization of
receptor (Mu activation)

2. Opioid receptors
mu receptor (m) Analgesia, Euphoria, GI effects
Respiratory depression, Dependence
Emetic
kappa receptor (k) Analgesia, Sedation
deta receptor (d) Analgesia, respiratory depression

4. SAR
The A ring and basic nitrogen (protonated at physiological pH) are the
most common structural features.
A tertiary amine is necessary for opioid activity with N-methyl displaying
good agonist properties. But as you increase size of group on the nitrogen
from 3 to 5 carbons, the agents become antagonist.
If change 3-OH to H, activity will be decreased by 10-fold.
If change 6-OH to H, activity will be increased.
If change 6-OH to ketone, activity will be decreased. (except 7,8 reduction)
If reduced the 7,8 double bond, activity will be increased.
If -14 OH is added, activity will be increased.
If methylate or acetylate 3-OH, activity will be decreased.
Acetylation of 6-OH will increase activity.
If you make the group on the Nitrogen a CH2CH2Phenyl, activity will
increase by 10-fold.

5. Morphine derivatives
Heroin NOT USED
ANALGESIC BECAUSE
Of ADDICTION in USA
sulfate salt
Administer by po and IV
Use: analgesic
Metabolism: N-demethylation,
Conjugation (3-OH)
Side effects: addiction,
Nausea and vomiting, constipation.

6. Dilaudid (Hydromorphone)
Mu agonist
5- 8 x more potent than morphine and
equally addictive
HCl and Bitartrate salts
IV, IM, po, SubQ.
Codeine
Treat mild to moderate pain
Combination with Aspirin
Use Analgesic and Cough suppressant
10% of oral is metabolized to morphine
Use IV causes side-effects such as
hypotension (release of histamine)

7. Lortab, Vicodin (Hydrocodone)
Treat moderate pain and
Cough
In combination acetaminophen
Numorphan (Oxymorphone)
Mu agonist (10 x more potent)
Treat severe pain
10 x more potent than morphine
IM, IV, SubQ, rectal

8. Oxycontin, Percodan, Tylox (Oxycodone HCl)
Equipotent with morphine
It has higher absorption
Use to treat severe pain
Administer po and subQ
Paracodin (Dihydrocodeine)
Reduction of codeine
Faster onset than morphine
Use in combination with
Aspirin and acetaminophen

9. Nubain (Nalbuphine HCl)
Mixed Antagonist (mu receptor)
agonist (kappa receptor)
Not as potent as antagonist
Equally potent as Morphine
Sedation
Administer IV
Conjugation of 3-OH in feces
Apomorphine HCl
Formed from Heat/HCl
Of Morphine (Dehydration)
Use emetic, orphan drug
Parkinson’s disease
Administer SubQ

10. Buprenex (Buprenorphine HCl)
Mixed agonist and antagonist
More potent than morphine
Use in combination with methadone
For treatment of addiction
Stadol (Butorphanol Tartrate)
Mixed agonist and antagonist
Use analegesic
Repiratory depression is controllable
Less addiction
Associated with racehorse doping
Side effects: cardiovascular related
Administered IV, IM and nasal spray

11. Paregoric (Opium extract)
Mixture
Use for diarrhea
Ultram (Tramadol HCl)
Synergistic effect
(+) isomer opioid receptor
(-) isomer blocks Norepi
5HT
O-Demethyl more potent
Additive effect makes it
Fairly good analgesic
In combination with acetaminophen
No addiction so not schedule
Administer po

12. Demerol related compounds (piperidine)
Demerol (Meperidine HCl)
Analgesic with anti-spasm activity
Labor pain allow with barbiturates
Administer IM, po
Control substance less dependence
Lomotil (Diphenoxylate HCl)
No analgesic
Use as anti-diarrhea agent

13. Zactane Citrate (Ethoheptazine citrate)
Use for moderate pain
Administer by po and IV (CNS stimulation)
No addiction
Combination aspirin
Toxic at high dose
Sublimaze (Fentanyl Citrate)
More potent than morphine
and Demerol
Rapid onset and short duration
Use in combination with anesthetics
Side effects Bradycardia and Resp
depression

14. Sufenta (Sufentanil Citrate)
Replace phenyl with thiophenyl
More potent than fentanyl and morphine
Administer IV
In combination with anesthetics
Faster onset and shorter duration Fentanyl
Alfenta (Alfentanil HCl)
Tetrazol-5-one
Less potent than Sufenta
Decrease pKa (-Log Ka)
Negative Log of Ka
Administer IV
In combination with anesthetics

15. Dolophine HCl (Methadone HCl)
More potent than morphine
Higher toxicity
Analgesic, cough suppression
Anti-spasm, addict treatment
(-) Isomer is responsible for its activity
Dependence liability
Ultiva (Remifentanil HCl)
More potent alfenta
Administer IV
In combination with anesthetics
Predictable recovery time (ester hydrolysis)
Rapid onset

16. Darvon, Dolene, Doxaphene (Propoxyphene HCl or Napsylate)
(+) isomer
Equal to codeine as far potency
Euphoric
Weak pain relief
Combination aspirin and Acetaminophen
Also use for addiction

17. Dalgan (Dezocine)
Agonist and Antagonist
Similar to morphine
Use for moderate to severe pain
Administered IM and IV
Talwin (Pentazocine HCl or Lactate)
Benzomorphan chemical class
(-) isomer is responsible for analgesia
Side effects respiratory depression
In combination with aspirin and acetaminophen
Administered p.o. and IV

18. -is a competitive antagonist at the opioid receptors
Narcotic Antagonists
Narcan (Naloxone HCl)
Trexan, Re Via (Naltrexone)
-is a competitive antagonist
at the opioid receptors
-is the drug of choice in treating
narcotic overdose
-has no agonist effects and shows
no withdrawal effect after long-term use .
-use is limited because of short duration
of action ~4h .
Administered by IM, IV, Sub Q
-An analog of naloxone with a
cyclopropylmethyl substituent
-Is the preferred drug for treating
former opiate addicts because it is long-acting.
-Is given only 3 x weekly to block
the high from narcotic analgesic such as heroin.
Administered by po and IM (Vivitrol) once a
month dosing

19. Revex (Nalmefene HCl)
6-methylene analog of ReVia
Pure antagonist
Use opioids overdose
Longer acting than Narcan
Administered by IM, IV, Sub Q