1. Analgesic Drugs

2. Non narcotic
NSAIDS
•Para – aminophenol derivatives:
Paracetamol
•Active metabolite of phenacetin

3. • MOA: weak prostaglandin
inhibitor, no anti inflam
• TOXIC METABOLITE: N- acetyl –
para – iminobenzoquinone
• SE: hepatic necrosis

4. NARCOTIC
• Source: Papaver somniferum
Papaver bracteatum

5. Opioids
• substances with morphine-like
activity
• Includes opioid peptides
(enkephalins, endorphins,
dynorphins)
• Acts on the mu (μ), kappa (κ),
delta (δ) receptors in the CNS

6. Biochemistry of Opioid
Receptors
• linked through G-proteins via
inhibition of adenylate cyclase.
• facilitate opening of potassium
channels
• inhibit opening of calcium channels
(inhibiting transmitter release)

7. ACTIONS OF
RECEPTORS
• MU
• Supraspinal analgesia
• Respiratory depression
• Euphoria/sedation
• Physical dependence
• Decrease GI motility
• Pupil constriction

8. ACTIONS OF
RECEPTORS
• KAPPA
• Spinal analgesia
• Sedation/dysphoria
• Pupil constriction

9. ACTIONS OF
RECEPTORS
• SIGMA
• Dysphoria
• Hallucinations
• Psychotomimetic effects
• Pupil dilation

10. ACTIONS OF
RECEPTORS
Delta
•analgesia

11. Selectivity of opioid drugs and
peptides for receptor subtypes
μ δ κ
Endogenous peptides
β-Endorphin +++ +++ +++
Leu-enkephalin + +++ -
Met-enkephalin ++ +++ -
Dynorphin ++ + +++

12. Opioids
• Full agonist
• Maximal effect
• morphine, meperidine, methadone,
fentanyl, heroine
• Partial agonist
• Less effect
• Codeine, propoxyphene,
hydrocodone, oxycodone,
buprenorphine

13. Opioids
• Mixed agonist/antagonists
• Agonist at certain receptors
antagonist at others
• Pentazocine, nalbuphine,
butorphanol
• Antagonist
Naloxone, naltrexone

14. Full agonists
1. Morphine
• Prototype/classic opiate
• juice of opium poppy seed
(Papaver somniferum

15. “HECk of a DREAM”
• “HECk”
histamine release- urticaria/
pruritus, brochoconstriction
Emesis
cardiovascular- hypotension

16. “HECk of a DREAM”
• DREAM
depression of cough reflex/
antitussive,
dec. GI motility/antidiarrhea,
depression of CNS/ sedative
respiratory depression
euphoria
analgesia
miosis

17. Morphine Uses
• First line drug for severe pain
• Pain associated with MI
• Pulmonary edema
• *Dextromethorphan- morphine
derivative; antitussive

18. Clinical Pharmacology of
Direct Agonists
• Morphine
• Highly potent opioid for severe
pain
• Variable duration of analgesia
• Long acting oral formulations/rapid
IM/IV

19. ADVERSE EFFECT
• Sedation
• Constipation
• N/V
• Urinary retention
• Potential for addiction
• Respiratory depression

20. Full Agonists
• Meperidine/Pethidine
• Anticholinergic pupil dilation
rather than miosis
• + MAO inhibitors resp
depression, fever, seizures
• Loperamide- meperidine analog for
diarrhea

21. Clinical Pharmacology of
Direct Agonists
• Meperidine
• Shorter duration of action than morphine
• Cause decrease in spasm and preferred
for pancreatitis
• Lowers seizure threshold
• Absolute contraindication for patients
taking MAOI to prevent serotonin
syndrome

22. Full Agonists
• Methadone
• Controlled withdrawal of addicts;
oral
• Fentanyl
• 80x more potent than morphine
• + droperidol dissociative
anesthesia
• IV, transdermal

23. Full Agonists
• Heroine
• Diacetylmorphine
• Lipophilic, crosses BBB more
quickly
• Hydrolyzed to morphine

24. Partial Agonists
• Codeine
• Antitussive
• For moderate pain

25. Clinical Pharmacology
of Direct Agonists
Codeine
Less potent than morphine
Used for moderate pain, antitussive and
for diarrhea
Additive analgesia when combined with
acetaminophen or aspirin

26. Clinical Pharmacology of
Direct Agonists
• Oxycodone
• Similar to codeine
• Typically combined with
acetaminophen
• Hydrocodone
• Similar to codeine
• Typically combined with
acetaminophen

27. Mixed
Agonist/Antagonist
• Nalbuphine
• Analgesia during labor

28. Clinical Pharmacology of
Mixed Agonist-antagonists• Pentazocine (Darvon)
• less potency and efficacy than morphine for
pain relief
• Less addictive and less respiratory depression
than morphine
• May cause cardiovascular stimulation at high
doses
• Nalbuphine
• Similar to pentazocine
• Morphine-like potency
• Butorphanol
• Similar to pentazocine
• Morphine-like potency

29. Clinical Pharmacology of
Partial Agonist-
Antagonists
• Buprenorphine
• Partial agonist than morphine due to receptor
dissociation
• used as an alternative to methadone for heroin
detoxification
ANTAGONIST
• Naloxone(Narcan)
• Partial antagonist used to treat opioid overdose
• Short half-life so repeated doses required
• Naltrexone
• Similar to naloxone
• Longer acting

30. NATURAL
• Morphine
• Codeine
• Thebaine – precursor substrate
for the synthesis of naloxone

31. SEMI - SYNTHETIC
• Heroin – diacetylmorphine,
diamorphine
• Apomorphine –emetic
• Hydrocodone – antitussive
• Oxycodone
• Hydromorphone –analgesic
• Oxymorphone

32. PURELY SYNTHETIC
• Methadone
• Loperamide,diphenoxylate
• Meperidine
• Fentanyl
• Tramadol
• pentazocine