CNS pharmacology
Opioids
• Opioids are natural, semisynthetic or synthetic
compounds that produce morphine like effect
means pain relieving effect.
Opioids receptors
• Mu receptors role in respiratory depression
• Delta receptor role in development of
tolerance
• Kappa receptors role in Decrease git motility
Mechanism of action:
Classification of opioids
Opioids agonists
Natural Semisynthetic Synthetic
Morphine Buprenorphine Fentanyl
Codeine Hydromorphone Meperidine
Hydrocodone Methadone
Oxycodone Tapentadol
Oxymorphone Tramadol
Actions of opioids:
• M_ miosis( except meperidine )
• O_orthostatic hypotension
• R_respiratory depression
• P_pain relief, pneumonia
• H_ histamine release
• N_ Nausea
• E_ Emesis, euphoria
Uses of opioids
• Analgesia
• Treatment of diarrhea
Diphenoxylate and
loperamide are
commanly used agents.
• Relief of cough
Codeine and dextromethorphan
Are commanly used.
• Treatment of acute pulmonary edema
• Anesthesia
Pharmacokinetics of morphine
• Orally used, subcutaneously and IV Injections
Available
• Commercially available as extended release
oral preparations
• significant 1st pass metabolism
• Crosses placenta
• Duration of action for morphine is 4_5 hours
Fate of morphine
• Conjugated with glucoronic acid in the liver to
2 active metabolites
1. M3G ( morphine 3 glucoronide )Very potent
analgesic
2. M6G ( Morphine 6
glucoronide)Neuroexcitatory effects
Side effects of opioids
• Respiratory depression
• Opioids induced constipation
• Nausea
• Emesis
• Tolerance and dependence
• Miosis
• Opioids induced androgens deficiency.
• Urinary retention
• Hypotension
Opioids effect on androgens.
Contraindications of opioids
• Head injury ( possible increased intracranial
pressure )
• Pulmonary dysfunction ( except pulmonary
edema )
• Thyroid or adrenal deficieny
• Pregnancy
• Asthma
• Hepatic or renal dysfunction
Opioids withdrawal effects:
Codeine
• Weak analgesic as compared to morphine
• Used for mild to moderate pain along with
acetaminophen
• At low doses exhibit antitussive property
And
Oxycodone Oxymorphone
• Semisynthetic analog of • Semisynthetic analog of
codeine morphine
• Avalaible as immediate • Ten times more potent
release formulations (Parentally)
• 2 times more potent than • 3 times more potent (
morphine orally
• Metabolized via the
CYP2D6 and CYP3A4 enzymes
Hydrocodone Hydromorphone
• Analgesic activity compared • 4 _ 7 times more potent
to morphine than oral Morphine
• Combination used along • Preferred Over morphine in
with acetaminophen Patients with renal
• Used as antitussive dysfunction
• metabolized by liver
Fentanyl
• 100 fold the analgesic potency of morphine
• Used for Anesthesia and acute pain management
• Transmucosally and nasally for cancer related
breakthrough pain
• Transdermally used for chronic management of
pain
• Used with local anesthetics to provide epidural
analgesia for labor and post operative pain
Pharmacokinetics of fentanyl
• Highly lipophilic
• Rapid onset and short duration of action ( 15_
30mins )
• Delayed onset of action for transdermal patch
( 12 hours )
• Used IV,epidurally and intrathecally
Methadone
• Synthetic effective orally
• used for both nociceptive and neuropathic
pain
• May be used for opioids withdrawal and
maintenance therapy
Adverse effects of methadone
• Toxicity due to long half live of 12_40hours
• Physical dependence
• Prolonged QT interval causing torsades de
pointes .
Antagonists
Naloxone:
• Competitive antagonist at mu,kappa and delta
receptors
• Used to reverse the effects of morphine overdose
• DOA 1_2 mins for IV dose
• DOA 2_5 mins when used IM,SC and intranasally
• Extensive 1st pass metabolism So not used orally
• Half life of 30_81mins
Naltrexone
• Longer DOA than naloxone
• Given Orally
• Used in combination with clonidine for rapid
opioid detoxification
• Decreases the craving of ethanol
• Side effect
• Hepatotoxicity
