Analgesics- Opioids Flashcards
What are the 3 major Opioid receptors and their effects?
1) μ- agonist receptor activation –> Respiratory depression
2) κ- receptors activation –> Sedation
3) δ- receptors activation –> Tolerance
4) κ+ δ receptor activation –> Slows the GI Transit
MoA of Opioid receptors?
Opioids are G-protein coupled receptors
* upon activation
pre-synaptically: ↓ ACh, ↓ Ca+2, ↓ NE, ↓ 5-HT, ↓ Glu and substance P
post-synaptically–> ↑ K+ conductance (inhibitory potential)
- Activation casues decreased neuronal transmission
Acute adverse effects Opioids
1) Analgesia
2) Sedation and Euphoria
3) Antitussive Actions
–> Suppression of the cough reflex
4) Respiratory Depression
–> Decreased response to CO2, can cause cerebrovascular dilation –> ↑ blood flow + ↑intracranial pressure.
* Contraindication in patients with head injuries.
5) Nausea and Vomiting
6) Gastrointestinal Effects
- Constipation –> due to decreased intestinal peristalsis
7) Smooth Muscle
–> Cause contraction of biliary tract smooth muscle (exception –> meperidine):
–> Avoid in biliary colic or spasm.
8)Miosis:
–> Pupillary constriction (except meperidine).
Meperidine has anti-muscarinic action.
Strong Opiate μ-agonist drugs
1) Morphine
2) Meperidine
3) Methadone
4) Fantanyl
Indications of Morphine
1) Analgesia for moderate-sever pain
2) Intra-operative Adjuvant (also Fantanyl)
Adverse effects of Morphine
1) Respiratory depression
2) Miosis
3) Constipation
4) Nausea, vomiting
MoA of Strong and moderate opioids?
All activated the μ - receptors, with varying activity on the κ and δ receptors.
Indication of Meperidine
1) Analgesia to moderate-sever pain
*Can be given to pregnant women
PK of Morphine
Undergoes first-pass metabolisim
* Therefore, contraindicated in patients with Hepatic failure
Adverse effects of Meperidine
1) Mydriasis
2) Respiratory depression
Indication of Methadone?
1) Analgesia for moderate-sever pain
2) Opioid withdrawal states
Indication of Fentanyl?
1) Analgesia for moderate-sever pain
2) Intra-operative adjuvant (also Morphine)
Moderate Opioids
1) Oxycodone
2) Codeine
Indication of Oxycodone
Moderate / chronic pain –> given in
combination with NSAID/Paracetamol.
Indication of Codeine
- Moderate / chronic pain –> given in
combination with NSAID/Paracetamol - Cough suppression
Toxic Adverse effects of Opioids
1) Constipation
2) Nausea, vomiting
3) Respiratory depression
Drug interactions of Opioids
Ethanol, anti-psychotics, TCAs, sedative-hypnotics, anesthetics –> casue **additive CNS depression **
Administration of Opioids
1) Most well absorbed when taken orally.
2) Parenteral administration and sustained-release forms (e.g.
morphine and oxycodone).
3) Transdermal patch (e.g. fentanyl)
Metabolisim of Opioids
Most metabolized by Hepatic enzymes to inactive glucuronide conjugates.
Weak Opiate
Buprenorphine
Opioids are contraindicated in?
1) Head injuries (possible increased intracranial pressure)
2) Pulmonary dysfunction (except pulmonary edema).
3) Hepatic/renal dysfunction (possible accumulation).
4) Adrenal or thyroid deficiencies (exaggerated responses).
5) Pregnancy (possible neonatal depression or dependence), except meperidine.
Pk of Codein
Metabolised by CYP2D6
Symptoms of Opioid overdose, Diagnosis and treatment
Sypmtoms: pupillary constriction (Miosis) , respiratory depression and comatose state
Diagnosis: Confirmed if an Antagonist drug promots signs of recovery
Treatment: Naloxone + Ventilatory support
Drug absue withdrawel symtpoms and managment
Withdrawal:
1) Yawning,
2) Lacrimation, rhinorrhea, salivation.
3) Anxiety, sweating, goose bumps
4) Muscle cramps, spasms, CNS-originating pain
Management of withdrawal:
- Supportive, methadone, clonidine.
Opiate Antagonist
1) Naloxone
2) Naltrexone
MoA of Naloxone
Opiate Antgonist
Indication of Naloxone
1) Opioid overdose
Indication of Naltrexone?
Maintance Treatment of Opioid overdose
PK of Naloxone and Naltrexone
Duration:
Naloxone –> 2 h.
Naltrexone –> >10 h
AE of Naloxone and Naltrexone
Rapid antagonism of all opioid actions.
