Analgesics- Opioids

Question 1

What are the 3 major Opioid receptors and their effects?

Answer 1

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

Question 2

MoA of Opioid receptors?

Answer 2

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

Question 3

Acute adverse effects Opioids

Answer 3

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.

Question 4

Strong Opiate μ-agonist drugs

Answer 4

1) Morphine
2) Meperidine
3) Methadone
4) Fantanyl

Question 5

Indications of Morphine

Answer 5

1) Analgesia for moderate-sever pain
2) Intra-operative Adjuvant (also Fantanyl)

Question 6

Adverse effects of Morphine

Answer 6

1) Respiratory depression
2) Miosis
3) Constipation
4) Nausea, vomiting

Question 7

MoA of Strong and moderate opioids?

Answer 7

All activated the μ - receptors, with varying activity on the κ and δ receptors.

Question 8

Indication of Meperidine

Answer 8

1) Analgesia to moderate-sever pain
*Can be given to pregnant women

Question 9

PK of Morphine

Answer 9

Undergoes first-pass metabolisim
* Therefore, contraindicated in patients with Hepatic failure

Question 10

Adverse effects of Meperidine

Answer 10

1) Mydriasis
2) Respiratory depression

Question 11

Indication of Methadone?

Answer 11

1) Analgesia for moderate-sever pain
2) Opioid withdrawal states

Question 12

Indication of Fentanyl?

Answer 12

1) Analgesia for moderate-sever pain
2) Intra-operative adjuvant (also Morphine)

Question 13

Moderate Opioids

Answer 13

1) Oxycodone
2) Codeine

Question 14

Indication of Oxycodone

Answer 14

Moderate / chronic pain –> given in
combination with NSAID/Paracetamol.

Question 15

Indication of Codeine

Answer 15

1. Moderate / chronic pain –> given in
   combination with NSAID/Paracetamol
2. Cough suppression

Question 16

Toxic Adverse effects of Opioids

Answer 16

1) Constipation
2) Nausea, vomiting
3) Respiratory depression

Question 17

Drug interactions of Opioids

Answer 17

Ethanol, anti-psychotics, TCAs, sedative-hypnotics, anesthetics –> casue **additive CNS depression **

Question 18

Administration of Opioids

Answer 18

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)

Question 19

Metabolisim of Opioids

Answer 19

Most metabolized by Hepatic enzymes to inactive glucuronide conjugates.

Question 20

Weak Opiate

Answer 20

Buprenorphine

Question 21

Opioids are contraindicated in?

Answer 21

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.

Question 22

Pk of Codein

Answer 22

Metabolised by CYP2D6

Question 23

Symptoms of Opioid overdose, Diagnosis and treatment

Answer 23

Sypmtoms: pupillary constriction (Miosis) , respiratory depression and comatose state
Diagnosis: Confirmed if an Antagonist drug promots signs of recovery
Treatment: Naloxone + Ventilatory support

Question 24

Drug absue withdrawel symtpoms and managment

Answer 24

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.

Question 25

Opiate Antagonist

Answer 25

1) Naloxone
2) Naltrexone

Question 26

MoA of Naloxone

Answer 26

Opiate Antgonist

Question 27

Indication of Naloxone

Answer 27

1) Opioid overdose

Question 28

Indication of Naltrexone?

Answer 28

Maintance Treatment of Opioid overdose

Question 29

PK of Naloxone and Naltrexone

Answer 29

Duration:
Naloxone –> 2 h.
Naltrexone –> >10 h

Question 30

AE of Naloxone and Naltrexone

Answer 30

Rapid antagonism of all opioid actions.