MSK 11

Question 1

Different types of Opioids

Answer 1

Natural: Morphine and codeine
Semisynthetic: Oxy, Naloxone, Hero
Fully synthetic: Tramadol, Methadone, Fentanyl, Pethidine

Question 2

Opioids can be classified as?

Answer 2

Strong opioids: used for severe pain: morphine, oxycodone, pethidine, fentanyl

Weak opioids: used for moderate pain: codeine, Tramadol.

Question 3

How opioids works?

Answer 3

They work on opioids receptor called Gprotein coupled receptor in particular Meu Delta and Kappa receptor these 3 receptors are known as opioid receptors and block the pain

The analgesic properties mediated mainly by MEU and KAPPA receptor.

Question 4

Mechanism of action of opioids?

Answer 4

They bind to opioid receptors and activate intra-cellular signalling events than all 3 receptors inhibit adenylate cyclase as a result Increase of K++ efflux or reducing presynaptic Ca++ influx by binding with meu receptor as a result inhibit neuronal activity and decrease or no transmission of “nociceptive impulse” resulting pain reduction.

Question 5

Opioids can be administered via different routes?

Answer 5

These are: 
Systemic 
Spinally
Rectally 
Orally

Question 6

Q: Most of the current opioid analgesics act at this opioid receptor subtype?

Answer 6

Meu>Delta> kapa

Question 7

What is Codeine phosphate?

Answer 7

Inside our body codeine metabolised into morphine. It is a prodrug. Works on CYP2D6
It also has anti-tussive (cough suppressant) effect
Available with combination with paracetamol
Side effect: Nausea vomiting and constipation

Question 8

How long is onset for oral codeine tablet?

Answer 8

15-30 minutes

Question 9

What is Tramadol?

Answer 9

It is a weak opioid
Metabolised in liver and excreted by the kidney
Time to effect is 30 minuets but last in the body for 5-6hours
Can cause nausea, vomiting dizziness
Abuse potential
Sedation is minimal

Question 10

Oxycodone vs fentanyl

Answer 10

Fentanyl is 80 to 100 times potent than morphine and it works on M and Delta Onset is 30min only
Oxycodone is 2 times potent the morphine and it works on M and Kappa 10-30 min only

Question 11

Q: Effect of fentanyl is over in 30-60 mins so if a patient needs constant analgesia what is the best delivery method?

Answer 11

Patches
Need adequate subcutaneous tissue.
Takes 12 hours for onset and 24 hours for maximum effects
Suitable for stable pain 
Change patch every 3 days or 72 hours

Question 12

What is Methadone?

Answer 12

People specially some sort of addiction with morphine
Supplied as a mixture
L methadone is a Mu agonist
D methadone is NMDA receptor antagonist
Good for neuropathic pain and long half-life 24 hours

Question 13

What are the Opioid related side effects?

Answer 13

GI: nausea, vomiting, Constipation
Sedation
Respiratory depression in overdose
Cough suppression
Risk of fracture 
Low sex hormones
Rash
addiction

Question 14

Opioids tolerance of patient how they behave?

Answer 14

People can develop tolerance on opioids when they use for extended period of time like cancer pain or intensive care unit. Tolerance is defined as Reduction of pharmacological effect. So after certain time period the patients need to increase the amount of dose to get same effects.

Question 15

Physical dependence and addiction of patient on opioids?

Answer 15

Using opioids extended periods of time, patients become dependent on it and can lead them addiction to opioids and drug seeking behaviour. So, monitoring required.

Question 16

Chemical structure of an opioid influence Pharmacodynamics and pharmacokinetics of the opioids in human body?

Answer 16

Different opioids make slightly different interaction with the opioid’s receptor ligand binding site. which depends on fully or partial agonism, and selectivity of the receptor.

Question 17

What is the Pharmacokinetics of Opioids?

Answer 17

Opioids receptor activation occur by binding drug with the receptor in the brain
Opioids can cross BBB

Question 18

Onset of action of opioids depends on?

Answer 18

Lipophilicity and Ionisation and ability to cross BBB.

Question 19

Common structure skeleton of opioids?

Answer 19

4-phynylpiperidine 
It has one tertiary nitrogen 
2 carbon chain
Aromatic or non-polar group
1 quaternary carbon

Question 20

Codeine and morphine are called?

Answer 20

Opiate

Semi-synthetic opiate is oxycodone, heroin

Question 21

fully synthetic or man-made compound are?

Answer 21

loperamide, fentanyl, tramadol

Question 22

What is the role of opioid agonist pharmacophore?

Answer 22

Give particular molecular 3D shape for binding to the opioid receptor

Question 23

How Morphine 3D shape looks like?

Answer 23

T-shaped

Question 24

What are the common structural features of opioids?

Answer 24

C3 phenol is important to bind with receptor
Tertiary amine pKa about 8 and it is predominantly ionised at physiological pH is essential for receptor binding
C6 is called hydroxy group it is not phenol and it is not essential for receptor binding

Question 25

Is the oxycodone being a prodrug?

Answer 25

Yes, so it needs H with O to activate so if you see a structure where H is not present with the O then add a H with it for activation.