MSK 11 Flashcards
Different types of Opioids
Natural: Morphine and codeine
Semisynthetic: Oxy, Naloxone, Hero
Fully synthetic: Tramadol, Methadone, Fentanyl, Pethidine
Opioids can be classified as?
Strong opioids: used for severe pain: morphine, oxycodone, pethidine, fentanyl
Weak opioids: used for moderate pain: codeine, Tramadol.
How opioids works?
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.
Mechanism of action of opioids?
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.
Opioids can be administered via different routes?
These are: Systemic Spinally Rectally Orally
Q: Most of the current opioid analgesics act at this opioid receptor subtype?
Meu>Delta> kapa
What is Codeine phosphate?
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
How long is onset for oral codeine tablet?
15-30 minutes
What is Tramadol?
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
Oxycodone vs fentanyl
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
Q: Effect of fentanyl is over in 30-60 mins so if a patient needs constant analgesia what is the best delivery method?
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
What is Methadone?
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
What are the Opioid related side effects?
GI: nausea, vomiting, Constipation Sedation Respiratory depression in overdose Cough suppression Risk of fracture Low sex hormones Rash addiction
Opioids tolerance of patient how they behave?
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.
Physical dependence and addiction of patient on opioids?
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.
Chemical structure of an opioid influence Pharmacodynamics and pharmacokinetics of the opioids in human body?
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.
What is the Pharmacokinetics of Opioids?
Opioids receptor activation occur by binding drug with the receptor in the brain
Opioids can cross BBB
Onset of action of opioids depends on?
Lipophilicity and Ionisation and ability to cross BBB.
Common structure skeleton of opioids?
4-phynylpiperidine It has one tertiary nitrogen 2 carbon chain Aromatic or non-polar group 1 quaternary carbon
Codeine and morphine are called?
Opiate
Semi-synthetic opiate is oxycodone, heroin
fully synthetic or man-made compound are?
loperamide, fentanyl, tramadol
What is the role of opioid agonist pharmacophore?
Give particular molecular 3D shape for binding to the opioid receptor
How Morphine 3D shape looks like?
T-shaped
What are the common structural features of opioids?
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
