This document discusses different types of analgesics including opioids, cyclooxygenase inhibitors, and gabapentin/pregabalin. It describes the mechanisms of action, pharmacokinetics, effects on organ systems, drug interactions, and appropriate uses of these analgesic drugs for pain management. Specifically, it explains that opioids work by binding to mu, kappa, and delta receptors and inhibit pain transmission, cyclooxygenase inhibitors reduce inflammation and pain by inhibiting COX enzymes, and gabapentin/pregabalin treat neuropathic pain by binding calcium channels.

1. Analegesia
Dr. Ibrahim Elkathiri

2. Analgesia
• Analgesia is pain relief without loss of consciousness and
without total loss of feeling or movement

3. • Appropriate use of analgesic can make the deference btw a
satisfied and an unsatisfied postoperative patient

4. • Studies have shown that outcome can be improved when
analgesia is provided in a multimodal format
• Multimodal analgesia is a pharmacologic method of pain
management which combines various groups of medications
for pain relief

5. Opioids
Mechanism of action:
• Bind to mu, kappa, and delta receptors
• Inhibit adenylate cyclase
• Activate phospholipase C
• Inhibit voltage-gated calcium channel and activate
potassium channel
• Opioid receptor activation inhibit the presynaptic and
postsynaptic response to excitatory neurotransmitters by
nociceptive neurons

6. Con,
• Pure opioid antagonist Naloxone, naltrexone
• Opioid main effect is on CNS, may affect somatic and
sympathetic peripheral nerves.

7. pharmacokinetics
Absorption:
• IM,SC ( hydromorphone, morphine, meperidine) peak
plasma 20-60min
• Oral (oxycodone, hydrocodone
• Oral transmucosal fentanyl citrate (rapid onset)
• Transdermal fentanyl patches

8. Con,
Distribution:
• After IV administration the distribution half life of opioid are
short 5-20 min
• Morphine low lipid solubility delay BBB so its onset of action
is slow and duration of action is long
• Fentanyl, Sufentanyl high lipid solubility::: Faster onset,
shorter duration
• Alfentanyl is less lipid soluble then fentanyl, but faster onset
and shorter duration cause of high nonionized fraction and
small volume of distribution

10. • Lung retain significant amount of lipid soluble opioids, when
systemic concentration fall they return to blood stream.
• Pulmonary uptake reduced by accumulation of the drugs and
concurrent inhalation anesthetic. And increase by history of
tobacco use

11. Con,
Biotransformation:
• Opioids except remifentanyl biotransform in liver
• Morphine : morphine 3 glucuronide and morphine 6
glucuronide ( glucuronic acid)
• Hydromorphone : hydromorphonr 3 glucuronide (GA)
• Meperidine: is N-demethylated to normeperidine (seizers)
• Nrofentanyl can be measured in urine long time after fentanul
no longer detected on blood.

12. • Codeine + CYP2D6 = momorphine.
• Tramadol + CYP2D6 = o-demethyl tramadol.
• Hydrocodone + CYP2D6 = hydromorphone.
• Remifentanyl have ester structure, susceptible to hydrolysis by
non specific esterease in RBC and tissue, with elimination half
life less then 10min.
• Hepatic failure has no adjustment on remifentanyl.
• Patient with pseudochloinestrease deficiency have normal
response to remifentanyl

14. Excretion
• Mainly renal
• Morphine and meperidine are 10% biliary and 90% renal,
10% of which is excreted unchanged(renal failure =
prolonged action)
• Morphine 3 glucuronide and morphine 6 glucuronide has
been associated with narcosis and ventilatory depression
• metabolites of remifentanyl is less potant then parent
componant.

15. Effects on organ systems
Cardiovascular:
• Menimum
• Meperidine increase HR
• Morphine, fentanyle, sufentanyl, remifentanyl, alfentanyl
cause bradicardia

16. Respiratory:
• Depress ventilation Particularly RR
• RR and end-tidal CO2 are early indication of respiratory
depression.
• Opioid increase partial pressure of CO2 (shift downword and
to the right
• The apneic threshold rises and hypoxic drive is decreased
• Naloxone reverse opioid induced apnea.

18. Con,
• Rapid administration of larger dose of opioid can induce chest
wall rigidity sever enough to make ventilation with bag and
mask impossible

19. Cerebral
• Decrease cerebral O2 consumption
• Decrease cerebral blood flow
• Decrease intracranial pressure
• Nausea and vomiting are more common following small dose
of opioids
• Intravenous meperidine (10-25mg) is more effective then
morphine or fentanyl for decreasing shivering in postanesthetic
care unit (best agent for this indication)

20. Con,
GIT:
• Slow motility (constipation)
• Biliary spasm
• Reversible by naloxone or glucagone.

21. Drug interaction
• Meperidine + monoamine oxidase inhibitor =
hemodynamic instability, hyperpyrexia, coma, respiratory
arrest or death
• Alfentanyl clearance my be impaired and half life
prolonged following treatment with Erythromycine.

22. Cyclooxygense inhibitors
Mechanism of action:
• NSAIDs inhibit COX
• COX-1 all over the body
• COX-2 produce in response to inflammation
• Agent inhibit COX nonselectivly (ex ibuprofen) control fever,
inflammation, pain, thrombosis
• COX-2 selective agents (etoricoxib) can be used without
concern about platelets inhibition
• COX-1 inhibition decrease thrombosis
• Selective COX-2 inhibition increase risk of MI and strok

23. Con,
• Aspirin in low dose is only NSAID prevent stork and MI.
Effect on COX-1 last for 1 week.
Effect on organ system:
• Cardiac
• Respiratory
• Gastrointestinal: gastrointestinal upset, bleeding

24. Gabapentin and
Pregabalin
• Introduced first as antiepileptic
• Chronic neuropathic pain
• Postheraptic neuralgia
• Diabetic neuropathy
• When used for treatment of pain start at low dose then
increase until side effect of dizziness or sedation appear