analgesics Flashcards
What is the mechanism of action of opioids?
opioids bind to opioid receptors (Gi coupled proteins), then inhibits AC, which lowers cAMP levels.
This leads to opening of K channels (stimulates K efflux) and closing of Ca channels (inhibits Ca influx).
As a result the neuron become hyperpolarized and there is reduced signal transmission.
Which opioids are partial agonists?
Buprenorphine
Which opioids are mixed agonist-antagonist?
Pentazocine, Nalbuphine and Butorphanol.
Which are opioid antagonists?
Naloxon and Naltrexon.
Morphine
- The golden standard - strong opioid.
- Acts fast, crosses the BBB but isn’t lipid soluble so slower.
- Undergoes first pass metabolism in the liver into 2 metabolites:
1. Morphine-6-glucuronide which is a potent analgesic.
2. Morphine-3-glucuronide which is inactive but has neuroexcitatory effect.
Codeine (methylmorphine)
- A weak pure opioid - opiate.
- Less potent and weaker.
- Used only for moderate pain and as an antitussive.
- Has less side effects…
Oxymorphone
- A semisynthetic pure agonist.
- A strong agonist (x10 times more than morphine).
- If it’s given orally it becomes less potent.
Oxycodone
- A semisynthetic pure agonist.
- Is strong agonist (x2 times more than morphine).
- Is metabolized by CYP2D6 and CYP3A4.
Hydromorphone
- Is a semisynthetic pure agonist.
- Is a strong agonist (x2-7 times more than morphine).
- Leads to less accumulated metabolites, so is preferred in patients with renal dysfunction.
Hydrocodone
- Is a semisynthetic pure agonist.
- Is a weak agonist.
- Can be used as an antitussive.
Fentanyl
- Is a synthetic pure agonist.
- Is very strong agonist (x100 times more than morphine).
- Is used for analgesia and anesthesia.
- Is administered as transdermal patches for management of chronic pain (bc it allows slow release to the bloodstream).
Sufentanil, Lofentanil, Carfentanil and Alfentanil
- Are synthetic pure opioids which are derived from fentanyl.
- All are stronger than fentanyl, only Alfentanil is weaker.
- Carfentanil is so strong (x100 times more) that it’s used for immobilisation of animals.
Methadone
- Is a synthetic pure agonist, NMDA antagonist and NE/S reuptake inhibitor.
- Is a strong agonist.
- It’s used in management of opioid withdrawal, because it has less side effects and longer duration of action. So its withdrawal is easier.
Buprenorphine
- Is a semisynthetic PARTIAL agonist.
- Is very lipophilic and has long duration of action.
- In high doses eventually reaches “ceiling effect” since the receptors are all saturated. This is why it can reduce effects of other agonists and used to treat opioid use disorder.
- Has respiratory depression effect, but less other unwanted SE. So it can be used for this property.
Pentazocine
- Is a mixed agonist-antagonist.
- Is a strong k agonist, and weak mu antagonist.
- Produces euphoria in low doses. But in higher doses can cause respiratory depression, increased BP, and tachycardia. So it’s dangerous in patient with CVS problems.
Nalbuphine
- Is a mixed agonist-antagonist.
- Has no side effects on the heart.
Butorphanol
- Is a mixed agonist-antagonist.
Tramadol
- Is a synthetic pure agonist.
- Is a weak mu agonist in CNS, causes serotonin release and inhibits NE reuptake. (is x10 times LESS potent than morphine)
- Is contraindicated in: intoxication with alcohol or other opioids, in 1st trimester in pregnancy, in co-administration of MAO inhibitors.
- Has advantage that it causes only weak cardiovascular and respiratory depression.
Tapentadol
- Is a mu agonist and NE reuptake inhibitor.
- Acts in the brain and spinal cord. And is contraindicated in high intracranial pressure.
- Is metabolized in the liver by glucouronidation to an inactive metabolite.
Naloxone, Naltrexone and Nalmefene
- Are pure competitive antagonists.
- Act on all 3 opioid receptors, so are non-selective.
- They are used for reversal of opioid overdose.
* Naloxone has short duration of action but rapid onset.
* Naltrexone has longer duration of action.
PAMORAs - Peripherally Acting Mu Opioid Receptor Antagonists
These are opioid antagonists that act peripherally because they cannot cross the BBB (blood brain barrier)
- Alvimopan - used to avoid postoperative ileus. - Methylnaltrexone bromide, Naloxegol and Naldemedine - used to treat opioid induced constipation.
Which drugs can be used to treat diarrhea?
Loparamide and Diphenoxylate.
