Analgesic Agents Flashcards
Does remifentanil undergo hepatic metabolism?
No. It is broken down by non-specific tissue and plasma esterases to remifentanil acid - essentially inactive
What is the CSHL of remifentanil?
3 mins
Why does remifentanil have a short duration?
Due to the high clearance and relatively small volume of distribution (steady state volume of distribution of 350 ml/kg)
Remifentanil has a short terminal elimination half-life of 3-10 minutes, consistent with its context sensitive half life of 3-6 minutes.
Therefore the duration of action of remifentanil is dependent on elimination rather than redistribution.
How do the potency of fentanyl and remifentanil compare?
Similar potency
Will remifentanil have a prolonged action in patients with pseudocholinesterase deficiency?
No
What do the pharmacological effects of morphine include?
- constipation
- biliary spasm
- histamine release
- release of ADH
- cough suppression
What is the potency of fentanyl compared to morphine?
Fentanyl is 100 times more potent
Is fentanyl water or lipid soluble?
Highly lipid soluble
What is the VoD of fentanyl?
Its lipid solubility gives fentanyl a large volume of distribution of 4 L/kg.
Does fentanyl accumulate?
Because of its large volume of distribution, fentanyl accumulates with repeated doses and has a variable context-sensitive half-life.
What is fentanyl metabolised to?
Fentanyl is N-demethylated to norfentanil and then hydroxylated for renal excretion. All metabolites are inactive.
How does diclofenac have an antipyretic effect?
Prostaglandins regulate body temp within the hypothalamus.
Therefore inhibition of prostaglandin synthesis reduces body temperature
What are NSAIDs avoided in pregnancy?
Use of NSAIDs in pregnancy can lead to premature closure of the ductus arteriosus and therefore Diclofenac is not used in pregnancy.
It is notable that low-dose aspirin is used in pregnancy and is now recommended in the primary prevention of pre-eclampsia in patients considered at high risk (eg Type I diabetes, previous pre-eclampsia).
What is the effect of diclofenac on platelets?
COX produces Thromboxane A2 which causes platelet aggregation. It also produces PGI2 in vascular endothelium which inhibits platelets.
However the overall action of COX inhibition by diclofenac is to reduce platelet aggregation as its effect on Thromboxane A2 production is greater than its effect on PGI2 production.
Which is the most to least lipid soluble out of pethidine, fentanyl and alfentanil?
(most) Fentanyl > alfentanil > pethidine (least)
What % of alfentanil is protein bound?
Alfentanil is 85-92% protein bound, mainly to alpha-1 glycoprotein.
Which is more potent, fentanyl or alfentanil?
Potency is a measure of drug activity expressed as the amount of drug required to give a certain clinical effect.
Alfentanil works quickly due to its pKa of 6.5, leaving it almost all unionized and therefore available to cross membranes and work at its effector site immediately. However, if time to effect is excluded, less fentanyl is required for the same clinical effect as alfentanil and therefore it is less potent than fentanyl
How is alfentanil metabolised?
Alfentanil is metabolised by CYP3A3/4 which also metabolises midazolam (therefore if used together in large enough doses, they will prolong each others’ elimination half life).
The product of metabolism is noralfentanil which is inactive.
Is tramadol a controlled drug?
Yes
What is the affinity of tramadol for the mu opioid receptor?
It has weak affinity for the mu opoid receptor of 2.1 micromolar compared with 0.0003 micromolar for morphine
How does tramadol work?
Whilst it is a mu agonist, it also acts as a serotonin and noradrenaline re-uptake inhibitor, NMDA antagonist and nicotinic/muscarinic Acetylcholine receptor antagonist.
Its main analgesic effect is due to the inhibition of NA and 5HT reuptake.
What drug class must tramadol not be used with and why?
Tramadol’s serotonergic modulating activities mean that patients are more susceptible to serotonin crisis if used with MAOIs or SSRIs.
What does the metabolism of morphine involve?
Morphine metabolism involves demethylation, oxidation and conjugation with glucuronide.
Some morphine is methylated to codeine.
70% of morphine forms Morphine 3-Glucuronide, a mu receptor antagonist. 30% becomes Morphine 6-Glucuronide which is 13 times more potent than morphine.
These metabolites are excreted by the kidneys and can accumulate in renal failure.
Which receptor does clonidine act at?
Clonidine has a 200 fold higher affinity for the alpha-2 adrenoceptor than the alpha-1 adrenoceptor and is an agonist at the alpha-2 adrenoceptor
What is the bioavailibility of oral clonidine?
It is very well absorbed orally with a bioavailability of 100% and an onset time of 30 minutes and reaching a peak plasma level around 60-90 minutes.
How does clonidine lower the MAC of volatiles?
It acts on alpha-2 adrenoceptors in the lateral reticular formation to reduce the MAC of volatiles and central Sympathetic Nervous System (SNS) outflow.
It also acts in the spinal cord to increase endogenous opoid and increase descending pathway inhibition (gate theory of pain)
What drugs can naloxone antagonise?
- bupranorphine
- dextropropoxyphene
- remifentanil
What is paracetamol oxidised to?
NAPQI which is a potent cell toxin. 10% of paracetamol is oxidised to NAPQI which is usually safely conjugated with glutathione. If glutathione is depleted, as in paracetamol overdose, it bonds to exposed protein SH groups causing inactivation and cell necrosis in a centrilobular pattern.
How does NAC work?
NAC replaces glutathione to allow safe metabolism of paracetamol.
How does paracetamol affect prostaglandin synthesis?
Paracetamol reduces the COX enzyme to reduce prostaglandin synthesis.
What effect does aspirin have on blood gases?
Aspirin (Salicylic acid) causes a metabolic acidosis and respiratory alkalosis in adults. It is an acid in itself and promotes hyperventilation by a direct effect.
