Question

(biochem)

refering to the paper

"A safer poppy" by Jenny Rood. It was published in The Scientist, January 2018, vol. 31, 1, page 61. You can access this journal/magazine, for free, at the

www.the-scientist.com

What makes opioid drugs "double-edged" swords? Can the two sides of opioid drugs be separated? Why is the effort worth working on it?

In what directions research on receptors is going trying to solve the crisis? Are there several strategies?

Discuss strategies for finding safer alternatives to opioids: from target point of view and/or mechanism point of view.

Are there safer pain killer commercially available?

Give a nut-shell statement about the research in this field at the present.

Answer 1

1)Usually opoids acts by blocking the mu,delta,kappa,nociceptin,zotin receptors. mu pain receptors that are located predominantly in the central nervous system either by partial/complete AGONIST or ANTAGONISTIC activity.By blocking mu reeptors in CNS it causes 2 effects-

on one hand it causes-REDUCTION IN PAIN AND RELIEF

on other hand it causes-EUPHORIC EFFECTS,TOLERANCE,DEPENDENCE and ADDICTION.

This bimodal effect is termed as DOUBLE EDGE SWORD which is best described as depending on drug for euphoric effects rather than analgesic effect.The side/additive effects cannot be avoided but reduced under Proper precise guidance and tolerable dose and with constant supervision.

2)When we studied the opoid receptors it was located all over the body.it inturn causes same effect on all receptors that are present in different parts of body for same drug.Reaserch helped to avoid unwanted effect by directing towars desired result.

There are some good startigies like SYNERGISTIC effect(which enhances the effect of drug at low doses)

for example ENDOCANNABINOID from marijuna have synergistic effect with opoid anlgesics and its receptors by enhancing thw action of opoid and giving good result from low dose of opoid.

Other startegy involves increasing opoid clearance in body by developing less shelf life opoids.

guiding the tolerance levels play a key role from misleading in to dependence.

3)Safer alternatives from point of entry to point of point of action on target,involves-

POINT OF ENTRY-Sub lingual route and intravenous route avoids first pass metabolism,which increases the efficacy of painkiller

PHARMCOKINETICS-

absorption-unionized form,water soulble drug,good bioavailability,

distribution-capillary permeability,hydrophobic form,plasma protein binding capacity,low lipid solublity,proper bio trnsformation.

metabolism-needed metabolism by microsomal/non;microsomal enzymes,proper optimal elimination.

PHARMACODYNAMICS-permabillity to ION channels,enzymatic or synerstic availability,avoiding drug-receptor interactions,proper dose response reltionship.no dependence and tolerance,addiction.

4)There is no such ideal drug that satisfies all the above criteria for ideal painkiller group but there are some alternatives that comes near to this and replaces opoids to some extent like NSAIDS-IBUPROFEN,ACETAMINOPHEN etc.we cannot bring perfect drug but we can develop a drug with less side effects and near to ideal nature,but not absolute ideal.

EXAMPLE 1)-opoid receptors present in brain and also in stomach;

in brain-pain control but in GIT-induces constipation.

EXAMPLE 2)-paracetmol decreses pain but also decreases prostaglandin synthesis which causes gastric ulcers.

To conclude it is impossible to constuct ideal drug due to multiple effects of drug.