Agents that decreases acute and some type of chronic pain
are referred as analgesics or analgetics.
Pain is defined as an unpleasant, sensory and emotional
experience associated with actual or potential tissue damage.
Pain is apart of our body’s defense system, it produces a
reflexive, retraction from the painful stimulus and to protect
the affected body part while it heals.
It is normally
E.g.: sprains &
It is unrelenting,
not-self limiting and
persist from months
Step:3 potent opioid +/-non
opioid or analgesic adjuvant.
Step:2 less potent opioid + non opioid
+/- analgesic adjuvant.
Step:1 non opioid +/- analgesic
The pharmacological management of pain is the foundation of
Analgesics can be classified as :
3. Adjuvant or co-analgesics.
Opioids are used for effective treatment of pain.
Non-opioids are effective analgesics for mild to moderate pain.
Adjuvant to some extent they give relief from pain , but are not
majorly used as analgesics. 7
Opium is the latex obtained from incisions
of unripe capsules of “papaver somniferum,” belongs
to family papaveraceae.
• Opium was well known to the ancients about 77 AD .
• It contains 30 alkaloids, the first group is morphine.
• Morphine consists of alkaloids which have a phenanthrene nucleus,
Whereas papaverine group have a benzylisoquinoline structure.
9 to 14
0.5 to 2
0.2 to 1
0.8 to 1
3 to 10
0.2 to 0.4
CLASS NAME OF
CHEMISTRY OF MORPHINE:
The morphine contains 5 rings.
It is ‘T’ shaped molecule.
(5α, 6α) 7,8-didehydro 4,5-epoxy 17-methyl morphinan
Natural morphine molecule exists as a single isomer.
Naturally occurring levorotatory (-) morphine has 5R,
6S, 9R, 13S, 14R configuration.
It undergoes epimerization at 14-position, but not
beneficial to analgesic activity.
Carbons at 5,6,9,13,14 positions are chiral centers.
CHEMICAL FEATURES OF OPIUM:
POSITION MODIFICATION EFFECTS
-OH to -OCH3
-OH to -OC2H5
Less analgesic, Cough
-OH to -OCH3
-OH to -OC2H5
5 × morphine.
2.4 × morphine.
-CH=CH- to –CH2CH2- 1.2 × morphine.
Tertiary nitrogen N-CH3 to NH
N-CH3 to NCH2CH3Ph
< active than
14 × morphine.
Morphine analogues were developed to combat the
problems due to usage of morphine.
1.VARIATION OF SUBSTITUENTS:
Alkylation of phenolic –OH and N-demethylation lead to
the loss of analgesic activity.
MORPHINE ANALOGUES AS CENTRAL
Introduction of OH group at C-14 increases activity.
Introduction of allyl cyclo propyl methylene group have
antagonist effect on NITROGEN atom.
E.g: Naltrexone, Naloxone.
allyl cyclo propyl methylene
Phenyl ethyl group increases activity by 14 folds.
A. Removing of ring E :-
Complete loss of activity.
NO ACTIVITY. 18
B.Removing of ring D:-
Removal of epoxy Bridge produces morphinan with
analgesic activity indicating oxygen is not essential for
C.Removing of ring C and D :-
Produces group of benzomorphous, which retain analgesic
D.Removing of ring B,C and D :-
It produces series of compounds known as 4-
The activity increases by 6 times by introducing the
CLASSIFICATION OF ANALGESICS & SAR:
Central analgesics are majorily classified into four types:-
1.Morphine &its analogues .
3.Diphenyl heptanones .
SAR OF MORPHINE & ITS ANALOGUES:
DRUG R1 R2 R3
Morphine -OH -OH -CH3 _
Heroin -OCOCH3 -OCOCH3 -CH3 _
Oxymorphine -OH =O -CH3 1,2
Levorphanol -OH -H -CH3 1,3
Codeine -OCH3 -OH -CH3 _
Oxycodone -OCH3 =O -CH3 1,2
1.Single bond instead of double bond between C-7 & C-8.
2. OH added to C-14.
3.No oxygen between C-5 & C-4.
SAR OF PHENYL PIPERIDERINES:
NAME R1 R2 R3 ANALGESIC
Meperidine -CH3 -C6H5 -COOC2H5 1.0
Properidone -CH3 -C6H5 -COOCH(CH3)2 15.0
Ketobemidone -CH3 -C6H4OH -OCOC2H5 6.2
α-Prodine -CH3 -C6H5 -OCOC2H5 5.0
SAR OF DIPHENYL HEPTANONES:
DRUG R1 R2
Methadone -COC2H5 -CH2CH(CH3)N
Isomethadone -COC2H5 -CH(CH3)CH2N
SAR OF BENZAZOCIN DERIVATIVES:
DRUG R1 R2
Pentazocine -CH2CH=C(CH3)2 H
Phenazocin -CH2CH2C6H5 H
Opioid receptors are of 3 types. They are µ , k , δ.
COMPOUND µ k δ
+ + +
+ + +
+ + +
+ + +
Opium and morphine are widely used as
analgesics to relieve pain.
Used as hypnotic.
Used to treat painful myocardial ischemia with pulmonary oedem.
Used to treat cough.
MANIFESTATION OF OPIATE WITHDRAWL:
6-12hrs Intense carving for the drug, lethargy,
12hrs Yawning, lacrimation, tremors &
48hrs Peak of withdrawal syndrome.
Fever, increase in B.P & heart rate.
7-10 days Symptoms clear up but restless, insomnia,
weakness & pain for several weaks. 33
Numerous reasons contribute to poisoning due to opioids.
It may occur due to clinical over dosage & many times when
drug is ingested in large amounts with suicidal intentions.
SYMPTOMS OF TOXICITY:
1. Coma, decreased respiration, pulmonary oedema.
2. Cyanosis, hypothermia, hypotension.
3. G.I spasm.
Toxic & Lethal Dose:
1.Re-establishment of vital function such as respiration and blood
circulation by the use of ABCD intervention.
2. Gastric lavage, which is done using KMnO4 solution,
followed by stomach wash with sodium sulphate.
3. If opioids are ingested through oral route, then emetics and
cathartics are used.
4.Respiratory depression can be reversed by the use of specific
antidotes like naloxone. 35
Dose for diagnosis of poisoning is 0.2-0.4mg
Dose should be repeated twice or thrice every 2-3
In neonates, respiratory depression which results
from administration of morphine to mother during
delivery, is treated using 10µg/Kg naloxone given
These are typically used to combat
The clinical features of inflammation have been
recognized since ancient times as swelling,
redness, pain & heat.
Inflammation can also cause disease due to
damage of healthy tissue.
ADJUVANT ANALGESICS IN THE TREATMENT OF
Antidepressants. Amitriptyline, Imipramine,
Antiepileptic. Gabapentin, Carbamazepine,
Topical. Ketorolac, lidocaine
Muscle Relaxation. Cyclobenzaprine, Baclofen.
Enkephalinase Inhibitors, Such as the
experimental drug RB120 Produce analgesia, together
with other Morphine – like effect, without causing
Agonists at nicotinic Ach receptors based on Epibatidine
(an alkaloid from frog skin), which is a potent nicotinic
agonist & unexpectedly a potent analgesic.
Pain management is a challenging task, as it adversely affects the
patient life style and there cannot be a permanent relief from the pain
due to terminal illness like cancer.
Use of medication depends on the symptom associated with disease
of the patient.
Now a days a variety of drugs are available in the market to combat
the consequences of pain.
They are useful for the treatment of the pain to improve the quality of
life of patient.
Foye’s principals of medicinal chemistry-7th edition(Pg:658-695).
Wilson & Gisvolds textbook of organic , medical & pharmacentical analysis –
Remingtions – The science & practice of pharmacy vol-II-22th
Basic & Clinical pharmacology by katzung – 11th edition(Pg:692-720).
Rang & Dale’s pharmacology-6th edition.
Trease & Evans pharmacognosy(Pg:357-363).
Pharmacology & Pharmacotherapeutics -R.S.Satoskar – 12th edition.