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4
MECHANISM OF PAIN 5
PAIN MANAGEMENT
If pain
persist
1. Opioids.
2. Non-opioids.
3. Adjuvant or co-analgesics.
Adjuvant to some extent they give relief from pain , but are not
7
majorly used as analgesics.
OPIUM
8
NAME OF % OF
CLASS OPIUM
DRUG
PRESENT
Morphine 9 to 14
Phenanthrene Codeine
series 0.5 to 2
Thebaine 0.2 to 1
9
CHEMISTRY OF MORPHINE:
IUPAC NAME:
10
MORPHINE
2
HO 3 1
A
4 11
12 B 16 10
O D E N-CH3
13(S) 9 (R) 17
5 (R)
C 14
(S)
H
8
6
HO 7
11
STEREOCHEMISTRY:
12
CHEMICAL FEATURES OF OPIUM:
14 × morphine.
MORPHINE ANALOGUES AS CENTRAL
ANALGESICS:
1.VARIATION OF SUBSTITUENTS:
14
2.DRUG DESECTION:
Introduction of OH group at C-14 increases activity.
HO
O
N-CH3
14
OH
OXYMORPHINE
15
Introduction of allyl cyclo propyl methylene group have
antagonist effect on NITROGEN atom.
HO
allyl cyclo propyl methylene
O
N
NALTREXONE 16
Phenyl ethyl group increases activity by 14 folds.
HO
O
N
Phenyl ethyl
HO
17
3.SIMPLIFICATION :
A. Removing of ring E :-
HO
NO ACTIVITY. 18
B.Removing of ring D:-
Removal of epoxy Bridge produces morphinan with
analgesic activity indicating oxygen is not essential for
activity.
HO HO
N
NH
LEVORPHANOL LEVALLORPHAN
19
C.Removing of ring C and D :-
Produces group of benzomorphous, which retain analgesic
activity.
OH
H N
N CH3
CH3
CH3
CH3
CH3
PHENAZOCIN
METAZOCINE
20
D.Removing of ring B,C and D :-
N
C2H5OOC
N
FENTANYL
21
CLASSIFICATION OF ANALGESICS & SAR:
Central analgesics are majorily classified into four types:-
2.Phenyl piperidines.
3.Diphenyl heptanones .
4.Benzazocin derivatives.
O
N R3
22
R2
R1 R2 R3 OTHER
DRUG CHANGES
-OH -OH -CH3 _
Morphine
Heroin -OCOCH3 -OCOCH3 -CH3 _
NAME R1 R2 R3 ANALGESIC
ACTIVITY
Meperidine -CH3 -C6H5 -COOC2H5 1.0
R2
R1
DRUG R1 R2 ANALGESIC
ACTIVITY
Methadone -COC2H5 -CH2CH(CH3)N 1
(CH3)2
25
O
Dextromoramide N
13
O C N
H
SAR OF BENZAZOCIN DERIVATIVES:
C
CH3 N R 1
R2
CH3
DRUG R1 R2
Pentazocine -CH2CH=C(CH3)2 H
Phenazocin -CH2CH2C6H5 H
Cyclozocin C
H
Ketazocin C
=O 26
SYNTHESIS OF METHADONE:
METHADONE 27
SYNTHESIS OF MPERIDINE:
CN Cl
spiroalkylation N
+ NH 2
COOC2H5
MEPERIDINE
28
MECHANISM OF ACTION:
Opioid receptors.
Causes hyper polarization & shows inhibitory pathway & relieves pain.
29
RECEPTORS
Opioid receptors are of 3 types. They are µ , k , δ.
COMPOUND µ k δ
PURE AGONIST:
Morphine +++ + +
+++ 0 0
Methadone
+ + 0
Codeine
PARTIAL ANTAGONIST:
Bupreorphine +++ _ 0
++ +++ 0
Butraphanol
++ 0 0
Propiram 30
USES:
Opium and morphine are widely used as
Used as hypnotic.
Euphoria, sedation.
Pupillary constriction.
31
ADVERSE EFFECTS:
Respiratory depression.
Hypotension.
Constipation.
Urinary retention.
CNS problems:
Mental clouding
Nausea.
Vomiting.
Headache.
Fatigue.
Tolerance.
Drug dependence.
32
MANIFESTATION OF OPIATE WITHDRAWL:
TIME MANIFESTATION
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.
3. G.I spasm.
34
Toxic & Lethal Dose:
Toxic dose-60mg.
Lethal dose-250mg.
TREATMENT:
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
DOSAGES:
37
CLASSIFICATION:
38
6.Oxicams: Pyroxicam, Meloxicam.
MECHANISM OF ACTION:
inhibitors of co-activity.
Co-enzymes.
1. Salicylates.
3. 3,5-pyrazolinediones.
4. Pyrazoline derivatives.
40
SALICYLATES: COOR 1
OR2
DRUG R1 R2
Salicylic acid H H
sodium salicylate Na H
NHCOCH 3 NHCOCH3
0C 2H5
PHENACITIN
ACETANILIDE
NHCOCH3
OH
PARACETAMOL
42
3,5-PYRAZOLINEDIONES:
H O
R4
N
O
N
DRUG R R4
Oxyphenbutazone OH -C4H9
43
Sulphinpyrazone H -(CH2)2SOC6H5
PYRAZOLONE DERIVATIVES:
CH 3
R4
O
N R2
N
DRUG R2 R4
Antipyrine CH3 H
Aminopyrine N(CH3)2
CH3
R1
R2
NH
R3
DRUG R1 R2 R3
Mefinamic acid CH3 CH3 H
46
SYNTHESIS OF PARACETAMOL:
47
SYNTHESIS OF NIMESULIDE:
48
SYNTHESIS OF MELOXICAM:
49
SYNTHESIS OF IBUPROFEN:
IBUPROFEN
50
USES:
Anti-inflammatory.
Analgesic.
Anti-pyretic.
Rheumatoid arthritis.
Oseto arthritis.
Gout.
Myocardial infraction.
51
52
NSAIDs GROUP SPECIFIC ADVERSE EFFECTS.
ADJUVANT ANALGESICS IN THE TREATMENT OF
PAIN:
CLASS DRUGS
Antiarrhythmics. Mexiletine.
Steroids. Prednisone. 53
They are useful for the treatment of the pain to improve the quality of
life of patient.
55
REFERENCES:
Foye’s principals of medicinal chemistry-7th edition(Pg:658-695).
12th edition(Pg:776-805).
edition(P.g:2679&2682).