“ANALGESICS”

PRESENTED BY:
Dr. Manish Chandila
JR-2
 ain

It an ill-defined, 6asant
I evoked by an sensation, external
usually
noxious stimulus. or internal

l. "Pain" is defined by lASP(lnternational

¡ association for the study of pain): "an
unpleasant sensory and emotional experience
arising from actual or potential tissue damage
oi• described in terms of such damage"
 Cox-1
inhibitors
Ketorolac (Toradol):
Postopei'atively for max 5 days
Reduce amount of opioid requirement,
reduce S.E’s
• Dose= 15 — 30 mg l V /1 M Q6hrs
Margo Me CaJeéy (196 t defined
"w
pain:fever the person expe ncing says it is,
existing whenever he says it does.”

Analgesia: AbSence of pain in response to

stimulation which would normally be
painful (e.g. using drugs)

Nociceptor: A sensory receptor of

the peripheral (somatosensory nervous
system) that transmits noxious Stlmuli to
CNS.
 Noxiou' stim ulus that
ds is
I
tissues (chemical, mechanical, age to
or threatens
'
thermal) nonnal
Pain threshold: The miniinuln intensity of
a
stimulus that is perceived as painful.

Neuropathic pain: Pain caused

by a lesion or disease of the
nervous system.
impulse

Nucleus

To next
NoxİOUs
stimulus

łOUCh activities

Vœihel him
 Pe r i p h e ra l N e r v e F i b e r s
A- A- A-gamma A- B
ap h a bemi delta

mye lin

Dia me ter( 12-20 5- 12 5-12 1-3 O. 5- 1

Ve l o c i t y O-12O 3O -7O 30-TO 12-TO 14 1.2

function moo
Gate control escri by Melzack
tlieoJ Wall in i and
1965.
This theory explains about a pain-modulating
system in which a neural gate present in the spinal
cord can opcn and close thei'eby modulating the
perception of pain.

The gate control theory suggests that psychological

factors play a role iii the perception of pain.
It also suggests that physical pain is not a
direct result of activation of pain i'eceptor
neurons, but rather its perception is modulated
by interaction between different neurons.
The hree systems located in'the
spinal cord act to influence perception of
pain
SUBSTANTIA
GELATINOSA
 Cuoeate
touch. fa6c ulus
pressure,
›baion.

Lateral
sełno1hałamic
cervical

AM PAR
The sa1 horn is responsib for passing
information which can be interpreted as pain.
on
This area is referred to as the 'gate' as it
prevents the brain from receiving too much
information too quickly.
 conduction

1. Prii6’ary: from
‘nociceptors’/ thepei'iphera l'erriari'

nerve fibi'e
1 to the
dorsal
horn of the spinal cord.

2. Secondary: ft on the
dorsal
.i horn to the thalainus.

3. Tertiary: from
thalainus to
@lechagiam:

Trsbm» Receptors
C bers

Al'ferent Patliira;'

c « 1
igher centers R! cular Formation
halamus
PAG(periaqueductal gray)
}•iééve fij¿ers Inv
The smaller, unmyelen ted e t a ) and C nerve
fibers nse pain such as sha niiiig and
aching feelings.

Larger, myelenated A (beta) skin nerves which carry

senses of touch, heat, cold and pressure.

The A (beta) nerves are faster, and also have priority

which effectively blocks out the pain messages to
the brain and closes the gate.

Stimulation of the large-diameter fibers (A-F

ibers)
inhibits the transmission of pain (closing the gate)
Sti ulatiq of the S P e t e r fibers (C-Fibeis)

stimulates the transmission of pay

ening the Gate) When $hc gate is
closed, signals kowi small diameter‘ pain
fibers do not excite the dorsal horn
When the gaie
iransiiiission is opcn pain signals excite dorsal
neurons.
horn

transmission cells.

The gating mechanism is influenced by nerve

iiiipulses that descend front the brain

 and closing
the ggte are:

• The amount of activity in the pain fibers.

The amount of activity in other peripheral

fibers

• Messages that descend from the brain.

 • PhyNcal Pain - Analgesic Re dies
• Emotional Pain Being in a ‘good’ mood
• Behavioral Pactoi s - Concentrating on things
other than the injury
n Relaxation and Contentment
. —
• Mental factOrs: work T.V. book
• Activity - Taking exercise,
• counter-stimulation- heat, massage,
acupuncture
 Gate is ened
by
Physical Factors Bodily injury
• Emotional Factors Anxiety & Depression
° Bchavioral Factors - Attending to the injury
and
i co»cer mating en the train
• Lack of Activity —
• Mental Factor's
 O#igandcosmgogtmlu
dc ndsuponnun zousCa on:

• The brain provides

infomntion about the
psychological state of an
ng
and emotional states and
previous
Diagnostic
classification
A. Nociceptive
pain,

B. Neuropathic
pain,

C. Idiopathic pain.
 AyNociceptirJ pain
I. Somatic: well ed; e.g, skin,
II.
I Visceral: poorlybones
loealize .
organs
lo the activation of noci ebtors at the site Of
tissue damage. These types of pain can Results by
mechanical, chemical, or thermal stimulus, such as
surgery, traumatic injury, and inflammatory
processes.
lt is divided into either
1.Somatic: localized pain in skin, bones or
iiioscles, i joint. Or
2. Visceral: poorly lOcalized (may be referred to
other areas)located in organs, characterized by
having deep pressure like squeezing.
B. Neuropathic pain
:I. Centralvfiocalized and difhisi ng,
dipain e.g. CNS stabbing
II. Perlpheral: localized neuropathies
Results from damage of afferent nerve fibers,
characterized by burning, stabbing, electi ical
numbing, radiating shooting pain. Either to CNS,
or to peripheral which further divides into
polyneuropathy, or rnooonetiropatliy (e.g. diabetic
neui•opathy)
C. Idiopathic

1. Usually in head, shoulders, or pelvic

areas.
2. Results of non-specific origin. due to
stress, anxiety, depression, or cold pressure
e.g. head, shoulders, abdomen, and pelvic
ai'eas.
C L I NI CA L TYPES

1. Acute pain
2. Chronic pain
 TO It I C p a I £1
Resu noxious noeiceptors,
from that ’
nociceptors activates
neuron
It accompanies 't It accompanies
traumatic injury. s chronic
damage, and u disease, untreated condition.
inflammatory r
¡ g
processes. e r resolYed as long
as
• Self-limited, resolves overr
persist for 3 months y, underlying cause is present.
days to weeks, but ter can
Treatment is ti
m s approaches.
 CAT T OF -
ALGESTCS
1. Non-Opioids,

2. Opioids,

; 3. Adjuvants.
. NON-OPIOIDS
 8
Inhiblt
*
Toradol il, Neumfen,
g PO, 4- Brufen)
6hrly ñ
Diclofenac
Mcfanemic Na/K
acid (Ponstan):- in acute pain-500mg PO,
(Voltar
once/day
Naproxen (Naprosyn)500mgPO 8hrly

Cox-2 Inhibitors
Celebrex (Ce1ecoxib)100-200rng PO
twice/day Etoricoxib (Arocoxia)
Meloxicam (Mobic)
Co 2
inhibitors:
Effective anti-inflammatory in
anhritis Carry cardiovascular risk
warning
Less GI S.E’s
 bleeding

Gastric erosions/ ulceration/

perfusion
Affect kidney funGtion:
' -Watei• / e1ecti•olyte balance
-Interfere with
diuretics/antihypertensive
-Renal injury / ncphi'otic
2. OPİOIDS TIC A GES CS
NA
 /
NAR
h broa'n, iesinous’ m rial ob
soinnifetjp ikaloids.

Phensnthrene dcrivatix'cs
Morphine t10% in opium 15 to 30 in orally every 4 hours as
Codcine t0.5% in opium needed
Tliebaioe (t1.2% in tipiuM),15 to 60 nip up to every 4 hours as needed

I Beuzoisoquintiline derivalives
Papavcrine ( l "/• l i
Nonaiiagcslc i 30 tt› f›0 mill igi atas
(ilig l iiijcctitiii
Noscapioc l f%, )
Noiiaiiagcslc
(50 Mg8 mostri yPO)
 Morphine is the principal alkaloid in opium
and still widely used. Therefore, it is
described as prototype.
; (a firsi or preliminary version from which oiher fonns
are
clevelopecl.)
 Mode of action

• Effects located in the Central Nervous System

• Specific receptors in the brain fbr diñbrent narcotics
lead to different side ef'fects

Analges& Euphoria

, •> Analgesia Sedation

6 -receptor (c ...”›e›• J
•> Analgesia Dysphoria
Morp has Site specific d ssañT nd stimulant
in the CNS by interacting primarily with ltte 1-1
actions
opioid
receptor as a full agonist. The depressant actions are:

1. Analgesia Morphine is a strong analgesic.

2. Sedation which is different from that produced

by hypnotics is seen. Drowsiness and indifference
to surroundings as well as to own body occurs without
motor in-coordination, ataxia or apparent excitement
(contrast alcohol). Higher doses progressively induce
3. Mood and ’ects Thcse
areprominent. Morphine has a calming effect; there
is loss of apprehension, feeling of detachment,
lack of initiative, limbs feel heavy and body
warm, iiiental clouding and inability to
concentrate occurs.

4. Respiratory centre Morphine depresses

rcspiratory ccntrc in a dosc dependcnt inannci;
rate and tidal volume are both decreased: death in
poisoning is due to respiratory failure.
 5. Cofigh centre: more sensitive to
morpliine than respiratory centre.

6. Temperature regulating centre: lt is

depressed; hypothermia occurs in cold
¡ surroundings.

7. Vasomotor centre: lt is depressed at higher

doses and contributes to the fall in BP.
 “ . :. . ”* ”J
1. H alamic influence p htm is
reduced.
2. As a result FSH, LH, ACTH levels are lowered,
while prolactin and GH lerels are raised (these
are under predominant inhibitory control).
3. The sex honnone and corticosteroid levels are
lowered in the shoe term, but tolerance develops in
the long term.
' 4. Only few chronic abusers suffer from loss of
libido, impotence, menstrual irregularities and
infeoility.
5. Morphine can release ADH and reduce urine
volume.
 Mob arses vasodilatation
due
“ release. ’ y'..
1. direct
3. histamaction decreasing toqe of blood vessels.
deoressi
There is a shift of blood from pulmonary to systemic circuit
due to greater vasodilatation in the latter. Therapeutic doses
cause little change in the BP of recumbent norrnovolaemic
patient. Postural hypotension and fainting do occur due to
impairment of vascular reflexes. Morphine has little direct
effect on heart; rate generally decreases due to stimulation of
vagal centre, but may increase reflexly if the BP falls.
Cardiac work is consistently reduced due io decrease in
peripheral resistance. Intracranial tension tends to rise as a
consequence of CO2 retention leading to cerebral
vasodilatation.
 ation is a pront few Morphine action.
'factors contribute:
1. Actinn directly on intestines and in S increases tone
and segiiientation but decreases impulsive movements.
Tone of duodenum and colon may be increased to the level
of spasm.

2. Spasm of pyloric, ileocaecal and awal spliincters.

3. Decrease in all gastrointestinal secretions: reduction in

transfer of water and electrolytes from mucosa to the
lumen. Absorption of fhiid is increased due to stasis.

4. Central action causing iiiattention to defecation reflex. No

tolerance develops to this action: addicts i ordain
chronically constipated.
 e)z THER 8 J O O T

aryJact:- Morphine causes spa of sphincter of

Oddi —• intrabiliary pressure is increased —+ may
cause biliary colic.
2. Urinary bladder:- Tone of both detrusor and
sphincter is increased —+ urinary iirscncy
and difficulty iii inicturitioii. Conti'actions of
rii'eter are also iiicreascd.
3. Uterus: The action is clinically insignificanl,
may
i s1›shtly prolong labour.
4. Broiichi:- Moiphine releascs histamine which can
cause broBchoconstriclion. This is of no consequence in
iioi'inal individuals, but can be dangerous in astliiratics.
 1. The orgt abso tion ofrnorphine iJ’ able because of
high able first pass metabolism; bioavailability
1/4t1i of parenterally administered
is
drug.
2. About 30°Zo is bound to plasma proteins.
3. Concentration in liver, spleen and kidney is higher than
that
in plasma. Only a small fraction enters brain rather slowly.
4. Morphine freely crosses placenta and can affect the foetus
more than the mother.
. 5. It is primarily metabolized in liver by glucuronide
i conjugation.
6. Effect of a parenteral dose lasts 4--6 hours.
7. Elimination is almost complete in 24 hours and morphine
is
nonciimulative.
8. Small amounts may persist due to enterohepatic
:'ADVERSVEFFEC

Nausea and vomiting

Constipation
BP may fall,
cspecially in
hypovolaeiuic
patient.
Irritable inoveincnt
Psycho mimetic cffects
Sedation
Bronclio-constrictioii
Respiratory Depressioii
 hine

It is accidental, suicidal or seen in drug abusers.

In the non-tolerant adult, 50 rug of loorphine I.M.
produces serious toxiCity. The human lethal dose
(amount of dose that can cause death) is
estimated to be abotit 250 mg. ManifestatiOns
are extensions of the phannacological action.
 Stu r or’ coma, (impaired c
iousness) flaccidity, (lack of muscle tone,
reflexes)
deep tendon
SlâRJlOw and occasional
breathing, cynosis,
pinpoint pupil,
fall in BP and shock
' convulsions may be seen in few patients,
pulmonary edema occurs at tenninal
stages, death is due to respiratory failure.
 rcspiration also

2. Maintenance Of B.P. (I.V. fluids, vasoconstrictors).

3. Gastric Lavaee should be done with potassium

permanyanate to remove unabsorbed drug. Lavage is
indicated even when morphine has been injected; being a
basic drug it is partitioned to ihe acid gastric juice,
ionizcs there rind does not diffuse back into blood.

1 4. Specific antidnte: Nal Eone tl.4-0.8 mg l.V. repeated everv 2-

3 min till respiration picks up. is the preferred spcc›1ic
antagonist becausc it does not have any agonistic action and
does not per se depress respiration.