3. CONTENTS
•
•
•
•
•
•
•
PHASES OF PAIN
METHODS IN PAIN CONTROL
WHO LADDER ANALGESICS REGIME
CLASSIFICATION OF ANALGESICS
APPLICATION OF ANALGESICS IN OMFS
RECENT ADVANCES IN PAIN CONTROL
REFERENCES
4. Pain
Derived from Greek ”Poin”; meaning penalty.
• Derived
from
Latin
punishment from God
“Poena”;
meaning
5. PHASES OF PAIN
• A) Phases I (Acute nociceptive pain ) :
• brief noxious stimuli--fairly simple & direct route-- centrally towards the
thalamus & cortex --- conscious perception of pain-- possibility for
modulation -- synaptic relays along the way
• Close correlation the discharges in peripheral nociceptors & subjective
expression pain
6. B)
Phase 2 ( Inflammatory pain )
•
Noxious stimulus very intense or prolonged
•
tissue damage & inflammation .
Increased activity and responsiveness of sensitized nociceptors.
•
Increased afferent inflow to CNS from injured area
•
Nociceptive neurons in spinal cord modify their responsiveness.
7. C)
Phase 3(NEUROPATHIC PAIN)
• Symptom of neurological disease
•Lesions of peripheral nerves or damage to any portion of
somatosensory system within the CNS.
• Spontaneous pain ,triggered by innocuous stimuli or are exaggerated
responses to minor noxious stimuli.
•Probable reason
1) Pathological changes in damaged neurons
2) Reactive changes in response to nociceptive afferent input and
to loss of portions of the normal afferent inputs
8.
9. Pain is perfect misery, the worst of evils, and excessive,
overturns all patience”.
John Milton (1608- 1674) Paradise Lost.
One of the greatest services doctors can do their patients
is to acquire skill in the management of pain.
12. Methods of pain control
•
•
•
•
•
Removing the cause.
Blocking the pathway of painful impulses.
Raising the pain threshold.
Preventing pain reaction by cortical depression.
Using psychosomatic methods.
13. Removing the cause
• It is the desirable method of controlling pain.
• If it is accomplished, the environmental change in tissue would
be eliminated.
• Free nerve endings would not be excited and no impulses
would be initiated.
• This method clearly affects pain perception.
14. Blocking the pathway of painful impulses
• It is the most widely used method in dentistry for controlling
pain.
• A suitable drug, possessing local anesthetic properties is
injected into the tissues in proximity to the nerves involved.
• It prevents depolarization of the nerve fibers at the area of
absorption, thus preventing those fibers from conducting any
impulses beyond that point.
• This method of pain control is possible by interfering with pain
perception.
15. Raising the pain threshold
• It depends on the pharmacologic actions of the drugs
possessing analgesic properties.
• These drugs raise the pain threshold centrally and therefore
interfere with pain reaction.
• The cause of the organic stimulus may still be present.
• Pain perception is unaffected, but pain reaction is decreased
and thus pain reaction threshold is raised, but it is impossible to
eliminate all pain of the most severe nature.
16. Preventing pain reaction by cortical depression
• Eliminating pain by this method by general anesthesia and
general anesthetic agents.
• The agent, by increasing depression of the CNS, prevents any
conscious action to a painful stimulus.
17. • Using psychosomatic methods
•
Relaxation Training
Relaxation involves concentration and slow, deep breathing to release tension
from muscles and relieve pain. Learning to relax takes practice, but relaxation
training can focus attention away from pain and release tension from all muscles.
Relaxation tapes are widely available to help you learn these skills.
•
Biofeedback
Biofeedback is taught by a professional who uses special machines to help you
learn to control bodily functions, such as heart rate and muscle tension. As you
learn to release muscle tension, the machine immediately indicates success.
Biofeedback can be used to reinforce relaxation training. Once the technique is
mastered, it can be practiced without the use of the machine.
•
Visual Imagery and Distraction
18.
19. The WHO advocates “This stepped approach of
administering the right drug in the right dose at the right
time is inexpensive and generally effective in managing
acute pain.
Simplicity,
Flexibility to a large variety of pain situations and also to
prescribers globally.
Emphasis on multimodal analgesia.
Its disadvantages include:
It may be too simplistic for management of certain types of
pain, especially neuropathic pain or for those who are
opioid dependant.
References
Organisation W. Analgesic Ladder. World Health
Organization; 1986.
21. PROSTANOIDS (PGs & Txs)
PGI2 (prostacyclin) is located
predominantly in vascular
endothelium. Main effects:
•vasodilatation
•inhibition of platelet aggregation
TxA2 is found in the platelets.
Main effects:
•platelet aggregation
•vasoconstriction
22. PGE2 causes:
• inhibition of gastric acid secretion
•contraction of pregnant uterus
•contraction of GI smooth muscles
PGF2α – main effects:
•contraction of bronchi
•contraction of miometrium
23. Cyclooxygenase (COX) is found
bound to the endoplasmatic
reticulum. It exists in 3 isoforms:
• COX-1 (constitutive) acts
in physiological conditions.
• COX-2 (inducible) is
induced in inflammatory cells
by pathological stimulus.
• COX-3 (in brain).
30. NSAIDs
Main actions
1.) Analgesic -effective against mild to moderate pain, do not
cause dependence
2.) Anti-inflammatory
3.) Anti-pyretic
4.)Anti-platelet- prevent thromboxane production, derived from
prostaglandins and cause platelet aggregation
Others
5.) Useful in treatment of dysmenorrhea, associated with
increased prostaglandin synthesis and increased uterine
contractility
6.) Used to close the patent ductus arteriosus
31. NSAIDs
Adverse effects
1.) Gastric or intestinal mucosal damage
- mucosal prostaglandins inhibit acid secretion, promote mucus
secretion, prevent back diffusion of acid into the gastric submucosa
- Inhibition thus results in erosions, ulceration, bleeding, perforation
2.) Disturbances of fluid and electrolyte balance
- inhibition of renal prostaglandin production results in sodium retention
and oedema, possible hyponatraemia, hyperkalaemia, antagonism of antihypertensive agents
3.) Analgesic nephropathy
- due to long term ingestion of mixtures of agents
- chronic interstitial nephritis, renal papillary necrosis, acute renal
failure
32. NSAIDs
Acetaminophen
• equivalent analgesic efficacy to aspirin
• no useful anti-inflammatory action
used for mild to moderate pain, but aspirin is preferred if due to
inflammatory process Metabolism
• is conjugated in the liver as the inactive glucuronide and sulphate
• a number of minor oxidation products inc.
N-acetylbenzoquinoneimine (NABQI) are also formed
• NABQI is highly chemically reactive and is usually inactivated by
conjugation with SH (thiol) groups of glutathione
• Supply of glutathione is limited and exhausted in overdose
NABQI then reacts with cellular macromolecules and causes cell death
Adverse effects
• rare in therapeutic usage
• occasional skin rash and allergy
• Overdose can result in fulminant hepatic necrosis and liver failure
33. Paracetamol overdose
• Ingestion of >4g of paracetamol may be fatal
• may be lower in chronic alcoholics or subjects with
underlying liver disease.
Clinical features
In severe poisoning
• up to 24 hours none or nausea and vomiting
• > 24 hoursnausea and vomiting, right
upper quadrant pain, jaundice,
encephalopathy
35. Metabolism of
Basic & Clinical Pharmacology – 10th Ed. (2007)
paracetamol
to hepatotoxic
metabolites
(NABQI etc.)
(GSH – glutathione;
SG – glutathione moiety)
Daily dose > 4gm
hepatotoxicity
and
nephrotoxicity
NB: Acetylcysteine and GSH
contain –SH groups.
NABQI
36. Management
• Blood for paracetamol at 4 hours post ingestion
• Check treatment curve for N-acetylcysteine infusion ( if
in doubt of severe poisoning, don’t delay)
• Check prothrombin time and plasma creatinine, pH
• acute renal (due to acute tubular necrosis) and hepatic
failure and occur at 36-72 hours after ingestion
• Indications for referral to liver unit are
- rapid development of Grade 2 encephalopathy
- PTT >45 secs at 48 hours or >50 secs at 72 hours
- rising plasma creatinine
- Arterial pH <7.3 more than 24 hours after ingestion
37. Bark of willow tree was used in folk medicine for years for mild pain and fever.
Salicylic acid was obtained by hydrolysis of the bitter glycoside obtained from
this plant.
Acetylsalicylic acid was synthesized in 1853
1875 sodium salicylate was used in fever and pain.
1899 it was found to be effective in arthritis and was well
tolerated.
38. Aspirin (acetyl salicylate)
Actions
• Analgesic - central and peripheral action
• Antipyretic - act in hypothalamus to lower the set
point of temperature control elevated by fever, also
causes sweating
• anti-inflammatory - inhibition of peripheral
prostaglandin synthesis
• respiratory stimulation direct action on
respiratory centre, indirectly by ↑ CO2
production
39. Effects of NSAIDs
1. Analgesic and antipyretic action
Aspirin is a weaker analgesic than morphine-type drugs
Aspirin 600 mg < Codeine 60 mg < 6 mg Morphine
Aspirin relieves inflammatory, tissue injury related,
connective tissue and integumental pain but is relatively ineffective in severe visceral and ischemic pain.
The analgesic action is mainly due to obtunding peripheral pain receptors and prevention of PG mediated
sensitization of nerve endings. A central subcortical
action, raising threshold to pain perception also contri-
butes.
No sedation, tolerance, and dependence are produced.
40. Aspirin (acetyl salicylate)
• Metabolic effects
i.) ↑ peripheral O2 consumption (uncoupled oxidative
phosphorylation) hence ↑CO2 production with ↑
respiration, and direct analeptic action - respiratory
alkalosis
ii) renal loss of bicarbonate with sodium, potassium
water
iii) dehydration
iv) metabolic acidosis - effects on Krebs cycle, ↑ ketone
body, salicylic acid in blood, renal insufficiency due
to vascular collapse, dehydration
v) hypoglycaemia or even hyperglycaemia can occur
41. Aspirin (acetyl salicylate)
• Uricosuric effects
reduces renal tubular reabsorption of urate but treatment of
gout requires 5-8g/d, < 2g/d may cause retention of urate.
antagonises the uricosuric action of other drugs
• Reduced platelet adhesion- irreversible inhibition of COX by
acetylation, prolongs bleeding time, useful in arterial disease
Note: low doses are adequate for this purpose since the
platelet has no biosynthetic capacity and can not regenerate
the enzyme
• Hypothrombinaemia : occurs with large doses ie >5g/day
42. Alcohol increases
GI toxicity of NSAIDs.
. Urate excretion. Aspirin in high dose reduces renal
tubular excretion of urate (both substances are transported by the same mechanism).
43. .
GIT. Aspirin and its metabolite salicylic acid irritate
gastric mucosa and cause epigastralgia, nausea, and
vomiting. In higher doses it also stimulates CTZ.
Aspirin (pKa 3.5) remains unionized and diffusible in
the acid gastric juice, but on entering the mucosal cell
(pH 7.1) it ionizes and becomes indiffusible. This
“ion trapping” in the gastric mucosal cell enhances
gastric toxicity.
44. Uses of Aspirin® (Bayer, 1899)
As analgesic (300 to 600 mg during 6 to 8 h) for headache, backache, pulled muscle, toothache, neuralgias.
As antipyretic in fever of any origin in the same
doses as for analglesia.
.
Acute rheumatic fever. Aspirin is the first drug of
choice. Other drugs substitute aspirin only when it
fails or in severe cases. Antirheumatic doses are 75 to
100 mg/kg/24 h (resp. 4–6 g daily) in the first weeks
.
Rheumatoid arthritis. Aspirin a dose of 3 to 5 g/24 h
after meal is effective in most cases. Since large
doses of aspirin are poorly tolerated for a long time, the
new NSAIDs (diclofenac, ibuprofen, etc.)
45. Aspirin (acetyl salicylate)
OVERDOSAGE
• Ingestion of > 10 g can cause moderate/severe
poisoning in an adult
• Clinical features - ‘salicylism’
tremor, tinnitus, hyperventilation, nausea,
vomiting, sweating
• Management- mainly supportive
46. Aspirin therapy in children with rheumatoid arthritis
has been found to raise serum concentration transaminases, indicating liver damage. Most cases are
asymptomatic but it is potentially dangerous.
An association between salicylate therapy and
“Reye’s syndrome”, a rare form of hepatic
encephalopathy seen in children, having viral infection
(varicella, influenza), has been noted.
Aspirin should not be given to children under 15
years unless specifically indicated, e.g. for juvenile
arthritis (paracetamol is preferred).
Postmyocardial infarction and poststroke patients.
By inhibiting platelet aggregation in low doses (100 mg
daily) aspirin decreases the incidence of reinfarction.
48. Drug interactions with NSAIDs
Drugs
Diuretics
Beta-blockers
ACE inhibitors
Anticoagulants
Sulfonylurea
Cyclosporine
Alcohol
Result
Decrease diuresis
Decrease antihypertensive effect
Decrease antihypertensive effect
Increase of GI bleeding
Increase hypoglycemic risk
Increase nephrotoxicity
Increase of GI bleeding
49. Ibuprofen is a derivative of phenylpropionic acid.
In doses of 2.4 g daily it is is equivalent to 4 g
of aspirin in anti-inflammatory effect. Oral ibuprofen is
often prescribed in lower doses (< 2.4 g/d), at which
it has analgesic but not antiinflammatory efficacy.
A topical cream preparation is absorbed into fascia and muscle.
A liquid gel preparation of ibuprofen provides
prompt relief in postsurgical dental pain.
It is effective in closing ductus arteriosus in preterm infants,
with much the same efficacy as indometacin.
50. Ketoprofen is a propionic acid derivative that
inhibits both COX (nonselectively) and lipoxygenase.
Concurrent administration of probenecid elevates
ketoprofen levels and prolongs its plasma half-life.
The effectiveness of ketoprofen at dosages of
100–300 mg/d is equivalent to that of other NSAIDs
in the treatment of rheumatoid arthritis, osteoarthritis,
gout, dysmenorrhea, and other painful conditions.
In spite of its dual effect on prostaglandins and
leukotrienes, ketoprofen is not superior to other
NSAIDs. Its major adverse effects are on the GIT
and the CNS.
Phenylbutazone is a derivative of pyrazolidinedione
with a high GI toxicity. It is rarely used now.
51. Indomethacin is a potent nonselective COX inhibitor
and may also inhibit phospholipase A and C, reduce
neutrophil migration, and decrease T cell and B cell
proliferation. Probenecid prolongs indometacin's
half-life by inhibiting both renal and biliary clearance.
Indometacin is indicated for use in juvenile rheumatoid
arthritis, gout and ankylosing spondylitis, etc.
It has been used to treat patent ductus
arteriosus.
An ophthalmic preparation seems to be
efficacious for conjunctival inflammation and to reduce
pain after traumatic corneal abrasion. Gingival
inflammation is reduced after administration of
indometacin oral rinse.
A high incidence (up to 50%) of GI and CNS side effects is produced: GI bleeding,
diarrhoea, frontal headache, mental confusion, etc.
52. Diclofenac is a phenylacetic acid derivative.
A 0.1% ophthalmic preparation is recommended for
prevention of postoperative ophthalmic inflammation
and can be used after intraocular lens implantation
and strabismus surgery. A topical gel containing
3% diclofenac is effective for solar keratoses.
Diclofenac in rectal suppository form can be
considered a drug of choice for
analgesia and postoperative nausea. It is also
available for intramuscular and oral administration
(Voltaren® and Feloran® – SR tablet: 100 mg/24 h).
Side effects occur in approximately 20%: GI distress
and occult bleeding, gastric ulceration. A preparation
combining diclofenac and misoprostol (PGE1) decreases upper GI ulceration but may result in diarrhoea.
53. • Postoperative analgesia in orthognathic
surgery patients: diclofenac sodium or
paracetamol
?
•
•
Ayşegül Mine Tüzüner Öncül, Emre Çimen, , Zuhal Küçükyavuz, Mine Cambazoğlu
Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Ankara University, Besevler, Pe
•
. Thirty patients were randomly allocated into two groups (n = 15 in each) using sealed
envelopes. The first group was given paracetamol 1 g intravenously and the second
diclofenac sodium 75 mg intramuscularly. The analgesics were given during the last 15
min of the operation while the mucosa was being sutured. The number of requests for
further analgesia, and the amount of analgesia given postoperatively (as diclofenac
sodium) were recorded. The intensity of postoperative pain was recorded on a visual analogue scale (VAS),
and postoperative requests for analgesia, haemodynamic variables (systolic blood pressure and heart rate), and
complications were compared. The groups were comparable. A single dose of diclofenac or
paracetamol effectively decreases the intensity of postoperative pain after bimaxillary
osteotomy.
British Journal of Oral and Maxillofacial
Surgery
Volume 49, Issue 2, March 2011,
54. PYRROLO-PYRROLE DERIVATIVE
(Ketorolac)
Ketorolac A novel NSAID with potent analgesic and
modest anti-inflammatory activity.
In postoperative pain it has equaled the efficacy of
morphine
no interaction with opioid receptors and is free of
respiratory
depressant,
dependence
producing, hypotensive and constipating side effects.
55. Pharmacokinetics Ketorolac is rapidly absorbed after oral and i.m.
administration. It is highly plasma protein bound and
60% excreted unchanged in urine. Major metabolic
pathway is glucuronidation; plasma t1/2 is 5-7 hours.
56. Adverse effects Nausea, abdominal pain, dyspepsia,
ulceration, loose stools, drowsiness, headache, dizziness,
nervousness, pruritus, pain at injection site, rise in
serumtransaminase and fluid retention have been noted..
No significant drug interactions have been reported and it
has been used concurrently with morphine. However, it
should not be given to patients on anticoagulants.
.
57. Piroxicam, an oxicam (enolate derivative), is a
nonselective COX-1/COX-2 inhibitor that at high
concentrations also inhibits polymorphonuclear
leukocyte migration, decreases oxygen radical
production, and inhibits lymphocyte function.
Its long half-life permits once-daily dosing.
Toxicity includes GI symptoms (20%
of patients), dizziness, tinnitus, headache, rash.
When piroxicam is used in dosages higher than
20 mg/d, an increased incidence of peptic ulcer
and bleeding is encountered. This risk is as much as
10 times higher with piroxicam than with other NSAIDs.
59. • Coxibs are selective COX-2 inhibitors. They exert
• antiinflammatory, analgesic, and antipyretic
action
• with low ulcerogenic potential. Coxibs can cause
• infertility. They have prothrombotic
cardiovascular
• risk. The ulcerogenic potential of preferential
• COX-2 inhibitors Meloxicam, Nabumetone, and
• Nimesulide (Aulin®) is significant
60. SULFONANILIDE DERIVATIVE
(Nimesulide )
Nimesulide- this newer NSAID is a relatively weak
inhibitor of PG synthesis (may be somewhat selective for
COX-2); appears to exert its effects by other mechanisms
like reduced generation of superoxide by neutrophils,
inhibition of PAF synthesis and TNF release, free radical
scavanging, inhibition of metalloproteinase activity in
cartilage.
62. Celecoxib is as effective as other NSAIDs in the
treatment of rheumatoid arthritis and osteoarthritis,
and in trials it has caused fewer endoscopic ulcers
than most other NSAIDs. Probably because it is
a sulfonamide, celecoxib may cause rashes.
It does not affect platelet aggregation at usual
doses.
63. Meloxicam is an enolcarboxamide related to
piroxicam that has been shown to preferentially
inhibit COX-2 over COX-1, particularly at its lowest
therapeutic dose of 7.5 mg/d. It is not as selective
as the other coxibs and may be considered “
preferentially" selective rather than
“highly” selective.
The drug has been approved for the treatment
of osteoarthritis and rheumatoid arthritis.
It is associated with fewer clinical GI
symptoms and complications than piroxicam,
diclofenac, and naproxen. Other toxicities are
similar to those of other NSAIDs.
64. NSAIDs
Non selective Vs selective COX2 inhibitors
↑ risk of cardiovascular adverse events with COX 2
inhibitors
• Rofecoxib was withdrawn from the market
• Higher BP, incidence of myocardial infarction, stroke
• Mechanism _ ? Unopposed effect of
cox
1
action
- ? Block protective effect of COX2 on
ishaemic myocardium or atherogenesis
68. Beneficial actions of NSAIDs due
to prostanoid synthesis inhibition
1. Analgesia
prevention of pain nerve ending sensitization
2. Antipyresis
connected with influence of thermoregulatory
centre in the hypothalamus
3. Antiinflammatory action
mainly antiexudative effect
4. Antithrombotic action
in very low daily doses
5. Closure of ductus arteriosus
69. Shared toxicities of NSAIDs due
to prostanoid synthesis inhibition
1. Gastric mucosal damage
connected with PGE inhibition
2. Bleeding: inhibition of platelet
function (TxA2 synthesis)
3. Limitation of renal blood flow
Na+ and water retention
4. Delay / prolongation of labour
connected with PGF2α inhibition
5. Asthma and anaphylactoid reactions
connected with PGF2α inhibition
70. Mechanisms by which NSAIDs may induce mucosal injury
Lüllmann, Color Atlas of Pharmacology – 2nd Ed. (2000)
73. Brain’s opiate system
Endorphin & Enkephalin
• multiple areas of brain show opiate receptors
• Enkephalin and Leu-Enkephalin---Brain stem
and spinal cord
• -Endorphine—Hypothalamus and spinal
cord
• Dynorphin-- Brain stem and spinal cord
74. Endorphins
• Behave like morphine & bind to opiate receptors to
obtund pain Like morphine
• B – endorphin closely related to pituitary function
• May act like hormone.
• The Enkephalin & endorphins have antinociceptive
effects,
• Underlying mechanism not fully analyzed
75. Brain’s Opiate system
•
•
3 major components
1. Periaqueductal gray and periventricular nucleus—
Enkephalinergic fibers
•
2. Raphe Magnus nucleus,—Serotonergic fibers
•
3. A pain inhibitory complex located in dorsal horns of
spinal cord—Enkephalinergic fibers
At this point, the analgesia signals can block the pain
before it is relayed to the brain.
•
82. OPIATE ANALGESICS
• Smooth muscle stimulation
GI muscle spasm causing delayed transit and constipation
Biliary spasm
Bronchospasm
• Cardiovascular
Dilation of resistance vessels (arterioles) and capacitance
vessels (veins)
83. OPIATE ANALGESICS
Dependence
• Up to 8 h- Mild psychological withdrawal stress
• 8-12 h - increasing nervousness, restlessness and anxiety
• 12-24h - yawning, sweating, runny eyes and nose
• 24 h - pupils dilate, waves of goose flesh
• 36 h
- twitching of muscles, leg & abdominal cramps
vomiting and diarrhoea and anorexia, insomnia
tachypnoea, ↑ BMR and mild pyrexia
• 48-72 h - peak withdrawal symptoms
• up to 10 d- symptoms gradually subside
• Complete recovery requires 3-6 months
• Note : Withdrawal syndrome can be in part alleviated by long
acting opioid such as methadone
84. OPIATE ANALGESICS
Opioid overdose
• Death usually due to respiratory depression
• Cardiovascular function usually well preserved
unless severe anoxia
• Treatment with iv naloxone
• May need infusion - naloxone has shorter t1/2
(1h), particularly for opioids with long t1/2 –
(methadone) and tight binding
(bupranorphine)
85. Morphine is naturally occurring
substance of the juice in the unripe
seedpods of the opium poppy.
It is a potent narcotic analgesic, and its primary clinical
use is for moderately severe and severe pain.
After heroin, morphine has the greatest dependence liability
of the narcotic analgesics in common use.
86. It is legally
available only in the
form of water-soluble
salts, such as
Morphine
sulfate and
Morphine hydrochloride.
taken orally, injected or
Morphine is
inhaled, or taken
through rectal suppositories.
87. Morphine is so effective because it acts directly at
pain-modulating receptors in the nervous system, termed
opioid receptors. The receptors respond to natural
compounds built by our bodies to control the level
of pain experienced at different times.
88. Although morphine
remains the most
effective drug for pain
relief, it is far from
perfect. Morphine’s
pharmacological effect is
on the nervous system
and the gastrointestinal
tract. Morphine is highly
addictive and tolerance
and physical and
psychological
dependence develop
quickly.
92. Acute Pain
• Many small studies vs. opioids
– Likley = morphine in equi-analgesic doses (T:M =
~10:1) up to 400 – 600mg/day maximum
• Many small studies vs. non-opioids
– Similar analgesia compared to NSAIDs postoperatively in a variety of doses
Grond S, et al. Clin Pharmacokin 2004;43:879-923.
93. How does it work?
• Weak -opioid receptor effects
– Structurally related to morphine and codeine
• ~10-fold less affinity for receptor than codeine and
up to 6000-fold less than morphine
• Metabolized to highly active M1 300-fold greater
affinity than parent compound
– Analgesia only partially blocked by naloxone
(~33%)
• Serotonin and norepinephrine reuptake
inhibition
Grond S, et al. Clin Pharmacokin 2004;43:879-923.
Raffa RB. J Clin Pharm Therap 2008;33:101-8.
94. •
•
•
•
•
•
•
Analgesic and adjuvant anesthetic effect of submucosal tramadol
after mandibular third molar surgery
Marcelo Minharro Ceccheti
University of Sao Paulo, São Paulo, Brazil( ORAL SURG ORAL PATHOL.ORAL RADIO 2012)
The aim of this study was to assess analgesic and adjuvant anesthetic effects of
submucosal tramadol after third
molar extraction.
. Submucosal tramadol injection after oral surgery improved postoperative analgesia, but
did not extend duration of anaesthesia
97. Acupuncture and Electroacupuncutre
1. Needle acupuncture
2. Electroacupuncutre
.release of B- endorphin into
Peripheral circulation
.current applied at specific site where
Deeper nociceptors available to be
stimulated
.profound analgesic effect for 1 hr
98. Pain – Gene THERAPY
• Gene transfer technology to
manipulate specific, localized
biochemicalpathways
involved in pain generation.
• useful in ch.pain
• viral mediated transfer of
genes
encoding
opiate
peptides to peripheral and
central neurons
99.
100. ELECTRONIC ANALGESIA
• History
in 46 AD, Scribonius Largus, physician to
emperor Claudius, used the torpedo fish to
relieve the pain of gout.
101. Mechanism of action (TENS )
• At the low frequency of 2Hz ,which is most often used in management of
pain, TENS produces measurable changes in the blood levels of 1tryptophan, serotonin, and beta endorphins.
• Serotonin possess analgesic actions, elevating the pain reaction
threshold
• Simultaneously levels of beta endorphins and encephalin increases in
the cerebral circulation
102. CONSCIOUS SEDATION
• Conscious sedation is a minimally depressed level of
consciousness that retains the patient’s ability to
maintain an airway independently and respond
appropriately to physical stimulation and / or verbal
command, such as ―open your eyes‖.
Pharmacological behaviour managment
102
103. Nitrous oxide
• Non- irritant, sweet smelling and colorless gas, not inflammable,
not explosive but support combustion.
• Concentrations of 35% to 40% enhance the sedative effects and
have the degree of analgesia equivalent of 15mg of morphine.
• It attains its peak effect in 3-5 min, first symptom appearing in
less than 1 min.
• It does not combine with any body tissue and is eliminated
unchanged through the lungs in less than 5 min.
104. DRUG
ROUTE OF
ADMINSTRATION
DOSAGE
MIDAZOLAM
ORAL
INTRAMUSCULAR
INTRAVENOUS
INTRANASAL
Oral Dosage in children under
25 kg of weight--0.3-0.5 mg/kg
Maximum dose 12 mg.
Children over 25kg of weight-12mg
1 to 0.15 mg/kg to a maximum
dose of 10 mg
Slow IV titration
It produces sedative effect
within
5
mins
of
administration.
FLUMAZENIL
(ROMAZICON)
INTRAVENOUS
0.01mg/kg upto 0.2mg
maximum dose of 1mg
CHORAL HYDRATE
(Noctec, Aquachloral
Supprettes)
ORAL
RECTAL
25 to 50 mg/kg to a maximum
of 1 gm
325, 500 and 650 mg.
Pharmacological behaviour managment
104
106. •
ANALGESICS:
- Codeine causes fetal toxicity (FDA-C)in 1st trimester can
use in 2nd or 3rd trimester.
- Morphine & Meperidine is safe for short period, chronic
use causes fetal toxicity (FDA-B).
- NSAID: Inhibition of prostaglandin synthesis can cause
premature closure of fetal ductus arteriosus constricture
which will induce primary pulmonary hypertension and
fetal bleeding tendencies.
Aspirin—not used (FDA-C/D).
Acetaminophen (FDA-B).-safe in all trimesters
Ibuprofen (FDA-B)- avoid in third trimester can close the
pda.
Cox-2 inhibitors (FDA-C) avoid in third trimester can close
the pda.
107. • BEST ANALGESICS EVER DISCOVERED OR
INVENTED TILL DATE !!!!!!
HEALTHY SMILES NURTURING OUR NEURONS
108. REFERENCES
• KD TRIPATI, ESSENTIALS OF MEDICAL
PHARMACOLOGY
• LIPPINCOTT
• WWW. SCIENCE DIRECT.COM
• Selzer—Pain control and diagnosis in dentistry
• Guyton—Textbook of physiology
Editor's Notes
T:M = 11-12:1 (IM/IV)vs. codeine: single dose, post-op