seminar is about the mechanism of action of the central and periphary acting analgesics. the pathway of pain and various analgesic and their properties

1. IT IS A SHAME THAT WE POSSESS SUCH
INSUFFICIENT KNOWLEDGE CONCERNING
THE CHARACTER OF PAIN—THOSE
SYMPTOMS WHICH REPRESENT THE
ESSENTIAL PART OF ALL BODILY SUFFERING
OF MAN (GOLDSCHEIDER 1894).

2. PRESENTED BY :- DR JAYESH
P.G STUDENT
DEPARTMENT OF ORAL AND MAXILLOFACIAL SURGERY
ANALGESIC

3. • INTRODUCTION
• FEW TERMS
• WHAT IS PAIN
• BRIEF THEORIES ABOUT PAIN
• BRIEF OF PAIN PATHWAYS
• CLASSIFICATIONS OF ANALGESICS
• OPIOID ANALGESICS
• VARIOUS OPIOID ANALGESICS AND THERE PROPERTIES
• CLASSIFICATION OF NSAIDS
• VARIOUS NSAIDS AND THERE PROEPRTIES
• CONCLUSION
• REFERENCES

4. A FEW TERMS
• ALGESIA(pain)- is an ill defined, unpleasent sensation, usually evoked by an external or internal
noxious stimulus
• Pain :- An unpleasant sensory and emotional experience associated with actual or potential
tissue damage, or described in terms of such damage.(IASP)
• Allodynia :- Pain due to a stimulus that does not normally provoke pain.
• Hyperalgesia :- Increased pain from a stimulus that normally provokes pain
ANALGESIcs :-Analgesics are a class of drugs which obtunds the perception of pain without
producing unconsciousness”
“Analgesics are drugs that selectively relieve pain by acting in the CNS or on the peripheral pain
mechanisms, without significantly altering consciousness”
• Nociceptor -A high-threshold sensory receptor of the peripheral somatosensory nervous system
that is capable of transducing and encoding noxious stimuli
• Neuropathic pain-Pain caused by a lesion or disease of the somatosensory nervous system

5. • THE WORD IS DERIVED FROM TWO GREEK WORDS
• AN + GESIC
• NO PAIN

6. WHAT IS PAIN
• It is a subjective expèrience which is hard to define even if we know what we
mean by it.
• Before treating pain we must know its proper etiology
• It can be of either or combination of the following two types
• A. Due to peripheral nociceptive afferent neuron, which is activated by noxious
stimuli. For eg :- direct response to an untoward incedence associated with tissue
damage like injury, inflammation, cancer. It can
• B. Central mechanism by which afferent input generates a pain sensation

7. BRIEF ABOUT PAIN
• Theories of pain
• The Specificity Theory refers to the
presence of dedicated pathways for each
somatosensory modality. The
fundamental tenet of the Specificity
Theory is that each modality has a
specific receptor and associated sensory
fiber (primary afferent) that is sensitive to
one specific stimulus (Dubner et al.
1978).
• This is the fundamental tenet of the
Specificity Theory, which postulates that
there is a dedicated fiber that leads to a
dedicated pain pathway to the sensory
modality's region of the brain. This model,
therefore, suggests that a pathway
specific to pain exists

8. • INTENSITY THEORY OF PAIN
• First, conceptualized in the fourth century
BCE by Plato in his oeuvre Timaeus (Plato
1998), the theory defines pain, not as a
unique sensory experience but rather, as an
emotion that occurs when a stimulus is
stronger than usual.
• This theory competed with the Specificity
Theory of Pain, which was championed by von
Frey. However, the theory lost support with
Sherrington's evolutionary framework for the
Specificity Theory and postulated the
existence of sensory receptors that are
specialized to respond to noxious stimuli, for
which he coined the term “nociceptor”.

9. • PATTERN THEORY OF PAIN
• J. P. Nafe postulated a “quantitative
theory of feeling” (1929). This theory
ignored findings of specialized nerve
endings and many of the observations
supporting the specificity and/or intensive
theories of pain. The theory stated that
any somaesthetic sensation occurred by
a specific and particular pattern of neural
firing and that the spatial and temporal
profile of firing of the peripheral nerves
encoded the stimulus type and intensity

10. • GATE CONTROL THEORY OF PAIN
• In 1965, Ronald Melzack and Charles Patrick
• Melzack and Wall accepted that there are nociceptors (pain fibers) and touch fibers and proposed
that that these fibers synapse in two different regions within the dorsal horn of the spinal cord:
cells in the substantia gelatinosa and the “transmission” cells. The model proposed that signals
produced in primary afferents from stimulation of the skin were transmitted to three regions within
the spinal cord: 1) the substantia gelatinosa, 2) the dorsal column, and 3) a group of cells that
they called transmission cells. They proposed that the gate in the spinal cord is the substantia
gelatinosa in the dorsal horn, which modulates the transmission of sensory information from the
primary afferent neurons to transmission cells in the spinal cord. This gating mechanism is
controlled by the activity in the large and small fibers. Large-fiber activity inhibits (or closes) the
gate, whereas small-fiber activity facilitates (or opens) the gate.

11. BRIEF ABOUT PAIN PATHWAY
• The ascending pathways that mediate pain
consist of three different tracts:
• 1.the neospinothalamic tract,
• 2. the paleospinothalamic
• 3.archispinothalamic tract.

12. • SITES OF ANALGESIC ACTION :
• PAIN PATHWAY :
• A and C-fibers provide the initial transduction mechanism for mechanical, thermal and chemical noxious
stimulus.
• The resultant action potentials evoked in the unmyelinated C-fibers and myelinated A fibers propagates to
the spinal and dorsal horn where they synapse with both spinal interneuron’s and projection neurons,
however it must also be appreciated that retrograde action potential transmission may evoke local “axon
reflex”-- mediated peripheral release of neuropeptides attributed to inflammation and peripheral
sensitization following injury.
• The axons of peripheral nociceptors project to the spinal cord, C-fibers synapse primarily in laminar II,
whereas A fibers synapse in both laminar I and V of the dorsal horn.
• Projection neurons from the spinothalamic, spinoreticular and other ascending tracts relay nociceptive
information through thalamic nuclei to cortical center of pain representation.
• The pharmacology of cortical representation is somewhat obscure, and it is at this sub thalamic levels that a
clear picture of the inhibiting mechanisms modulating afferent nociceptive input emerges.

14. • GENERAL PRINCIPLESOF PAIN CONTROL:
• It is not considered a good practice to treat pain or distress without first understanding the
cause of of the symptoms.
• If the cause cannot be determined immediately from a short but adequate history and
appropriate physical examination, it is permissible to control the pain or distress
symptomatically for time being.
• A suitable programme for the control of pain can be selected to fit the individual case when the
specific causative factor for the occurrence of pain has been established .
• As for as the control of pain by the use of drug is concerned ,it is accomplished by 3 major
pharmacological actions.
• Counteracting the cause of pain.
• Blocking the peripheral pain impulses.
• Modifying the central reception of pain

15. CLASSIFICATIONS
• Analgesics are divided into two groups,
• A. Opioid/narcotic/morphine-like analgesics
• B. Nonopioid I non-narcotic/ aspirin-like I antipyretic or anti-inflammatory analgesics

16. OPIOIDS
• What are opioids?
• Opioids are a class of drugs that are commonly prescribed for their analgesic, or pain-killing,
properties. They include substances such as morphine, codeine, oxycodone, and methadone
• Opium A dark brown, resinous material obtained from poppy (Papaver somniferum) capsule
• It contains two types of alkaloids.
Phenanthrene derivatives
• Morphine (10% in opium)
• Codeine (0.5% in opium)
• Thebaine (0.2% in opium),
Benzoisoquinoline derivatives
• Papaverine (1 %)
• Noscapine (6%)

17. OPOIDS
• Opium, the source of morphine, is obtained from the poppy, Papaver somniferum and P
album .
• Among the remedies which it has pleased Almighty God to give to man to relieve his
sufferings, none is so universal and so efficacious as opium. Thomas Sydenham

18. • OPIOID ANALGESICS
CHARACTERISTICS :
• Morphine like drugs produce analgesia, drowsiness, changes in mood and
mental clouding.
• Action is relatively selective in that other sensory modalities are not affected.
• Continuous dull pain is relived more effectively than sharp, intermittent pain,
but with sufficient amount of opioids.
• Behavioral and pharmacological evidence of mood alterations point to the role
of dopaminergic pathway particularly involving the nucleus accumbens (NACC)
in dry-induced reward.

19. • Alters the hypothalamic thermostat of the patient  lower temperature by
chronic use.
• Inhibits the secretion of GnRH and CRF, thus decreasing concentrations of
FSH, ACTH and -endorphin.
• Therapeutic doses increases accommodative power and lowers intraocular
tension in both normal and glaucomatous eyes.
• Excess dosage causes convulsions which are antagonized by naloxone.

20. C LASSI FICATION OF O P I O I DS
1. Natural opium alkaloids:
Morphine, Codeine
2. Semisynthetic opiates:
Diacetylmorphine (Heroin), Pholcodeine.
3. Synthetic opioids:
Pethidine (Meperidine),Fentanyl, Methadone, Dextropropoxyphene,
Tramadol.

21. CONTDD...
• Opioid drugs include
• 1. full agonists:- Natural: morphine, codeine
synthetic: pethidine, methadone
• 2.partial agonists:- naloxone, naltrexon
• 3. antagonists:- pentazocain, nalorpine,nalbupine

22. SYNTHETIC DERIVATIVES
1.Phenylpiperidine series :- eg. Pethidine. 1° synthethic morphine like drug. Is chemically
unlike morphine but pharmacologically similar
Other egs- Fentanyl and Sufentanil
2. Methadone series – eg methadone. Structurlly its not at all similar to mprphine but in
solution assumes a similar conformation. Longer acting than morphine .
Other eg- Dextropropoxyphene (no longer used as is cardiotoxic)

23. 3. Benzomorphan series :- eg pentazocine and cyclazocin. They differ from morphine in
receptor binding site
4. Thebain series:- eg Etorphine and buoreirophine

24. ENDOGENOUS OPIOIDS
• Discovered during the 1970s
• One of the observation that naloxone administration had little effect , although the drug
was effective in reversing or preventing the effects of exogenous opioids.
• 1° physiological evidence of them came when analgesia produced by electrical
stimulation of brain was reversed by naloxone.
• And in 1973 3 labs demonstrated opiate binding sites in brain.
• Up until now the actions of morphine, heroine as antinociceptive abd addicitve properties
were described in context of interaction with other neurotransmitter systems.
• In 1975 Hughes and associates identified ENKEPHALIN and then dynorphine and
endorphines where identified

25. OPIOID RECEPTORS

28. AGONISTS AND ANTAGONISTS
1. Pure Agonist – eg morphine, have high affinity for mue receptor and less for kappa
and delta sites
2. Partial agonists and mixed agonist-antagonist- nalorphone and pentazocine. Have a
degree of agonist and antagonist acitivity on different receptors

31. ANALGESICS
• MORPHINE
• Morphine is the principal alkaloid in opium and still widely used
• Is named after the greek god of dream MORPHEUS
• Isolated inpure form first by Sertumer in 1806
• Followed by Codein in 1832 by Robiquet and Papaverine in 1848
• The drugs toxic and adictive side effects have led to a search for a synthetic substitue
which dont share the same side effects,
• The search of opoid agonist lead to synthesis of opoid antagonist and compounds with
agonist-antagonist properties

32. PHARMACOLOGICAL
ACTIONS
1. CNS :-Morphine has site specific depressant and stimulant actions in the CNS
by interacting primarily with the mue opioid receptor as a full agonist. The
depressant actions are
• Analgesia :- Is a strong analgesic depending on dose.
• Has spinal and Supraspinal components.
• Acts in the substantia gelatinosa of dorsal horn to inhibit release of excitation
transmitters from primary afferents carrying pain impulses.
• Causes orthostatic hypotension through peripheral vasodilatation causing
decrease in peripheral resistance in supine

33. • SEDATION :
• Drowsiness and indifference to surroundings occurs without motor
incoordination, ataxia or apparent excitement (contrast alcohol ).
• Higher doses progressively cause sleep and coma
• MOOD AND SUBJECTIVE EFFECTS :
• Has a calming effect.
• Loss of apprehension, feeling of detachment.
• Has got euphoric effect.
• RESPIRATORY CENTER:
• Depresses respiratory center in a dose dependent manner.
• TEMPERATURE
• It is depres'd; hypothermia occurs in cold surroundings.
• Vasomotor centre
• It is depressed at higher CONCENTRATIONs and contributes to the fall in BP.

34. • Morphine stimulates:
1. chemoreceptor trigger zone (CTZ)
2. Edinger Westphal nucleus of III nerve
3. Vagal centre- It is stimulated bradycardia is the usual response.
4. Neuro-endocrine
5. CVS
6. GIT
7. Other smooth muscles

35. • PHARMACOKINETICS :
• can cross placenta freely
• Oral absorption is unrelaible with high 1° pass.
• Oral bioavalibility is 1/6 to ¼.
• 30% is bound to plasma protein
• In liver by glucuronide conjugation to morphine 6 glucuronide which is actove
and a poten metabolite
• Plasma half life is 2-3 hours and parentral is 4-6 hours.
• 90% is exctreted within 24 hours

36. AADVERSE EFFECT OF MORPHINE
• Acute posioning – in non tolerant adults even 50 mg i.m produces toxicity
• seen as coma,flacciity,shallow and occasional breathing, canosis, fall in B.P shock,
convulsions
• Treatment – respiratory support, Maintaincence of I.V fluids, gastric lavage with pot.
Permanganate
• Naloxone 0.4-0.8mg I.V repeated every 2-3 minutes till respiration picks uo

37. TOLERANCE AND DEPENDENCE
• Mainkly due to enhanced metabolism and cellular tolerance. With addicts tolerating
morphine in grams( much beyond the normal lethal dose)
• Treatment – substituion with oral methadone with later gradual taper of methadone
• PRECAUTIONS
• 1. infants and elderly more susceptible to respiratory deprresant action of morphine
• 2. patients with respiratory insufficiency
• 3.bronchial asthma- as morphine can precipitate histamine release
• 4.head injuries- a. Retains CO2--- increased intracranial pressure
b.vomiting,miosis and altered mental state interferes with patient
assesment
c.respiratory depression

38. • 5.Hypotension and hypovolumeia
• 6.elderly male- urinary retention
• 7.hypothyroid, liver and kidney disease- patients are more sensitive
• 8.Unstable personalities
• DOSAGE
• 10-50 mg oral, 10-15 mg i.m or s.c
• 2-6 mg i.v
• 2-3 mg epidural/intrathecal
• Children 0.1-0.2mg/kg

39. MORPHINE AND ITS CONGENERS
• CODEINE
• Methyl-morphine, converted to morphine in body.
• Less potent than morphine in actions(1/10th )
• Almost comparable to aspirin
• Has got more selective cough suppressant action.
• Good activity by oral route (4 to 6 hrs action).
• Prominent side effect- constipation.
• Analgesic action is due to generation of morphine due to demethylation
• HEROIN :
• 3 times more potent than morphine
• Has got more euphoric effect and is highly addictive.

40. • PETHIDINE :
• Was synthesized as an atropine substitute in 1939.
• Chemically unrelated to morphine but has similar actions with less unwanted
actions.
• Used as an analgesic (substitute of morphine).
• As a preanesthetic medication but not for cough or diarrhoea.
• Dose to dose 1/10° in analgesic potency but efficacy approaches near
morphine and more than codeine
• Metablolized in liver
• T1/2 is 2-3 hours
• Overdose -> tremors. Mydriasis,delerium due to accumulation of norpethidine
• Dose  50-100 mg IM, SC.

41. • FENTANYL- 80-100 times more potent than morphine
• Fast acting (5 minutes after i.v)
• Short duration 30-45 minutes.
• T1/2 is 4 hours
• Transdermal Fentanyl is used for chronic pain like cancer
• METHADONE- synthetic opioid
• Actions similar to morphine
• High oral to parentral ratio
• In single doses its slightly more potent than morphene but on repeate dosages the
potency increases due to release of the medicine from absorption sites(has a high affinity
to tissue proteins),
• T1/2 on chronic use -24-36 hours
• Metabolized in liver by demethylazition and cyclization
• Excreted in urine
• Used mainly in Morphene addiction withdrawal.
• 1mg for 4 mg of morphene
• DOSAGE :- 10mg i.m

42. • TRAMADOL
• Centally acting
• Releaves pains by opioid and other mechanisms
• Mue receptor affinity
• Activates monoaminergic spinal inhibtion
• Action only partially reversed by antagonist naloxine
• 100mg iv tramadol = 10 mg of morphine
• Oral:parentral is 1.2:1
• T1/2 is 3-5 hours
• Well tolerated
• For mild to medium short lasting pain as well as chronic pain of cancer but is not effective
in severe pain
• DOSAGE- 20-100 oral/i.v/slow i.v
• Children 1-2mg/kg 4-6 hourly

43. USES OF MORPHINE AND ITS CONGENERS
1. ANALGESIC – in severe pain of any type
2. Preanaesthetic mediciation- morphine and pethidine
3. Relief of anxiety and apprehenson- morphine and pehtidine . Esp in myocardial infarction
,internal bleeding
4. Acute left ventricular failue- morphine .
5. Cough- codeine is used
6. Diarrhoea- codeine constipating action

44. OPIOID COMPLICATIONS AND SIDE EFFECTS:
COMMON SIDE EFFECTS:
SEDATION, DIZZINESS, NAUSEA, VOMITING, CONSTIPATION(highest incidence),
PHYSICAL DEPENDENCE, TOLERANCE AND RESPIRATORY DEPRESSION
LESS COMMON SIDE EFFECTS:
DELAYED GASTRIC EMPTYING, HYPERALGESIA, IMMUNOLOGICAL AND HORMONAL
DYSFUNCTION, MUSCLE RIGIDITY AND MYOCLONUS.
Proper patient screening, education, and preemptive treatment of potential side effects
may aid in maximizing effectiveness while reducing the severity of side effects and
adverse events.

45. • ENDOGENOUS OPIOID PEPTIDES :
• Have morphine like actions, isolated from brain, pituitary, spinal cord and GIT.
• Have high affinity for opioid receptor.
• 3 Distinct types include
• Endorphins ( endorphin)
• Enkephalins (Methionin-enkephalin)
• Dynorphins (DYN-A, DYN-B).
• Has got neuromodulator or neurotransmitter actions.

47. A HISTORY

50. IMPORTANCE OF CYCLOOXYGENASE

51. MECHANISM OF ACTION OF NSAID’S

53. SALICYLATES
• Eg :- Aspirine ie acetyl salicylic acid
• Pharmacological action
1. Analgesia :- good analgesic.as they inhibit PG sysnthesis
2. Antipyretic :-good anti pyretic.
3. Anti inflammatory :- at higher dosage aspirin is a good anti inflammatory

54. 4.Acid –Base and Electrolyte Balance :- a. Anti inflammatory doses. B. At Toxic
levels
5.Ductus Arteriosus closure:-
6.GI tract:- all NSAIDs are gastric irritants to various levels.
7.Respiratory:-A. at therapeutic dosaes..B. Toxic dosage
8.CVS :- A. Therapeutic dosage. B. Toxic dosage
9. Immunological:- interferes AB-AG rxn . Helps in rheumatic fever
10. Uric acid:- 1-2 gm /day – increases plasma urate by preventing excretiing
from DCT. At 5gm /day increase excretion by preventing resorption from
PCT(such such hig dose are not advisable)

55. 11. blood-irreversibly inhibit platelet cyclooxygenase
TXA2 is generated from prostaglandin H2 by thromboxane-A synthase
TXA2(Thromboxane A2)

56. PHARMCOKINETICS
• Salicylates are well Absorbed in stomach and upper small intestine(aspirin is a exception)
• Aspirin is deacetylated in liver, plasma and other tissues to release salicylic acid
• Plasma T1/2 of aspirin is 3-5 hours
• Elimination is dose dependent and follows 1° order kinetics in small and zero order
kinetics in higher dosages
• Excreted in urine

57. ADVERSE EFFECTS
1. GI tract :- nausea, epigastric distress
2. Allergy :- is uncommon. As rash, urticaria,photosensitivity,rhinorrhoea,asthma
3. Hemolysis :- in patient with G6PD deficiency
4. Nephrotoxicity :- All NSAIDs are nephrotoxic on long term usage . Salt and water retention
with impaired renal function
5. Hepatotoxicity :-
6. Reyes syndrome:- is a form of hepatic encephalapahy, seen in children following a viral
fever.. Can be fatal. So asprin is contraindicated in children with viral fever
7. Pregnancy and infancy :- as PG synthesis is inhibited leads to delay of onset of labor at
term. Premature closire of ductus arteriosus maylead to portal hypertension in foetus
8. Salicylism:- chronic use of salicylates. Seen as headache ,vertigo , dizziness, tinnitus
,vomiting. reversble

58. DOSAGE, PRECAUTION AND CONTRA
INDICATIONS
• Aspirin :- analgesic 300-600 mg every 6-8 hrs
• Anti inflammatory :- 4-6 gm/day
• Anti platelet :- 75-300 mg /day
• Precaution :- in peptic ulcer, liver diseases, bleeding tendencies, viral fever in children,
Pregnancy ,
Treatment with NSAIDs should be stopped one week before any surgery

59. USES
• Analgesic :- headache, backache,myalgias, neuralgias, dysmenorrhoea,
• Fever :-
• Inflammatory condition :_ arthritis
• Acute Rheumatic fever :- 4-6 gm /day in 4-6 divided doses
• Rheumatoid artheritis :- symtomatic relief only. 4-6 gm /day in 4-6 divided doses
• Osteoartheritis
• Post myocardial infarction. 50-300 mg /day.

60. FEW OTHER NSAIDS
• PARA-AMINO PHENOL DERIVATIVES
• (paracetamol )
• Is a meabolite of phenacetin(1° drug of the gruop)
Actions :-
• Analgesic, good antipyretic and weak antiinflammatory(due to weak PG inhibitory activity)
• Acts on cyclooxygenase on the brain (antipyretic)
• No action on respiration,acid base balance , cellular metabolism, cardio vascular system
and platelet function

61. • Pharmacokinetics :- well absorbed orally
• Metabolised by hepatic microsomal enzymes by glucoronide conjugation and glutathione
conjugation
• Adverse reaction:- in large dose> acute paracetamol poisoning can occur.
• children more susciptable
• Hepatotoxic . Seens as
• Increased serum transaminase. Jaundice,liver tenderness, and prolonged
prothrombin time.
• nephrotoxic

62. • USES :- headaches, musculoskelatal pain, toothache ,
• Dose to dose is equally affective as aspirin for non inflammatory condition
• DOSE :- 0.5-1 gm TDS
• infants -50mg
• Children – 1-3 yrs 80-160 mg
• 4-8 years 240-320 mg
• 9-12 yrs – 300-600 mg

63. • PROPIONIC ACID DERIVATIVE
• Eg :- ibuprofen,
• Antiinflammatory efficacy >high dose aspirin
• Adv effect :- same as aspirin but it is better tolerated. Asthma,
• Not prescribed to pregnant women and in patients with peptic ulcer
• Pharmacokinetics decrease diuretic and anti hypertensive action of thiazides and beta
blockers
• Uses:-
• analgesic and anti pyretic as aspirin
• Rheumatoid artheritis
• Soft tissue injuries, toooth extraction, fractures,post partum, supressing swelling and
inflammation (ibuprofen 400mg better than aspirin 650+codeine 60mg)

64. OTHER PROPIONIC ACID DERIVATIES AND
DOSAGE
s.No Drug Plasma t1/2 Dose
1. Ibuprofen 2hr 400-600mg TID
2 Naproxen(most potent) 12-16 hrs 250 mg BD-TD
3 Ketoprofen 2-3 hrs 50-100mg BD-TD
4 Flurbiprofen 4-6 hrs 50mg BD-QID

65. ANTHRANILIC ACID DERIVATIVE
• MEPHENAMIC ACID :- is a analgesic,antipyretic and anti inflammatory .
• It inhibits COX and antagonises certain actions of PG’s
• Adverse effect – diarrhoea, epigastric distress
• PHARMACOKINETICS
• :- oral absorption is slow but complete
• :- plasma t1/2 2-4
• Uses :- analgesic in painjoint soft tissue pain where strong antiinflammatory action is not
needed
• DOSE :- 250-500 mg TDS

66. ARYL- ACETIC ACID
• DICLOFENAC SODIUM :- is analgesic- antipyretic-anti inflammatory . Similar in efficacy
to naproxen
• Inhibits PGs synthesis and has short lasting anti platelet action
• Plasma t1/2 is 2 hrs
• Adv – mild epigastric pain. Nausea vomiting.
• Uses. Rheumatoid and osteosrthritis. Toothache. Ankylosing spondilitis. Post operative
inflammatory conditions.
• DOSE- 50 mg TDS the BD oral
• 75 mg deep I.M

67. OXICAM DERIVATIVE
PIROXICAM
• Long acting.
• Potent anti inflammatory . Good analgesic and antipyretic action
• Reversible inhibitor or COX
• Lower PG in synovial fluids . Decreases IgM . So inhibits inflammation
• Prolongs bleeding time
PHARMACOKINETICS
• Metabloised in liver by hydroxylation and glucuronide conjugation.
• Excreted in urine.
• Plasma t1/2- upto 2 days
• Adv – heart burns, nausea
USES – short term analgesic and long term anti inflammatory
DOSE – 20 mg BD for days followed by 20 mg OD

68. PYRROLO-PYRROLO DERIVATIVE
• Eg ketorolac
• Potent analgesic and modest antiinflammatory
• Postoperative efficacy is as good as morphine but free of opioids side effects
• In short lasting pain is comparable to aspirin
Pharmacokinetics
• Metabolism in liver by glucurinidation
• Plasma t1/2 is 5-7 hrs
Use :- postoperative pain, musculoskelatal pain.
Dose :- 10-20 mg 6 hrs for short term
# in dental pain it is rated superior to
Aspirin 650 mg,PCM 600 mg, and equivalent to ibuprofen 400mg
Not to be used for more than 5 days

69. INDOLE DERIVATIVE
• Eg :- indomethacine
• Antiinflammatory and prompt antipyretic. Only relieves inflammatory or tissue related pain
• High potency inhibitor or PG and supresses neutrophil motility
Pharmacokinetics :-
• Partly metabolized in liver.
• Excreted by kidneys
• Plasma t1/2 – 2-5 hours
Adv- GI and CNS side effects
-increased risk of bleeding
Contraindicatied in – machinary operators, drivers, psychatric patients, epileptics, kidney
disorders , pregnant women
Dose :- 25-50 mg BD-QID
USE- because of the contraindications its used as a reserve drugs where potent
antiinflammatory drugs are needed like gouts, ankylosing spondilitis,and in closure of patent
ductus arteriorus

70. PYRAZOLONES
• Eg – Metamizol
• Potent analgesic and antipyretic but poor antiinflammatory .
• Can be given orally or iv (can cause fal of B.P sometimes)
Adverse - agranulocytosis
Dose – 0.5-1.5 mg oral/i.m/i.v
Eg- Propiphenazone(saridon)
Better than metamizol
No report of agranulocytosis

71. PREFERENTIAL COX 2 INHIBITOR
Eg- Nimesulide
• Weak PG inhibitor and relative COX 2 selective
• Used for short lasting painful inflammatory conditions like sports injuries, sinusitis,
T1/2 is 2-5 hrs
Adverse – GI troubles, dermatological, and central(dizziness)
Usefull only in patient .asthamatics and those who develop bronchospasm to aspirin
Dose – 100 mg BD
Eg- Meloxicam
congenar of piroxicam.
More selective for COX 2
same as piroxicam
DOSE – 7.5 mg-15mg OD

72. SELECTIVE COX 2 INHIBITOR
• COX 2 have a theoratical advantage of inhibiting COX2 without affecting cox 1.
• Eg :- celecoxib
• Is antiinflammatory, analgesic and antipyretic with low ulcerogenic potential
• In rheumatoid artheritis 0 naproxen or diclofenac
• T1/2 is 11 hrs
• In osteroartheritis and rheumatoid artheritis
Dose – 100-200 mg BD
Eg- Etriocoxib
Dose – 60-120 mg OD

74. • IMPLICATIONS FOR DENTISTRY :
• Dental pain is most amenable to treatment by NSAID analgesics and acetaminophen
• Opioid combination drugs are most useful in patients with a strong emotional component
to their pain.
• The co-administration of L.A and parenteral opioid analgesics is a common and generally
safe practice. HOWEVER,
• Large doses display supradditive toxicity with likely respirators of acidosis caused by an
opioid can increase the entry of a local anesthetic into the CNS.
• In general, the co-administration of CNS depressants produces summation of effects and
occasionally a greater than anticipated depression (i.e. supradditive effect).

75. • CONCLUSION:
• Nociception is the ability to perceive potentially tissue damaging energy to promote
avoidance behaviour & minimize the insult.Pain perception also aids in the repair of minor
tissue injuries by limiting activity & splinting the injured tissue..Beyond this neuronal
activity can be attenuated by analgesic pharmacotherapy.
• With the acknowledgement that nociceptive pathway can suffer these deleterious
changes, preemptive therapy may be able not only to attenuate the nociceptive signal but
also prevent the progression to chronic, recalcitrant neurogenic pain, Appreciation of
currently available analgesics & an anticipation of those in development will allow for the
judious management of the pain patient.

76. REFERENCES
• http://www.iasp-pain.org/Taxonomy
• RANG AND DALE’S PHARMACOLOGY 6° EDITION
• BASIC AND CLINICAL PHARMACOLOGY .BERTRAM G KATZUNG AND ANTONY J
TREVOR 13° EDITION
• K.D. Tripathi - Essentials of Medical Pharmacology, 6th ed
• Textbook Of Medical Pharmacology By Padmaja Udaykumar
• Good man and gillman the pharmacological basis of therapeutics
• Theories of pain: from specificity to gate control Massieh Moayedi, Karen D. Davis
Journal of Neurophysiology Published 1 January 2013 Vol. 109 no. 1, 512
• ORAL & MAXILLOFACIAL SURGERY CLINICS OF NORTH AMERICA-PHARMACOLOGY
2002