analgesics and corticosteroids in OMFS

1. ANALGESICS
&CORTICOSTEROIDS
IN OMFS
Guided By : Dr Madan N
Presented By : Sanskriti Shah

2. Contents
● Introduction
● Analgesics
● Classification of analgesics
● NSAID’s
– History
– Classification of NSAID’s
– Mechanism of action
– Adverse effects
– Individual drugs

3. Contents
● Opioids
– Classification of opioids
– Individual drugs
– Opioid receptors
– Complex action opioids and opioid antagonists
- Opioids in dental pain
● Analgesics and Medical conditions
● Future ofAnalgesics
● Corticosteroids
● Biosynethesis
● Hpa axis
● Mineralocorticoids
● Glucocrticoids
● Steroids in OMFS

4. Pain
“ An unpleasant emotional experience usually
initiated by a noxious stimulus and transmitted over
a specialized neural network to the central nervous
system where it is interpreted as such ”
- Monheim’s
Introduction

5. Analgesics
Definition -
“Analgesics are drugs that selectively relieve
pain by acting in the CNS or on the peripheral
pain mechanisms, without altering
consciousness”

6. History of Analgesics
● BC: Ancient Greeks and Romans used salicylate
extracts derived from willow leaves as analgesics
and antipyretics
● Middle Ages: Medicinal herb gardens featured
salicylate containing wintergreen and meadowsweet
plants
● 1763: Edward Stone reported on use of willow bark
powder as an anti-inflammatory agent.
● 1853: Von Gerhardt synthesized a crude form of
aspirin (acetylsalicylic acid)
● 1860: Felix Hoffman synthesized pure aspirin

7. ● Opiates are one of the oldest types of drugs in history
● Opium is extracted from poppy seeds (Paper
somniforum)
● Use of Opium was first recorded in China over 2000
years ago
● Greeks dedicated the Opium poppy to the Gods of Death
(Thanatos), Sleep (Hypnos), and Dreams (Morpheus)
● Sixteenth Century is the first reported use of Opium for
its Analgesic qualities

8. ● 1949: The NSAID Phenylbutazone was introduced
● 1963: Indomethacin was introduced
● 1971: Vane and Piper demonstrated that NSAIDs inhibit
prostaglandin production
● 1974: Ibuprofen was introduced
● 1976: Miyamoto et al identified the COX-1 enzyme
● 1989: Simmons et al identified the COX-2 enzyme
● 1999: The COXIBs celecoxib and rofecoxib were introduced
● 2004: Rofecoxib was banned in india due to its cardiotoxic effect .

9. Classification of NSAIDs

10. Cellular Arachidonic Acid Metabolism
Inflammatory
Stimulus
Phospholiapase A2
Lipoxygenases
Leukotrienes

11. Beneficial actions due to PG
synthesis inhibition
● Analgesia
● Anti pyresis
● Anti inflammatory
● Anti thrombotica

12. Toxicities due to PG synthesis
inhibition
● Gastric mucosal damage
● Bleeding: inhibition of platelet function
● Limitation of renal blood flow: sodium and water
retention
● Delay / prolongation of labour
● Asthma and anaphylactic reactions in susceptible
individuals

13. Adverse effects of NSAID’s
● Gastrointestinal
– Gastric irritation, erosions, peptic ulceration,
gastric bleeding / perforation, esophagitis
● Renal
– Sodium and water retention, chronic renal
failure
● Hepatic
– Raised transaminases, hepatic failure (rare)

14. Adverse effects of NSAID’s
● CNS
– Headache, mental confusion, behavioural
disturbances, seizure precipitation
● Haematological
– Bleeding, thrombocytopenia, hemolytic
anaemia, agranulocytosis
● Others
– Asthma exacerbation, nasal polyposis, skin
rashes, pruritis, angioedema

15. NSAID - GI toxicity

16. Salicylates -Asprin
● Is acetylsalicylic acid
● Pharmacological actions
– Analgesic, antipyretic, anti inflammatory actions
• Analgesic action is due to prevention of PG mediated
sensitization of nerve endings
• Anti inflammatory at high doses
– Blood
• Irreversibly inhibits TXA2 synthesis thus interferes
with platelet aggregation and BT is prolonged
• Long term use of large doses decreases synthesis of
clotting factors in liver

17. Aspirin
– Respiration
• Anti inflammatory doses – stimulates respiration
• Hyperventilation in salicylate poisoning, in doses
higher than this there is respiratory depression
– CVS
• No direct effect in therapeutic doses

18. Aspirin
– GIT
• Aspirin irritates gastric mucosa & causes epigastric
pain, nausea and vomiting
• ‘Ion trapping’in gastric mucosa increases gastric
toxicity
• Acute ulcers, erosive gastritis, congestion and
microscopic hemorrhages

19. Aspirin
● Pharmacokinetics
– Absorbed from stomach and small intestine
● Precautions and contraindications
– Contraindicated in patients sensitive to it and in
peptic ulcer, bleeding tendencies, & in children
suffering from chicken pox or influenza. (due to
risk of Reye’s syndrome)
– In chronic liver disease
– Pregnancy and lactating mothers

20. Asprin
● Adverse effects
– Most important – gastric mucosal damage and
peptic ulceration
– Acute salicylate poisoning
– Assosiated with Reye’s syndrome

21. Propionic acid derivatives
Ibuprofen –
● first introduced member of this class
● Anti inflammatory efficacy is lower than asprin
● Inhibit Prostaglandin synthesis
● Adverse effects
– Milder and better tolerated than asprin
– GI disturbances are present
– Precipitate asprin-induced asthma

22. Propionic acid derivatives
● Pharmacokinetics
– Well absorbed orally
● Uses
– Analgesic andAntipyretic and anti-inflammatory
– Soft tissue injuries, tooth extraction, fractures, post
operative pain.
– Rheumatoid arthritis, osteoarthritis and
musculoskeletal disorders… where pain is more
prominent than inflammation

23. Anthranilic acid dervative
● Mephenamic acid-
– Inhibits COX & antagonises certain actions of PG’s
– Exerts peripheral as well as central analgesic action
● Pharmacokinetics
– Oral absorption is slow but complete
● Adverse effects- Diarrhoea
● Uses
– Muscle, joint and soft tissue pain
– Effective in dysmenorrhoea
Dose : 250-500mg TDS

24. Acetic acid derivative
● Diclofenac sodium
– Inhibits PG synthesis
– Has short lasting anti platelet action
– Adverse effects are mild
● Pharmacokinetics
– Well absorbed orally
– Excreted both in urine and bile
● Uses
– Toothache
– Post operative and post traumatic inflammatory conditions
– Rheumatoid arthritis and osteoarthritis

25. • Ketorolac
 Potent analgesic but modest anti-inflammatory
activity
 Used in post-operative dental pain
 It has been reported superior to aspirin(650mg),
paracetamol(600mg) and equivalent to
ibuprofen(400mg)
 Available in dispersible forms.
Dose – 10-20mg BD-QID

26. Oxicam derivatives
Piroxicam -
– Long acting NSAID – plasma t-half : 2 days.
– Reversible inhibitor of COX
– Rashes, pruritis are noted.
Dose : 20 mg for BD for two days followed by 20mg OD

27. Indole derivative
● Indomethacin
– Potent antiinflammatory and antipyretic action
– High incidence of GI and CNS side effects.
– Used in ductus arteriosus.
Pyrazolones derivative
● Metamizol and propiphenazone are used as analgesic and
antipyretics

28. Preferential COX-2 inhibitors
● Nimesulide
– Completely absorbed orally
– Used in patient with history of asthma and
anaphylactic reactions to other NSAIDs.
– Used for short-lasting painful inflammatory
conditions like -
- sports injuries,
- sinusitis and other ENT disorders
- fever and low back pain
Adverse effect – Hepatotoxic in pediatric patients,
banned in India.

29. Diclofenac Sodium
Aceclofenac
 Somewhat cox-2 selective.
 Anti-platelet is not appreciable due to sparing of Cox 1
 Extensively used NSAID
 Comparitive studies have found its gastric toxicity similar to
coxibs
Dose : 50mg TDS, then BD oral, 75 mg deep IM
 Similar properties of diclofenac
 Enhancement of glycosaminoglycans synthesis may confer
chondroprotective
Dose : 100 mg BD

30. Para-amino phenol derivatives
● Paracetamol (Acetaminophen) -
– Central analgesic action similar to asprin, i.e it raises pain
threshold
– Has weak peripheral anti inflammatory component
– Promptly acting antipyretic
● Pharmacokinetics
– Well absorbed orally
– Effects after oral dose last for 3-5 hours
● Adverse effects
– Acute paracetamol poisoning – children at larger doses
That is >150mg per kg or > 10 g in adults.
Hepatotoxicity

31. Paracetamol (Acetaminophen)
● Uses –
– Most commonly used drug & One of the best
antipyretic drugs
– Can be used in all age groups, also in pregnant and
lactating women
– Clinical studies have found paracetamol and asprin to
be equally effective in relieving pain after 3rdmolar
extraction
– And it is more safer than asprin – lesser GI
disturbances and bleeding tendencies
Dose – 325-650 mg ( total daily dose – 2600mg)

32. Selective COX-II inhibitors
 These inhibit cox II without affecting COX I function
 Do not depress TXA2
 Do not inhibit platelet aggregation or prolong bleeding
time.
 Reduce PGI2 production by vascular endothelium
 Celecoxib, Parecoxib, Etoricoxib available in India.
 Risk of cardiovascular diseases
 Celecoxib dose – 100 – 200 mg BD
 Etoricoxib dose – 60 – 120 mg OD
 Parecoxib dose – 40mg oral,IM,IV repeated after 6-12
hours

33. DRUG INTERACTIONS

34. Opioid
analgesics

35. Classification of opioids
● Natural opium alkaloids
– Morphine, codeine
● Semi synthetic opiates
– Diacetylmorphine (heroin), oxycodone
● Synthetic opioids
– Pethidine (meperidine), fentanyl, methadone,
tramadol

36. Morphine
– Alkaloid of opium
– Widely used
● Pharmacological actions
● CNS
– Analgesia
• Strong analgesic
• Nociceptive pain arising from peripheral pain
receptors is better relieved than neuritic pain
• Reactions associated with intense pain –
apprehension, fear are also depressed

37. – CNS
– Sedation
• Drowsiness and indifference to surroundings as well
as to own body , ataxia and apparent excitement also
occur
• Higher doses produce sleep and coma
– Mood and subjective changes
• Calming effect
• Loss of apprehension, feeling of detachment,mental
clouding and inability to concentrate

38. – Respiratory and cough centres
• Depresses Repiration and Cough centre
– Temperature regulating and vasomotor centre
• Depressed
– CTZ, vagal centre & certain cortical areas are
stimulated
– GIT
• Constipation is a prominent feature

39. ● CVS
– Causes vasodilation
– Cardiac work is consistently reduced due to decrease in
peripheral resistance

40. ● Pharmacokinetics
– Oral absorption is unreliable – high and variable first
pass metabolism
– Freely crosses placenta, affects foetus more than the
mother
● Adverse effects
– Mental clouding, sedation and lethargy
– constipation
– Acute morphine poisoning
• Human lethal dose is 250mg .
• Death is due to respiratory failure

41. ● Tolerance and dependence
– Partly pharmacokinetic (enhanced rate of metabolism)
but mainly pharmacodynamic (cellular tolerance)
– Treated by substitution with oral methadone
Precautions and contraindications
– Infants and elderly
– Bronchial asthma
– Head injury
Dose: 10-15mg oral or IM or IV, 2-6mg IV, 2-3mg intrathecal

42. Codeine
● Is methyl morphine
● Less potent than morphine (1/10th as analgesic)
● Is more selective cough suppressant

43. Pethidine
● Synthesized as an atropine substitute
● Interacts with opioid receptors (mu)
● Similar to morphine in most of its properties
– Uses
• As analgesic (substitute to morphine)
• In pre anaesthetic medication

44. Methadone
● Chemically dissimilar but pharmacologically
similar to morphine
● Used
– primarily as substitution therapy for opioid
dependence
– Also in methadone maintenance therapy
Dose: 5-10mg per ml syr, 5,10,20,40 mg for
maintenance therapy

45. Tramadol
● Centrally acting analgesic
● It is believed to work through modulation of serotonin
and norepinephrine in addition to its relatively-weak μ-
opioid receptor agonism
● 100mg tramadol IV is equally analgesic to 10mg
morphine IM
● Uses
– Mild to moderate intensity short lasting pain due to
surgery, dental procedures, injury etc
Dose: 50-100mg oral or IM or slow IV infusion 4-6 hourly

46. Opioid receptors
● Opioids interact with specific receptors present on neurons
in the CNS and peripheral tissues
● Radioligand binding studies divide receptors into
– mu, kappa and delta
● Pattern of effect of particular agent depends on the nature
of its interaction with different opioid receptors and also
its relative affinity to these receptors

47. Complex action opioids and opioid
antagonists
● Agonist- antagonist
– Nalorphine
– Pentazocaine
– Butorphanol
● Partial /weak agonist
– Buprenorphine
● Pure antagonist
– Naloxone, naltrexone

48. Pentazocaine
● Indicated in post operative and moderately severe
pain in trauma, cancer and burns
Oral dose- 50-100mg, parenteral dose: 30-60mg IM
or SC
Naloxone
● Competitive antagonist for all opioid receptors
● Injected i.v (0.4- 0.8mg) it antagonizes all actions
of morphine
● Drug of choice in morphine poisoning

49. Opioids in dental pain
● Opioids are less effective and suitable than NSAID’s for
dental pain
● Mostly used as additional drugs with NSAID’s to boost
their analgesic effect
● Among opioids oral codeine is most suitable
● Oral tramadol and pentazocine are alternatives
● Injectable opioids like morphine, pethidine are limited
to intra-operative use to supplement anaesthesia and to
allay apprehension

50. Analgesics & Medical conditions
● NSAIDs should be given in 2n
d triemister of
pregnancy and opioids should be avoided .
● Paracetamol is the safest drug to use in pregnancy
● Aspirin & Ibuprofen should not be given in asthmatic
patients
● Aspirin & Paracetamol should not be given in
nephropathy.
● Codein should not be used in renal dysfunction while
fentanyl & methadone are safe .

51. NEWER
Patient controlled transdermal system
● Fentanyl patches
● Tramadol patches
● Diclofenac patches

52. CORTICOSTERIODS
▣ The adrenal gland is the source of a diverse group of
hormones essential for metabolic control, regulation of water
and electrolyte balance, and regulation of body’s response to
stress.
▣ Using cholesterol as a substrate, the adrenal cortex produces a
large number of substances collectively known as
corticosteroids.
▣ These have glucocorticoid, mineralocorticoid, and weakly
androgenic activities.
▣ Conventionally the term corticosteroid, or corticoid include both
natural gluco and mineralocorticoid and their synthetic analogues

53. Adrenal glands
Zones of adrenal
Hormones
cortex
Zona glomerulosa Aldosterone
Zona fasciculata
Cortisone
Cortisol
Zona reticularis Androgens

54. BIOSYNTHESIS

55. Rate of secretion of the
principal steroids
 Glucorticoids 20-25 mg daily
 Mineralocorticoids – 0.125 mg daily

56. Fate of Corticosteroids
 Degraded mainly in liver
 Conjugated to form glucuronides and to a lesser extent
form sulphates
 25% - excreted in bile and feces
 75% - excreted in urine

57. HPA AXIS

58. DIURNAL RHYTHM
 ACTH is secreted in irregular pulses throughout the day which
cause parallel increases in plasma cortisol . Both the frequency and
the amplitude of the pulses are the greatest in the early morning.
 This early morning increase in ACTH release is initiated by
the release of CRH (corticotropin releasing hormone) and
starts approximately a couple of hours before waking.
 The lowest levels of ACTH in blood occur just before or after
falling asleep. This results in the characteristic diurnal rhythm in
ACTH and cortisol secretion

59. MINERALOCORTICOIDS
ACTIONS
1. On Sodium Metabolism
Increase in the reabsorption of sodium from renal tubules
2. On ECF Volume
• Sodium reabsorption from renal tubules
• Simaltaneous water reabsorption
• Increase in ECF volume
3. Increases BP
4. Increase in the excreation of potassium from renal tubules

61. Increase in K+ concentration
Decrease in Na+ Concentration
Decrease in ECF volume
Decrease in K+ concentration
Increase in Na+ Concentration
Increase in ECF volume
Juxtaglomerular
apparatus
Excretion of K+
Retention of Na+
Retention of water
kidneys
Lungs
Aldosterone
Adrenal cortex
angiotensinogen
Angiotensin - 1
Angiotensin - 2
Renin
Converting
enzyme
Stimulation
Feedback
inhibition
Regulation of aldosterone secretion

62. GLUCOCORTICOIDS
ACTIONS
1. On carbohydrate metabolism
• Promotes gluconeogenesis
• Inhibits glucose uptake and utilization by peripheral cells
2. On protein metabolism
• Promote catabolism of protein in cell
• Increase plasma amino acid and protein content in the cell
3. On mineral metabolism
• Enhances sodium retention
• Slightly increase potassium excretion
• Decreases blood calcium by inhibiting absorption from intestine
4. On water metabolism - Accelerate the excreation of water

63. 5. On Vascular Response
• Upregulates Alpha 1 adrenergic rexeptor in blood causing
vasoconstriction
6. On CNS
• Essential for normal functioning
• Insufficiency causes personality changes like irritablity and lack of
concentration
7. Anti- Inflammatory actions
• Decreases Recruitment of WBC & monocyte- macrophage into affected
area & elaboration of chemotactic substances
• Decreases IL1 from monocyte-macrophage Expression of
cyclooxygenase II

64. 8. Anti- allergic action
• Suppress all types of hypersensitivity and allergic phenomena.
• Suppression of recruitment of leucocytes at the site of contact with
antigen and of inflammatory response to immunological injury.
9. Immunosuppresive effects
• Suppress the immune system of the body by decreasing the number
of circulating T lymphocytes.
• Prevent release of interleukin-2 by T cells

65. CLASSIFICATION
GLUCOCORTICOIDS
Short acting
(t1/2 < 12 hr)
• Hydrocortisone
• Cortisone
Intermediate
acting:
(t1/2 12 – 36)
• Prednisole
• Methyl prednisole
• Triamcinolone
Long acting:
(t1/2 > 36 hrs)
• Para
methasone
• Dexamethasone
• Betamethasone

66. MINERALOCORTICOIDS
• Desoxycorticosterone
acetate(DOCA)
• Fludrocortisone
• Aldosterone

67. Agent Anti-
inflammator
y
Topical Equivalent
oral dose
(mg)
Forms
Available
Hydrocortisone 1 1 20 O, I, T
Cortisone 0.8 0 25 O
Prednisolone 5 4 5 O, I
Triamcinolone 5 5 4 O, I, T
Flu-prednisolone 15 7 1.5 O
Betamethasone 25-40 10 0.6 O, I, T
Dexamethasone 30 10 0.75 O, I, T
ACCORDING TO POTENCY

68. STEROIDS IN OMFS
TMDs
The most common signs and symptoms of TMDs are pain, altered
mandibular movements, and the elicitation of joint noise
Intracapsular injection of glucocortcoids has been reported to decrease pain
in patients with both pain and limited mouth opening secondary to
inflammatory disorders of the joint, such as arthritis and capsulitis

69. ORAL LESIONS
Injectable (Intralesional)
Topical

70. Systemic corticosteroids

71. KELOIDS AND HYPERTROPHIC SCARS
• Glucocorticoids have suppressive effects on the inflammatory
process in the wound, diminishing collagen and glycosaminoglycan
synthesis, inhibition of fibroblast growth, and enhancing collagen
and fibroblast degeneration.
• Used in conct of 10-20 mg/ml (can be given at a dose of 40 mg/ml
for a tough bulky lesion)
• The concentration depends upon the size and site of the lesion and
age of the individual.
• Side effects of steroid injection include hypopigmentation, dermal
atrophy, telangiectasia, etc

72. BELL’S PALSY
For adults, prednisolone at doses of 1 mg/kg/day for 7 to 10 days, taken in
divided doses in the morning and evening, is suggested
MANAGEMENT OF POST-OPERATIVE MORBIDITIES AW
MAXILLOFACIAL SURGERIES
Facial pain, edema, ecchymosis and limitation of mouth opening are the
expected sequelae of oral and maxillofacial surgeries
The most commonly administered types of corticosteroids are
betamethasone, dexamethasone, and methylprednisolone, administered
intravenously, orally

73. SIDE EFFECTS OF
CORTICOSTEROIDS
• weight gain,
• impaired growth,
• adrenal insufficiency,
• electrolyte abnormalities,
• increased susceptibility to infection,
• myopathy,
• osteoporosis, osteonecrosis,
• cataract,
• glaucoma,
• diabetes,
• peptic ulcer.

74. REFERENCES
✓ Essentials of Pharmacology for Dentistry by
K.D.Tripathi – 3rd edition
✓ Lippincott Illustrated Reviews Pharmacology
✓ Pharmacology – DALE andRANG (4th Ed.)
✓ Pharmacology and Therapeutics for Dentistry –
Yagiela
✓ Pharmacology and pharmacokinetics – R. S.
Santoskar
✓ Medical pharmacology – Seventh Edition – Padmaja
Udaykuamr

75. THANK YOU