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nsaids and opiods in pmr
1. ROLE OF OPIOIDS and NSAIDS IN
PMR
MODERATOR:
• Dr Sandeep Kumar Gupt
Assisstant prof
DEPT OF PMR
KGMU
PRESENTED BY:
• Dr Joe Antony
JR1
DEPT OF PMR
KGMU
2. Contents
• Opiods
– Classification
– Moa
– Pharmacological action
– Specific opiods
• Nsaids
– Classification
– Moa
– Pharmacological action
– Specific drugs
• Who pain ladder
3. OPIODS
⚫Opiod analgesics are one of the oldest remedies for
relief pain.
⚫Opium is
obtained
the dark brown
from the poppy
gummy
capsule
exudate
(papaver
somniferum)
⚫Opium has been in use since 4000BC.
5. MORPHINE
In CNS mu ( ),kappa( k)and delta( ) receptors
Stimulationof opioid receptors (Morphine)
Decrease the Intra cellular Calcium Level
Decrease the release of Neurotransmitter
It decreases the visceral Pain
6. Pharmacological action
⚫1.Analgesia:
Morphine is a potent analgesic and relieves pain without loss of
consciousness.in higher doses it relieves severe pain as that of biliary
colic.
⚫2.Euphoria ,sedation and hypnosis
Rapid IV inj of morphine produces a warm flushing of the
skin and an immensely pleasurable sensation.
It also produces drowsiness
7. 3.Respiration
Morphine produce respiratory depression. It
directlydepresses the respiratory center in the
brain stem
4.Cough center
Itdirectlydepress thecough center and thereby
suppress cough.opioids should be used as
antitussiveonly in the dry cough
8. 5.Nausea and emesis
Morphine directly stimulates the CTZ in the medula causing
nausea and vomitting.in higher doses it depress the
vomitting center and hence there is no vomitting in
poisoning .
6.pupil
Morphine produces miosis resulting in a characteristic
pinpoint pupil in high doses.
7.vagus
Morphine stimulates vagal center causing bradycardia.
9. 8.Heat regulation
Opioids shift the equlibirium point of heat regulating
center so that body temperature falls slightly.
9.Truncal rigidity
Higher dose of fentanyl found to enhance the tone of
the large trunk muscles by acting at supraspinal
levels.
10.Excitatory effect
In high doses opioids produce convulsion
10. • In therapeutic dose morphine produces
hypotension by;
• Direct peripheral vasodilatation.
• Inhibition of baroreceptor reflexes.
• In higher doses ,it causes depression of vasomotor
center and histamine release both contributing to a fall
in BP.
Cardiovascular system
11. • GIT
Opioids decrease the motility of the gut.
• Stomach
Gasric motility is decreased resulting in increased gastric empting time.gastric
acid secretion is reduced.
• Intestine :
Morphine diminises all secretions,delays digestion of food in the small
intestine.
• Other Smooth Muscles
Biliary tract – Morphine causes spasm of the sphincter of Oddi.Atrophine partially
antagonise this .
Urinary Bladder and Ureter – Opioids inhibit urinary voiding reflex, as a result of this
urinary retention occurs especially in the elderly males with Prostatic hypertrophy.
Bronchi –Morphine causes release of histamine from the mast cells leads to broncho
constriction.
13. Dosage
• 10-50mg
• 5 times daily
• No respiratory depression
until pain relief is there
Routes
• Oral
• Sc
• Intrathecal
• iv
14. TOLERANCE
• Tolerance is defined as the capacity of the body to
endure or become less responsive to a substance.
• Lethal dose of Morphine is 250 mg, addict can tolerate
morphine in gms .
15. DEPENDENCE
⚫Its ability to produce euphoria, makes it a drug of
addiction.
⚫Opioids produce both psychological and physical
dependence.
16. OTHER OPIOIDS
Heroin
It is converted to morphine in the
body.
It has higher lipid solubility.
It gives euphoric effects faster and
greater.
It is used as analgesics and banned in most
countries.
17. OTHER OPIOIDS
Codiene- It is Commonly used anti tussives. It is
also available with Paracetamol for analgesia.
Dexomethorphan -It acts centrally to elevate the
threshold forcoughing. It is effectiveas codeine.
18. Fentanyl
It is about 100 times more potent than morphine. It is
highly lipid solubleand fastacting.
Epidural fentanyl is used for postoperative and
obstetricanalgesia
Itcan also used in chronic pain .
-Routes – transdermal patches
ADVERSE EFFECT
Cough musclerigidity,
Nausea & Vomiting
Respiratory Depression
19. Tramadol
• Centrally acting atypical opiod
• it inhibits reuptake of NA and 5-HT, increases
5-HT release, and thus activates
monoaminergic spinal inhibition of pain
• i. v. I 00 mg tramadol is equianalgesic to IO mg
i.m. morphine.
20. • Oral bioavailability of
tramadol is good
• The t½ is 5-6 hours and
effects last for 4-6 hrs.
• Tramadol causes
insignificant respiratory
depression, sedation,
constipation or urinary
retention.
• nausea and dizziness may
be prominent.
• sleepiness, dry mouth,
sweating
• lowering of seizure
threshold, therefore
contraindicated in epileptics
• risk of 'serotonin syndrome‘
in patients on ssri
21. • Tramadol is indicated for mild-to-moderate
short-lasting pain
– due to diagnostic procedures, injury, surgery, etc,
as well as for chronic pain including cancer pain,
but is not effective in severe pain.
• Little tendency to dose escalation by chronic
users is seen and abuse potential is low.
• Dose: 50---100 mg oral/ i.m./slow i.v. infusion
(children I 2 mg/kg) 4 6 hourly.
22. • Roll in PMR
– Both nociceptive and neuropathic pain
– Chronic non malignant low back pain ( resistent to
nsaids)
– treating post herpetic neuralgia, phantom limb pain,
diabetic neuropathy, and polyneuropathy of various
etiologies
– American College of Rheumatology (ACR)
recommends tramadol for OA patients who failed to
achieve adequate benefit from nonnarcotic analgesic
medications
23. Tapentadol
• Newer atypical opiod
• Similar mechanism to tramadol
• useful alternative to tramadol for acute as well
as chronic pain of moderate severity. With less
nausea
• Dose· 50 I 100 mg 2-4 times/day.
24. Specific roll of opiods in PMR
• Post op analgesia- transdermal patches
• 2nd and 3rd line drugs for neuropathic pain
syndromes- phantom limb pain, diabetic
neuropathy
• Procedural pain
• Non productive cough suppression ( which
disturbs sleep)
• Diarrhoea treatment
25. NSAIDS
• Inflammation is the immediate response of our
body in response of harmful stimulus.
• The treatment of patients with inflammation
involves two primary goals
– Relief of symptoms and the maintenance of function:
usually the major continuing complaints of the patient;
– Slowing or arrest of the tissue-damaging process.
• Reduction of inflammation with NSAIDs often
results in relief of pain for significant periods
26. NSAID
• Aspirin, the original NSAID, has a number of adverse
effects.
• Many other NSAIDs have been developed in attempts
to improve upon aspirin’s efficacy and decrease its
toxicity.
• Although there are many differences in the kinetics of
NSAIDs, they have some general properties in common
• Most are well absorbed, and food does not
substantially change their bioavailability.
• Most are highly metabolized, some by
– Phase I followed by phase II mechanisms
– others by direct glucuronidation (phase II) alone
27. Pharmacokinetics
• NSAID metabolism proceeds, in large part, by way
of the CYP3A or CYP2C families of P450 enzymes
in the liver.
• While renal excretion is the most important
route for final elimination
• Nearly all undergo varying degrees of biliary
excretion and re-absorption
• Most of the NSAIDs are highly protein-bound
(∼ 98%), usually to albumin
• All NSAIDs can be found in synovial fluid after
repeated dosing
28. Pharmacodynamics
• Mediated chiefly through inhibition of prostaglandin
biosynthesis
• Various NSAIDs have additional possible mechanisms
of action
– inhibition of chemotaxis,
– down-regulation of interleukin-1 production,
– decreased production of free radicals and superoxide
– interference with calcium-mediated intracellular events
• NSAID’s may be either non-selective COX inhibitor or
preferentially/selective COX-2 inhibitor
31. Prefferential/selective COX-2
inhibitors
• Do not affect platelet function at their usual
doses.
• Efficacy of COX-2-selective drugs equals that
of the older NSAIDs, while GI safety may be
improved.
• Selective COX-2 inhibitors may increase the
incidence of edema and hypertension.
– Only celecoxib has FDA approval
32. Adverse Effect
• Central nervous system: Headaches, tinnitus, and dizziness.
• Cardiovascular: Fluid retention, hypertension, edema, and
rarely, myocardial infarction, and congestive heart failure.
• Gastrointestinal: Abdominal pain, dysplasia, nausea, vomiting, and
rarely, ulcers or bleeding.
– all NSAID are gastric irritants and can be associated with GI ulcers to
some extent
• Hematologic: Rare thrombocytopenia, neutropenia, or even
aplastic anemia.
• Hepatic: Abnormal liver function tests and rare liver failure.
• Pulmonary: Asthma.
• Skin: Rashes, all types, pruritus.
• Renal: Renal insufficiency, renal failure, hyperkalemia, and
proteinuria
33. Aspirin
• Rarely used as an anti-
inflammatory
medication
• But it has proved to be
beneficial for CVS
patient in terms of its
anti-platelet effects
34. Other uses of Salicylates
• Salicylates are used to treat:
– rheumatoid arthritis
– juvenile arthritis
– osteoarthritis
– other inflammatory disorders
• 5-Amino salicylates (mesalamine, sulfasalazine):
Crohn's disease.
• Salicylic acid is used topically to treat:
– plantar warts
– fungal infections
– Corns
35. Adverse Effect
• Common side effects listed earlier
• Adverse effects at antithrombotic doses are
gastric upset (intolerance) and gastric and
duodenal ulcers
• Hepatotoxicity, asthma, rashes, GI bleeding,
and renal toxicity rarely if ever occur
at antithrombotic doses.
• Contraindicates its use by patients with
hemophilia
36. Adverse effects
• The use of aspirin and
other salicylates to
control fever during viral
infections in children and
adolescents is totally
contraindicated
• Is associated with an
increased incidence of
Reye's syndrome,
characterized by
– vomiting,
– hepatic disturbances,
– Encephalopathy that has a
35% mortality rate.
37. PROPIONIC ACID DERIVATIVES -
Ibuprofen
• Better tolerated alternative to aspirin
• All have similar pharmacodynamic properties
• But differ considerably in potency and to some extent
in duration of action.
• The analgesic, antipyretic and anti-inflammatory
efficacy is rated somewhat lower than high dose of
aspirin
• All inhibit PG synthesis: Naproxen being the most
potent
• Inhibition of platelet aggregation is short-lasting with
ibuprofen, but longer lasting with naproxen.
38. Clinical Use: Ibuprofen
• Available as an 'over-the-counter’ drug as 200
mg, 400 mg, 600 mg
• Used as a simple analgesic and antipyretic
• Effective in dysmenorrhoea
• Ibuprofen and its congeners are widely used in
rheumatoid arthritis, osteoarthritis and other
mucoskeletal disorder
• indicated in soft tissue injuries, fracture, tooth
extraction and to relieve post- partum pain
39. Clinical Use: Ibuprofen
• oral and intravenous routes are
equally effective
• Topical cream preparation appears
to be absorbed into fascia and
muscle;
– Relieve joint pain in osteoarthritis
• A liquid gel preparation 400 mg,
provides prompt relief and good
overall efficacy in postsurgical
mucosal pain.
40. Adverse Effect
• Common adverse effects are already listed
• Contraindicated in individuals with nasal polyps,
angioedema, and bronchospastic reactivity to
aspirin
• Aseptic meningitis (particularly in patients with
systemic lupus erythematosus), and
fluid retention have been reported
• Concomitant administration of ibuprofen
and aspirin
– Antagonistic effect
41. Diclofenac
• Phenylacetic acid derivative
that is relatively non-
selective as a COX inhibitor.
• Its available as diclofenac
sodium salt.
• Antiplatelet action is short
lasting.
• T1/2 : 2 hrs
• Good tissue penetrability
42. Diclofenac – Clinical Use
• Most extensively used NSAID
• Combination of diclofenac and omeprazole: effective
with respect to the prevention of recurrent bleeding
– but renal adverse effects were common in high-risk
patients.
– Dosage above 150 mg/d: impair renal blood flow and
glomerular filtration rate
• Other combination includes ibuprofen+diclofenac:
excellent pain management
43. Diclofenac – Clinical Use
• Can be used after intraocular lens implantation
and strabismus surgery.
• Rectal suppository form can be considered for
preemptive analgesia and postoperative nausea
• Also available as an oral mouthwash and for
intramuscular administration
• osteoarthritis, bursitis, ankylosing spondylitis,
toothache, dysmenorrhoea - quick relief of pain
• Td patches- 1/3% diclofenac epolamine- used
for minor soft tissue injuries
44. KETOROLAC
• Novel NSAID with potent
analgesic and moderate
anti-inflammatory effect.
• In post operative pain it
has equivalent efficacy of
morphine
– But it does not interact
with opoid receptors and
is free of opioid side effect
45. KETOROLAC
• Rapidly absorbed after oral and i.m. administration.
• T1/2 5-7 hrs, highly plasma bound and 60% excreted
unchanged.
• Metabolic pathway is glucuronidation conjugation
• Clinical use
– frequently used in postoperative pain management: dental
• and acute musculoskeletal pain
– When used with an opioid, it may decrease the opioid
requirement by 25–50%.
• inflammatory conditions.
46. KETOROLAC – Clinical Use
• renal colic and pain due to bony metastasis
• Orally it is used in a dose of 10-20mg
• Rated superior to aspirin, paracetamol (600
mg) and equivalent to ibuprofen (400 mg)
• Continuous use for more than 5 day is not
recommended - renal toxicity
47. Paracetamol
• Acetaminophen: de-ethylated active
metabolite of phenacetin
• Central analgesic action of paracetamol is like
aspirin, i.e. it raises pain threshold
• It is a poor inhibitor of PG synthesis in
peripheral tissues, but more active on COX in
the brain.
• Its a good and promptly acting antipyretic, but
negligible anti-inflammatory action
48. Pharmacology
• Analgesic action of aspirin and paracetamol is
additive.
• Well tolerated orally, but only about 1/4th is
protein bound
• It is uniformly distributed in the body
• Metabolism occurs mainly by conjugation of
glucuronic acid and sulfate
• Plasma t1/2 2-3 hrs, effects after an oral dose last
for 3-5 hours
50. Clinical Use
• One of the most commonly OTC drug for
analgesic: headache, migraine,
musculoskeletal pain, dysmenorrhea
• But is relatively ineffective when inlflamation
is prominent.
• First choice analgesic for osteoarthritis
• Drug of choice: as antipyretic, especially in
children (no risk of Reye's syndrome)
51. Clinical Use
• Equally efficacious as aspirin for non-
inflammatory conditions, without its side
effect
– Insignificant gastric irritation, mucosal erosion and
bleeding
– Occurs rarely in overdose.
– does not affect platelet function, clotting factors
– Used in combination with opiods
– Decrease dose requirement of both
52. Adverse Effect
• Safe and well tolerated
• Nausea and rashes occur occasionally and other side
effects are similar to other NSAID
• Analgesic nephropathy: after years of heavy use
– Personality defect.
– Pathological lesions like necrosis, tubular atrophy followed
by renal fibrosis
• Acute paracetamol poisoning: especially in small
children who have low hepatic glucuronide conjugating
ability.
• If a large dose > 150 mg/kg or > 10 g in an adult: serious toxicities
• Fatality is common > 250 mg/kg.
53. Celecoxib
• selective COX-2 inhibitor—about 10–20 times
more selective for COX-2 than for COX-1
• associated with fewer GI ulcers than most other
NSAIDs
• Probably because it is a sulfonamide, celecoxib may
cause rashes
• does not affect platelet aggregation at usual
doses.
• It interacts occasionally with warfarin
• Adverse effects are the common toxicities listed above.
• Use – in patients with concomitant use of other
anticoagulants, before spinal or intra articular
injections
