Ecosystem Interactions Class Discussion Presentation in Blue Green Lined Styl...
NONOPIOID ANALGESICS
1.
2. PAIN
-The means by which the body is made
aware of the presence of tissue
damage
There are two components of pain:
• Perception is the process by which
pain is recognized by the brain
• Reaction is any involuntary act
occurring in response to a stimulus
causing sharp pain
3. Nonopioid (nonnarcotic)
Analgesics
• relieve pain with only a minor alteration of
consciousness
• safer than opioids, produce fewer side
effects, and are not addicting
• act principally at the peripheral nerve
endings
• inhibit the synthesis of prostaglandins,
which occurs at sites of tissue inflammation
and produce their analgesic effects
peripherally and their antipyretic effect
centrally
4. CLINICAL
CONSIDERATIONS:
1. Nonopioid analgesics are more
effective if given before the pain
and inflammation associated with
prostaglandin synthesis occur.
2. Nonopioid analgesics are not
completely effective because they
do not affect the formation of
primary pain mediators.
5. Principal Pharmacologic Actions:
1. Analgesia
2. Antipyresis
3. Antiinflammatory action
• Of these actions the salicylates and
NSAIAs exhibit all three in
therapeutically useful amounts, and
acetaminophen exhibits only analgesia
and antipyresis.
6.
7. Salicylates
- Came from the extracts of willow bark
containing the bitter glycoside salicin
1. Acetylsalicylic acid (Aspirin, Bayer,
A.S.A.)
2. Sodium salicylate (Uracel)
3. Magnesium salicylate (Mobidin, Doan’s
pills)
4. Salsalate (Disalcid, Monogesic)
5. Salicylamide (Uromide)
6. Diflunisal (Doloboid)
7. Methylsalicylate (oil of wintergreen)
8. Salicylic acid (Salacid, Freezone)
8. Acetysalicylic acid (Aspirin)
• most widely employed drug in medical and
dental practice
• Described as the prototype salicylate
Ascriptin Ecotrin
Aspro Entrophen
Bayer Halfprin
Bex Novasen
Bufferin Solprin
Disprin Spren
9. Uses:
1. Treatment of mild to moderate pain
2. In control of fever
3. Treatment of rheumatic fever and
arthritis
4. Treatment of thromboembolic disorders
5. Treatment of transient ischemic attacks
in men
6. Treatment in post-MI
10. Mechanism of Action
• The inflammatory stimulus activates
or releases a phospholipase, which
cleaves the essential fatty acid
(arachidonic acid) from membrane
lecithin, thereby making it available
for prostaglandin synthesis by the
enzyme cyclooxygenase. Aspirin-like
drugs inhibit the cyclooxygenase by
acytelating a serine at its site of
action.
11. Pharmacologic effects:
1. Analgesia
The inhibition of prostaglandin synthesis
by aspirin-like drugs leads to analgesia by
decreasing the sensitivity of pain fibers
to the presence of pain-producing
substances.
2. Antipyresis
The antipyretic action of aspirin-like
drugs results from inhibition of
prostaglandin synthesis in the
hypothalamus.
12. 3. Anti-inflammatory effects
The inhibition of prostaglandin synthesis
leads to decreased redness and swelling
of the inflamed area.
4. Uricosuric effect
Large doses of aspirin (over 5gm/24 hr)
increase uric acid secretion and decrease
plasma urate concentrations. Smaller
doses of aspirin (1-2gm/24hr) may
decrease the secretion of uric acid and
elevate the plasma urate concentration.
13. 5. Platelet effects
At therapeutic doses, aspirin prolongs
bleeding time. The mechanism of action is
related to acytelation of platelet
cyclooxygenase and subsequent reduction
in thromboxane A2 (TXA2), a potent
aggregating substance. This effect on the
platelet is irreversible and lasts for the
life of the platelets exposed.
• Aspirin has been shown to be effective in a few
selected trials in males, such as in prevention of
myocardial infection with unstable angina and prevention
of stroke in patients with transient cerebral ischemia.
14. Adverse effects:
1. Gastrointestinal effects
- Dyspepsia
- Nausea and vomiting
- GIT bleeding
- Ulcer
These effects are produced in 2 ways:
- Local irritation
- Inhibition of prostaglandin
15. GIT effects can be reduced through:
1. Ingestion with food or with a full glass
of milk or water
2. In solution
3. Ingestion of liquid antacid
16. 2. Hypoprothrombinemia
- can result after long-term use
- Aspirin is known to prolong prothrombin
time and inhibit platelet function
3. Thyroid-Stimulating Effect
- Results from long-term aspirin
consumption
- Elevated free thyroid hormone in the
blood
17. 4. Metabolic Effect
- Aspirin uncouples oxidative
phosphorylation and reduces
lipogenesis
- Affects CHO metabolism so that the
blood sugar may be elevated or lowered
5. Hepatic and Renal Effects
- hepatotoxicity
- Reye’s syndrome
- Papillary necrosis and interstititial
nephritis
18. 6. Effects on Pregnancy
- Pregnancy Risk Category: C
- Salicylates readily cross placental
barrier and are excreted in breast milk
- Prolonged gestation, delayed
parturition, increased risk of
hemorrhage in mother and newborn,
increased risk of stillbirth or neonatal
death, and decreased birthweight
19. 7. Hypersensitivity
- Results from inhibition of
cyclooxygenase
- SRS-A symptoms include
bronchospasm, angioneurotic edema,
rhinitis, urticaria, wheezing,
hypotensive shock, abdominal cramps
and nasal polyps
8. Glucose-6-Phosphate Dehydrogenase
Deficiency
- A common inborn error of metabolism
- Symptoms of hemolysis includes
abdominal or back pain, anemia,
hemoglobinuria
20. Toxicity
• Salicylism – mild toxic reaction produced
by salicylates
• Signs and Symptoms:
1. Tinnitus
2. Headache
3. Nausea and vomiting
4. Dizziness
5. Dimness of vision
• The lethal adult dose of aspirin is
between 10 and 30 gm (30 to 100 of the
5-grain tablets)
21. Severe acidosis and electrolyte
imbalance are usually the causes of
death resulting from:
1. Depression of the respiratory
center (CO2 accumulation)
2. Renal impairment from dehydration
and hypotension (inorganic &
metabolic acids accumulate)
3. Impaired CHO metabolism that
increases the production of
metabolic acids
22. When aspirin is prescribed for a child,
one should ensure that:
1. The dosage is accurately
determined
2. Adequate fluid intake is maintained
3. The parent is cognizant of the
dangers of poisoning
4. The child does not have chicken pox
or flu.
23. Treatment:
1. By inducing emesis, gastric lavage, or by
the administration of activated charcoal.
2. Severe toxic reaction require immediate
hospitalization and the use of IV fluids to
correct acidosis and electrolyte imbalance
3. Bathing in tepid water and IV fluid must
be promptly administered in case of
hyperthermia and dehydration.
4. Alkaline diuresis should be maintained by
the administration of sodium bicarbonate
5. Hypoglycemia and hypokalemia are
treated symptomatically.
24. DRUG INTERACTIONS
1. Warfarin (Coumadin)
- oral anticoagulants
- aspirin displaces warfarin from
plasma protein binding sites which
increases active warfarin in the
blood and amplifies its toxic effect
- administering salicylates to
patients can increase prothrombin
time and promote GIT bleeding and
hemorrhage
25. 2. Probenecid & Sulfinpyrazone
- used in treatment of gout
- aspirin has been reported to
precipitate an acute attack of gout
3. Sulfonylureas
- used in the treatment of adult-
onset diabetes mellitus
- Aspirins may enhance the
hypoglycemic response to
sulfonylureas
26. 4. Methotrexate
- used as a cancer chemotherapy
agent or in the treatment of
psoriasis
- Methotrexate can be displaced
from its plasma protein binding
sites, leading to an increased
concentration of free methotrexate
27. Dosages:
Arthritis
Adult: PO 2.6-5.2 g/day in divided doses q4-
6h
Child: PO 90-130 mg/kg/day in divided doses
q4-6h
Pain/fever
Adult: PO/REC 325-650 mg q4h prn, not to
exceed 4 g/day
Child: PO/REC 40-100 mg/kg/day in divided
doses q4-6h prn
29. Preparations:
1. Regular aspirin
2. Enteric-coated aspirin
3. Sustained-release aspirin
4. Combinations
a. With antacid-buffering agent
b.With another analgesic
c. With sedatives or antihistamines
d.With caffeine
32. Drug Interactions
GI ulceration, bleeding: aspirin,
steroids, alcohol, indomethacin and
other NSAIDs
Hepatotoxicity, Nephrotoxicity:
acetaminophen (prolonged use)
33.
34. Mechanism of Action
• NSAIAs inhibit the enzyme
cyclooxygenase, resulting in a
reduction in the formation of
prostaglandin precursors and
thromboxanes from arachidonic acid.
36. Pharmacokinetics:
• The NSAIAs peak in usually 1 to 2
hours
• They are metabolized in the liver
and excreted by the kidney.
• Fecal excretion occurs with fenamic
acids, piroxicam, sulindac, and
tolmetin.
• Food can reduce the rate of
absorption but oral antacids have
minimal or no effect on the rate of
absorption
42. Adverse effects:
4. Blood Clotting
- inhibition of platelet
aggregation remains only as long
as the drug is present in the
blood
5. Other effects
- muscle weakness, ringing ears,
blurred vision
- ulcerative stomatitis, gingival
ulceration
43. Adverse effects:
6. Hypersensitivity
- hives or itching
- angioneuretic edema
- chills and fever
- Steven Johnson syndrome
- exfoliative dermatitis
- anaphylactoid reactions during
bronchospasm
44. Adverse effects:
7. Pregnancy and Nursing
- prolonged gestation
- delayed parturition
- dystocia or premature closure
of the ductus arteriosus
- most NSAIDs are exreted in
breastmilk; piroxicam has been
shown to inhibit lactation
46. Ibuprofen
• The oldest member of the NSAIAs
and has the most clinical experience
• Rapidly absorbed orally, and food
decreases absorption, antacids have
no effect
• Undergoes hepatic metabolism end
excreted by the kidney
• Peak=1-2 hr; Half-life=2-4 hr;
Duration=4-6 hr
53. Contraindications
• Hypersensitivity
• Asthma
• Severe renal disease
• Severe hepatic disease
Precautions
• Pregnancy category C (avoid
prescribing for dental use in last
trimester), lactation, children,
bleeding disorders, GI disorders,
cardiac disorders, hypersensitivity
to other antiinflammatory agents
54. Drug Interactions
GI ulceration, bleeding: aspirin,
alcohol, corticosteroids
Nephrotoxicity: acetaminophen
Risk of increased effects: oral
anticoagulants, oral antidiabetics,
lithium, methotrexate
Decreased antihypertensive effects
of: diuretics
55.
56. Acetaminophen (Paracetamol;
N-acetyl paraaminophenol)
• Para-aminophenol derivative from
acetanilid
• Metabolized in liver, excreted by
the kidneys
• Crosses the placenta and is also
found in breast milk
• Rapidly and completely absorbed in
the GIT: onset 10-30 min, peak ½-
2hr, duration 4-6 hr, half-life 1-3 hr
58. Advantages:
1. Therapeutic doses have no effect on
cardiovascular and respiratory
system.
2. It does not produce gastric
bleeding.
3. It does not affect platelet
adhesiveness or affect uric acid
excretion.
4. It enhances water transport in
kidney.
59. Adverse effects:
1. Hepatic necrosis
- may occur in adults after ingestion
of a single dose of 10-15 gm
acetaminophen
- symptoms include N & V, anorexia,
and abdominal pain
60. Treatment:
1. Ingestion of gastric lavage
2. Administration of activated
charcoal and magnesium or sodium
sulfate solution
3. Administration of N-acetylcysteine
to reduce or prevent liver damage
4. Hemodialysis or hemoperfusion may
be used if oral acetylcysteine does
not improve the patient
61. Adverse effects:
2. Nephrotoxicity
- associated with long-term
consumption
- primary lesion appears to be a
papillary necrosis with secondary
interstitial nephritis