Term
| Name 3 isoenzymes and their distribution: |
|
Definition
COX1: Widely distributed
COX2: Limited distribution, macrophages and sites of inflammation.
COX3: mainly in brain |
|
|
Term
| Name 3 types of antipyretics with examples: |
|
Definition
1. NSAIDS:
ASA, aspirin
Ibuprofen- diclofenac.
2. Acetaminophen:
Tylenol - paracetemol
3. Selective COX 2 inhibitor:
eg: celecoxib |
|
|
Term
| Do all NSAIDS cause irreversible inhibition of COX enzyme? |
|
Definition
|
|
Term
| Mechanism of action of ASA: |
|
Definition
↓ production of prostaglandins (PGs) and
thromboxanes (Txs) |
|
|
Term
• Pharmacological actions of ASA: |
|
Definition
Analgesic
– Antipyretic
– Anti-platelet
– Anti-inflammatory (high dose) |
|
|
Term
| Therapeutic indications of ASA: |
|
Definition
Pain:
– Mild to moderate (less effective than opioids)
– Mechanism (through inhibition of PGs synthesis):
• Peripheral action (main action): prevents sensitization
of pain-transmitting nerve fibres to chemical mediators
released by tissue injury
• Central action: inhibits action of transmitters involved
in pain pathways
– No tolerance
– Different types of pain including headaches and
migraine |
|
|
Term
| Therapeutic indications of ASA ( Fever, inflammation, thromboembolic disease) |
|
Definition
Fever:
– Mechanism (through inhibition of PGs synthesis):
• Reset temperature center in hypothalamus
• No effect on normal body temperature
• Inflammation:
– Rheumatic fever
– Rheumatoid arthritis
– Gout (high dose)
– …
• Thromboembolic disease:
– Through antiplatelet effect
– Treatment or prophylaxis |
|
|
Term
|
Definition
Bleeding: e.g., GI bleeding
• GIT: e.g., dyspepsia, gastritis, peptic ulcer
• Tinnitus (ringing in the ears)
• Bronchial asthma
• Acid base imbalance:
– Metabolic acidosis
– Respiratory alkalosis
• Chronic nephritis: with long term use
• Hypersensitivity reactions
• Reye’s syndrome:
– Brain and liver damage (can be fatal)
– Occurs in children or adolescents who have viral infection and
take aspirin |
|
|
Term
| Contraindications of ASA: |
|
Definition
Bleeding tendencies
• Peptic ulcer
• Bronchial asthma
• Allergy to aspirin or other NSAIDs
• Chronic renal disease
• Children or adolescents with viral infection |
|
|
Term
Pharmacokinetics of Aspirin:
Absorption:
Protein bound:
Metabolism:
Excretion: |
|
Definition
(a) Stomach- small intestine.
(b) 50-80%
(c) Liver (80%)
(d) Kidney |
|
|
Term
Acute Aspirin Toxicity
• Manifestations: |
|
Definition
Vomiting, abdominal pain
– Tinnitus
– Hypoglycemia, hypokalemia
– Hyperthermia, hyperventilation
– Metabolic acidosis, respiratory alkalosis
– Pulmonary edema, hypotension, CV collapse
– Confusion, seizures, coma |
|
|
Term
| Acute aspirin toxicity: Treatment |
|
Definition
No specific antidote
Supportive measures:
Stabilise airways and breathing and circulation
Fluids and electrolytes (eg: K)
Restore pH
Glucose
±
charcoal ingestion
–±
gastric lavage
|
|
|
Term
| Mechanism of action of acetaminophen: |
|
Definition
Not fully understood but inhibits cox enzyme (2/3...?)
No anti-platelet or anti-inflammatory action |
|
|
Term
| Pharmacokinetics of acetaminophen: |
|
Definition
Absorbed from GIT
Metabolised by liver
Excreted through the kidneys |
|
|
Term
| Adverse effects of acetaminophen: |
|
Definition
Safe in proper doses
Safe in pregnancy
Main side effects:
Liver damage.
Renal damage. |
|
|
Term
| Acute toxicity of acetaminophen: |
|
Definition
Commonly due to suicide.
Acute liver damage (can be fatal). |
|
|
Term
| Treatment of acute toxicity: |
|
Definition
Antidote: N-acetylcysteine (NAC)
–
Supportive measures
–±
gastric lavage
|
|
|
Term
|
Definition
Selective inhibitors of COX-2 isozyme
•
Less COX-1 induced side effects:
–
e.g., asthma, gastric irritation & bleeding
–
more theoretical!!
•
More risk of thrombosis and cardiovascular morbidity and mortality
•
e.g., celecoxib Dr |
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|
