Aceclofenac + Paracetamol + Tizanidine Pharmacology
Aceclofenac + Paracetamol + Tizanidine
Aceclofenac
1. It inhibits cyclooxygenase (COX) activity and to suppress the PGE2 production by inflammatory cells, by inhibiting IL-Beta & TNF in the inflammatory cells (Intracellular Action).
2. It blocks degeneration and stimulates synthesis of extra cellular matrix of cartilages by inhibiting the action of different cytokines.
3. Drug and its metabolites inhibit IL-6 production by human chondrocytes. This leads to inhibition of increase of inflammatory cells in synovial tissue, inhibition of IL-1 amplification, inhibition of increased MMP synthesis and thus ensuring proteoglycan production.
4. It inhibits IL-1 and TNF production by human chondrocytes, inflammatory cells and synovial cells and therefore blocks suppression of GAG and collagen synthesis and stimulates growth factors mediated synthesis of GAG and collagen.
5. 4`-hydroxyaceclofenac a metabolite of aceclofenac inhibits pro MMP1 and pro MMP3 produced by synovial cells (Rheumatoid Synovial Cells) in serum and in synovial fluid and thus inhibits progressive joint destruction by MMPs.
6. Aceclofenac inhibits Neutrophil Adhesion & Accumulation at the inflammatory site in the early phase and thus blocks the pro-inflammatory actions of Neutrophils.
7. Aceclofenac is also an NSAID with greater COX-2 specificity
Distribution- Widely distributed in the body as protein-bound form. It is highly protein-bound (>99.7%). Aceclofenac penetrates into the synovial fluid, where the concentrations reach approximately 60% of those in plasma.
Metabolism- Metabolized into metabolites in the liver. Main metabolite is 4-hydroxyaceclofenac
Excretion- It is excreted through urine mainly as conjugated hydroxymetabolites
2. Abdominal pain
3. Dizziness
4. Vertigo
5. Pruritis
6. Rash
7. Dermatitis
8. Nausea
9. Diarrhoea
10. Flatulence
11. Gastritis
12. Constipation
13. Vomiting
14. Ulcerative stomatitis
15. Elevation of circulating levels of hepatic enzymes.
2. Bleeding from the stomach or intestines
3. Moderate to severely decreased kidney function
4. Hypersensitivity to other NSAIDs
5. Active peptic ulcer
2. Bleeding tendencies
3. Blood disorders
4. Crohn`s disease
5. Decreased heart function
6. History of peptic ulcers
7. Inflammation of the bowel and back passage
8. Mildly decreased kidney function
9. Recent major surgery
10. Stomach disorders
11. Decreased liver function
12. Intestinal disorders
2. Osteoarthritis
3. Symptomatic treatment of pain and inflammation in Post-Traumatic pain
4. Cervical pain
5. Low back pain
6. Acute gout
Anticoagulants: Activity of anticoagulants may be increased.
Diuretics : Aceclofenac inhibits the activity of diuretics. When concomitantly administrated with potassium sparing diuretics, serum potassium should be monitored.
Cyclosporin: Aceclofenac may enhance cyclosporin nephrotoxicity.
Quinolones : Aceclofenac may precipitate convulsions when coadministered with quinolone antibiotics.
Adult (general dose)-
100mg twice daily
Paracetamol
It is more active on cyclo-oxygenase enzyme in brain. Peripherally it is a poor inhibitor of prostaglandin synthesis.
Analgesic action: Paracetamol raises the pain threshold and produces analgesic effect.
Antipyretic action: Paracetamol lowers fever by direct action on the thermoregulatory centre in the Hypothalamus and block the effects of endogenous pyrogen.
Distribution: It is distributed mostly in the body in unbound form.
Metabolism: It is extensively metabolised in the liver.
Excretion: Excreted in the urine.
2. Abdominal distress
3. Allergic reactions
4. Rash
2. Renal impairment
3. Hypertension
NEONATES : Contraindicated
2. Acute gout
3. Migraine
Charcoal: Activated, administered immediately reduces absorption of paracetamol.
Domperidone and metochlopramide: Enhance absorption of paracetamol.
Alcohol: Chronic excessive ingestion of alcohol potentiates hepatotoxicity of paracetamol.
Zidovudine: Effects zidovudine may be decreased.
500 - 1000 mg in 3 times daily
Maximum dose: 4 g / day
For migraine: 500 mg to be taken at the first sign of migraine attack and repeated 4 - 6 hourly until suppress mild attacks.
Children:
60 mg / kg body weight /day in 4 divided doses.
Maintenance dose: 75 mg / kg orally every 4 - 6 hours for 2 - 3 days. Haemodialysis can be done in emergency conditions.
Tizanidine
Distribution- Widely distributed throughout the body. 30% bound to the plasma proteins.
Metabolism- Metabolized in the liver to its metabolites.
Excretion- Excreted through urine.
2. Upset stomach
3. Vomiting
4. Tingling sensation in the arms, legs, hands, and feet
5. Dry mouth
6. Increased muscle spasms
7. Yellowing of the skin or eyes
8. Unexplained flu-like symptoms
2. Liver disease
3. Low blood pressure or are on medication to treat high blood pressure
4. Birth control pills use
2. Following surgery for disc prolapse/osteoarthritis of the hip
Adult-
Muscle spasm - 2 mg thrice a day.
Spasticity- Initial dose 6 mg/day in 3 divided doses, then increase stepwise to 12-36 mg/day.
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