Nsaids: A Detailed Overview PDF

MUSCUL AR SYSTEM Prepared by DR/ MOHAMMAD ABDUL BASET BADR TOPICS : A) NSAIDS B) SKELETAL MUSCLE RELAXANTS C) OSTEOPOROSIS D) OSTEOARTHRITIS NSAIDs  Theraputic effect of NSAIDs : 1- Platelets : Antiplatelet effect ( ASPIRIN ) Aspirin and (NSAIDs) inhibit platelet cyclo...

MUSCUL AR SYSTEM Prepared by DR/ MOHAMMAD ABDUL BASET BADR TOPICS : A) NSAIDS B) SKELETAL MUSCLE RELAXANTS C) OSTEOPOROSIS D) OSTEOARTHRITIS NSAIDs  Theraputic effect of NSAIDs : 1- Platelets : Antiplatelet effect ( ASPIRIN ) Aspirin and (NSAIDs) inhibit platelet cyclooxygenase, thereby blocking the formation of thromboxane A2. These drugs produce a systemic bleeding tendency by impairing thromboxane-dependent platelet aggregation and consequently prolonging the bleeding time. 2- GIT : Inhibit COX 1 so Block formation of PG that protect the Gi lead to ulceration and bleeding. Selective COX 2 inhibitors have less effect on GI.  3- Heart : NSAIDs with selective COX -2 inhibitor have high risk for cv events. 4- kidney : NSAIDs can reduce renal blood flow and glomerular filtration rate producing acute renal failure that is reversible upon discontinuation of the drug. 5- lung: NSAIDs block cox and shift arachidonic acid to lox pathway ( leukotrienes formation ) that cause bronchospasm.  NSAIDs are used to treat: 1- Anti inflammatory , analgesic and antipyretic : Pain of Rheumatoid arthritis (RA), Osteoarthritis Muscle aches Backaches Dental pain Pain caused by gout. Menstrual cramps. Fever  2- Antiplatelet : Low dose aspirin ( 75- 160 mg ) used as prophylaxis from cv events. In men, 160 mg/day consistently lowered the risk of MI. In women, the appropriate dose in women must exceed 100 mg/day. The appropriate dose for the primary prevention of stroke in men and women 160 mg/day. The lowest dose to prevent recurrent MI or death in patients with stable coronary artery disease (CAD) is 75 mg/day. In patients with a history of stroke or transient ischemic attack (TIA), 50 mg/day has been shown to be effective in men and women. In acute stroke, 160 mg/day is effective in preventing recurrent stroke or death.  3- In pregnancy : Low-dose aspirin has been used during pregnancy most commonly to prevent or delay the onset of preeclampsia. Prevention of stillbirth, fetal growth restriction, preterm birth, and early pregnancy loss.  Adverse Effects of NSAIDs : Gastric adverse effects : due to the inhibition of COX-1, preventing the creation of prostaglandins that protect the gastric mucosa. The use of COX-2 selective NSAIDs is a lower-risk alternative. Renal adverse effects : Prostaglandins play a role in renal hemodynamics. Complications that can occur include acute renal dysfunction, fluid and electrolyte disorders and nephrotic syndrome/ interstitial nephritis. Cardiovascular adverse effects : these include MI, thromboembolic events, and atrial fibrillation. Diclofenac and selective COX-2 inhibitors seems to be the NSAID with the highest reported increase in adverse cardiovascular events. Hepatic adverse effects : Diclofenac has a higher rate of hepatotoxic effects.  Non selective NSAIDs COX-1 are more likely to cause gastrointestinal side effects. Selective COX-2 have a higher risk of cardiovascular effects but less gastrointestinal effects. Contraindications : 1- In children aged under 16 due to it linked with Reye's syndrome. 2- NSAID hypersensitivity or salicylate hypersensitivity. 3- Who have undergone coronary artery bypass graft surgery 4- During the third trimester of pregnancy 5- Asthma, as NSAIDs can worsen the symptoms of this asthma. 6- Heart disease  NSAIDs are pregnancy category C in the 1st and 2nd trimester. NSAIDs are pregnancy category D in 3rd trimester. Most NSAIDs displace bilirubin so contraindicated in lactating women if a neonate have jaundice. Ibuprofen and naproxen are safe in lactating women. Reye's syndrome symptoms : For children younger than age 2, the first signs of Reye's syndrome may include: Diarrhea - Rapid breathing For older children and teenagers, early signs and symptoms may include: Persistent or continuous vomiting - Unusual sleepiness or lethargy Additional signs and symptoms Confusion, disorientation or hallucinations Seizures - Decreased level of consciousness  Reye's syndrome symptoms : For children younger than age 2, the first signs of Reye's syndrome may include: Diarrhea - Rapid breathing For older children and teenagers, early signs and symptoms may include: Persistent or continuous vomiting - Unusual sleepiness or lethargy Additional signs and symptoms Confusion, disorientation or hallucinations Seizures - Decreased level of consciousness Types of NSAIDs A) Acetic acid derivatives : As Diclofenac – Aceclofeac - Ketorlac – Indomethacin Diclofenac ( Voltaren – Rofenac – Cataflam )  Diclofenac Is one of the most potent NSAIDs. Maximum daily dose is 150 mg. Is the 1st choice in renal colic. Has very high risk for CV events and moderate risk of GI events. Used with caution in children younger than 3 years ( dose 1mg/kg/day) The most significant difference between the potassium and sodium salts is in the rate of absorption and the related onset of action making it more useful for acute pain.. Following ingestion of diclofenac potassium tablets, mean peak plasma diclofenac concentrations are attained after 30 to 54 minutes compared with 2-4 hours after ingestion of oral diclofenac sodium tablets. The potassium content of OTC diclofenac potassium is low.  Indomethacin : (Rothacin ) One of the most potent NSAIDs. Preferred in gout and rheumatoid arthritis due to its potent anti inflammatory effect. Has moderate risk in CV events and very high risk in GIT events. Not used in children younger than 15 years. Aceclofenac : (Gladio ) Low risk on GIT.  Ketorlac The most potent NSAIDs. Used for short duration in moderate-severe pain due to high side effects. Not used more than 5 days. High risk on CV and GIT.  B) PROPIONIC ACID DERIVATIVES IBUPROFEN : – KETOPROFEN – NAPROXEN IBUPROFEN : ( BRUFEN – SAPOFEN – OMAFEN )  IBUPROFEN Moderate potency as analgesic. Lowest risk on GIT. Ibuprofen CV risk is dose and duration dependent. Effective in closing patent ductus arteriosus in preterm infants. Maximum daily dose : 3200 mg/day (prescription strength); 1200 mg/day (over- the-counter) Pediatric dose : 4-10 mg/kg/dose. every 6-8 hours. Maximum daily dose is 40 mg/kg/day up to 1200 mg/day.  Naproxen : ( PROXEN – RIAPROXEN ) Has the lowest risk of CV events. Effective in migraine prophylaxis or acute attack as combination. C) Enolic acid derivatives : PIROXICAM – MELOXICAM – LORNOXICAM ( FELDENE – MOBIC – XEFO ) High risk in GIT except meloxicam. Moderate risk of CV events. Lornoxicam has rapid onset of action and short half life ( 2-3 times daily)  D) MEFENAMIC ACID : ( PONSTAN - MAFEPAIN ) Block COX and act as prostaglandin receptor antagonist in uterus so preferred in dysmenorrhea. E) SELECTIVE COX-2 INHIBITORS : CELECOXIB – ETORICOXIB CELEBREX – CELECT – ARCOXIA - ETORIA Have less GIT side effects than other NSAIDs. Have similar or more risk of CV events. Contraindicated in patient with sulfa allergy.  PARACETAMOL : PANADOL – FEVADOL – ADOL - PANADREX  Paracetamol (acetaminophen) is a pain reliever and a fever reducer. The exact mechanism of action of is not known. Paracetamol is used to treat many conditions such as Headache Muscle aches, Backache, Toothaches, Fevers It relieves pain in mild arthritis but has no effect on the underlying inflammation and swelling of the joint.  Dosing Two 500 mg tablets orally every 4 to 6 hours Usual Pediatric Dose : 10 to 15 mg/kg/dose every 4 to 6 hours as needed (Maximum: 5 doses in 24 hours) The maximum amount of paracetamol for adults is 1 gram (1000 mg) per dose and 4 grams (4000 mg) per day.  Paracetamol is the drug of choice in A- Pregnancy and beast feeding. B- Children with viral infection C- Asthmatic patient D- Patient with CV risk or GI complications Combination of paracetamol plus caffeine ( PANADOL EXTRA® ) , accelerate absorption and enhance the analgesic effect of paracetamol. Paracetamol is contraindicated in severe hepatic impairment. Antidote of paracetamol toxicity : N-acetyl cysteine Oral : loading dose 140mg/kg then70 mg/kg every 4h for 17 doses.  DIFFERENCE BETWEEN PANADOL TYPES PANADOL Paracetamol 500m mg Standard formula COATED PANADOL Paracetamol 500m mg The OPTIZORB formulation ADVANCE PANADOL Paracetamol 500 mg + Enhance the analgesic caffeine 65 mg effect of paracetamol. EXTRA PANADOL Paracetamol 665 mg patented bi-layer technology that allows EXTEND for sustained release of paracetamol for long lasting pain relief. PANADOL + Paracetamol 500 mg Panadol Actifast is Sodium 176mg absorbed twice as fast Paracetamol 500 mg PANADOL NIGHT and 25 mg diphenhydramine HCL Paracetamol - 500 PANADDOL SINUS mg; pseudoephedrine hydrochloride - 30.mg Paracetamol 500 mg. PANADOL Chlorpheniramine = 2 mg. COLD&FLU Pseudoephedrine HCL 30 mg Paracetamol 500mg PANADOL Caffeine 25mg Phenylephrine HCL COLD&FLU DAY 5mg Paracetamol = 600 VAPOUR mg PANADOL HEADAC HE Types of headache  The most common types include: Tension Headaches The most common type of headache among adults and teens. They cause mild to moderate pain and come and go over time. Migraine Headaches Pounding, throbbing pain. They can last from 4 hours to 3 days and usually happen one to four times a month. Along with the pain, people have other symptoms, such as sensitivity to light, noise, or smells; nausea or vomiting; loss of appetite; and upset stomach.  Cluster headache : The most severe. Patient has intense burning or piercing pain behind or around one eye. It can be throbbing or constant. Sinus Headaches Deep and constant pain in cheekbones, forehead, or on the bridge of the nose. happen when cavities in head ( sinuses ) get inflamed. The pain usually comes along with other sinus symptoms, like a runny nose, fullness in the ears, fever, and a swollen face.  Illness. infections, as meningitis Ear infection colds and fevers. Trauma or head injury sinusitis and allergic rhinitis Hypertension eye problems Brain tumor stroke Genetics. Headaches, especially migraine headaches, tend to run in families.  Stress. Emotional stress and depression alcohol use, Caffeine withdrawal skipping meals, changes in sleep patterns, Medication as nitrates , OCCs and PDEs neck or back strain due to poor posture. Environment secondhand tobacco smoke, strong smells from household chemicals or perfumes, allergens, and certain food, pollution noise  Refer any child with headache posttraumatic headaches. SKELETAL MUSCLE RELAXANTS  SMRs Are drugs that are used to relax and reduce tension in muscles. Used for : Spasticity ( stiff and rigid muscles ) caused by conditions such as cerebral palsy, multiple sclerosis, or stroke. Muscle spasms which are temporary muscular contractions that are often associated conditions such as tension headache, low back pain, or fibromyalgia  Types of Skeletal muscle relaxants : A) centrally acting muscle relaxants : as BACLOFEN and TIZANIDINE. B) peripherally acting muscle relaxants : as DANTROLENE and the different types of botulinum toxin.  A) Centrally acting muscle relaxants : 1- BACLOFEN : LIORESAL Is a muscle relaxer and an antispasmodic agent. ( GABA agonist ) Baclofen is used to treat muscle pain, spasms, and stiffness in people with multiple sclerosis or spinal cord injury or disease. Baclofen is given intrathecally (directly into the spinal cord) or orally (by mouth). Dose : 5 mg TID initially for 3 days after 3 days, may increase by 5 mg/dose every 3days up to 20 mg TID Maximum dose : 80 mg/day (20 mg QID)  Warnings Do not stop using baclofen suddenly, to prevent withdrawal symptoms. Cause sedation , Do not drive or operate heavy machinery Side effects Drowsiness, dizziness, weakness, tiredness Headache Nausea, constipation Urinating more often than usual.  2- TIZANIDINE : SIRDALUD – TILAX Short-acting muscle relaxer. It works by blocking nerve impulses (pain sensations) that are sent to brain. Tizanidine is used to treat spasticity by temporarily relaxing muscle tone.  Dose : Initial: 2 mg tid. Maintenance: 8 mg tid Not to exceed 36 mg/day To discontinue taper gradually; decrease by 2-4 mg daily Side effects : Drowsiness, dizziness, weakness Blurred vision Dry mouth, trouble speaking Urination problems, painful urination  3- CYCLOBENZAPRINE : ( BENZAFLEX ) It works by blocking nerve impulses (or pain sensations) that are sent to brain. is used together with rest and physical therapy to treat skeletal muscle conditions such as pain or injury.  CONTRAINDICATIONS: cyclobenzaprine should not be used in 1- Hyperthyroidism 2- Heart block, congestive heart failure, a heart rhythm disorder, recently had a heart attack. 3- Concomitant use or within 14 days of discontinuing MAO inhibitors Use only for short periods (2-3 weeks) Use caution in urinary retention, glaucoma , or concomitant use of other anticholinergic drugs  Safe in pregnancy Dose : 5 mg tid may increase dose to 7.5-10 mg tid. Side effects : Drowsiness, tiredness; Headache, dizziness; Dry mouth Upset stomach, nausea, constipation.  4- Chlorzoxazone : ( Relaxon – Parafone – Paraxone ) is a centrally acting skeletal muscle relaxant indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomfort associated with acute, painful musculoskeletal conditions.  side effects Gastrointestinal bleeding Drowsiness and Dizziness Lightheadedness Usual Adult Dosage : 250-750 mg q6-8hr WARNINGS Serious hepatocellular toxicity has been reported rarely in patients receiving chlorzoxazone.