Christine G. Bujung080111186Ruang 17

MedicationThree main drugs have been mentioned in relation to DCS. No definitive studies support their use. Thus, no consensus exists about dosages. Case reports suggest that they may be helpful.

I. Antiplatelet agentsWith the potential for activation of coagulation factors, as discussed above, therapy aimed at mitigating this effect is helpful. Obtain guidance from a specialist in diving medicine or HBO. Adult Dosing & UsesAnalgesic/Antipyretic325-650 mg PO/PR q4-6hr PRNControlled/extended/delayed-released products: 650-1300 mg enteric coated PO q8hr; no more than 3.9 g/dayAcute Myocardial Infarction160-325 mg as soon as possible (within minutes of symptoms)Myocardial Infarction Prophylaxis75 to 325 mg PO qDayIschemic Stroke & Transient Ischemic Attack160-325 mg PO qDayOsteoarthritisUp to 3 g/day PO in divided dosesPercutaneous Transluminal Coronary Angioplasty325 mg PO 2 hours presurgery160-325 mg PO qDay maintenanceRheumatoid Arthritis3 g/day PO in divided dosesIncrease as needed for anti-inflammatory efficacy with target plasma salicylate levels of 150 to 300 mcg/mLSpondyloarthropathiesUp to 4 g/day PO in divided dosesUnstable Angina Pectoris75-325 mg PO qDaySee Also Comboswith oxycodonewith acetaminophenButalbital, Codeine, Propoxyphene, Other

Other Indications & UsesPain, fever, inflammatory conditions, dyspepsia, platelet aggregation prophylaxis, thromboembolism, transient ischemic attackPrimary prevention of MI

Adverse EffectsFrequency Not DefinedAngioedema, Bronchospasm , CNS alteration, Dermatologic problems, GI pain/ulceration/bleeding, Hepatotoxicity, Hearing loss , Nausea, Platelet aggregation inhibition, Premature hemolysis, Pulmonary edema (salicylate-induced/noncardiogenic), Rash, Renal damage, TinnituS, Urticaria, Vomiting

Contraindications & Cautions

ContraindicationsHypersensitivity to aspirin or NSAIDsAllergy to tartrazine dyeAbsolute

Bleeding gastrointestinal ulcers, hemolytic anemia from PK & G6PD deficiency, hemophilia, hemorrhagic diathesis, hemorrhoids, lactating mother, nasal polyps associated with asthma, sarcoidosis, thrombocytopenia, ulcerative colitis

Relative appendicitis, asthma (bronchial), chronic diarrhea, bowel outlet obstruction (for enteric-coated), dehydration,

erosive gastritis, hypoparathyroidism

CautionsAnemia, GI malabsorption, history of peptic ulcers, gout, hepatic disease, hypochlorhydria, hypoprothrombinemia, renal impairment, thyrotoxicosis, vitamin K deficiency, renal calculiTake with food or 8-12 oz water to avoid GI effectsUse of salicylates in pediatric patients with varicella or influenza-like illness is associated with increased incidence of Reye's Syndrome

PharmacologyHalf-Life: 2-3 hr (low dose); 15-30 hr (higher dose)Peak Plasma Time: 0.25-3 hr (PO); 4-5 hr (PR)Peak Plasma Concentration: 30-100 mcg/mL (analgesia/antipyresis); 150-300 mcg/mL (anti-inflammatory); 250-350 mcg/mL (rheumatic fever)Onset: PO 5-30 min; PR 1-2 hrDuration: PO 3-6 hr; PR >7 hrBioavailability: 80-100%Vd: 0.15-0.2 L/kgMetabolism: liver, microsomal enzyme systemMetabolites: salicylurate, salicyl phenolic glucuronide, salicyl acyl glucuronide, 2,5-dihydroxybenzoic acid (gentisic acid), 2,3-dihydroxybenzoic acid, 2,3,5-trihydroxybenzoic acid, gentisuric acid (active)Enzymes inhibited: cyclooxygenase (insignificant)Renal Clearance: 80-100% 24-72 hrExcretion: principally in urine (80-100%), sweat, saliva, fecesDialyzable: yes

Protein Bound90-95% with concentrations up to 100 mcg/mL70-85% with concentrations up to 100-400 mcg/mL25-60% with higher concentrations

Pharmacogenomics Aspirin associated hypersensitivity reactions include: Aspirin-induced urticaria: associated with HLA-DRB1*1302-DQB1*0609 haplotype Aspirin-intolerant asthma: associated with HLA-DPB1*0301

Mechanism of ActionInhibits prostaglandin synthesis by cyclooxygenase; inhibits platelet aggregation

Aspirin (Anacin, Ascriptin, Bayer aspirin) Blocks prostaglandin synthetase action, inhibiting prostaglandin synthesis and preventing formation of platelet-aggregating thromboxane A2. Mechanism of action in treatment of DCS unclear.

II. CorticosteroidsThese agents have anti-inflammatory properties and cause profound, varied metabolic effects. In addition, these agents modify the body's immune response to diverse stimuli. Which mechanism provides the potential for benefit is unclear. Adult Dosing & UsesMethylprednisoloneRange: 2-60 mg/day divided QD/QID POAllergic Conditions

Day 1: 8 mg PO BID (before breakfast & HS) & 4 mg PO BID (after lunch & dinner) Day 2: 4 mg PO TID & 8 mg HS Day 3: 4 mg PO QID Day 4: 4 mg PO TID (before breakfast, after lunch, & HS) Day 5: 4 mg PO BID (before breakfast & HS) Day 6: 4 mg PO before breakfast May taper drug over 12 days (decreases chances of flare-up of dermatitis)

Methylprednisolone AcetateRange: 10-80 mg IM q1-2WeeksIf given as temporary substitute for PO, give same IM dose qDay as oralFor prolonged effect, give 7x daily oral dose IM qWeekOnly methylprednisolone sodium succinate may be given IVMethylprednisolone Sodium SuccinateRange: 10-250 mg IM/IV x upto 6 doses/day PRNPneumocystis jiroveci pneumonia in AIDS patients (off-label)

30 mg IV BID x5 days, THEN 30 mg IV qDay x5 days, THEN 15 mg IV qDay x11 days

Shock 30 mg/kg IV (over 3-15 minutes) q4-6hr PRN, OR Initial: 30 mg/kg IV (over 3-15 minutes), THEN 30 mg/kg IV infusion q12hr x24-48hr; do not continue beyond 48-72 hours

Acute spinal cord injury (off-label) 1st hour: 30 mg/kg IV (over 15 minutes) Next 23 hours: 5.4 mg/kg/hr IV infusion

Severe lupus nephritis (off-label) 1 g IV over 1 hour x3 days

Other Indications & UsesConditions treated with immunosuppression (autoimmune disease, inflammatory conditions, hypersensitivity reactions, serum sickness etc), corticosteroid-responsive dermatoses, aspiration pneumonitis, ophthalmic inflammatory conditionsAdrenocortical insufficiency (hydrocortisone/cortisone are drugs of choice)Acute exacerbations of multiple sclerosisNephrotic syndromeShockCongenital adrenal hyperplasiaHypercalcemia of malignancyTuberculous meningitisTrichinosis with neurologic or myocardial involvementOff-label: Chemotherapy-induced vomiting, spinal cord compression, P. jiroveci pneumonia, severe lupus nephritis, hypercalcemia of sarcoidosis or vitamin D intoxication

Adverse EffectsFrequency Not SpecifiedAdrenal suppression , Psychosis , Insomnia , Vertigo , Pseudotumor cerebri (on withdrawal), Acne, Osteoporosis, Myopathy , Delayed wound healing

Contraindications & Cautions ContraindicationsUntreated serious infectionsPatients receiving live or attenuated live vaccine

However, ACIP & AAFP state administration of live virus vaccines usually is not contraindicated if receiving corticosteroid therapy as short-term (<2 wk) therapy, in low-to-moderate dosages, as long-term alternate-day treatment with short-acting preparations, in maintenance physiologic dosages (replacement therapy)

Hypersensitivity to methylprednisoloneMethylprednisolone acetate or methylprednisolone sodium succinate: Do not administer intrathecally IM route contraindicated in idiopathic thrombocytopenic purpuraTraumatic brain injury (high doses)CautionsCirrhosis, ocular herpes simplex, HTN, diverticulitis, hypothyroidism, myasthenia gravis, PUD, osteoporosis, ulcerative colitis, psychotic tendencies, renal insufficiency, pregnancy, DM, thromboembolic disordersLong-term treatment: Risk of osteoporosis, myopathy, delayed wound healingMinimal mineralocorticoid activityPatients receiving corticosteroids should avoid chickenpox or measles-infected persons if unvaccinatedLatent TB may be reactivated: Monitor patients with positive tuberculin testSome suggestion of slightly incr cleft palate risk if corticosteroids used in pregnancy, but not fully substantiated

Metabolic clearance decreased with hypothyroidism May cause hypothalamic-pituitary adrenal (HPA) axis suppression, Cushing’s syndrome, and hyperglycemiaMethylprednisolone preserved with benzyl alcohol

Do not administer if preserved with benzyl alcohol, to neonates, infants, pregnant women, or breastfeeding women

Benzyl alcohol associated with serious adverse events and death, particularly in pediatric patients (gasping syndrome; characterized by central nervous system depression, metabolic acidosis, and gasping respirations)

PharmacologyHalf-Life: 2-3 hrOnset: PO: 1-2 hr, IM: 4-8 dDuration: PO: 30-36 hr, IM: 1-4 wkPeak Plasma Time: IV: 31 minVd: 1.5 L/kgMetabolism: extensively, in liverTotal Body Clearance: 16-21 L/hrExcretion: mainly in urine as metabolites, minimally in fecesDialyzable: HD: slightly dialyzablePharmacogenomics Several single-nucleotide polymorphisms (SNPs) in the glucocorticoid receptor gene have been identified and correlate with an altered sensitivity to glucocorticoids Polymorphisms within specific glutathione-S-transferase (GST) genes may be of clinical importance in glucocorticoid resistance Homozygous deletion of GSTT1 conferred a 6.7-fold reduction in risk of prednisone poor response Mechanism of ActionGlucocorticoid; controls or prevents inflammation by controling the rate of protein synthesis, suppressing migration of PMNs & fibroblasts, reversing capillary permeability, & stabilizing lysosome at cellular level

Methylprednisolone (Solu-Medrol, Depo-Medrol) Useful in treating inflammatory and allergic reactions. By reversing increased capillary permeability and suppressing PMN activity, may decrease inflammation. Mechanism of action in treatment of DCS unclear.

III. AnestheticsThese agents stabilize the neuronal membrane and prevent initiation and transmission of nerve impulses, thereby producing local anesthetic activity. Their effect in DCS is unclear. Adult Dosing & UsesCardiac Arrhythmias1-1.5 mg/kg slow IV bolus over 2-3 minutes May repeat doses of 0.5-0.75 mg/kg in 5-10 minutes up to 3 mg/kg totalContinuous infusion: 1-4 mg/minIf IV not feasible may use IO/ETMonitor: ECGLidoPen IM: Administer 300 mg (3 mL of 10% solution) in deltoid or thighSwitch to IV lidocaine or oral antiarrhythmic as soon as possible

Other Indications & UsesAcute management of ventricular arrhythmias (cardiac surgery, acute MI)Off-label: Peds with premature ventricular beats during cardiac arrestIM dose indicated when IV admin is not possible or when ECG monitoring is not available and danger of ventricular arrhythmia is great

Adverse EffectsFrequency Not DefinedCommon

Cardiovascular: Hypotension Dermatologic: Edema, erythema at injection site, petechiae, skin irritation Gastrointestinal: Constipation, Nausea, vomiting

Neurologic: Confusion, dizziness, headache, paresthesia, somnolence, tremor Other: Irritation symptom, Topical products; ie, erythema, edema

Serious Cardiovascular: Cardiac arrest, cardiac dysrhythmia Hematologic: Methemoglobinemia Neurologic: Seizure Anaphylactoid reactions Malignant hyperthermia

Contraindications & Cautions ContraindicationsHypersensitivity to lidocaine or amide-type local anestheticAdams-Stokes syndrome, SA/AV/intraventricular heart block in the absence of artificial pacemakerCHF, cardiogenic shock, 2nd and 3rd degree heart block (if no pacemaker is present), Wolff-Parkinson-White SyndromeCautionsLidocaine effects incr by beta-blockers & cimetidineNot recommended as prophylaxis in AMI (controversial)Liver dz, CHF, bradycardia, Wolff-Parkinson-White syndrome, marked hypoxia, severe respiratory depression, hypovolemia, incomplete heart blockGood for automatic and reentrant arrhythmias, not PSVT's

PharmacologyHalf-Life: parent drug: 2.5-8 hr, metabolite: MEGX 2 hr, GX 10 hr; half-life prolonged in pts w/ CHF or liver dzOnset: IV: 45-90 secDuration: 10-20 minBioavailability: PO:35%Protein Bound: 60-80%Vd: 1.7 L/kgMetabolism: liver by de-ethylation to form active mets: monoethylglycinexylidide (MEGX) and glycinexylidide (GX)Metabolites: monoethylglycinexylidide (MEGX) and glycinexylidide (GX) (active met)Clearance: less if CHF, shock, digoxin toxicity, geriatricExcretion: 90% urineDialyzable: HD: yesMechanism of ActionClass 1B antidysrhythmic; combines with fast Na channels and thereby inhibits recovery after repolarization, resulting in decreasing myocardial excitability & conduction velocity

Lidocaine (Dilocaine)Decreases permeability to sodium ions in neuronal membranes, inhibiting depolarization and blocking transmission of nerve impulses. Mechanism of action in DCS is unknown.