Bupicaine Heavy

Uses

Bupivacaine Hydrochloride & Dextrose is used for-

• • Bupivacaine is used for lower abdominal surgery (including Caesarean section), urological and lower limb, including hip surgery, lasting 1.5 to 3 hours.
• • Bupivacaine are used for intrathecal (subarachnoid, spinal) anesthesia for surgical and obstetrical procedures.
• • Bupivacaine produces motor blockade of the abdominal muscles makes the solution suitable for performance of abdominal surgery lasting 1.5-2 hours. The duration of motor blockade does not exceed the duration of analgesia.

Bupicaine Heavy is also used to associated treatment for these conditions: Acute Gouty Arthritis, Adrenal cortical hypofunctions, Alopecia Areata (AA), Ankylosing Spondylitis (AS), Berylliosis, Bullous dermatitis herpetiformis, Congenital Adrenal Hyperplasia (CAH), Congenital Hypoplastic Anemia, Dermatomyositis, Discoid Lupus Erythematosus (DLE), Edema of the cerebrum, Epicondylitis, Hemolytic Anemia, Keloid Scars, Leukemias, Mycosis Fungoides (MF), Necrobiosis lipoidica diabeticorum, Ocular Inflammation, Ophthalmia, Sympathetic, Osteoarthritis (OA), Pain, Labor, Polymyositis, Postoperative pain, Psoriatic Arthritis, Psoriatic plaque, Pure Red Cell Aplasia, Regional Enteritis, Rheumatoid Arthritis, Secondary thrombocytopenia, Stevens-Johnson Syndrome, Synovitis, Systemic Lupus Erythematosus (SLE), Temporal Arteritis, Trichinosis, Tuberculous Meningitis, Ulcerative Colitis, Uveitis, Acute Bursitis, Acute Idiopathic Nephrotic Syndrome, Acute Lupus Erythematosus, Acute Multiple sclerosis, Acute Rheumatic heart disease, unspecified, Acute nonspecific tenosynovitis, Cancer-associated hypercalcemia, Cystic tumors of aponeurosis, Cystic tumors of tendon, Disseminated Pulmonary Tuberculosis, Exfoliative erythroderma, Inflammatory lesions of granuloma annulare, Inflammatory lesions of lichen planus, Inflammatory lesions of lichen simplex, Non-suppurative Thyroiditis, Permphigus, Severe Allergic Reactions, General Anesthesia, Regional nerve block therapy, Local anesthesia therapyArrhythmia, Caloric Deficit, Edema of the cerebrum, Metabolic Alkalosis, Hypoglycemic reaction, Blood Specimen Collection, Electrolyte replacement, Nutritional supplementation, Parenteral Nutrition, Parenteral rehydration therapy, Plasmapheresis, Positive cardiac inotropic effect, Total parenteral nutrition therapy, Urine alkalinization therapy, Fluid and electrolyte maintenance therapy

How Bupicaine Heavy works

Local anesthetics such as bupivacaine block the generation and the conduction of nerve impulses, presumably by increasing the threshold for electrical excitation in the nerve, by slowing the propagation of the nerve impulse, and by reducing the rate of rise of the action potential. Bupivacaine prevents depolarization by bindng to the intracellular portion of sodium channels and blocking sodium ion influx into neurons. In general, the progression of anesthesia is related to the diameter, myelination and conduction velocity of affected nerve fibers. Clinically, the order of loss of nerve function is as follows: (1) pain, (2) temperature, (3) touch, (4) proprioception, and (5) skeletal muscle tone. The analgesic effects of Bupivicaine are thought to potentially be due to its binding to the prostaglandin E2 receptors, subtype EP1 (PGE2EP1), which inhibits the production of prostaglandins, thereby reducing fever, inflammation, and hyperalgesia.

Glucose supplies most of the energy to all tissues by generating energy molecules ATP and NADH during a series of metabolism reactions called glycolysis. Glycolysis can be divided into 2 main phases where the preparatory phase is initiated by the phosphorylation of glucose by a hexokinase to form glucose 6-phosphate. The addition of the high-energy phosphate group activates glucose for subsequent breakdown in later steps of glycolysis and is the rate-limiting step. Products end up as substrates for following reactions, to ultimately convert C6 glucose molecule into two C3 sugar molecules. These products enter the energy-releasing phase where total of 4ATP and 2NADH molecules are generated per one glucose molecule. The total aerobic metabolism of glucose can produce up to 36 ATP molecules. This energy-producing reactions of glucose is limited to D-glucose as L-glucose cannot be phosphorlyated by hexokinase. Glucose can act as precursors to generate other biomolecules such as vitamin C. It plays a role as a signaling molecule to control glucose and energy homeostasis. Glucose can regulate gene transcription, enzyme activity, hormone secretion, and the activity of glucoregulatory neurons. The types, number and kinetics of glucose transporters expressed depends on the tissues and fine-tunes glucose uptake, metabolism, and signal generation in order to preserve cellular and whole body metabolic integrity .

Dosage

Bupicaine Heavy dosage

The following dosage recommendations should be regarded as a guide for use in the average adult. The patient's physical status and concomitant medication should be considered when deciding the dose, and the lowest dose required for adequate anesthesia should be used. Duration varies with dose, while segmental spread may be difficult to predict, especially with the isobaric (plain) solution.The dose should be reduced in the elderly and in patients in the late stages of pregnancy.Spinal anesthesia for surgery.

The spread of anesthesia obtained with Bupivacaine is dependent on several factors, the most important being volume of solution injected, position of patient and rate of injection.

• 1.5-4 mL Bupivacaine (7.5-20 mg Bupivacaine hydrochloride).

• When 3 mL Bupivacaine was injected into the L3 - L4 interspace and patients were kept in the sitting position for 2 minutes before being placed supine, blockade spread to the T7 - T10 segment.

When a similar injection was made in patients in the lateral position who were then immediately placed supine, blockade spread to the T4 - T7 segment.

PediatricsBupivacaine may be used in children. One of the differences between small children and adults is a relatively high CSF volume in infants and neonates, requiring a relatively larger dose/kg to produce the same level of block as compared to adults.< 5 kg: 0.40-0.50 mg/kg5 to 15 kg: 0.30-0.40 mg/kg15 to 40 kg: 0.25-0.30 mg/kg

It should not be administered by SC or IM route. Dextrose should be infused through the largest available peripheral vein.

Side Effects

The adverse reaction profile for Bupivacaine is similar to those for other long acting local anesthetics administered intrathecally. Adverse reactions caused by the drug per se are difficult to distinguish from the physiological effects of the nerve block (e.g. decrease in blood pressure, bradycardia, temporary urinary retention), events caused directly (e.g. nerve trauma) or indirectly (e.g. epidural abscess) by the needle puncture or events associated to cerebrospinal leakage (eg. postdural puncture headache).

Toxicity

The mean seizure dosage of bupivacaine in rhesus monkeys was found to be 4.4 mg/kg with mean arterial plasma concentration of 4.5 mcg/mL. The intravenous and subcutaneous LD 50 in mice is 6 to 8 mg/kg and 38 to 54 mg/kg respectively. Recent clinical data from patients experiencing local anesthetic induced convulsions demonstrated rapid development of hypoxia, hypercarbia, and acidosis with bupivacaine within a minute of the onset of convulsions. These observations suggest that oxygen consumption and carbon dioxide production are greatly increased during local anesthetic convulsions and emphasize the importance of immediate and effective ventilation with oxygen which may avoid cardiac arrest.

Oral LD50 value in rats is 25800mg/kg. The administration of glucose infusions can cause fluid and/or solute overloading resulting in dilution of the serum electrolyte concentrations, over-hydration, congested states, or pulmonary oedema. Hypersensitivity reactions may also occur including anaphylactic/anaphylactoid reactions from oral tablets and intravenous infusions.

Precaution

1.When any local anesthetic agent is used, resuscitative equipment and agents, including oxygen, should be immediately available in order to manage possible adverse reactions involving the cardiovascular, respiratory or central nervous systems.

2. The safety and effectiveness of Bupivacaine depend on proper dosage, correct technique and adequate precautions. Standard textbooks should be consulted for specific techniques and precautions for spinal anesthetic procedures. If signs of acute systemic toxicity or total spinal block appear, injection of the local anesthetic should be stopped immediately.

3. Patients in poor general condition due to ageing or other compromising factors such as partial or complete heart conduction block, advanced liver or renal dysfunction require special attention although regional anesthesia may be the optimal choice for surgery in these patients.

4. The possibility of hypotension and bradycardia following epidural or subarachnoid blockade should be anticipated and appropriate precautions taken, including the prior establishment of an intravenous line and the availability of vasopressor agents and oxygen.Hypotension is common in patients with hypovolaemia due to haemorrhage or dehydration and in those with aortocaval occlusion due to abdominal tumours or the pregnant uterus in late pregnancy. Hypotension is poorly tolerated by patients with coronary or cerebrovascular disease.

5. Bupivacaine should be used with caution in patients with known medicine sensitivities.

6. Bupivacaine should be used with caution in patients with genetic predisposition to malignant hyperthermia as the safety of amide local anesthetic agents in these patients has not been fully established. A standard protocol for the management of malignant hyperthermia should be available.

7. Spinal anesthesia can be unpredictable and very high blocks are sometimes encountered with paralysis of the intercostal muscles, and even the diaphragm, especially in pregnancy. On rare occasions it will be necessary to assist or control ventilation.

8. Chronic neurological disorders, such as multiple sclerosis, hemiplegia due to stroke etc. are not thought to be adversely affected by spinal anesthesia, but call for caution.

9. There is an increased risk for high or total spinal blockade in the elderly and in patients in the late stages of pregnancy. The dose should therefore be reduced in these patients (see DOSAGE AND ADMINISRATION).

Interaction

Bupivacaine should be used with care in patients receiving antiarrhythmic drugs with local anaesthetic activity, as their toxic effects may be additive. Phenothiazines and Butyrophenones may reduce or reverse the pressor effect of epinephrine.

Volume of Distribution

The mean volume of distribution after intravenous infusion is 10.6L.

Elimination Route

Systemic absorption of local anesthetics is dose- and concentration-dependendent on the total drug administered. Other factors that affect the rate of systemic absorption include the route of administration, blood flow at the administration site, and the presence or absence of epinephrine in the anesthetic solution.

Bupivacaine formulated for instillation with meloxicam produced varied systemic measures following a single dose of varying strength. In patients undergoing bunionectomy, 60 mg of bupivacaine produced a C_max of 54 ± 33 ng/mL, a median T_max of 3 h, and an AUC_∞ of 1718 ± 1211 ng*h/mL. For a 300 mg dose used in herniorrhaphy, the corresponding values were 271 ± 147 ng/mL, 18 h, and 15,524 ± 8921 ng*h/mL. Lastly, a 400 mg dose used in total knee arthroplasty produced values of 695 ± 411 ng/mL, 21 h, and 38,173 ± 29,400 ng*h/mL.

Polysaccharides can be broken down into smaller units by pancreatic and intestinal glycosidases or intestinal flora. Sodium-dependent glucose transporter SGLT1 and GLUT2 (SLC2A2) play predominant roles in intestinal transport of glucose into the circulation. SGLT1 is located in the apical membrane of the intestinal wall while GLUT2 is located in the basolateral membrane, but it was proposed that GLUT2 can be recruited into the apical membrane after a high luminal glucose bolus allowing bulk absorption of glucose by facilitated diffusion . Oral preparation of glucose reaches the peak concentration within 40 minutes and the intravenous infusions display 100% bioavailability.

Half Life

2.7 hours in adults and 8.1 hours in neonates.

Bupivacaine applied together with meloxicam for postsurgical analgesia had a median half-life of 15-17 hours, depending on dose and application site.

The approximate half-life is 14.3 minutes following intravenous infusion. Gut glucose half-life was markedly higher in females (79 ± 2 min) than in males (65 ± 3 min, P < 0.0001) and negatively related to body height (r = -0.481; P < 0.0001).

Clearance

The mean metabolic clearance rate of glucose (MCR) for the 10 subjects studied at the higher insulin level was 2.27 ± 0.37 ml/kg/min at euglycemia and fell to 1.51±0.21 ml/kg/ at hyperglycemia. The mean MCR for the six subjects studied at the lower insulin level was 1.91 ± 0.31 ml/kg/min at euglyglycemia.

Elimination Route

Only 6% of bupivacaine is excreted unchanged in the urine.

Glucose can be renally excreted.

Pregnancy & Breastfeeding use

It is reasonable to assume that a large number of pregnant women and women of child-bearing age have been given Bupivacaine. No specific disturbances to the reproductive process have so far been reported, e.g. no increased incidence of malformations. It should be noted that the dose should be reduced in patients in the late stages of pregnancyWith recommended doses, Bupivacaine enters breast milk in such small quantities that there is generally no risk of affecting the breast-fed child.

At maternal serum levels of up to 0.45 µg/mL produced by the epidural use of Bupivacaine for vaginal delivery, Bupivacaine could not be detected in breast milk during the first 24 hours after delivery (detection limit 0.02 µg/mL).

Contraindication

Bupivacaine in Dextrose is contraindicated in patients with a known hypersensitivity to it or to any local anaesthetic agent of the amide type. The following conditions preclude the use of spinal anaesthesia: Severe hemorrhage, severe hypotension or shock and arrhythmias, such as complete heart block, which severely restrict cardiac output,Local infection at the site of proposed lumbar puncture ,Septicemia.

Special Warning

Use in children: Bupivacaine Hydrochloride is not recommended in patients younger than 18 years of age.

Use in elderly and renal impairment: Patients in poor general condition due to ageing or other compromising factors such as partial or complete heart conduction block, advanced liver or renal dysfunction require special attention, although regional anesthesia may be the optimal choice for surgery in these patients.

Acute Overdose

Acute emergencies associated with the use of local anesthetics are generally related to high plasma levels. Since the dose required for spinal anesthesia is so small (20% or less than that required for epidural anesthesia), acute systemic toxicity is extremely unlikely and has not been reported.With accidental intravascular injections of local anesthetics, the toxic effects will be obvious within 1 - 3 minutes. With over dosage, peak plasma concentrations may not be reached for 20 - 30 minutes, depending on the site of injection and toxic signs will be delayed. Toxic reactions mainly involve the central nervous and cardiovascular systems.

Storage Condition

Bupivacaine should be stored at 25°C or below. Do not freeze.Local anesthetics react with certain metals and cause the release of their respective ions which, if injected, may cause severe local irritation. Adequate precautions should be taken to avoid prolonged contact between Bupivacaine and metal surfaces such as metal bowls, cannulae and syringes with metal parts.The ampoules are designed for single use only; any unused portions of solutions should be discarded. The solution should be used immediately after opening the ampoule. Solutions showing discoloration should not be used.

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