Antidotes & their MOAGROUP NO. 06CLINICAL PHARMACY (TOXICOLOGY)

FlumazenilASRA HAMEED12859

Flumazenil (GABA Modulators)Imidazobenzodiazepine derivativeAntagonizes the actions of benzodiazepines on the CNSCompetitively inhibits the activity at the benzodiazepine recognition site on the GABA/benzodiazepine receptor complex

BenzodiazepineMechanism Of Action

Benzodiazepines enhance the effect of the neurotransmitter gamma-aminobutyric acid (GABA) at the GABAA receptor, resulting in sedative, hypnotic (sleep-inducing), anxiolytic (anti-anxiety), anticonvulsant, and muscle relaxant properties.All benzodiazepines act by enhancing the actions of a natural brain chemical, GABA (gamma-aminobutyric acid). GABA is a neurotransmitter, an agent which transmits messages from one brain cell (neuron) to another. The message that GABA transmits is an inhibitory one: it tells the neurons that it contacts to slow down or stop firing. Since about 40% of the millions of neurons all over the brain respond to GABA, this means that GABA has a general quietening influence on the brain: it is in some ways the body's natural hypnotic and tranquilliser. This natural action of GABA is augmented by benzodiazepines which thus exert an extra (often excessive) inhibitory influence on neurons *

symptoms of BZD overdoseCentral nervous system depressionAtaxiaSlurred speechDizzinessConfusionDrowsinessBlurred visionUnresponsivenessAnxietyAgitation

Severe symptoms include coma and respiratory depression

Benzodiazepine ToxicityDifferential DiagnosesAcute HypoglycemiaAlcohol ToxicityAntidepressant ToxicityEncephalitisHypernatremia (rise in serum sodium concentration by decrease in total body water)Hyponatremia [abnormally low serum Sodium

(helps regulate the amount of water in and around cells)]Neuroleptic Agent ToxicitySedative-Hypnotic ToxicityStroke, IschemicToxicity, Antihistamine

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Tests and procedures depend on the presentation, as follows:Obtain a blood glucose level immediately if the patient has an altered mental statusObtain an arterial blood gas (ABG) if respiratory depression is presentObtain an electrocardiogram (ECG) to evaluate for co-ingestants, particularly cyclic antidepressantsObtain a chest radiograph if respiratory compromise is presentObtain a pregnancy test in women of childbearing age

Overall, the laboratory detection of benzodiazepines (BZDs) depends upon the screening method used. Immunoassay screening techniques are performed most commonly and typically detect BZDs that are metabolized to desmethyldiazepam or oxazepam; thus, a negative screening result does not rule out the presence of a BZD. Qualitative screening of urine or blood may be performed but rarely influences treatment decisions and has no impact on immediate clinical care.*

In patients with an intentional overdose, measure the following:Serum electrolytesGlucoseblood urea nitrogen (BUN)Creatinine clearanceEthanolAcetaminophen level

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Approach ConsiderationsAs with any overdose, the first step is to assess the patient's airway, breathing, and circulation and to address these rapidly as needed. The cornerstone of treatment in benzodiazepine (BZD) overdoses is good supportive care and monitoring.

activated charcoalSingle-dose activated charcoal is not routinely recommended, as the risks far outweigh the benefit. BZD are very rarely fatal in overdoses, and the altered mental status from BZD overdose greatly increases the risk of aspiration following oral charcoal dosing.

FlumazenilFlumazenil is a specific antidote for BZDs, but its use in acute BZD overdose is controversial and its risks usually outweigh any possible benefit.It should be considered only in isolated iatrogenic BZD overdose in BZD-naive patients (e.g., during conscious sedation on BZD-naive patient). In long-term BZD users, flumazenil may precipitate withdrawal and seizures; in patients taking BZDs for a medical condition, flumenazil may result in exacerbation of the condition.

FlumazenilCommon adverse events with flumazenil include agitation and gastrointestinal symptomsSerious adverse events include supraventricular arrhythmia and convulsions

Vitamin C

MECHANISM OF ACTION Necessary for collagen formation and tissue repair; plays a role in oxidation/reduction reactions as well as other metabolic pathways including synthesis of catecholamines, carnitine, and steroids; also plays a role in conversion of folic acid to folinic acid*

MethemoglobinemiaHemoglobin within red blood cells attaches (binds) to oxygen molecules in the lungs, which it carries through the bloodstream, then releases in tissues throughout the body. Instead of normal hemoglobin, people with methemoglobinemia, have an abnormal form called methemoglobin, which is unable to efficiently deliver oxygen to the body's tissues.

It promote the heme iron to change from ferrous to ferric. The ferric iron cannot bind oxygen and causes cyanosis and the brown appearance of blood.

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Cyanosis is a bluish discoloration, especially of the skin and mucous membranes, due to excessive concentration of deoxyhemoglobin in the blood caused by deoxygenation.

Treatment andPatients with G6PD deficiencyMethylene blue is the primary emergency treatment for methemoglobinemiaMethylene blueshould not be administered to patients with glucose 6-phosphate dehydrogenase (G6PD) deficiency, MB may not only be ineffective but it is also potentially dangerousPretreatment screening of G6PD deficiency is not usually possible in emergency. If methylene blueis contraindicated, only moderate doses of ascorbic acid Dose:300 to 1000 mg/day orally in divided doses

Methylene blue is the primary emergency treatment for documented symptomatic methemoglobinemiaMethylene blueshould not be administered to patients with known glucose 6-phosphate dehydrogenase (G6PD) deficiency, since the reduction of methemoglobin by MB is dependent upon NADPH generated by G6PD. As a result, MB may not only be ineffective but it is also potentially dangerous, since MB has an oxidant potential that may induce hemolysis in G6PD deficient subjects.Pretreatment screening of G6PD deficiency is not usually possible in emergency. If methylene blueis contraindicated, only moderate doses of ascorbic acid (300 to 1000 mg/day orally in divided doses) should be given, as this drug may also cause oxidant hemolysis in G6PD deficient patients when given in very high doses.*

Repair the damaged hemoglobin

The use of methylene blue to repair the damaged hemoglobin. That is, methylene blue, in its reduced form, is a colorless, water-solulble molecule. When it has been oxidized, it becomes blue. The blue tint that this gives to urine accounts for the last quote in Kathy Trost's article, that "I can see that old blue running out of my skin." The use of vitamin C by Dr. Deeny in Ireland achieves the same result of repairing damaged hemoglobin. However, vitamin C is colorless, so there is no excretion of blue pigment. *

GlucagonNEELAM SHARIF12886

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Beta Blockers and CCBs OverdoseSome beta blockers may antagonize sodium channel blockage QRS widens and some beta blockers cause efflux blockade long QT Beta blockers overdose results in bradycardia and hypotension

CCBs prevent the opening of these voltage-gated calcium channels (myocardial cells, smooth muscle cells and -islet cells of the pancreas) and reduce calcium entry into cells during phase 2 of an action potential. In an overdose situation, receptor selectivity is lost, and effects not normally seen at therapeutic doses can occur.

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Mechanism of Action of ToxicityCalcium enters open voltage-sensitive calcium channels to promote the release of calcium from the sarcoplasmic reticulum. The released calcium combines with troponin to cause muscle contraction via actin and myosin fibers. AC catalyzes the conversion of ATP to cAMP, which activates protein kinase A (PKA), which promotes the opening of dormant calcium channels, enhances release of calcium from the sarcoplasmic reticulum, and facilitates release of calcium by troponin during diastole. Glucagon bypasses -receptors and acts directly on Gs to stimulate conversion of ATP to cAMP. Amrinone inhibits PDE(Phosphodiestrase) to prevent the degradation of cAMP. Insulin promotes the uptake and use of carbohydrates as an energy source.

Mechanism of action of toxicity

Specific features and Symptomsof Beta Blockers Overdose

Specific Features and Symptoms Of CCBs Overdose

Antidote GlucagonGlucagon is generally recognized as first-line therapy. Glucagon is a hormone secreted by the 2 cells of the pancreatic islets of Langerhans..High-dose glucagon is recommended for cardiotoxicity produced by -blocker poisoning.

Mechanism of antidote glucagon

Glucose (Dextrose 50%)AMMARAH UROOJ12852

MECHANISM OF INSULIN:

SYMPTOMS OF INSULIN TOXICITY:High doses of insulin can lead to: dyselectrolytemia.Salt and water retention hyponatremiahypoglycemia hypokalemiadizziness and mild confusionanxiety or nervousnessshakinessrapid heartbeatHungerIrritability

EMERGENCY TREATMENT : provide immediate attention to patient before they lead to dangerously low blood sugar. People who have low blood sugar levels are advised to consume 15 grams of a fast digesting carbohydrate, such as glucose tablets or a high-sugar food immediately. High-glucose foods include:raisins soda fruit juice honey candy

symptoms should improve within 15 minutes. If they dont, or if a test shows your levels are still low, repeat the above steps until your blood sugar is above 70 mg/dL. If your symptoms still dont improve, seek medical help immediately. Be sure to eat a meal after treating a low blood sugar reaction.

MANAGEMENT OF HYPOGLYCEMIAManagement includes the following steps:Restoration of normal plasma

glucose levelsPrevention of relapse in the

short termPrevention of recurrent episodes

in the long term.

RESTORATION OF NORMAL PLASMA GLUCOSE LEVEL:In non-severe hypoglycemia, the oral consumption of carbohydrates is usually adequate to restore plasma glucose levels above the lower limit of the normal range. Patients starting insulin for the treatment of their diabetes should be taught to recognize the symptoms of hypoglycemia and how to react in case of a hypoglycemic event. Self-monitoring blood glucose (SMBG) is strongly recommended for these patients If hypoglycemia is suspected, a blood glucose measurement using a portable glucose meter is recommended in order to confirm low plasma glucose

Prevention of relapse in the short term

Restoration of plasma glucose levels after an acute hypoglycemic event usually follows quickly after the administration of carbohydrates, either orally or intravenously, or after a glucagon injection. It is very important, however, to keep in mind that hypoglycemia tends to relapse in some cases, this tendency depending on the etiology of the initial decline in plasma glucose

Prevention of recurrent episodes in the long term

Recurrent hypoglycemia requires a thorough evaluation of diabetes management A careful history is usually adequate to identify hypoglycemia unawareness. In other cases, careful follow-up with frequent SMBG or even the use of a glucose sensor for continuous subcutaneous glucose monitoring may be recommended

DEXTROSE 50% SOLUTION:50% Dextrose Injection, USP is a sterile, nonpyrogenic, hypertonic solution of dextrose in water for injection for intravenous injection as a fluid and nutrient replenisher. Each mL of fluid contains 0.5 g dextrose, hydrous which delivers 3.4 kcal/gram

Mechanism of Action: Provides immediate source of glucose for cellular metabolism. It provide free water that pass through membrane pores both intracellular and extracellular spaces.its smaller size allow the molecule to pass more freely between compartment thus expanding both compatments simultaneously

Contraindications: 1. There are no absolute contraindications to the IV administration of dextrose 50% in the emergency setting.2. Relative contraindication: Use with caution in patients with increasing Intracranial pressure as the added glucose may worsen the cerebral edema.

Side Effects: 1. Patients may complain of warmth, pain or burning at the injection site.2. Dextrose can cause severe neurologic symptoms (Wernicke's encephalopathy or Korsakoff's psychosis) if patient is thiamine deficient.

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Routes of Administration: IV, IO. Onset and Duration of Actions: Onset will be 30-60 seconds but duration depends upon degree and cause of hypoglycemia. Dosages: ADULT: 25 gm (50 ml solution preload) IVP/IOMay repeat once in 5 minutesOver 2 years: 1 ml/kg slow IVP/IO of a 50% solution (same solution as for the adult)May repeat once in 5 minutes.

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ThiamineSABIHA GUL131027

INTRODUCTIONalso known as vitamin B1, anti beriberi factor or antineuritic vitaminIt is an important water-soluble vitamin is involved in carbohydrate, fat, amino acid, glucose, and alcohol metabolism.is required as a coenzyme in enzymatic reactions that involve the transfer of an aldehyde group. is essentially nontoxic

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CHEMISTRY Thiamine contains a substituted pyrimidine ring (dimethyl 6-amino pyrimidine) connected to a substituted thiazole ring (Methyl hydroxy ethyl thiazole) by means of Methylene bridge

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*SYNTHESIS

Thiamine can be synthesized by plants and some microorganisms, but not usually by animals. Human beings require thiamine from diet, though small amounts may be obtained from synthesis by intestinal bacteria. Whole wheat flour, unpolished rice, beans, nuts and yeast are the good sources of thiamine .It is also present in liver, meat and eggs. The body can only store up to 30 mg of thiamine in its tissues

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It is present in large amounts in skeletal muscle, heart, liver, kidney, and brain.It has a widespread distribution in foods, but there can be a substantial loss of thiamine during cooking above 100C (212F).The half-life of thiamine is 9-18 days. It is excreted by the kidney

*OCCURRENCE

RECOMMENDED DAILY ALLOWANCE:

Depends on calorie intake (0.5 mg/1000 cals ) RDA is 1-1.5 mg/day Requirement increases with increased carbohydrate intake Pregnancy Lactation Smoking Alcoholism Prolonged antibiotic intake Serious or prolonged illness

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METABOLISM Thiamine has a central role in energy-yielding metabolism, and especially the metabolism of carbohydrates Thiamine pyrophosphate is an essential cofactor for enzymes that catalyze the oxidative decarboxylation of -keto acids to form an acylated coenzyme A (acyl CoA). These include pyruvate dehydrogenase , -keto glutarate dehydrogenase and branched-chain - keto acid dehydrogenase. These three enzymes operate by a similar catalytic mechanism

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THIAMINE AS AN ANTIDOTE*Thiamine use a antidote : Persons with alcoholismEthylene Glycol PoisoningWernickeKorsakoff syndrome(WKS)

WernickeKorsakoff syndrome(WKS)WernickeKorsakoff syndrome(WKS) is the combined presence ofWernicke's encephalopathy(WE) andKorsakoff's syndrome. Due to the close relationship between these two disorders, people with both are usually diagnosed with WKS, as a single syndrome.It is due tothiamine (vitamin B1) deficiency, which can cause a range of disorders includingberiberi, Wernicke's encephalopathy, and Korsakoff's psychosis.

SIGN AND SYMPTOMS These disorders may manifest together or separately. WKS is usually secondary toalcohol abuse, It mainly causes vision changes,ataxia impaired memory.

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CAUSESWKS is usually found in chronic alcoholics. WernickeKorsakoff syndrome results from thiamine deficiency. It is generally agreed that Wernicke's encephalopathy results from severe acute deficiency ofthiamine(vitamin B1)

Alcoholthiamine interactionsStrong evidence suggests that ethanol interferes directly with thiamine uptake in the gastrointestinal tract. Ethanol also disrupts thiamine storage in the liver and the transformation of thiamine into its active form.The role of alcohol consumption in the development of WKS has been experimentally confirmed through studies in which rats were subjected to alcohol exposure and lower levels thiamine through a low-thiamine diet*

TREATMENTThiamine administration should be initiated immediately when the disease is suspectedminimum dose of 500mg ofThiamine hydrochlorideSuch prompt administration of thiamine may be a life-saving measure. Banana bags, a bag ofintravenousfluids containing vitamins and minerals, is one means of treatment.

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Persons with alcoholism It is well known that chronic alcoholics are at high risk for being deficient in vitamin B1 (thiamine), which is known to put the patient at an increased risk for Wernicke-Korsakoff Syndrome, cerebellar degeneration, and cardiovascular dysfunction.

TREATMENTThe current standard of treatment for such patients is to give them thiamine 100 mg intravenously (IV) before administering glucose containing IV fluids and then to continue this dose for several days.

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Ethylene glycol poisoningIt is a sweet kilerEthylene glycol poisoningis caused by the ingestion ofethylene glycol the primary ingredient in automotiveantifreeze Ethylene glycol is a toxic, colorless, odorless, almostnonvolatileliquid with a sweet taste that is sometimes accidentally consumed by children and animals due to its sweetness. symptoms of poisoning progress from signs similar tointoxicationandvomiting tohyperventilation,metabolic acidosis andcardiovasculardysfunction; and finallyacute kidney failure

CAUSESThe major cause of toxicity is not the ethylene glycol itself but itsmetabolites, mainlyglycolic acidandoxalic acid. LETHAL DOSELethal dose is estimated as 1 -1.5 mls/kg or 100mls *

TREATMENTInhibit Absorption i.e Gastric lavage , syrup of ipecac and activated charcoal Correct Acidosis i.e Bicarp drip Inhibition of Metabolism i.e Thiamine Fomepizole (4 -methylpyrazole) Ethanol Pyridoxine Elimination of parent compound and the metabolites I,e remove ethylene glycol and glycolate effectively

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TREATMENT

THIAMINE : MOAPrevents the formation of oxalic acid by facilitating the conversion of glycoxylic acid to alpha Hydroxy Beta ketoadipic acid.

DOSE100 mg IV q6 until ethylene glycol can no longer be measured in the serum

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Hydroxocobalamin&Sodium ThiosulphateNOSHEEN HAYAT131018

CYANIDE POISONING Cyanide poisoningoccurs when a living organism is exposed to a compound that produces cyanideions (CN) when dissolved in water.

CYANIDE ANTIDOTESAntidotes to cyanide include hydroxocobalamin and sodium nitrite and sodium thiosulfate. Sodium thiosulfate may be given in combination with sodium nitrite or hydroxocobalamin, or may be given alone. These agents are administered intravenously.

FomepizoleAISHA ABDULLAH12850

Ethyiene glycol Toxicity & its Mechanism of Toxicity

Stages of Ethylene Glycol IntoxicationSevere ethylene glycol poisoning may go through three stages:

CNS depression cardiopulmonary toxicity renal toxicity

Stage 1At 4-12 hours after glycoaldehyde forms , these symptoms may appear:seizurescomacerebral edema (in some cases)gastrointestinal irritation (nausea and vomiting)

Stage 2The following cardiorespiratory symptoms may appear 12-24 hours after ingestiontachycardia,tachypnea, andhypertension or hypotension.The following conditions may develop in this stagepulmonary edema,pneumonitis,congestive cardiac failure, andshock.Formation of oxalic acid may lead to deposition of calcium oxalate crystals inthe meninges,blood vessel walls,lung, andmyocardium.

Stage 3Kidney damage usually develops 24-72 hours after exposure. Acidosis and acute renal failure may result from deposition of calcium oxalate crystals in the kidneys.The following conditions characterize the third phaseflank pain,costovertebral angle tenderness, andoliguric renal failure.

DiagnosisIt is most reliably diagnosed by the measurement of the blood ethylene glycol concentration. Ethylene glycol in biological fluids can be determined by gas chromatography.Many hospital laboratories do not have the ability to perform this blood test and in the absence of this test the diagnosis must be made based on the clinical presentation of the patient.In this situation a helpful test to diagnose poisoning is the measurement of the osmolal gap. Large anion gap acidosis is usually present during the initial stage of poisoning. diagnosis of ethylene glycol poisoning should be considered in any patient with a severe acidosis. Urine microscopy can reveal needle or envelope-shaped calcium oxalate crystals in the urine which can suggest poisoning.

TreatmentThe most important initial treatment for ethylene glycol poisoning is stabilizing the patient. As ethylene glycol is rapidly absorbed, gastric decontamination is performed within 60 minutes of ingestion. Patients with significant poisoning often present in a critical condition. In this situation stabilization of the patient including airway management with intubation should be performed in preference to gastrointestinal decontamination.Patients presenting with metabolic acidosis or seizures require treatment with sodium bicarbonate and ticonvulsives such as a benzodiazepine respectively.Sodium bicarbonate should be used cautiously as it can worsen hypocalcemia by increasing the plasma protein binding of calcium. If hypocalcemia occurs it can be treated with calcium replacement although calcium supplementation can increase the precipitation of calcium oxalate crystals leading to tissue damage.Intubation and respiratory support may be required in severely intoxicated patients; patients with hypotension require treatment with intravenous fluids and possibly vasopressors.[

Fomepizole & its MOA

DosingThe dosing and administrationof fomepizole is the same for children and adults.Loading dose :15 mg/kg IV maximum of 1500 mg12 hours later, give the 1st maintenance dose of 10 mg/kg IV. Repeat every 12 hoursContinue treatment until EG or methanol levels are below 20 mg/dl and the patient is asymptomatic with normal pH.

HeparinZABAB KHAN131066

Ergotamineis a naturally occurring ergot alkaloid Used for Preventing or treating acute migraine headache Partial agonist or antagonist activity against tryptaminergic, dopaminergic and -adrenergic receptorsPotent vasoconstrictor, analgesic, Oxytocics

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Ergotamine doses of more than 15 mg/24 hours or more than 40 mg over a few days are likely to cause toxicity. Death has been reported in a 14-month-old toddler after an acute ingestion of 12 mg

vasospastic effectsnausea and vomitingimpaired mental functionconfusion depression drowsinessrapid and weak pulseunconsciousnessspasms of the limbs

Reverses hyper-coagulable state by interacting with anti-thrombin III to prevent local thrombosis and ischemia.Heparin binds to antithrombinIII (AT)The activated AT then inactivatesthrombin,factor Xaand other proteases.The conformational change in AT on heparin-binding mediates its inhibition of factor Xa.The formation of a complexbetween AT, thrombin, and heparin results in the inactivation of thrombin.

Vitamin KZABAB KHAN131066

Most widely prescribed anticoagulant (a drug which reduces the risk of blood clots forming). decreases the clotting ability of the blood so reduces the risk of blood clots formingBlood clots can be dangerous because they can lead to serious life-threatening conditions such asstroke.It is very effective at significantly reducing the risk of stroke in people withatrial fibrillation(AF)

People taking warfarin need to have a regular blood test called an international normalised ratio (INR). INR measures the time it takes your blood to clot. It is increased by taking warfarin, which, in turn, increases the INR. Patients on warfarin, their target INR is 2.5 If youre not on warfarin your INR is around 1The lowesttoxic dosein humans ranges from 10 mg/kg to 15 mg/kg The probable lethaloraldosein humans is believed to be between 50 and 500 mg/kg

Red spots on your skin that look like a rashSevere headache or dizzinessHeavy bleeding after an injuryHeavy bleeding during monthly period in womenYou have severe stomach pain or you vomit bloodPink, red, or dark brown urineBlack or bloody bowel movements

Vitamin K is a fat-solublevitaminVitamin K is known as the clotting vitamin, because without it blood would not clot.Found in Green leafy vegetables, such as spinach mustard greens, parsley and green leaf lettuceVegetables such as broccoli, cauliflower, and cabbageFish, liver, meat, eggs, and cerealsVitamin K is also made by the bacteria in the lower intestinal tract.Essential co-factor in the synthesis of blood clotting factors ll, Vll, lX and X and proteins C and S Antagonist of some oral anticoagulants (warfarin)

Prothrombin time (PT) determinations(The prothrombin test is sensitive to the levels of three of the vitamin Kdependent clotting factors (II, VII, and X)Rregular prothrombin level determinations are recommended to determine responsiveness to and need for additional vitamin K therapy.

Allergic reactions, Blue color or flushing or redness of skindizzinessfast and/or weak heartbeat

Leucovorin calciumMISHA MEHMOOD

INDICATION For the treatment of osteosarcoma (after high dose methotrexate therapy). Used to diminish the toxicity and counteract the effects of impaired methotrexate elimination and of inadvertent overdosages of folic acid antagonists, and to treat megaloblastic anemias due to folic acid deficiency. Also used in combination with 5-fluorouracil to prolong survival in the palliative treatment of patients with advanced colorectal cancer.

MOA OF FOLATE ANATAGONIST

MECHANISM OF ACTIONLEUOCOVORINAs leucovorin is a derivative of folic acid, it can be used to increase levels of folic acid under conditions favoring folic acid inhibition (following treatment of folic acid antagonists such as methotrexate). Leucovorin enhances the activity of fluorouracil by stabilizing the bond of the active metabolite (5-FdUMP) to the enzyme thymidylate synthetase.

Thank You for listening US

Benzodiazepines enhance the effect of the neurotransmitter gamma-aminobutyric acid (GABA) at the GABAA receptor, resulting in sedative, hypnotic (sleep-inducing), anxiolytic (anti-anxiety), anticonvulsant, and muscle relaxant properties.All benzodiazepines act by enhancing the actions of a natural brain chemical, GABA (gamma-aminobutyric acid). GABA is a neurotransmitter, an agent which transmits messages from one brain cell (neuron) to another. The message that GABA transmits is an inhibitory one: it tells the neurons that it contacts to slow down or stop firing. Since about 40% of the millions of neurons all over the brain respond to GABA, this means that GABA has a general quietening influence on the brain: it is in some ways the body's natural hypnotic and tranquilliser. This natural action of GABA is augmented by benzodiazepines which thus exert an extra (often excessive) inhibitory influence on neurons *

*Overall, the laboratory detection of benzodiazepines (BZDs) depends upon the screening method used. Immunoassay screening techniques are performed most commonly and typically detect BZDs that are metabolized to desmethyldiazepam or oxazepam; thus, a negative screening result does not rule out the presence of a BZD. Qualitative screening of urine or blood may be performed but rarely influences treatment decisions and has no impact on immediate clinical care.*

*MECHANISM OF ACTION Necessary for collagen formation and tissue repair; plays a role in oxidation/reduction reactions as well as other metabolic pathways including synthesis of catecholamines, carnitine, and steroids; also plays a role in conversion of folic acid to folinic acid*

*Methylene blue is the primary emergency treatment for documented symptomatic methemoglobinemiaMethylene blueshould not be administered to patients with known glucose 6-phosphate dehydrogenase (G6PD) deficiency, since the reduction of methemoglobin by MB is dependent upon NADPH generated by G6PD. As a result, MB may not only be ineffective but it is also potentially dangerous, since MB has an oxidant potential that may induce hemolysis in G6PD deficient subjects.Pretreatment screening of G6PD deficiency is not usually possible in emergency. If methylene blueis contraindicated, only moderate doses of ascorbic acid (300 to 1000 mg/day orally in divided doses) should be given, as this drug may also cause oxidant hemolysis in G6PD deficient patients when given in very high doses.*The use of methylene blue to repair the damaged hemoglobin. That is, methylene blue, in its reduced form, is a colorless, water-solulble molecule. When it has been oxidized, it becomes blue. The blue tint that this gives to urine accounts for the last quote in Kathy Trost's article, that "I can see that old blue running out of my skin." The use of vitamin C by Dr. Deeny in Ireland achieves the same result of repairing damaged hemoglobin. However, vitamin C is colorless, so there is no excretion of blue pigment. *

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