Injection Thiamine HCl- The most commonly drug in casualty.pptx

Thiamine deficiency is most common in alcoholics or bed ridden cases. It causes Wernicke encephalopathy and Wernicke-Korsakoff syndrome (WKS). Learn why thiamine is important.

1. THIAMINE HYDROCHLORIDE (vitamin B1) Dr. Pawan Shukla DM Resident (Toxicology) Dept of FMT, AIIMS Raipur, CG 1

2. Thiamin (vitamin B1) is one of the water-soluble B vitamins found in brown rice, grains, soyabean, peas, nuts, dried beans, green leafy vegetables, meat, and eggs. Thiamin can only be stored in the body for a short time before it is readily excreted (half-life of 14 to 18 days), a regular dietary intake of thiamin is recommended RDI for adults is 1.2 mg/day for men and 1.1 mg/day for women Pregnant women of any age should take 1.4 mg/day During energy metabolism, thiamin plays a critical role in the human body. It serves as a cofactor for many enzymes during the metabolism of glucose, proteins, and lipids. 2

3. BIOCHEMISTRY In blood, thiamine is converted into its active form, thiamine pyrophosphate (TPP). TPP involved in metabolism of carbohydrates, lipids, and branched-chain amino acids. TPP acts as a cofactor at several steps during glycolysis and oxidative decarboxylation of carbohydrates. 3

4. BIOCHEMISTRY CNTD… . coenzyme TO pyruvate dehydrogenase complex process links glycolysis to the Krebs cycle, where overall aerobic metabolism produces 38 mol of ATP from 1 mole of glucose When pyruvate cannot be converted to acetyl-CoA because of thiamine deficiency , only 2 mol of ATP can be generated by anaerobic  metabolism from 1 mole of glucose Also leads to accumulation of lactic acid. Lactic acidosis may cause focal damage to brain structures, such as mamillary bodies and the posteromedial thalamus, which can be seen on MRI. 4

5. BIOCHEMISTRY CNTD… . In krebs cycle , TPP acts as a coenzyme for the mitochondrial enzyme complexes α- ketoglutarate dehydrogenase Thiamine deficiency leads to accumulation of a-ketoglutaric acid which is converted to glutamate, causing excitatory neurotoxicity Thiamine is also important in maintaining normal neuronal conduction 5

6. BIOCHEMISTRY CNTD… . In PPP, TPP is required by the erythrocyte transketolase enzyme for nucleotide synthesis and provides reduced NADPH for several synthetic pathways Thiamine is highly water soluble, allowing it to leach out of foods following prolonged washing or cooking in water Thiamine requirements are determined by total caloric intake and energy demand, with a minimum daily requirement of 0.5 mg/1000 calories 6

7. PHARMACOLOGY Maximum absorption in duodenum Lesser absorption from stomach and large bowel Chronic liver disease, folate deficiency, steatorrhea, and other forms of malabsorption all significantly decrease the absorption of thiamine In experimental studies, when healthy volunteers were given small amounts of ethanol, a 50% reduction in gastrointestinal thiamine absorption resulted Bariatric surgery is recognized to predispose patients to thiamine deficiency Thiamine is eliminated from the body largely by renal clearance In an animal model, furosemide, acetazolamide, chlorothiazide, amiloride, mannitol, and salt loading all significantly increased urinary elimination of thiamine 7

8. THIAMINE DEFICIENCY PATHOPHYSIOLOGY Animal studies suggests development of encephalopathy 10 days after thiamine deficient due to destruction of blood-brain barrier with resultant cerebral edema. Alcoholic patients with Wernicke-Korsakoff syndrome demonstrate decreased function of pyruvate dehydrogenase, a-ketoglutarate dehydrogenase, and trans ketolase when compared with controls In other animal models of thiamine deficiency, neuronal tissues are also directly injured by oxidative stress and lipid peroxidation. 8

9. CLINICAL MANIFESTATIONS When thiamine is completely removed from the human diet, clinical manifestations typically develop within 2 to 3 weeks Early symptoms mainly arise from gastrointestinal, neurological, and cardiac systems, where patients may experience weight loss, anorexia, confusion, short-term amnesia, malaise, muscle weakness, and cardiac symptoms The clinical symptoms present as two distinct patterns: " wet " beriberi or " dry " beriberi Wet beriberi presents as a high-output cardiac failure with signs of edema, enlarged heart, warm extremities, tachycardia, and respiratory distress. It is induced by peripheral vasodilation and the formation of Arterio-Venous fistulae secondary to thiamine deficiency. 9

10. CLINICAL MANIFESTATIONS cntd … Dry beriberi is predominantly a neurological complication involving the peripheral nervous system and presents with peripheral neuropathy, malaise, muscle weakness, seizures, or brisk tendon reflexes. If deficiency is prolonged or left untreated, an individual is at risk of advanced-stage symptoms. This condition is called Wernicke-Korsakoff syndrome (WKS). It presents in two phases. Wernicke encephalopathy (WE) occurs early and presents with polyneuropathy, ataxia, ophthalmoplegia, and gait abnormalities. If left untreated, it can eventually evolve into Korsakoff psychosis (KS) with signs of severe short-term amnesia, disorientation, confabulation, and hallucinations 10

11. CLINICAL MANIFESTATIONS cntd … Korsakoff psychosis, an irreversible disorder of learning and processing of new information characterized by a deficit in short-term memory and confabulation Laboratory studies reflect metabolic acidosis with elevated lactate concentration brought by excessive anaerobic glycolysis resulting from thiamine deficiency. A 10% to 20% mortality rate is associated with Wernicke encephalopathy, with survivors having an 80% risk of developing Korsakoff psychosis. 11

12. POPULATIONS AT RISK Alcoholic dependence Incarcerated prisoners patients in drug rehabilitation patients with renal failure or hemodialysis patients with hyperemesis gravidarum or anorexia nervosa patients receiving parenteral nutrition patients with acquired immunodeficiency syndrome ( AIDS ) patients with malignancies Starvation or fasting Elders Post-bariatric surgery patients with congestive heart failure on furosemide therapy 12

13. Monitoring The serum level of thiamin is not a reliable indicator of thiamin status Thiamin function can be measured by erythrocyte transketolase activity ( ETKA ) 0 to 15% of EKTA is considered adequate 15 to 25% is considered a moderate risk 25% or higher is considered high risk for thiamin deficiency Direct measurement of erythrocyte TPP can be done using whole-blood testing and has more sensitivity, specificity, precision, and robustness ( Normal value: 70 to 180 nmol/L ) Urinary thiamin excretion can be used to measure adequate dietary intake in adults Thiamin excretion of <100 mcg/day suggests inadequate intake Thiamin excretion of <40 mcg/day suggests thiamin deficiency 13

14. THIAMINE DOSING Thiamine hydrochloride is included as initial therapy for any patient with an altered mental status, potentially acting as both treatment and prevention of Wernicke encephalopathy. Many patients with altered mental status have had or will have a poor nutritional status, or will be hospitalized without oral intake for a number of days 14

15. THIAMINE DOSING Glucose loading increases thiamine requirements, which can exacerbate marginal thiamine deficiencies, elevate lactate concentrations, or even precipitate coma in the absence of parenteral thiamine supplementation. It is prudent to administer 100 mg of parenteral thiamine at the time of initial dextrose administration. Because the morbidity and mortality associated with Wernicke encephalopathy are severe, and treatment is benign and inexpensive, thiamine hydrochloride is included in the initial therapy for all patients who receive dextrose , all patients with altered consciousness, and every alcoholic or nutritionally deprived individual 15

16. THIAMINE DOSING cntd … Initial therapy consists of the immediate parenteral administration of 100 mg of thiamine hydrochloride (either intramuscularly or intravenously) daily For patients at risk of deficiency or with confirmed deficiency, parenteral thiamin of 100 mg and 200 mg TDS respectively, in clinical practice. (GOLDFRANKS) For prevention of WE: IV/IM 100 mg/day For treatment of WE: IV 500 mg TDS for 2 days f/b IV 250 mg OD for next 5 days f/b oral 100mg OD For CHF IV 100mg twice/week 16

17. THIAMINE DOSING cntd … Oral route should be avoided because of its unpredictable absorption. If thiamine propyl disulfide or benfothiamine (a lipid-soluble preparation) is available, the oral route is equally efficacious Because of the safety of thiamine hydrochloride, and the urgency to correct the manifestations of thiamine deficiency, up to 1000 mg of thiamine hydrochloride can be used in the first 12hours if a patient demonstrates persistent neurologic abnormalities. 17

18. THIAMINE DOSING cntd … Routine thiamine administration should also be considered inpatients with congestive heart failure and long-term use of diuretics . Diuretics enhance renal thiamine elimination. In one randomized trial, 200 mg of daily intravenous thiamine was able to increase cardiac ejection fraction by 22% at 7 weeks. 18

19. ADVERSE Effects Very few complications are associated with the parenteral administration of thiamine. Rare reports of anaphylactoid reactions associated with intravenous thiamine Although IM route is theoretically efficacious in a healthy individual, many patients requiring thiamine may have diminished muscle mass or a coagulopathy, exacerbating the potential for pain and unpredictable absorption. PREGNANCY : Thiamine hydrochloride is listed category A and also safe in lactating mothers. 19

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