Thiamine

Usage

• Thiamine (vitamin B1) is essential for carbohydrate metabolism and nerve function. It’s used to treat and prevent thiamine deficiency, including beriberi and Wernicke-Korsakoff syndrome (WKS). It’s also prescribed for patients with alcohol use disorder, those undergoing refeeding after malnutrition, and those with certain genetic disorders affecting thiamine metabolism.

• Pharmacological Classification: Vitamin, essential nutrient.

• Mechanism of Action: Thiamine is a cofactor for several enzymes involved in carbohydrate metabolism, including pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase. These enzymes are crucial for energy production, particularly in the brain and nervous system.

Alternate Names

• Vitamin B1, aneurine hydrochloride

• Brand Names: Numerous brands are available, including Betalin, Thiamilate

How It Works

• Pharmacodynamics: Thiamine’s primary role is as a coenzyme in the decarboxylation of alpha-keto acids. It is essential for the synthesis of acetylcholine and the pentose sugars required for DNA and RNA production. Thiamine deficiency leads to impaired carbohydrate metabolism, resulting in energy deficits, especially in neural tissues.

• Pharmacokinetics: Thiamine is absorbed in the small intestine, primarily by passive diffusion at low concentrations and active transport at higher concentrations. It is then converted to its active form, thiamine pyrophosphate (TPP). TPP is widely distributed in the body, with higher concentrations in skeletal muscle, heart, liver, kidneys, and brain. Thiamine is metabolized in the liver and excreted primarily by the kidneys.

• Mode of Action: Thiamine, in its active form (TPP), acts as a cofactor for critical enzymes in the Krebs cycle and pentose phosphate pathway, including pyruvate dehydrogenase and transketolase.

• Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: No direct receptor binding or enzyme inhibition actions are involved. Thiamine’s effect is primarily mediated through its coenzyme activity.

• Elimination Pathways: Primarily renal excretion, with minor hepatic metabolism.

Dosage

Standard Dosage

Adults:

• Deficiency Prevention: 1.2 mg/day for males, 1.1 mg/day for females.
• Mild Deficiency: 5-30 mg/day orally for several weeks.
• Severe Deficiency (Beriberi/WKS): Initial: 50-100 mg IV, followed by 10-20 mg IM or IV tid for 2 weeks. Maintenance: 5-10 mg/day orally for 1 month.

Children:

• Deficiency Prevention: 0.2-1.2 mg/day depending on age.
• Deficiency Treatment: 10-50 mg/day orally or IM/IV, divided into doses, based on severity.

Special Cases:

• Elderly Patients: Standard adult dose, monitor for adverse reactions.
• Patients with Renal Impairment: Dose reduction may be necessary, especially in severe impairment.
• Patients with Hepatic Dysfunction: Monitor closely for side effects.
• Patients with Comorbid Conditions: Consider the interaction of thiamine with other medications.

Clinical Use Cases

• Intubation: Administer 100 mg IV before glucose administration.
• Surgical Procedures: Prophylactic dose for malnourished patients.
• Mechanical Ventilation: Supplementation may be necessary for patients with risk of deficiency.
• Intensive Care Unit (ICU) Use: Consider supplementation in at-risk patients.
• Emergency Situations (e.g., status epilepticus, cardiac arrest): 100 mg IV prior to glucose.

Dosage Adjustments:

• Dose adjustments are necessary for patients with renal impairment, hepatic dysfunction, and for those on interacting medications. Therapeutic drug monitoring may be used.

Side Effects

Common Side Effects:

• Generally well-tolerated. Rarely, some individuals might experience sweating, nausea, restlessness, or tightness in the throat.

Rare but Serious Side Effects:

• Anaphylaxis (rare), pulmonary edema (rare).

Long-Term Effects:

• No significant long-term adverse effects associated with usual doses.

Adverse Drug Reactions (ADR):

• Anaphylaxis requires immediate medical intervention.

Contraindications

• Known hypersensitivity to thiamine.

Drug Interactions

• May interact with certain neuromuscular blocking agents (e.g., vecuronium), potentially enhancing their effects. Loop diuretics can increase thiamine excretion. Certain antibiotics may decrease thiamine absorption.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: Generally considered safe during pregnancy at recommended doses.
• Fetal Risks/Teratogenicity: No evidence of teratogenicity at recommended doses.
• Drug Excretion in Breast Milk: Present in breast milk, generally considered safe for infants.

Drug Profile Summary

• Mechanism of Action: Coenzyme for carbohydrate metabolism.
• Side Effects: Generally well-tolerated; rare allergic reactions.
• Contraindications: Hypersensitivity to thiamine.
• Drug Interactions: Neuromuscular blocking agents, loop diuretics, some antibiotics.
• Pregnancy & Breastfeeding: Generally safe at recommended doses.
• Dosage: Refer to dosing section above.
• Monitoring Parameters: Thiamine levels can be measured but not routinely done. Monitor for clinical response and adverse reactions.

Popular Combinations

• Often used in combination with other B vitamins in B-complex preparations.

Precautions

• General Precautions: Screen for allergies before administration, particularly with parenteral routes.
• Specific Populations: Adjust dose based on renal/hepatic function and age.
• Lifestyle Considerations: No specific lifestyle restrictions.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Thiamine?

A: The dosage varies depending on the indication and patient population. See the detailed dosage guidelines above.

Q2: How should thiamine be administered in cases of suspected Wernicke’s encephalopathy?

A: Administer 50-100 mg IV initially, followed by IM or IV doses for several days, then oral thiamine.

Q3: What are the common signs and symptoms of thiamine deficiency?

A: Fatigue, muscle weakness, nerve damage (peripheral neuropathy), memory problems, confusion, and cardiovascular issues.

Q4: Can thiamine be given prophylactically?

A: Yes, prophylactic thiamine is indicated for at-risk individuals, such as those with alcohol use disorder, malnutrition, or before administering glucose to potentially deficient patients.

Q5: Is thiamine safe during pregnancy and breastfeeding?

A: Yes, considered safe at recommended doses. Consult with a healthcare professional for specific guidance.

Q6: Are there any serious side effects associated with thiamine?

A: Serious side effects are rare and primarily involve allergic reactions. Anaphylaxis, though uncommon, can occur, particularly with parenteral administration.

Q7: How long should thiamine treatment be continued?

A: The duration of treatment depends on the severity and cause of the deficiency. Treatment may range from several weeks to months, and sometimes indefinitely, such as in cases of chronic alcohol misuse.

Q8: How does thiamine interact with alcohol?

A: Chronic alcohol use often leads to thiamine deficiency because alcohol interferes with its absorption and utilization.

Q9: What is dry beriberi, and how is it treated?

A: Dry beriberi affects the nervous system, leading to muscle weakness, numbness, and pain. It is treated with thiamine supplementation.

Q10: What is wet beriberi, and how is it treated?

A: Wet beriberi affects the cardiovascular system, causing heart failure and edema. It is treated with thiamine supplementation along with other supportive measures for heart failure.