Antidot Adalah

[Annemie]

Antidotuntuk beberapa racun didapat dengan cara menyuntikkan racun ke badan binatang dalam dosis kecil, lalu mengekstraknya kembali dari darah binatang tersebut. Ini mengeluarkan terjadinya sebuah antidot yang dapat melawan racun yang diproduksi oleh binatang-binatang seperti ular, laba-laba, dan binatang beracun lainnya. Beberapa racun tidak ada antidotnya, dan ini kadang menimbulkan kematian apabila racun tersebut memasuki tubuh makhluk hidup lainnya. Beberapa racun dari binatang, khususnya yang diproduksi oleh arthropoda (seperti laba-laba atau kalajengking) hanya berbahaya ketika mereka membuat reaksi alergik dan menyebabkan shok anapilaktik.

Beberapa racun lainnya tidak memiliki antidot. Contohnya adalah racun risin, yang diproduksi dari limbah minyak goreng, dan akibatnya kadang fatal ketika memasuki badan manusia dalam jumlah yang cukup.

Acetylcysteine atau asetilsistein antidot adalah obat untuk intoksikasi paracetamol. Obat ini digunakan untuk melindungi hati saat terjadi keracunan atau overdosis paracetamol. Berbeda dengan acetylcysteine mukolitik yang digunakan untuk terapi simptomatik bronkitis, emfisema, pneumonia, dan sistik fibrosis.[1,2]

Efek terapi obat acetylcysteine antidotum overdosis paracetamol atau acetaminophen adalah dengan menjadi hepatoprotektor. Mekanisme kerja dengan cara memperbanyak glutation pada hati, bekerja sebagai pengganti glutation, dan meningkatkan konjugasi sulfat non toksik dari paracetamol.[1,2]

Acetylcysteine memiliki nama kimia N-Asetilsistein (N-Acetylcysteine/NAC), merupakan turunan sintetik dari asam amino endogen L-sistein (L-cysteine). L-sistein merupakan prekursor antioksidan enzim glutation.[1,2]

Acetylcysteine antidot bekerja sebagai hepatoprotektor dengan cara memperbanyak glutation pada hati, bekerja sebagai pengganti glutation dan meningkatkan konjugasi sulfat non toksik dari paracetamol. L-sistein merupakan prekursor antioksidan enzim glutation. Sekitar 4% fraksi metabolit dari paracetamol dimetabolisme di hati oleh isoenzim CYP2E1 dan sitokrom P450 (CYP) menjadi N-acetyl-p-benzoquinoneimine (NAPQI) yang merupakan zat yang toksik untuk hepar.[10,11]

Senyawa NAPQI dapat diikat oleh glutation sehingga membentuk metabolit yang non toksik yaitu konjugasi metabolit sistein dan mercapturic acid. Ketika terjadi overdosis paracetamol, maka semakin besar paracetamol yang dimetabolisme oleh enzim CYP dan dan jumlah glutation sedikit, sehingga menyebabkan jumlah NAPQI yang banyak.[2,9,11]

Acetylcysteine dimetabolisme di hati dan dinding saluran cerna. Acetylcysteine dapat dimetabolisme menjadi sistein, disulfida dan konjugat (N, N-diacetylcysteine, N-acetylcysteine, N-acetylcysteine-glutation, N-acetylcysteine-protein).

Acetylcysteine diekskresi melalui urin. Waktu paruh obat acetylcysteine yang digunakan secara intravena adalah 5,58 jam. Waktu pengeluaran rata-rata (mean clearance/CR) acetylcysteine adalah 0,11 liter/kgBB/jam.[1,2,5]

Enoxaparin is low molecular weight heparin (LMWH) and was first approved for medical use in 1993 and is derived from heparin. It has FDA approval for the following clinical conditions - acute coronary syndromes, deep venous thrombosis (DVT) treatment and prophylaxis, treatment for pulmonary embolism (PE), venous thromboembolism (VTE) treatment, and prophylaxis in a variety of scenarios, percutaneous coronary intervention (PCI), and periprocedural anticoagulation, among others. This activity will highlight the mechanism of action, adverse event profile, pharmacology, monitoring, and relevant interactions of enoxaparin, pertinent for interprofessional team members in treating patients with conditions where this agent is indicated.

Objectives:Describe the therapeutic mechanism of action of enoxaparin.Review the many indications for enoxaparin use.Summarize the adverse event profile of enoxaparin use.Explain the importance of improving care coordination among the interprofessional team to enhance the delivery of care for patients when using enoxaparin.Access free multiple choice questions on this topic.

Two low molecular heparins are available in the United States: dalteparin and enoxaparin. Enoxaparin is low molecular weight heparin (LMWH) and was first approved for medical use in 1993 and is derived from heparin.

Enoxaparin is low molecular weight heparin (LMWH) with a mean molecular weight of 4000 to 5000 Daltons. It has a quick onset of action when given in the intravenous form. Enoxaparin is an indirect anticoagulant that binds and potentiates antithrombin III (serine protease inhibitor) through a specific pentasaccharide sequence to form a complex that irreversibly inactivates factor Xa. The primary difference between unfractionated heparin and enoxaparin is their relative inhibition of thrombin (factor-IIa) and factor-Xa. Smaller heparin fragments cannot bind antithrombin and thrombin simultaneously. Due to their smaller chain length and lower molecular weight, LMWH has better activity against factor-Xa and inhibits thrombin to a lesser degree. Thus, enoxaparin has less activity against factor IIa (thrombin) than unfractionated heparin. The anti-factor Xa-to-IIa activity ratio for the LMWHs varies from 2:1 to 4:1.[10]

Excretion: Enoxaparin follows first-order kinetics and is eliminated primarily in the urine. The elimination half-life of enoxaparin is approximately 3 to 4.5 hours following a single dose. Following repeated doses, the half-life of enoxaparin increases to approximately 7 hours. As enoxaparin is primarily eliminated by renal excretion, there is a concern for drug accumulation and bleeding risk in patients with renal impairment.[10][12]

Enoxaparin has an advantage over heparin because of its bioavailability. Ninety percent of the drug is available when given in the subcutaneous form. Enoxaparin can also be administered in intravenous formulations.[10] The intravenous formulation should not be mixed or co-administered with other medications. The port should be flushed before use with normal saline or 5% dextrose water. An IV injection is usually given during the primary PCI and at the time of STEMI. Subcutaneous administration should alternate between the left or right anterolateral and left or right posterolateral abdominal wall. There is a small risk of bruising that can be minimized by not rubbing the injection site. There is no topical form available. Intramuscular administration is generally avoided. One mg of enoxaparin is equal to 100 units of anti-Xa activity. The dose of enoxaparin depends upon indications, adverse events profile, and renal/hepatic impairment.

Treatment of Acute Deep Vein Thrombosis with or without Pulmonary Embolism: The recommended dose of enoxaparin is 1 mg/kg SC every 12 hours or 1.5 mg/kg SC daily. Anticoagulation should be started immediately in the case of suspected or proven pulmonary embolism. Patients with pulmonary embolism usually require inpatient therapy, according to the PERT Consortium.[14][15]

STEMI: According to the ACCF/AHA (American College of Cardiology Foundation/American Heart Association) guidelines for ST-elevation myocardial infarction (STEMI), in patients treated with fibrinolytic therapy, doses are suggested according to age and renal function. If the age of patients

NSTEMI: The suggested dose of enoxaparin in Non-ST-elevation myocardial infarction is 1 mg/kg SC every 12 hours. Guidelines suggest decreasing the dose of enoxaparin to 1 mg/kg SC once daily in patients with creatinine clearance

Patients with Hepatic Impairment: A clinical trial demonstrated that enoxaparin decreased the rate of portal vein thrombosis and hepatic decompensation and increased the probability of survival by preventing microvascular thrombosis in patients with cirrhosis. An increased risk of bleeding on anticoagulation therapy is seen in patients with liver cirrhosis due to disequilibrium between procoagulant and anticoagulant states. In addition, older age, increased INR, female sex, prior history of bleeding, hypertension, peptic ulcer disease, active cancer, hypertension, prior stroke, renal impairment, and alcohol abuse augments the risk of bleeding in patients with cirrhosis. In liver cirrhosis, enoxaparin can increase the risk of bleeding; caution is required before initiating enoxaparin.[18]

Patients with Renal Impairment: In patients with renal impairment, increased bleeding tendency is seen due to increased exposure to enoxaparin. Dose adjustment of enoxaparin is recommended in patients with severe renal impairment (creatinine clearance 30 mL/min.[19]

Pregnancy Considerations: Pregnant women have a significantly increased risk of thromboembolism than nonpregnant women. Venous thromboembolism (VTE) is the major cause of maternal mortality in the United States. Enoxaparin doesn't cross the placenta and is considered safe in pregnancy. According to ACOG (American College of Obstetricians & Gynecologists) guidelines, enoxaparin, 40 mg SC once daily, is recommended for VTE prophylaxis. Therapeutic anticoagulation with enoxaparin, 1 mg/kg every 12 hours, is recommended for women with acute thromboembolism during the current pregnancy and women with a history of recurrent thrombosis.[7]

Breastfeeding Considerations: Available evidence suggests that maternal enoxaparin in doses up to 40 mg daily does not cause adverse drug reactions in breastfed infants. Enoxaparin has a high molecular weight and is not expected to be excreted into breast milk or absorbed from the infant's gastrointestinal tract. Therefore, no special precautions are required.[20]

COVID-19 Considerations: In 2022, the American Society of Hematology (ASH) guidelines advised using prophylactic intensity over therapeutic-intensity anticoagulation for patients with critical illness due to COVID-19 (who do not have suspected or confirmed venous thromboembolism). The guidelines suggested that higher intensity anticoagulation may be reasonable for patients evaluated to be at low bleeding risk and high thrombotic risk.[21]

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