Digoxin Pharmacokinetics PDF

thumbelina's Digoxin - tx & failure. ↑ house mo...

thumbelina's Digoxin - tx & failure. ↑ house monitored -> easy to get toxicity if not closely. L related to toxicity. (DRP) -> Img/L (minimum therapeutic dose) I served to treat ocdema ↓micro gram. electrolytes watch -> accumulation of. ↳ atrici fibrillation *.  Administration = fam after ohrs taken = sample & 7 : 50-7 stai : (bradmi) & tox check incase taken G , , if found subtherap within I nony. V ~ almost distributed proce to toxicity. ↓ 10w concent disturb electrolytes , ↳ metabolism ↑  ① know the indication for before formulating C / the dose. I - bioavailability N -1 0. - - normal Rex. 0 ~1 0Mg/L-2 S.. X AF ? - - COF ? ~ for CHE Eoccursvery sudden & needs immediate intervention- Feature ① fluid overload/oedema : ② SOB ↓ goes to lung M chart : input output pulmonary oedema  if obese : use ideal body weight ① calculate BM1 - of cral for calculation 1730) ~ ↑M// min xm2 CHE -> -> AF -> clearance I sample before take next day dosing. [calculate actual clearance ] - HE Com) - 3600 x weight (9 ↓ obese = use actual weight. ↓ lab =new dose ↓ maintenance ↓ ↓ dose 24Ur 24hr Eg : 250 mcg/day = toxic & toxic= AD should ↓ ② subop. = AD 4 · -M1/mine not neute G it dol tablet. Q only use or it =62mmol/ - -  11/11/20 CLINICAL PHARMACOKINETICS OF DIGOXIN ADD A SLIDE TITLE - 1 1 2 Introduction PK Method development — A history of over 200 years of clinical used — Lalonde & Pao (1984) compared the accuracy of and research. eighteen dosing methods. — Controversy continues concerning its — The method of Dobbs (1977) & Koup (1975) as efficacy and safety. modified by Koda-Kimble (1978) , appeared to — Two of the most prominent features: produce the best balance of minimum bias and ◦ Its narrow therapeutic index greatest precision. ◦ An endpoint of therapy is difficult to define and ◦ Using a target concentration of 1.2 ug/L, the later measure. method achieves a concentration between 0.9 – 1.5 — Digoxin toxicity is frequently encountered ug/L in 80% of cases. drug-related causes of hospitalization. ◦ However, some patients will have measured serum digoxin concentration well outside this range. 3 4 Monitoring Parameters Pharmacokinetic Characteristics (2) — Digoxin serum levels, obtain level within 24 — Digoxin is well absorbed, with peak serum hours of digitalization, weekly until stable, and at concentrations occurring within one hour. steady state. — A large volume of distribution (4–7 l/kg) reflects that ◦ The usual DGX therapeutic range is 0.8 to 2.0 ug/L. digoxin concentrates in the tissues, with the active site — BUSE and serum creatinine, measure every 2 being within myocardial. days, or every day in unstable renal function. — Redistribution from serum to tissue takes at least six hours — Weigh patient daily — Samples taken within six hours of a dose will falsely — Measure and monitor urine output daily. imply elevated tissue concentrations, and inappropriate — Monitor pulse daily dose reduction may result. 5 6 1  11/11/20 Pharmacokinetic Characteristics (1) Pharmacokinetic Characteristics (3) — Proper timing of serum sampling is critical. — Factors affecting DGX pharmacokinetics ◦ Serum samples should be drawn just prior to the ◦ Factors which predispose to DGX toxicity: daily dose and no sooner than six hours post – Diuretics: amiloride, triamterene , furosemide administration of the drug. – Antiarrhythmics: quinidine, amiodarone – Calcium antagonists: verapamil, minimal effect with nifedipine and diltiazem – Macrolide antibiotics: erythromycin, clarithromycin, roxithromycin – Benzodiazepines: alprazolam – HypoK, hypoMg, hypercalcemia, CAD, cor pulmonale, uncorrected hypothyroidism, renal dysfunction 7 8 Pharmacokinetic Characteristics (4) Pharmacokinetic Parameters — Factors affecting DGX pharmacokinetics — Therapeutic concentration 0.8 – 2 mcg/L ◦ Factors which predispose to suboptimal — F - tablets 0.75 clinical response: - elixir 0.8 – HyperK, uncorrected hyperthyroidism, drug interaction (antacids, cholestyramine, - Capsule 0.95 metoclopramide & rifampicin — Vd 7.3 L/kg — Cldgx 57 ml/min + 1.02ClCr — t1/2 36 hrs 9 10 Therapeutic concentrations Approach procedure — In congestive cardiac failure — Before calculating an initial dose or ◦ concentrations lower than the currently recommended adjusting the maintenance dose, one must limit of the therapeutic range (