Dialyzable drugs.pptx FOR THE DIALYSIS TECHNOLOGY

dialyzable drugs

1. Dialyzable Drugs

2. Dialyzable drugs These are pharmaceutical agents that are capable of being dialyzed. C apable of diffusing through a dialyzing membrane. The amount of drug dialyz ed determines whether supplementa ry dosing is required during or following dialysis.

3. What determines drug dialyzability? Dialyzability of drug determined by several physicochemical characteristics. Concentration of drug in plasma – High plasma concentration of drug undergo high diffusion through dialytic membrane. Molecular size – Drugs having large molecular size unable to diffuse through dialytic membrane. Protein binding – Protein bound drug have large molecular size so unable to cross the membrane. Drugs available in free form in plasma undergo high diffusion through membrane.

4. Volume of distribution – Large Vd , means low plasma concentration of drug thus minimally dialysed and vice versa. Water solubility – Dialysate used for dialysis is aqueous solution. Drugs with more water solubility will dialyze to greater extent as compared to the lipid soluble drugs. Plasma clearance – Type of clearance preferred for drug. Renal clearance is replaced by dialysate clearance. D i a l y s i s p r o c e d u r e – HD or PD (Pores of PD membrane are larger as compared to HD) Dialysis Membrane - Pore size, surface area, and geometry are the primary determinant.

5. Common Dialyzable Drugs 1. Barbiturates 2 . L i t h i u m 3. Isoniazid 4. Salicylates 6 . C a f f e i n e 7. Methanol, metformin 8. Ethylene glycol 9 . D e pa k o t e 10. Carbamezepine 5. Theophyline

6. P heno b a r b i t one It’s a medication of barbiturates class, recommended by WHO for the treatment of all types of epilepsy except absence epilepsy. It is on the WHO’s List of Essential Medicines, the most effective and safe medicines needed in a health system . Phenobarbitone is absorbed slowly in GIT. P eak blood conc. (PO) reached in 8-12 hours and peak brain conc. in 10-15 hours. When administered IV, the onset of action occurs within 5 minutes and maximum effects achieved within 30 minutes. IM or SC administration results in a slightly slower action.

7. Th e m a j o r inactive m e t a b o li t e i s t h e p a r a h y d r o x y derivative, which is excreted in the urine. The inactive metabolites of the barbiturates are excreted as conjugates of glucuronic acid. Dose available 30, 60mg tabs, Phenobarbitone sodium 200mg/ml inj.

8. Lithium Lithium was used during the 19th century to treat gout. Salts such as lithium carbonate (Li2CO3), lithium citrate, and lithium orotate are mood stabilizers. They are used in the treatment of bipolar disorder . They counteract both mania and depression. I t i s a l s o s o m e t i m e s p r e s c r i b e d for preventive treatment of migraine and cluster headaches. The mechanism of action is still unknown.

9. Me t h a nol Methanol , also known as methyl alcohol . A chemical with formula CH 3 OH (a methyl group linked to a hydroxyl group). Methanol acquired the name wood alcohol because it was once produced by the destructive distillation of wood . M e t h a n o l i s a b s o r be d t h r o u g h i n h a l a t i o n or ingestion. Methyl alcohol is readily absorbed from GIT and respiratory tracts.

10. In the first step, oxidation to formaldehyde by hepatic alcohol dehydrogenase, which is a rate- limiting process. In the second step, formaldehyde is oxidized by aldehyde dehydrogenase to formic acid or formate depending on the pH. In the third step, formic acid is detoxified by a folate-dependent pathway to carbon dioxide. Absorption, Distribution, Metabolism, Excretion

11. Drug and Dosing in Dialysis Patients

12. Measurement of Renal Function the rate of elimination of drugs excreted by the kidneys is proportional to the glomerular filtration rate. The serum creatinine , creatinine clearance is needed to determine renal function before prescribing many drugs . The Cockcroft and Gault equation is useful for this purpose, as shown in the following formula: CrCl (ml/min ) = (140-age)x (BW in kg)( x0.85if female) 72x Scr(mg/dl)

13. Dosing of antimicrobial drugs in renal patients Antimicrobial and antiprotozoal drugs Dr u g Dosage for severe renal failure A m o xyc ill in Half-life N o r m a l / ES R D (h) 0.09-2.3/5-20 Maximum 500 mgq 8h Amoxycillin Clavulanic acid PO Maximum 375 mg q12 h ampicillin A m ox y c i lli n 0.9-2.3/5-20 C l a v ul a n i c acid1/3-4 0.8-1.5/7-20 250-500 mg q6h Cefotaxime IV 1 / 1 5 1g loading dose then 50% standard dose

14. D r u g Dosage for severe renal failure Ceftazidime IV Half-life N o r m a l/ E SR D (h) 1.2/13-25 0.5-1 g q24h 1-2 g q24h 750 mg q12h Standard dose 250-500 mg q12h Ceftriaxone IV Cefuroxime IV Cefuroxime PO Cephalexin Chloroquiine 7-9/12-24 1.2/17 1.2/17 0.7/16 7-14 days/5- 50 days Treatment:50% standard do s e 50% standard dose q12h 250 mg q12h PCP treatment:Standard dose q48h PCP prophylaxis 25% Standard dose q48-72h Ciprofloxacin IV/PO Calrithromycin C o t r i m o x a z o l e IV/PO Sulphamethoxazole/ Trimethoprime Erythromycin IV/PO 3-6/6-9 2.3-6.0/- Sulphamethoxazole 10/20-50 T ri m et h o p r i m e 9-13/20-49 1.4/5-6 50-75% Standard dose Max 1.5g in 24h

15. D rug Half-life N o r m a l / E S RD (h) Dosage for severe renal failure Flucloxacillin Gentamicin IV 0.8-1/3 1.8/20 - 6 Max PO 500 mg q6hIV 1g q 6 h Titrate to levels Impenem/ cilastin IV 250 mg or 3.5 mg/kg q12 h Meropenem IV Impenem ¼ C i la st i n1/ 1 5 - 24 1.1/6-8 50% standard dose q24h Penoxymethyl-pencillin 0.6/4.1 Standard dose Piperacillin IV 0.8-1.8/3.3-5.1 4 g q12 h Piperacillin/dihydrochloride IV 4.5 g q12 h Quinine difydrochloride IV Treat,emt 5-10 mg/kg q24h Trimethoprim Piperacillin 0.18-0.3/3.3-5.1 Dihydrochloride 1/7 9 healthy,18 malaria/ unchanged 9-13/20-49 50% standard dose Vancomycin IV 6 - 8/20 - 2 5 Titrate to levels

16. Dosing of common drugs in renal patients  Allopurinol-GFR 30 ml/min use 100mg,60ml/min use 200mg,90ml/min use 300mg  Corticosteroids-no need to change the dose  NSAIDs :-most are metabolized in the liver , aspirin is a good choice in renal impairment ,

17.  In patients with low urine output avoid sulindac owing to renal stone formation.  Reduce dose of ketoprofen  Penicillamine ,avoid if GFR less than 50ml/min  Cyclosporine, no dose adjustment in renal insufficiency, however use of Cyclosporine can worsen renal insufficiency  Gold , if GFR 50-75ml/min use 50% of usual dose ,if less than 50% avoid gold

18.  Methotrexate ,take care from hematologic toxicity  Sulfasalasine ,no change in dose.  Mycophenylate mofetil ( cellcept ), mainly hepatic metabolism ,but if GFR less than 25 ml/min reduce dose by 25%.  Tramadol, give dose every1 2 h instead of every 6h  Narcotics, avoid using Darvon and Mepiridine, for others if GFR less than 10ml/min cut 50% of the dose ,if GFR 10- 50ml/min use 75% of the dose