1, the kidney function status of dialysis patients mainly has the following conditions: ① most patients have no urine; ② some patients have little urine; ③ some patients have urine, but the urine color is light, the urine specific gravity is low, and the tangible fraction is small; ④ the glomerular filtration rate (GFR) is almost zero in Wu Hua, the nephrology department of Beijing Hospital, and the excretion of drugs by the kidneys is almost zero. The half-life of drugs excreted mainly by the kidneys is significantly prolonged, such as the normal dose of drugs, the concentration of drugs accumulating in the body is increasingly high, the chances of toxic side effects of drugs increase, and toxic side effects not seen in normal people can be seen; ⑤ Hemodialysis can remove some of the small molecules, drugs that are not bound to plasma proteins and tissue proteins.
2.Factors affecting the dialyzability of drugs
2.1 Drug transport mode
In hemodialysis treatment, drug is removed from blood by diffusion, convection and adsorption of semi-permeable membrane.
2.2 Influence of the molecular mass of the drug
The size of the drug molecular mass determines whether it can be cleared from the dialysis membrane. Drug molecules smaller than 992 IU can be removed by diffusion. Where the size of drug molecules can pass through the membrane pores of a semipermeable membrane, they can be removed by convection, and semipermeable membranes with adsorption can remove drugs by adsorption. Activated carbon or resin can also adsorb lipid-soluble, or protein-bound drugs.
2.3 Drug-protein binding properties
Most drugs in the body are bound to proteins or tissues, while drugs that are free in the blood can only be removed by dialysis. For example, drugs with high protein binding rate or drugs bound to tissue proteins cannot be cleared by dialysis, but can be cleared by adsorption and perfusion. When severe hypoproteinemia is present, drug freeing increases and clearance increases. When peritonitis occurs, peritoneal permeability is increased and certain proteins can pass through the peritoneum, and it is possible that drugs bound to proteins are cleared together.
2.4 Volume of drug distribution (Vd)
It refers to the extensive distribution of the drug to the body tissues. drugs with large Vd have a large tissue distribution and are removed by hemodialysis in small amounts, and conversely drugs with small Vd can be removed in larger amounts. Factors affecting the volume of distribution: the degree of water and lipid solubility, the degree of binding to tissues or proteins. drugs with Vd < 1L/kg are easily cleared by dialysis, while those with Vd > 2L/kg are rarely cleared by dialysis.
2.5 Timing of drug administration
For drugs with high protein binding rate, the blood concentration is not greatly affected when administered before or after dialysis; while drugs with small molecular mass and low protein binding rate are not easily cleared by dialysis only when administered after dialysis.
3.The influence of dialysis mode on drug excretion
3.1 Hemodialysis
Conventional hemodialysis can only remove smaller molecules, water-soluble drugs that do not bind to proteins. High-flow dialysis and high-flux dialyzer dialysis can increase drug removal. Factors affecting drug clearance, related to dialysis: dialyzer membrane pore size, membrane area, membrane structure, membrane surface charge, membrane ultrafiltration coefficient; blood flow rate and dialysate flow rate, hemodialysis time, intermittent dialysis or continuous dialysis.
3.2 Peritoneal dialysis
The drug relies on the diffusion effect of the concentration gradient difference and moves intraperitoneally through the peritoneal capillaries into the peritoneal cavity. Drug clearance is related to the amount of peritoneal dialysis fluid exchange, ultrafiltration, peritoneal area, and peritoneal vascular lesions. The clearance of drugs by peritoneal dialysis is lower than that by hemodialysis, mainly due to the slow flow rate of peritoneal dialysis fluid (7 ml/min). Charged drug molecules disperse more slowly than uncharged drug molecules. Combined hypotension, mesenteric vasculopathy, large omental vascular sclerosis, and reduced blood flow can reduce drug clearance. High volume peritoneal dialysis or hypertonic peritoneal dialysis fluid, increased peritoneal dialysis fluid temperature, and peritonitis can increase drug clearance.
3.3 Hemoperfusion
Fat-soluble, protein-bound drugs and toxicants can be removed.
3.4 Continuous hemodialysis
Continuous renal replacement therapy (CRRT) has a stronger removal of plasma water and unbound solutes than conventional hemodialysis (HD) due to the use of high-flux hemofiltration devices, prolonged continuous treatment, and high-dose replacement fluid. Drugs with a molecular mass of 4960 Iu can be cleared. The clearance of drugs (drug molecular size, clearance amount) differs between continuous and intermittent RRT depending on the duration of treatment and the dialyzer applied.
3.5 Plasma replacement
Drugs bound to plasma proteins can be removed, but drugs bound to tissues are not easily removed. the clearance of contrast agent by AN69 membrane is increased by 1.5-3.0 times compared to cellulose membrane vancomycin molecular mass 1 474 Iu, not cleared by cellulose membrane, half-life about 3-7d.
4.The mechanism of action and application methods of different antibiotics
4.1 β-lactam antibiotics
4.1.1 Penicillins By interfering with the synthesis of bacterial cell wall, the
produce antibacterial effect, is the bactericidal agent of bacterial reproduction period.
Types: ① oral penicillin: amoxicillin, penicillin V potassium, (amoxicillin + potassium clavulanate), etc.; ② semi-synthetic, enzyme intolerant, broad-spectrum penicillin: ampicillin, hydroxyampicillin, piperacillin, etc.; ③ penicillinase resistant penicillin: mainly used for Staphylococcus aureus, benzocillin, oxycloxacillin, dicloxacillin, etc.; ④ anti-pseudomonas penicillin: [ticarcillin + potassium clavulanate ( Temetin)], [piperacillin
+ tazobactam ( Tegretol)]. Pharmacokinetics: After oral, intramuscular and intravenous administration, it is rapidly absorbed and reaches its peak in 0.5~1.5h, with a plasma protein binding rate of about 20%~40% and wide tissue distribution; short half-life, about 1h, 60%~70%~40%. Adverse reactions, allergic reactions; gastrointestinal symptoms, such as diarrhea, nausea, vomiting, loss of appetite, pseudomembranous enteritis; temporary liver function abnormalities, cholestatic jaundice; central nervous system symptoms, such as headache, anxiety, irritability, severe cases of convulsions, seizures, mental disorders, etc. Diarrhea, nausea, and mental abnormalities are common in dialysis patients.
Dosage: In case of renal insufficiency and Ccr < 40mg/min, each dose should be reduced and the dosing interval should be extended from 6-8h to 10-12h. Dialysis patients should be given once in 12-24h and after each dialysis.
Adverse reactions: allergic reactions, gastrointestinal symptoms, increased liver enzymes, eosinophilia, etc. Dialysis patients are prone to serious toxic side effects if the drug is administered in regular doses. Neurological symptoms such as mental abnormalities, hallucinations, hallucinations, abnormal thinking, non-answers, restlessness or drowsiness, coma and other symptoms are common, most often after the application of ceftazidime.
Usage: For renal insufficiency, Ccr < 20ml/min, reduce the dosage by half each time and extend the interval between doses. Dialysis patients should be given the drug once in 12-24 hours and after each dialysis.
4.1.3 β-lactamase inhibitors Bacteria cause resistance to β-lactam antibiotics by producing β-lactamases, which hydrolyze the β-lactam ring. Substances that bind to β-lactamase and inhibit its hydrolysis are called β-lactamase inhibitors. Currently, there are 3 types of clavulanic acid, sulbactam and tazobactam. Commonly used synthetic drugs include: (amoxicillin + potassium clavulanate), [ticarcillin + potassium clavulanate ( Temetin)], [piperacillin + tazobactam (Terzicin)], [ampicillin + sulbactam (Ulixin, Sultamicillin)], [cefoperazone + sulbactam (Sulphen)].
4.1.4 Carbapenems Imipenem (Tylenol), Meropenem ( Mepin).
Features: broad-spectrum, enzyme-resistant, bactericidal agent.
Pharmacokinetics: After absorption, the drug is widely distributed; protein binding rate is 20% for Tylenol, 2% for Mepin, half-life is 1h, 70% is excreted by kidney, and Mepin can be cleared by hemodialysis. Adverse reactions: rash, gastrointestinal symptoms, central nervous system symptoms, such as dizziness, convulsions, muscle spasms, drowsiness, mental abnormalities, and even seizures if the dose is too high; may further aggravate renal damage, reduced urine output, creatinine, urea nitrogen elevation. In addition, prolonged medication leads to dysbiosis and secondary fungal infections.
Dosage: Select the dose of medication according to the severity of infection and renal function. In renal insufficiency, Ccr < 50ml/min, the dosing interval should be prolonged, and dialysis patients should be dosed after each dialysis, once a day.
4.2 Aminoglycosides
Broad-spectrum, bactericidal agents, acting on the ribosomes of bacteria, inhibit bacterial protein synthesis and disrupt bacterial cell membrane integrity, mainly used for Gram-negative bacilli, including Pseudomonas aeruginosa and methicillin-sensitive Staphylococcus aureus infections. Pharmacokinetic characteristics: low protein binding rate, mainly distributed in the extracellular; reach the peak quickly 0.5 ~ 1.0h, half-life 2.0 ~ 3.0h, by glomerular filtration, urinary excretion 40% ~ 90%, with nephrotoxicity and ototoxicity.
Dosing method: Intramuscular or intravenous injection, those with normal renal function can use the drug once a day, the efficacy is not affected, and can reduce otorhinotoxicity. In patients with renal insufficiency, the half-life of the drug is significantly prolonged, and the number of doses should be reduced and the dosing interval extended. Hemodialysis clears the drug and should be administered after each dialysis session. Peritoneal dialysis does not clear the drug as well as hemodialysis, removing only 15% to 20% of the systemic dose. The drug can be absorbed into the blood quickly after administration via the peritoneal cavity. If available, the administration time and dose can be adjusted according to the blood concentration. The current application of netilmicin and etilmicin ototoxicity is significantly reduced.