EXTRACORPOREAL REMOVAL OF DRUGS

Presented by: Arjan Aryal5th PharmD

Patients with ESRD or who have been intoxicated due to overdose of a drug may require supported treatment to remove accumulated drugs.

Methods:DialysisHemofiltrationHemoperfusion.

Objective:Rapidly remove undesirable drugs and metabolites without disturbing the fluid and electrolyte balance in the patient.

Artificial Process, acculmulation of drug removed by diffusion into dialysis fluid.

Two Methods: Peritoneal Dialysis. Hemodialysis.

Dialysis

Helps to clean the blood and remove excess of water in the body – peritoneal Membrane in the abdomen.

A catheter inserted in peritoneal cavity, dialysis fluid enters into the peritoneal cavity via tube -> filters blood and remove waste products from the body.

Two Types CAPD(Continous Ambulatory Peritoneal Dialysis))) APD (Automated Peritoneal Dialysis)

Peritoneal Dialysis

CAPD ( Continous Ambulatory Peritoneal Dialysis)

Fluid flows in and out of the body using gravity.

Over time, waste and fluid build up in the blood which slowly float across into peritoneal membrane by diffusion and exchange remove dialysis fluid from the peritoneal cavity and replaces with new fluid.

To be done everyday 1 Exchange takes 30 mins.

Solution is clear. Check the solution type and % is correct. Expiration date has not passed. Volume is correct. No leaks after gentle squeezing.

Precaution to be taken before starting peritoneal dialysis.

Machine does the exchange Done by Dialysis team or taught to use .

FLUID AND DIALYSIS SOLUTION Important to achieve right balance of water in body. Determined in 3 ways.

Weight BP Swelling

Dialysis Solution Dianeal (1.5%, 2.5%, 4.25%) Neutroneal (1.1 %) Extraneal (7.5%)

PRECAUTIONInfection

APD (Automated Peritoneal Dialysis)

Process that uses artificial kidney to remove waste products through the process called diffusion.

Artificial kidney contains a number of tubes with a semi permeable lining, suspended in a tank filled with dialysing fluid.

HEMODIALYSIS

Process

1.• One line connected to artery which is connected to one end of dialysis where blood is collected from patient for filtration.

2.• Waste Product from the blood passes into dialysing fluid by diffusion.

3.• Purified Blood is pumped back into the vein which is connected to other end of dialysis device.

Heparin is used to prevent blood clotting during dialysis. It is much more effective method for rapid removal of drug

( overdose , poisoning) and preferred method in ESRD. Dialysis may be required from every 2 days to 3 times a

week, one dialysis period is of 2-4 hrs depending on patient’s size, weight and renal function.

CHARACTERISTICS OF DIALYSING MACHINE

Higher Blood flow rate. Permeable dialysis membrane. High Transmembrane pressure.

Important notes.

• Insoluble or fat soluble drugs are not solubilized.( eg glutethimide – a water insoluble drug.)Water Solubility

• Tightly bound protein are not dialysed. (eg propranolol)Protein Binding

• Mol Wt less than 500 are dialysed. ( eg Vancomycin is poorly dialysed )

Molecular Weight

Factors Affecting Dialyzability of Drugs

Drugs with large volume of distribution

• Widely distributed drugs are dialysed slowly, drug concentrated in tissues are difficult to remove by dialysis.

In dialysis involving uremic patient receiving drug for therapy, drug is removed depending on the flow rate of the blood to the dialysis machine which is described by the term Dialysance.

Defined by the equation :ClD = Q(Ca –CV)

Ca

where, Ca = Drug Concentration in arterial blood. CV =Drug Concentration in Venous blood. Q= Rate of Blood flow to kidney.ClD = Dialysance.

Dialysance

Removing the drugs by passing the blood from the patient through an adsorbent material and back to the patient.

Molecules which have greater affinity for the materials will be removed.

HEMOPERFUSION

Useful in accidental poisoning and drug overdose.

Materials use:◦ Activated Charcoal (both polar and non polar

drugs)◦ Amberlite resins (non polar organic molecules).

Affinity of the drug for the absorbent. Surface area of the absorbent. Absorptive capacity of the absorbent. Rate of blood flow through the absorbent. Equilibrium rate of the drug from the

peripheral tissue into the blood.

Important Factors to be considered.

An alternative to hemodialysis and hemoperfusion.

A process by which fluid, electrolytes, small molecular weight substances are removed from the blood using hollow artificial fibre.

Loss of water and electrolytes takes place, that leads to production of ultrafiltrate. As a result equal volume of fluid is replaced.

HEMOFILTRATION

Synthetic, high flux(permeability), hollow fibre membrane. Pore size 50000 da High Surface Area ( 0.6-1.2 m2).

Notes • Flow rate of 20-35 ml/kg/hr is usually required.• No benefit shown with higher flow rate, more expensive.• Although higher flow rate may be used if rapid solute

clearance is necessary.

Filter Properties

Hemodialysis vs Hemofiltration

Hemodialysis involves diffusion across a semipermeable membrane Where as Hemofiltration is a convection process with loss of water Due to ultrafiltration accompanied by convicted loss of salts.

The clearance of the drug depends on sieving coefficient and ultrafiltration rate.

The sieving coefficient reflects the solute removal ability during hemofiltration.

When S=1 solute passes freely through the membrane whereas is S=0 solute is retained in plasma.

S is constant and independent of blood flow , soCl=S * Ultrafiltration rate

The Concentration of the drug in the ultrafiltrate is also equal to the unbound drug concentration in the plasma , so, amount of drug removed is given as :

Amount removed = CP + ∞ * rate of ultrafiltration

THANK YOU !!