ELIMINATION
ENHANCEMEN
T
RINDHIYA.R.K
PHARM.D 4TH YEAR
INTRODUCTION - ELIMINATION
• Elimination is defined as the act of removing or getting
rid of bodily discharged waste matter
• The elimination system in our body, eliminates about 2
pounds of material per day in the normal healthy adult.
• If any one of the channel becomes overloaded or clogged
and slowed down, there will be an accumulation of toxic
material in the body tissues.
ELIMINATION SYSTEM
There are 5 elimination systems in the body,
* The bowel (colon)
* Kidney
* Lungs
* Skin
* Liver
The lymph system works with these 5 systems by serving as a
“GARBAGE COLLECTOR” to carry metabolic by-products and
accumulated cellular waste from tissue to the elimination
organs.
ELIMINATION ENHANCEMENT
• Accidental and intentional poisonings or drug overdoses
constitutes a significant source of aggregate morbidity,
mortality, and healthcare expenditures.
• Management of the poisoned patient begins with a
thorough evaluation, identification of the agents involved,
assessment of severity and prediction of toxicity.
• Therapy involves the provision of supportive care,
prevention of poison absorption, the administration of
antidotes and enhancement of elimination of the poison.
METHODS OF ENHANCEMENT
The various methods of eliminating absorbed poisons from the body
include the following:
(i) Forced Diuresis
(ii)Extracorporeal techniques
* Haemodialysis
* Haemoperfusion
* Peritoneal dialysis
* Haemofiltration
* Plasmapheresis
* Plasma perfusion
* Cardiopulmonary bypass.
(I) FORCED DIURESIS
• Most drugs taken in overdose are extensively detoxified by the liver to
produce inactive metabolites which are voided in the urine. Sometimes
hepatic degradation produces active metabolites, but the secondary
compounds are then converted to non-toxic derivatives. Under these
circumstances, forced diuresis is inappropriate.
• The procedure should be undertaken only if the following conditions are
satisfied:
■ A substantial proportion of the drug is excreted
unchanged.
■ The drug is distributed mainly in the extracellular fluid.
■ The drug is minimally protein-bound.
•.
PRINCIPLE
• Most drugs are weak electrolytes, meaning they only partially ionize in
solution.
• Their degree of ionization depends on:
• The pKa of the drug (a measure of its tendency to donate or accept protons).
• The pH of the surrounding medium.
• Understanding pKa
• pKa = negative log of Ka (acid dissociation constant).
• The lower the pKa, the stronger the acid.
• The higher the pKa, the stronger the base.
• When pH = pKa, 50% of the drug is ionised, 50% non-ionised.
Drug Permeability
• Non-ionised (uncharged) forms are more lipid-soluble and cross cell
membranes more easily.
• Ionised (charged) forms are water-soluble and less membrane-permeable.
Renal Excretion & pH
• Drugs are filtered into the urine but can be reabsorbed if they're non-ionised.
• Ionised drugs remain in the urine, leading to greater excretion.
• Therefore:
• Acidic drugs are more ionised in alkaline urine → excretion increases.
• Basic drugs are more ionised in acidic urine → excretion increases.
• Clinically, this principle is used to manipulate urinary pH to speed up drug
elimination in overdose or poisoning cases.
Example:
• Phenobarbital (a weak acid): excretion is enhanced in alkaline urine.
• Amphetamines (weak bases): excretion is enhanced in acidic urine.
Drug Type Urine Type Needed Effect
Acidic drugs Alkaline urine ↑ Ionisation → ↑ Excretion
Basic drugs Acidic urine ↑ Ionisation → ↑ Excretion
■ Forced alkaline diuresis :
This is most useful in the case of phenobarbitone, lithium, and salicylates.
Administer 1500 ml of fluid IV, in the first hour as follows :– 500 ml of 5%
dextrose– 500 ml of 1.2 or 1.4% sodium bicarbonate– 500 ml of 5% dextrose.
■ Forced acid diuresis :
Forced acid diuresis is no longer recommended for any drug or poison,
including amphetamines, strychnine, quinine or phencyclidine.
EXTRACORPOREAL TECHNIQUES
1. Haemodialysis
Introduction
• First used experimentally in 1913; clinical use began in 1950 for salicylate overdose.
• Popularity declined due to limited utility, complications (infection, thrombosis, air
embolism).
Requirements for Effective Haemodialysis
Substance must:
• Diffuse easily across dialysis membrane.
• Be present or equilibrate rapidly in plasma water.
• Have pharmacological effects linked to blood concentration.
Ineffective for:
• High plasma protein binding, water insolubility, high molecular weight.
PROCEDURE:
Hemodialysis machine works as an artificial kidney by:
• Removing waste and extra fluids in your body to prevent them from building up in the
body
• Keeping safe levels of minerals in your blood, such as potassium, sodium, calcium, and
bicarbonate
• Helping to regulate your blood pressure.
The machine has a special dialyzer filter to clean the blood. To get your blood to the
dialyzer, a surgeon will make an opening into one of your blood vessels. This opening is
called a vascular access, and it is done with minor surgery, usually in your arm.
There are 03 types of accesses:
*Arteriovenous (AV) fistula- connection between an artery and a vein, usually in the arm
you use less often. This is the preferred type of access because of effectiveness and safety.
*AV graft- If blood vessel are too small to form AV fistula, creates a path between an artery
and vein using flexible synthetic tube called a graft
*Central venous catheter- In case of emergency hemodialysis, a plastic tube (catheter) may be
inserted into a large vein in your neck. The catheter is temporary.
Inside the dialyzer or filter, there are two sides—one for blood and the other for dialysate fluid. A thin
film, called a membrane, separates these two sides.Blood cells, proteins, and types of cells remain in
your blood because they are too big to pass through the membrane. Smaller waste products, such as
urea and creatinine, and extra fluid, move from your blood through the membrane and are removed.
Dialysis begins at a blood flow rate of 50 to 100 ml/min, and is gradually increased to 250 to 300
ml/min, to give maximal clearance
INDICATIONS:
(i)Best indications: after heavy metal chelation in patients with renal failure, and
ethylene glycol or methanol ingestion.
(ii)Very good indication: patients with severe intoxications with the following agents:
- Phenobarbitone -Salicylates –Theophylline- Lithium
(iii)Fairly good indications: Alcohols - Amphetamines - Anilines - Antibiotics - Boric acid
- Barbiturates (short acting) - Bromides - Chlorates - Chloral hydrate – Iodides- Isoniazid -
Meprobamate - Paraldehyde - Fluorides - Quinidine - Quinine - Strychnine – Thiocyanates
(iv)Poor indications: can be considered as a supportive measure in the presence of
renal failure, following exposure to: - Paracetamol - Antidepressants - Antihistamines -
Belladonna alkaloids -Benzodiazepines - Digitalis and related glycosides - Glutethimide -
Opiates - Methaqualone -Phenothiazines - Synthetic anticholinergics.
COMPLICATIONS:
* Infection (especially AIDS, hepatitis B)
* Thrombosis
* Hypotension
* Air embolism
* Bleeding (due to use of heparin as a systemic anticoagulant).
