Forced diuresis
Encyclopedia
Forced diuresis may enhance the excretion of certain drugs in urine and is used to treat drug overdose
or poison
ing of these drugs and hemorrhagic cystitis
.
s or weak base
s. When urine is made alkaline, elimination of acidic drugs in the urine is increased. The converse applies for alkaline drugs.
This method is only of therapeutic significance where the drug is excreted in active form in urine and where the pH of urine can be adjusted to levels above or below the pK
value of the active form of drug. For acidic drugs, urine pH should be above the pK
value of that drug, and converse for the basic drugs. It is because the ionization of acidic drug is increased in alkaline urine and ionized drugs cannot easily cross plasma membrane so cannot re-enter blood from kidney tubules. This method is ineffective for drugs which are strongly protein bound (eg tricyclic antidepressant
s) or which have a large apparent volume of distribution
(eg paracetamol
, tricyclic antidepressants).
Forced alkaline diuresis has been used to increase the excretion of acidic drugs like salicylates and phenobarbitone, while forced acid diuresis has been used to enhance the elimination of cocaine
, amphetamine
, quinine
, quinidine
, and strychnine
when poisoning by these drugs has occurred.
For forced alkaline diuresis, a diuretic
like furosemide
is given intravenously and sodium bicarbonate
is added to the infusion fluid to make blood and, in turn, urine alkaline. Potassium replacement becomes of utmost importance in this setting because potassium is usually lost in urine. If blood levels of potassium are depleted below normal levels, then hypokalemia
occurs, which promotes bicarbonate ion retention and prevents bicarbonate excretion, thus interfering with alkalinization of the urine.
For forced acid diuresis, ascorbic acid
(vitamin C
) is used. Ammonium chloride
has also been used for forced acid diuresis but it is a toxic compound. Usually however, this technique only produces a slight increase in the renal clearance of the drug. Forced acid diuresis is rarely done in practice.
Forced alkaline diuresis is also recommended for rhabdomyolysis
.
Drug overdose
The term drug overdose describes the ingestion or application of a drug or other substance in quantities greater than are recommended or generally practiced...
or poison
Poison
In the context of biology, poisons are substances that can cause disturbances to organisms, usually by chemical reaction or other activity on the molecular scale, when a sufficient quantity is absorbed by an organism....
ing of these drugs and hemorrhagic cystitis
Hemorrhagic cystitis
Hemorrhagic cystitis or Haemorrhagic cystitis is diffuse inflammation of the bladder leading to dysuria, hematuria, and hemorrhage. The disease can occur as a complication of cyclophosphamide, ifosfamide and radiation therapy...
.
Diuretics
Most of the drugs are either weak acidWeak acid
A weak acid is an acid that dissociates incompletely. It does not release all of its hydrogens in a solution, donating only a partial amount of its protons to the solution...
s or weak base
Weak base
In chemistry, a weak base is a chemical base that does not ionize fully in an aqueous solution. As Brønsted–Lowry bases are proton acceptors, a weak base may also be defined as a chemical base in which protonation is incomplete. This results in a relatively low pH compared to strong bases...
s. When urine is made alkaline, elimination of acidic drugs in the urine is increased. The converse applies for alkaline drugs.
This method is only of therapeutic significance where the drug is excreted in active form in urine and where the pH of urine can be adjusted to levels above or below the pK
Acid dissociation constant
An acid dissociation constant, Ka, is a quantitative measure of the strength of an acid in solution. It is the equilibrium constant for a chemical reaction known as dissociation in the context of acid-base reactions...
value of the active form of drug. For acidic drugs, urine pH should be above the pK
Acid dissociation constant
An acid dissociation constant, Ka, is a quantitative measure of the strength of an acid in solution. It is the equilibrium constant for a chemical reaction known as dissociation in the context of acid-base reactions...
value of that drug, and converse for the basic drugs. It is because the ionization of acidic drug is increased in alkaline urine and ionized drugs cannot easily cross plasma membrane so cannot re-enter blood from kidney tubules. This method is ineffective for drugs which are strongly protein bound (eg tricyclic antidepressant
Tricyclic antidepressant
Tricyclic antidepressants are heterocyclic chemical compounds used primarily as antidepressants. The TCAs were first discovered in the early 1950s and were subsequently introduced later in the decade; they are named after their chemical structure, which contains three rings of atoms...
s) or which have a large apparent volume of distribution
Volume of distribution
The volume of distribution , also known as apparent volume of distribution, is a pharmacological term used to quantify the distribution of a medication between plasma and the rest of the body after oral or parenteral dosing...
(eg paracetamol
Paracetamol
Paracetamol INN , or acetaminophen USAN , is a widely used over-the-counter analgesic and antipyretic . It is commonly used for the relief of headaches and other minor aches and pains and is a major ingredient in numerous cold and flu remedies...
, tricyclic antidepressants).
Forced alkaline diuresis has been used to increase the excretion of acidic drugs like salicylates and phenobarbitone, while forced acid diuresis has been used to enhance the elimination of cocaine
Cocaine
Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system, an appetite suppressant, and a topical anesthetic...
, amphetamine
Amphetamine
Amphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...
, quinine
Quinine
Quinine is a natural white crystalline alkaloid having antipyretic , antimalarial, analgesic , anti-inflammatory properties and a bitter taste. It is a stereoisomer of quinidine which, unlike quinine, is an anti-arrhythmic...
, quinidine
Quinidine
Quinidine is a pharmaceutical agent that acts as a class I antiarrhythmic agent in the heart. It is a stereoisomer of quinine, originally derived from the bark of the cinchona tree.-Mechanism:...
, and strychnine
Strychnine
Strychnine is a highly toxic , colorless crystalline alkaloid used as a pesticide, particularly for killing small vertebrates such as birds and rodents. Strychnine causes muscular convulsions and eventually death through asphyxia or sheer exhaustion...
when poisoning by these drugs has occurred.
For forced alkaline diuresis, a diuretic
Diuretic
A diuretic provides a means of forced diuresis which elevates the rate of urination. There are several categories of diuretics. All diuretics increase the excretion of water from bodies, although each class does so in a distinct way.- Medical uses :...
like furosemide
Furosemide
Furosemide or frusemide is a loop diuretic used in the treatment of congestive heart failure and edema. It is most commonly marketed by Sanofi-Aventis under the brand name Lasix...
is given intravenously and sodium bicarbonate
Sodium bicarbonate
Sodium bicarbonate or sodium hydrogen carbonate is the chemical compound with the formula Na HCO3. Sodium bicarbonate is a white solid that is crystalline but often appears as a fine powder. It has a slightly salty, alkaline taste resembling that of washing soda . The natural mineral form is...
is added to the infusion fluid to make blood and, in turn, urine alkaline. Potassium replacement becomes of utmost importance in this setting because potassium is usually lost in urine. If blood levels of potassium are depleted below normal levels, then hypokalemia
Hypokalemia
Hypokalemia or hypokalaemia , also hypopotassemia or hypopotassaemia , refers to the condition in which the concentration of potassium in the blood is low...
occurs, which promotes bicarbonate ion retention and prevents bicarbonate excretion, thus interfering with alkalinization of the urine.
For forced acid diuresis, ascorbic acid
Ascorbic acid
Ascorbic acid is a naturally occurring organic compound with antioxidant properties. It is a white solid, but impure samples can appear yellowish. It dissolves well in water to give mildly acidic solutions. Ascorbic acid is one form of vitamin C. The name is derived from a- and scorbutus , the...
(vitamin C
Vitamin C
Vitamin C or L-ascorbic acid or L-ascorbate is an essential nutrient for humans and certain other animal species. In living organisms ascorbate acts as an antioxidant by protecting the body against oxidative stress...
) is used. Ammonium chloride
Ammonium chloride
Ammonium chloride NH4Cl is an inorganic compound with the formula NH4Cl. It is a white crystalline salt that is highly soluble in water. Solutions of ammonium chloride are mildly acidic. Sal ammoniac is a name of natural, mineralogical form of ammonium chloride...
has also been used for forced acid diuresis but it is a toxic compound. Usually however, this technique only produces a slight increase in the renal clearance of the drug. Forced acid diuresis is rarely done in practice.
Forced alkaline diuresis is also recommended for rhabdomyolysis
Rhabdomyolysis
Rhabdomyolysis is a condition in which damaged skeletal muscle tissue breaks down rapidly. Breakdown products of damaged muscle cells are released into the bloodstream; some of these, such as the protein myoglobin, are harmful to the kidneys and may lead to kidney failure...
.
Other
- Immersion diuresisImmersion diuresisImmersion diuresis is a type of diuresis caused by immersion of the body in water . It is mainly caused by lower temperature and by pressure....
is a type of diuresis caused by immersion of the body in water (or equivalent liquid). It is mainly caused by lower temperature and by pressure.
See also
- Ion trappingIon trappingThe term ion trapping is used to describe the build-up of a higher concentration of a chemical across a cell membrane due to the pKa value of the chemical and difference of pH across the cell membrane...
- Haemodialysis
- Peritoneal dialysisPeritoneal dialysisPeritoneal dialysis is a treatment for patients with severe chronic kidney disease. The process uses the patient's peritoneum in the abdomen as a membrane across which fluids and dissolved substances are exchanged from the blood...
- Haemoperfusion
- Haemofiltration
- CharcoalCharcoalCharcoal is the dark grey residue consisting of carbon, and any remaining ash, obtained by removing water and other volatile constituents from animal and vegetation substances. Charcoal is usually produced by slow pyrolysis, the heating of wood or other substances in the absence of oxygen...
- PoisonPoisonIn the context of biology, poisons are substances that can cause disturbances to organisms, usually by chemical reaction or other activity on the molecular scale, when a sufficient quantity is absorbed by an organism....