INCOMPATIBILITIES

Incompatibilities Incompatibles are substances which have opposite medicinal properties, or substances when mixed together, react chemically to produce other substances. An understanding of incompatibilities can save the pharmacist valuable time in compounding as well as ensure the therapeutic efficiency of the products. Incompatibilities range from minor to dangerous.

Incompatibilities Incompatibilities are divided into three classes: Therapeutic incompatibilities Physical incompatibilities Chemical incompatibilities

Types of Incompatibilities 1. Therapeutic Incompatibility They exist when the response to one or more drug is of different nature or intensity than that intended by the prescriber. When circumstances produce a feeling of doubt on the part of the pharmacist, the prescribing physician should be consulted.

Therapeutic incompatibility 1. Synergistic (or additive) combination When certain drugs having the same pharmacologic action are prescribed together, the combined action they produce is greater than the sum of their individual actions. Such combinations should be in reduced amount. The synergistic action will sometimes be desired to decrease toxicity or reduce cost of prescription

Therapeutic incompatibility Synergistic (cont.); examples of useful synergistic effect Combinations of sulfonamides show less nephrotoxicity than a single sulfonamide. Neomycin – erythromycin combination has a broader spectrum than either antibiotic alone. Aspirin – codeine combination reduces the amount of expensive codeine required.

Therapeutic incompatibility 2. Antagonistic combinations When two or more drugs having opposite pharmacological action are prescribed together, their actions cancel each other and the resulting prescription will have no therapeutic action. Stimulants with sedatives (hypnotics) e.g. caffeine with chloral hydrate. Purgatives with antidiarrheals e.g. MgSo4 with tannins Acidifiers with alkalinizers e.g. aspirin with AL(OH)3.

Therapeutic incompatibility 3. contraindication Are drugs when prescribed together may lead to increased toxicity or decrease activity. Tetracycline is contraindicated with any drug containing Ca2+ ions as it form non-absorbable complex. Inactivation of sulfa drugs by procaine HCI.

Therapeutic Incompatibility 4. Dosage Error: can result from the administration of a single high dose, or the too frequent administration. R/ Atropine sulphate 6 mg Phenobarbital 360 mg Ft. caps, i mitte xii sig. caps, i t.d.s

- Dosing errors, unclear prescription

Therapeutic Incompatibility Dosage errors Rx Codeine phosphate 15 mg Ammonium chloride 500 mg Ft. caps, i mitte xx sig; caps, ii q.h.

2. Physical Incompatibilities Physical  incompatibilities  are  often  called  phar-maceutical  incompatibilities  and  are  evidenced  by  the failure of the drugs to combine properly. These incompatibilities produce a mixture which is unacceptable in appearance and taste and may result in non-uniform dosage form. 1.Incomplete solution: Gums are insoluble in alcohol. resins are insoluble in water

Physical Incompatibilities 2. Precipitation: Resins are precipitated from alcoholic solution when water is added Camphor and volatile oils are salted out from their aromatic water when soluble salts are added 3. Separation of immiscible liquids. 4. Eutexia; formation of eutictic mixture. 5. Incorrect form prescribed,e.g. alkaloidal salt dissolve in liquid paraffin. 6. Adsorption at solid surface; Adsorption on solid surfaces; such as adsorption of anti-microbial agents on rubber closure or plastic container.

3. Chemical Incompatibilities This type of incompatibility exists when agents are prescribed that react chemically when mixed, altering the composition of one or more of the constituents.  Examples; - formation of precipitate - evolution of gas - colour change

Evolution of gas: R/ amm. Carbonate Amm. Chloride Acetic acid syrup of cherry Fait solution Amm. Carb. + acetic acid CO2

Manifestations of Incompatibility Insolubility of prescribed agent in vehicle (physical) Immiscibility of two or more liquids (physical) Precipitation due to change in menstrum that results in decreased solubility (physical) Eutexia-the liquefaction of solids mixed in dry state (physical) Cementation of insoluble ingredients in liquid mixtures (physical)

Manifestations of Incompatibility Change in color (chemical) Oxidation-reduction or explosive reaction (chemical) Precipitation due to chemical reaction (chemical) Inactivation of sulfa drugs by procaine HCI (therapeutic) Inactivation of tetracycline by calcium ions (therapeutic)

Corrective Measures

Corrective Measures Addition of an ingredient that does not alter the therapeutic value. Change of an ingredient. Minor changes such as a soluble form of an ingredient for an insoluble form are included. Change of a solvent. The utilization of special techniques in compounding, such as treating each ingredient separately. Omission of an agent that has no therapeutic value, or that may be dispensed separately. Utilization   of   special   techniques   in   com- pounding

Intentional incompatibilities

Intentional Therapeutic incompatibilities Such circumstances rarely occur, but when they do it does not necessarily indicate a moment of forgetfulness on the part of the physician. Such agents may have been used together in order for one agent to modify the activity of the other. Examples: Atropine should antagonize the depressant effect of morphine to the respiratory tract. Central nervous system stimulants may be used to overcome the drowsiness produced by anti-histaminic. A mild laxative antacid such as Mg(OH)2 may be used to overcome the constipating effect of an astringent antacid such as AL(OH)3.

Intentional Chemical Incompatibility Strong iodine solution U.S.P. (Lugol’s solution) R/ Iodine 50 gm Potassium iodide 100 gm purified water ad 1000 ml Iodine dissolves in potassium iodide to form the water soluble I3 complex.

Intentional chemical incompatibles Carbonaeous mixture (Postion Revier Mixture): Solution A: R/ Sodium bicarbonate 3.5 gm Simple syrup 30.0 ml Water to 150 ml Solution B: R/ Citric acid 4.0 gm Syrup lemon 30.0 ml Fait Mist. A and B, Mitte 50 ml of each Sig.: one tablespoonful from solution A is mixed with an equal volume of solution B and the mixture is taken when effervescence is about to cease

Intentional Physical incompatibilities Tincture myrh is diluted with water to give a precipitate which is used as a gargle in the treatment of tonsillitis.