INCOMPATIBILITIES

1. INCOMPATIBILITIES

2. 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.

3. Incompatibilities • Incompatibilities are divided into three classes: • Therapeutic incompatibilities • Physical incompatibilities • Chemicalincompatibilities

4. 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.

5. 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

6. 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.

7. 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.

8. 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.

9. 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

10. - Dosing errors, unclear prescription

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

12. 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

13. 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.

14. 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

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

16. 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)

17. 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)

18. Corrective Measures

19. 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

20. Intentional incompatibilities

21. 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.

22. 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.

23. 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 Water to 150 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

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