Drug Incompatibility PDF

 DEFINITION  It is the result of prescribing or mixing two or more substances which are antagonist in nature and an undesirable product is formed which may affect the safety, purpose or appearance of the preparation. 3 Importa...

 DEFINITION  It is the result of prescribing or mixing two or more substances which are antagonist in nature and an undesirable product is formed which may affect the safety, purpose or appearance of the preparation. 3 Importance Of Determining Incompatibility: Incompatible products may affect: 1- Safety of medicament. 2- Efficacy of product. 3- Appearance of a medicine. 4- Purpose of medication.  CLASSIFICATION Incompatibility can be classified into three groups: 1. Pharmaceutical or physical incompatibility 2. Chemical incompatibility 3. Therapeutic incompatibility  Physical incompatibility and chemical incompatibility together called 4 physico-chemical incompatibility.  PHYSICAL INCOMPATIBILITY: Interaction between two or more substances which lead to change in color, odor, taste, viscosity and morphology.  A visible physical change takes place  An unacceptable, non-uniform, unpalatable product is formed.  Diffi cult to measure an accurate dose.  Can be corrected by applying pharmaceutical skill. 5 MANIFESTATIONS OF PHYSICAL INCOMPATIBILITY:  Insolubility of prescribed agent in vehicle  Immiscibility of two or more liquids  Liquification of solids mixed in a dry state 6 1.Insolubility: The following factors affect the solubility of prescribed agent in vehicle : 1) Change in pH 2) Milling 3) Surfactant 4) Chemical reaction 5) Complex formation 6) Co-solvent 2.Immiscibility of two or more liquids: Example: Flavoring agent such as orange oil, lemon oil or their alcoholic solution are added in aquous preparation they may not mix well and droplets of the oils may b float on the water surface. They make the solution turbid, having a hazy appearance. 7  Examples of prescriptions: Rx Olive oil 30 ml Water up to 120 ml Directions for Pharmacist: Make an emulsion. Comments: Physical incompatibility. 3. Liquification of solids mixed in a dry state: It means that when two solid substances are mixed together, conversion to a liquid state take place. Example: Certain low melting points solids when mixed together liquefy due to formation of eutectic mixtures, they form a soft mass when mixed together thus the physical integrity of the preparation may be lost. Ex- menthol, thymol, aspirin form eutectic mixture when 8 two of them are mixed together.  CHEMICAL INCOMPATIBILITY Chemical Incompatibility: Reaction between two or more substances which lead to change in chemical properties of pharmaceutical dosage form. Types of chemical changes: 1.Oxidation 2.Hydrolysis 3.Polymerization 4.Decarboxylation 5.Formation of insoluble complexes 9  THERAPEUTIC INCOMPATIBILITY: Therapeutic incompatibilities are unintentional pharmacodynamic or pharmacokinetic interactions that take place in vivo after administration of medicinal products. Example: Amine containing drugs are incompatible with mono amino- oxidase inhibitors.  CAUSES: It may be due to the administration of : ⚫ Overdose or improper dose of a single drug. ⚫ Improper Dosage form. ⚫ Contraindicated drug. 1 1 ⚫ Synergistic and antagonistic drugs DIFFERENT KINDS OF DRUG INTERACTION Mainly two types of drug interaction: 1- Pharmacodynamic interaction 2- Pharmacokinetic interaction Other interactions:  Drug - Drug interaction  Drug - Excipient interaction  Excipient - Excipient interaction  Drug - Food interaction  Excipient - Packaging interaction  Pharmacodynamic Interaction: are those in which drugs having similar or antagonistic pharmacological effects or side effects are administered concurrently and situation in one drug is altered by another.  Pharmacokinetic Interaction: are those in which one agent alters the absorption,distribution,metabolism and excretion of a second drug with a resultant change in the plasma concentration of the later agent. 13  Pharmacokinetic interactions are classified as: 1. Absorption Drug absorptio Transport of interactions n the drug inside the body 2. Distribution interactions Drug displacement 3. Metabolism (protein-binding) interactions Drug metabolism (biotransformation) Drug excretion 4. Excretion interactions. 15 DRUG-DRUG INTERACTION  Drug-drug interactions occur when a drug interacts, or interferes, with another drug. This can alter the way of one or both of the drugs act in the body, or cause unexpected side effects.  This action can be synergistic (when the drug's effect is increased) or antagonistic (when the drug's effect is decreased) or a new effect can be produced. Examples of this include:-  the use of codeine with paracetamol to increase its analgesic effect.  the combination of clavulanic acid with amoxicillin in order to 17 overcome bacterial resistance to the antibiotic. 18 More drug = More interactions 19 DRUG-EXCIPIENT INTERACTION  Drug-excipient interaction occurs between the API and excipient materials. Example: Certain amine drugs (paracetamol) react with lactose (diluent) in the presence of Magnesium stearate to form brown color compound. This may cause darkening of the tablets 20 and the integrity of the tablet DRUG-EXCIPIENT INTERACTION  This type of interaction occurs between two or more excipients in a drug molecule. Example: In proper addition of electrolyte such as- Ca++ or Mg++ ion in suspension containing sodium carboxymethyl cellulose (Na CMC) which will cause formation of Calcium/Magnesium CMC. The suspending agent will be destroyed and cannot perform its function. DRUG-Food INTERACTION  A drug-food interaction happens when the food we eat affects the ingredients in a medicine we are taking so the medicine cannot work the way it should.  Example- 1. Consumers taking digoxin for heart failure or ACE inhibitors for high blood pressure should be careful with salt substitutes, which most often replace sodium with potassium. 2.Blood-thinning drugs such as warfarin interfere with vitamin K-dependent clotting factors. Eating too much green leafy vegetables, which are high in vitamin K, can 22 decrease the ability of blood-thinners to prevent Examples of prescriptions: Rx Tetracycline Hydrochloride 250 g Directions for Pharmacist: Make Capsules. Send 10 capsules. Label: Take one capsule every six hours with milk. Comments: Therapeutic incompatibility 23 DRUG-PACKAGING MATERIAL INTERACTION  In some pharmaceutical formulation excipient and packaging material may interact with each other and thus can cause ex- packaging interaction. Example: Many commercial glass products such as containers are made of soda-lime glass, and therefore have a substantial percentage of sodium ions in their internal structure. Since sodium is an alkali element, its selective removal from the surface results in a alkali 24 leaching. HOW TO PREVENT DRUG INTERACTIONS?  We should tell our doctor about everything we are taking, including prescription drugs, OTC medications, vitamins and herbal supplements.  We should read the consumer information sheet with our prescriptions and read it carefully.  We should read the labels on OTC medications, paying special attention to the “Warnings”section.  Before buying a new OTC medication, vitamin or herbal supplement, we should ask our pharmacist if there 25 are any potential drug interactions with the prescriptions or not  Practical Prescriptio n Practical Prescription R/ Calcium chloride 10% w/v solution 10 ml Sodium bicarbonate 5.6% w/v solution 15 ml Label: To be mixed for IV administration. Calculations 1. To prepare 10 ml of calcium chloride 10 % w/v solution: 10% w/v that mean 10 g/ 100ml 10 g 100 ml X 10 ml X = 1g CaCl2 2. To prepare 15 ml of sod. bicarbonate 5.6 % w/v solution: 5.6% w/v that mean 5.6 g / 100 ml 5.6 g 100 ml X 15 ml X = 0.84g Sod. bicarbonate Procedure: 1- Weigh 1 g of CaCl2 and dissolve it in 10 ml water in a beaker by hand shaking. 3- Add NaHCO3 White solution on CaCl2 PPt 2- Weigh 0.84 g of NaHCO3 solution and dissolve it in 15 ml water in a beaker by hand shaking. It will take a time to dissolve. Type of incompatibility: Chemical and physical reaction as the following: 1. Chemical incompatibility: chemical reaction occur between sodium bicarbonate and CaCL2 as below 2NaHCO3​+CaCl2​→ CaCO3​+2NaCl+CO2​+H2​O 2. Physical incompatibilty: related to change in appearence through forming insoluble white precipitate. Risk: This preparation is not applicable for IV administration due to ppt formation that induce imbolsim in blood stream. Correction: administer the two solutions in a separate manner, in another words, time interval must be considered. 26