DISPENSING LEC (MIDTERM)

Incompatibility

the problem that arises during compounding, dispensing or administering the medication

elegance, safety, therapeutic efficacy of the drug

Incompatibility adversely effect (3)

(1) Develop Good Formulation, (2) Develop quality, safe, and effective medicines, (3) save time, material and money

Importance of checking compatibilities (3)

Two types of Incompatibilities

In vitro and In vivo

Physical

An incompatibility in which no other product is formed

chemical

An incompatibility in which a new product is formed

Therapeutic ) In-vivo

An incompatibility that involves ADRs and DI, what happens to the drug once administered.

How is the incompatibility manifested?

Which of the ingredient/s is are causing the incompatibility?

What is the type of Incompatibility present?

How can it be corrected?

5 questions of Analysis of Incompatibility

Insolubility

Incompatibility that usually happens between solid and liquid

Insolubiliity

camphor + water (incompatibility)

Insolubility

Gum + Alcohol (incompatibility)

Immiscibility

An incompatibility that usually happens between 2 liquids

Immiscibility

oil + water (incompatibility)

Physical Precipitation

An incompatibility it involves the separation of solids but have no new product is formed

Salting out (Precipitation)

a process in which a solution of electrolytes is mixed with non-electrolytes.

Precipitation of volatile oil

aromatic water + salt (incompatibility)

Loss of Water

“Dehydration” this will cause an increase in the potency or concentration

crumble

ointment when dry ________ decreasing base

syneresis, in gels

contraction of gel accompanied by the separation to the liquid part

Loss of water

emulsion cracking or swelling

Liquefaction

it is the transformation of solid into liquid

Deliquescence

a condition referring to absorption of moisture to form water of hydration leading to gradual dissolution of liquefaction

Efflorescence

release of water of crystallization and leads to dissolution of crystal

Eutexia

refers to depression or lowering in the melting point of 2 solids that comes in contact with others

Polymorphism

Refers to the ability to exists in different crystallization

Polymorphism

Cocoa butter (alpha and beta) and chloramphenicol (incompatibility)

Change in solvent system

Camphor + Alcohol + Water (incompatibility)

Endothermic reaction

Absorbs heat from the surrounding, Increases temperature of the solution increasing solubility.

Endothermic reaction

ammonium chloride and water (incompatibility)

Decrease temperature of the solution

Decreased solubility

Exothermic reaction effect

Exothermic reaction

Lime water (incompatibility)

Change in pH

Phenobarbital Na + Syrup Orange & Codeine sulfate + NaOH (incompatibilty)

Citric acid, atropine sulfate, and ferrous sulfate

Efflorescent Substances (3)

eutectic mixture of local anesthetic

EMLA meaning

Vaporization

Volatilization , liberation to active ingredients

Vaporization

is the liberation of the active ingredient

Vaporization

Nitroglycerin (Incompatibility)

Monday’s Disease

vaporization of nitroglycerin can cause ____________

Reduction

Hydrogenation reaction, gain of electrons and occurs in metallic salts

Reduction

silver nitrate—> silver oxide (metallic silver) (incompatibility)

oxidation reaction

dehydrogenation reaction, an incompatibility manifested in change in color

Oxidation

factors that causes oxidation, light, temp, pH, oxygen

Ascorbic acid- yellow to white

Epinephrine- yellow to pink

Ascorbic acid and epinephrine (Incompatibility) give color

Hydrolysis

decomposition or breakdown of a substance in the presence of water

hydrolysis

Aspirin (incompatibility)

Chemical Precipitation

a precipitation in which there is a new substance formed

Chemical precipitation (calcium carbonate precipitate)

calcium carbonate upon long standing will have a chance to interact with CO2 which leads to what incompatibility

Photolysis

refers to the decomposition upon exposure to sunlight

Cisplatin, Amphotericin B, Adriamycin, Doxorubicin, Nifedipine, Phenothiazine, Nitroprusside

Give 7 drugs that undergo photolysis

racemization

the conversion of the optically active compound to optically inactive compound

Explosive

usually happens when mixing oxidizing and reducing agent with the aid of friction

explosive

potassium permanganate + sugar or potassium permanganate + glycerin (incompatibilty)

gelatinization

an incompatibility that results in the formation of gel

gelatinization

acacia + ferric salts, collodion + phenol (incompatibility)

Cementation

it involves the formation of cake or cement in the bottom of the container

Cementation

Acacia + bismuth salts (incompatibility)

polymerization

it involves the formation of polymers or large molecules

Polymerization

Dextrose —> 5-hydroxymethylfurfural derivative (incompatibility)

Precipitation

Calcium hydroxide (Ca(OH)₂ + CO₂ → CaCO₃↓ + H₂O) (incompatibility)

Evolution of gas/ Effervescence

is desired to mask salty and bitter-tasting drugs

(ELIA)

Esters (local anesthetics)

Lactams (penicillin, cephalosporins)

Amides (local anesthetics)

Imines (benzodiazepines, barbiturates)

4 susceptible groups of hydrolysis

Solvolysis

This involve the degradation of the drug or excipients through reaction with the solvents other than water

(Active form - for morning sickness; inactive form - teratogenic) RACEMIZATION

Thalidomide active and inactive form (incompatibility)

(Active form - NSAID; Inactive - Hepatotoxic)

Naproxen active and inactive form (incompatibility)

Therapeutic Incompatibility

undesirable pharmacological interaction between two or more ingredients.

Improper Doses

Synergistic and Antagonistic combination

Wrong Drug

Contraindicated drug

Formation of toxic compounds

Reduction or Delay in therapeutic Effectiveness

Manifestations of Therapeutic Incompatibility

Drug interaction

A situation in which the effects of one drug are altered by prior or concurrent administration of another drug, of food, of laboratory test, presence of disease and influence of environmental chemicals and smoking

Precipitant

component of DI which initiates the interaction

Object

component which is affected in the interaction

Multiple pharmacological effects

Multiple prescribers

Use of nonprescription drugs

patient noncompliance

Drug abuse

Factors leading to DI (5)

Age

Genetic factors

Disease states

Renal function

Hepatic function

patient variables leading to DI’s

DRUG-DRUG, DRUG-FOOD, DRUG-LAB

3 classifications of DI

a. Pharmaceutic Interaction

b. Pharmacokinetic Interaction

c. Pharmacodynamic Interaction

3 interactions DRUG-DRUG

Pharmaceutic interaction

Caused by a chemical or physical incompatibility when two or more drugs are mixed together. Occurs when drugs are mixed inappropriately in syringes or infusion fluids prior to administration

precipitate

Phenytoin Na will _________ in acidic pH

epinephrine

Aminophylline (basic pH) should not be mixed with_________ which decomposes at alkaline pH

pharmacokinetic interactions

“What the body does to the drug?” are interactions in which the precipitant alters the ADME of the object drug. Accompanied by a change in plasma concentration of the object

sig: drug metabolism

least: drug distribution

most significant and least significant pharmacokinetic interactions

Alteration in ADME

Manifestation in pharmacokinetic interactions

Physiologic absorption

Rate and extent of disappearance of drug from the site of administration

Pharmacokinetic absorption

Rate and extent of drug entry into the systemic circulation

drug absorption

Combining one drug with another drug, or with food, can cause interactions that increase or decrease _________

1. Alteration of gastric pH

2. Complexation

3. Adsorption

4. Alteration of gastric emptying time

5. Alteration of gastrointestinal metabolism

6. Alteration of gastrointestinal flora

mechanisms leading to alteration in absorption (6)

alteration of gastric pH

A drug to be absorbed must be nonionized and lipophilic, an acidic drug is best absorbed in the small intestine.

alteration in gastric pH

what alteration is Ketoconazole + Antacids

alteration in gastric pH

what alteration is Bisacodyl + antacids

Alteration of gastric pH

what alteration is ASA + Caffeine

complexation

involves the formation of complexes which are insoluble and large compounds that are difficult to absorb

complexation

Tetracyclines + metals, Fluroquinolones + metals

Adsorption

adsorbents usually bind with substance concurrently administered with them, they also lead to the formation of large compounds that are difficult to absorb.

Adsorption

Cholestyramine + Vitamin K

adsorption

Colestipol + warfarin

Adsorption

penicillamine + metals

Gastric emptying time (GET)

refers to the time for the stomach to empty its contents and be transported into the intestines. affects the rate, but not the extent of absorption

Alteration of GET

• Cathartics + Antacid

• Metoclopramide + Antiinfectives

• Atropine + Antacid

• Atropine + Antifungals

Alteration in the GI flora

Changes in the microbial flora of the gastrointestinal tract may affect the metabolism of some drug

Alteration of GI flora

Anticoagulants + Antibiotics

• Anticoagulants + Digoxin

• OCP + Antibiotics

Alteration of Gastric Emptying Time (GET)

mechanism of cathartics and antibiotics

reduce absorption of antibiotics

Effect of cathartics and antibiotics

cathartics (precipitant), antibiotics (object)

precipitant and object; cathartics and antibiotics