PHARMACOLOGY LABORATORY: INCOMPATIBILITY

INCOMPATIBILTY 2. Synergistic Effect

 Interactions between two substances which lead to o Two or more drugs, with or without the same overt
changes in chemical, physical, therapeutic properties of the effect are used together to yield a combined effect that
pharmaceutical dosage form has an outcome greater than the sum of the single-
drugs active components alone
Types of Incompatibility 3. Potentiation Effect
1. Therapeutic o Describes a synergistic effect
2. Physical o Drug interaction that is made greater by the presence
3. Chemical of the second drug
4. Mechanical 4. Antagonistic
o Reactions have opposite effect of synergism and
THERAPEUTIC INCOMPATIBILITY result in a combined effect that is less than either
 Modification of the therapeutic effect of one drug by prior active component alone
concomitant administration of another
 Drug interactions PHYSICAL INCOMPATIBILITY
 interaction between two or more substances which lead to
change in color, odor, taste, viscosity and morphology
Mechanisms  also called pharmaceutical incompatibilities

Pharmacokinetics Manifestations of Physical Incompatibility

 Involve the effects of a drug on anther from the point of view 1. Insolubility
that includes absorption, distribution, metabolism o Insolubility of prescribed agent in vehicle
o Factors that affect solubility:
Interactions  Change in pH
1. Altered GIT Absorption  Milling
a. Altered pH  Chemical Reaction
b. Altered bacterial flora  Complex Formation
c. Formation of drug chelates or complexes  Co-solvent
d. Drug induced mucosal damage altered GIT motility o Any change in previous factors may lead to precipitation
2. Displaced protein binding of drugs and change in their properties
o Depends on the affinity of the drug to plasma protein 2. Immiscibility
o Most likely bond drugs is capable to displace others o Immiscibility of two or more liquids
o Free drug is increased by displacement by another o Appears clearly in emulsions, creams, lotion, some type
drug with higher affinity of ointments
3. Altered metabolism o Separation in two phases is noticed in this
o Enzyme Induction pharmaceutical dosage forms
o Enzyme Inhibition o Storage must be in room temperatures to prevent
o First-pass Metabolism separation
4. Altered renal excretion o Factors that lead to immiscibility:
o Inhibition of renal tubular secretion  Incomplete mixing
o Alteration of urine flow and pH  Addition of surfactant in:
 Unsuitable concentration
Pharmacodynamics  False time of addition
 Related to the pharmacological activity on the interacting  Unsuitable for type of immersion
drugs  Presence of microorganisms
 Synergism  Temperature
 Antagonism 3. Liquefaction
 Altered Cellular Transport o Liquefaction of solids in mixed and dry state (Eutexia)
 Effect in the receptor site o Conversion to a liquid state after two solid substances
are mixed together
Interaction
 Alteration of the drug action without change in its serum CHEMICAL INCOMPATIBILITY
concentration by pharmacokinetic factors  Reaction between two or more substances which lead to the
change in chemical properties of pharmaceutical dosage
1. Additive Effect form
o Two or more drugs having the same effect are
combined and the result is the sum of the individual Types Of Chemical Changes
effects relative to the dosage used 1. Oxidation
o May be beneficial or harmful  Loss of electron or gain of oxygen

Apostol, Balibalos, Agao-Agao, Era, Gafate, Aguirre, Comenta, Brillantes, Genterola

PHARMACOLOGY LABORATORY: INCOMPATIBILITY

 Auto-oxidation: 7. Combination
o Reaction of oxygen with oxygen of air which occur  Takes place when pharmaceutical dosage form contain
spontaneously without other factors substances with different charges.
 Pre-oxidants:
o Are substances that catalyze oxidation process 8. Formation of insoluble complexes
 Chemical group which undergo oxidation;
o Phenolic compounds
o Catechol Derivatives MECHANICAL INCOMPATIBILITY
o Some of the Antibiotics  Occurs when physical barrier between species prevent
o Oils: fixed/ volatile fertilization
o Vitamins
 Factors that lead to oxidation:
o Presence of O2
o Light (photo-chemical rxns)
o Temperatures (inc temp inc speed of oxidation rxn)
o pH
o Pharmaceutical dosage form
o Presence of pre-oxidants as metals and peroxides
o Type of solvent used
o Presence of unsaturated bonds

2. Hydrolysis
 Chemical reaction which water is used to breakdown a
compound
 Achieved by breaking the covalent bond in the compound
by inserting water molecule across the bond
 Chemical groups that undergo Hydrolysis:
o Esters
o Amides
o Nitriles
 Factors that induce Hydrolysis
o Presence of water
o pH
o high temperature
 Types of Hydrolysis
o Ionic hydrolysis
o Molecular Hydrolysis

3. Polymerization
 Small repeating units called monomers are bonded to form
a long chain polymer

4. Isomerization
 Conversion of drug to its isomers
 Identical molecular formula
 Different arrangements of atoms
 Types:
o Optical isomerization: conversion of an optical active
drug into non active
o Geometric isomerization: expressed by cis or trans

5. De-carboxylation
 Chemical reaction that removes a carboxyl group and
releases carbon dioxide

6. Absorption of CO2

Apostol, Balibalos, Agao-Agao, Era, Gafate, Aguirre, Comenta, Brillantes, Genterola