INCOMPATIBILITY

INCOMPATIBILITY IS DEFINED AS:

 It refers to problems which arise during the compounding and dispensing of prescriptions
or during drug administration
 It is a result of prescribing together substances that adversely affect the appearance or
elegance, safety or therapeutic efficacy of the product
 It is a result of prescribing together substances that adversely affect the appearance or
elegance, safety or therapeutic efficacy of the product.
Importance of checking incompatibilities
 Develop Good Formulation (no discoloration, free from grittiness, different colors or melted
suppositories are avoided)
 (Dispense) Develop quality, safe and effective medicines (must come up with a good
production)
 Save time, material and money
DIFFERENT TYPES OF INCOMPATIBILITIES: (physical, chemical, therapeutic)
 PHYSICAL- A condition arising in the prescription due to
conflicting physical properties of drugs.
PHYSICAL INCOMPATIBILITIES (A condition arising in the prescription due to conflicting
physical properties of drugs) (no other product form)
1. INSOLUBILITY- It is the inability of a solid material to dissolve in a particular solvent
system
o It usually happens between solids and liquids. (different solvent system)
o It is the inability of a solid material to dissolve in a particular solvent system
o Examples:
 Camphor + Water
Camphor is insoluble in water
 It can be corrected by changing the solvent system,
instead of water use alcohol. (because camphor is soluble to
alcohol)
 Gum + Alcohol
Gum is insoluble in alcohol. (gum such as acacia gum)
 It can be corrected by changing the solvent system,
instead of alcohol use water.
2. IMMISCIBILITY- a condition wherein two or more liquids fail to dissolve or mix with one
another
o It usually happens between two liquids.
o It is a condition wherein two or more liquids fail to dissolve or mix with one
another.
o Example:
 Oil + Water
 Oil and water are immiscible with one another.
So instead of forming a solution, you can change the dosage form
[solution to emulsion] and add a therapeutically inactive ingredient
[emulsifying agent].
3. PRECIPITATION- It involves the separation of a solid by physical causes but no new
product is being formed. (SEPARATION OF A SOLID)
o It involves the separation of a solid by physical cause but no new product is
being formed.
o It is caused by the following:
 Salting-Out
 A process where solute which was previously dissolved in a system
is now being thrown out of the solution; when concentrated solution of
electrolytes are mixed with a solution of nonelectrolytes, there will be a
competition for water and the electrolytes will be left out without water and
comes out from the solution.
 Change of Temperature
 Change of pH
Examples:
Camphor + Alcohol + Water are mixed together there will be a precipitation of
camphor (camphor is a volatile oil)
There will be a precipitation of camphor because of a greater attraction of water
to alcohol compared to camphor.
Gum + Water + Alcohol are mixed together there will be a precipitation of gum.
There will be a precipitation of gum because of a greater attraction of water to
alcohol compared to gum.
Aromatic water + Salt will result in the precipitation of volatile oil.
The volatile oil will be left out with water because of the stronger attraction
between salt and water.
4. LOSS OF WATER/DEHYDRATION- A significant manifestation with liquid
preparations.
DEHYDRATION will cause an increase in its potency/concentration
o The probable effect of loss of water in the ff preparation:
A. Ointment (oily in nature): Crumble/sandy  dry ointment  base is
lessen
B. Gel: Syneresis (Contraction of a gel accompanied by the separation of the
liquid part)
C. Emulsion: Cracking or Swelling
o Example:
 Emulsions o/w type due to loss of water will result to phase inversion, so
from o/w type it will become w/o type.
 Solutions and suspensions upon dehydration will lead to increased potency
[concentrated form].
5. LIQUEFACTION- It is the transformation of a solid into liquid.
o It is caused by the following:
 Deliquescence- A condition referring to absorption of moisture to
form water of hydration leading to gradual dissolution and
liquefaction.
Example: Sodium chloride
 Efflorescence- A condition referring to the release of water of
crystallization and leads to the dissolution of the crystal
Example: Alum (tawas), Ferrous sulfate, Citric acid, Atropine sulfate
  Eutexia- A condition which refers to the depression or lowering in
the melting point of two solids that come in contact with each
another
Examples: Camphor, Menthol, Thymol, Phenol, Ibuprofen,
Acetophenidine
6. POLYMORPHISM- It refers to the ability to exist in different crystalline or physical
states
o Examples:

 Cocoa butter having alpha and beta forms. Beta form is more
stable.
 Chloramphenicol having A, B, and C forms. B form is therapeutically
active.
CHEMICAL- A condition arising in the prescription due to chemical reactions that change the
original composition of the substance. (new product form)
1. VAPORIZATION: Liberation of the active ingredient
Example: (NITROGLYCERIN  sensitive when removed to the container:
MONDAY’S DISEASE) “Monday disease”: Industrial workers who are exposed
to nitrates during the work week develop a tolerance over the course of the
week. No exposure during weekends leads to loss of tolerance. Reexposure
on Monday causes dizziness, tachycardia, and headache.
2. REDUCTION- Also known as “hydrogenation” reaction.
o It involves the gain of electrons.
o It usually occurs with metallic salts.
o Example:

 Ag[+1]NO3 (silver nitrate) when reduced will be converted to

Ag[0] metallic silver which will produce a silvery mirror image at the walls of
the container. *A reaction applied in Tollen’s test, a test for aldehydes.
3. OXIDATION
o Also known as “dehydrogenation” reaction.
o It involves the loss of electrons.
o It is triggered by the presence of light and oxygen.
o It is usually manifested by a change in color.
o Examples:
 Ascorbic acid is originally white in color but when oxidized it
turned yellow or straw-colored.
 Epinephrine is yellow but once oxidized becomes pink.
Oxidation It is triggered by the presence of light and oxygen. It is usually
manifested by a change in color.
o FACTORS that leads to oxidation:
 Presence of oxygen
 Light: photo chemical reaction; chemical reaction in the presence
of light
 Temperature: Elevated temperature which accelerates oxidation
 pH: Any change in PH affect drug stability and may accelerate
oxidation reaction
4. Hydrolysis- It involves the decomposition or the breakdown of a substance in
the presence of water.
o Example:
  ASA + Water  Acetic acid [vinegar-like odor] + Salicylic acid
 Lactams >>> esters >> amides
5. Precipitation- It involves the separation of a solid and accompanied by the
formation of a new substance.
o Example:

 Calcium hydroxide upon long standing will have a chance to

interact with carbon dioxide in the atmosphere and this will lead to the
formation of calcium carbonate precipitates.
6. Photolysis- “Photo” means “light”; It refers to the decomposition of a
substance upon exposure to sunlight
Examples:
 Cisplatin (cover in foil or turn off lights) *These drugs should be stored in light-resistant
 Amphotericin B containers [>95% UV light].
 Adriamycin
7. Racemization- It is the conversion of the optically active compounds to
optically inactive compounds.
o It usually involves racemic mixtures – levorotatory and dextrorotatory
forms.
o *Which is more therapeutically active L or D form? Levo, except
dextromethorphan
8. Explosive combination- It usually happens when mixing oxidizing and
reducing agents with the aid of friction/pressure.
o Examples:

KMnO4 (Potassium permanganate) + Sugar  explosion

KMnO4 (Potassium permanganate) + Glycerin  explosion

9. Gelatinization- It involves the formation of gels.

o Example:

Acacia + ferric salts  gels

Colloidon + phenol  gels
10. Cementation- It involves the formation of cakes or cements at the bottom of
the container. (seen in suspension preparations must be shake well)
o Example:

Acacia + bismuth salts  cement

11. Polymerization- It involves the formation of polymers [large molecules]
o Example:

Dextrose [clear] but when autoclaved will be converted to 5-

hydroxymethylfurfural derivative [straw-colored].
THERAPEUTIC- A condition arising in the prescription due to conflicting activities of drugs.
THERAPEUTIC INCOMPATIBILITY- A condition arising from conflicting property in the
actions of drugs, it may also result from the doses not intended by the doctor.
Examples:
 Drug Interactions
  Adverse Drug Reactions (A,B,C,D,E,F)
Methods of Correcting Incompatibilities:
Modify the order of mixing
Change in the kind or concentration of solvent
Change the form of ingredient (such as changing to emulsion)
Adjustment of the volume of the prescription
Addition of therapeutically inactive substance/s (excipients such as emulsifying agent)
Omission of an ingredient of little or no therapeutic value
Change of dosage form
Dispensing separately
Compounding by special technique
Proper storage
 In Vitro incompatibilities- Includes physical and chemical incompatibilities. What happens to
bottles drugs that are compounded and dispensed? (We are after the product)
 In Vivo incompatibilities- Includes therapeutic incompatibilities. What happens when as drug is
already administered? (what is the effect of the drug once administered to the patient)
Analysis of Incompatibility:
• How is the incompatibility manifested? (such as sedimentation, precipitation, etc)
• Which of the ingredient/s is/are causing the incompatibility?
• What is the type of incompatibility present?
• How can it be corrected?

Module 4: Different Types of Medication Incompatibilities

M4-Lesson 1: Physical Incompatibilities

Physical Incompatibility is that form of disagreement depending chiefly on the question of

relative solubility, which is evidenced by the failure of the ingredients to combine in such a way as
to make a satisfactory product. Or simply, we may define it as that form of disagreement in
prescriptions which do not involve any chemical reaction.
The diagram below shows the different physical incompatibilities.

**Watch video**
 M4-Lesson 1.1: Remedies for Physical Incompatibilities

Physical incompatibilities may be remedied by any one of the following as the case may be:
1. Omission of an unimportant ingredient of little therapeutic value.
Rx
Tr. of Iodine ….....................2cc
Muc. Of acacia …................4cc
Alcohol …...........................10cc
M.S.A
Sig. As directed.
Intervention:
A disagreeable looking preparation results, due to the precipitation of acacia by the alcohol. The
acacia if left out will produce a nice preparation.
 
2. Dispensing the ingredients separately.
Rx
Phenylsalicylate… …....................ii oz
Acetylsalicylic acid ........................i oz
Strychnine sulfate…....................1/4 gr
M. ft. cap. No. 24
Intervention:
With the exception of strychnine sulfate the two other ingredients are sources of trouble. When
mixed together will produce either a wet mass or a liquid. With the consent of the physician the
phenylsalicylate may be dispensed in a separate capsule and the instruction changed accordingly.
Or if 1 grain of kaolin is triturated with acetyl salicylic acid then the strychnine sulfate and
phenylsalicylate added in the the order named, the product will be stable for at least two weeks.
Gentle trituration must be used throughout and avoid tight packing of the contents of the capsules.
Besides kaolin any other absorbent powder like starch glycyrrhiza, or magnesium oxide may be
used, but in the case of magnesium oxide the consent of the physician should be secured
because of its therapeutic value.
 
3. Addition of an inert ingredient to correct the difficulty.
Rx
Tr. Cannabis Ind. /aa …........................i foz
Tr. auranti Aurora/Tr. Rhei .........................i foz
M.
Sig. ½ tsp. At night.
Intervention:
The above physical incompatibility is caused by mixing highly alcoholic resinous tincture of
cannabis with tincture of lower alcoholic strength, resulting in the precipitation of the resinous
matter of cannabis.
In such case, the addition of an equal volume of honey to the highly alcoholic liquid before mixing
with lower alcoholic or even aqueous liquid will help in satisfactory suspension of the resin. This
may also be applied, when tr. of asafaetida, guaiac, lupulin, myrrh and similar substances are to
be mixed with aqueous liquid. The separation in bulk of the resinous matter may also be
prevented by addition of other protective agents like syrup or glycerin.
 
4. Alteration in the solvents used (substituting alcohol or glycerin for water or vice versa).
Rx
Potassium Bromide/ aa ..................................v oz
Chloral hydrate / Aromatic Elixir ..........................iv foz
M. ft. sol.
Sig. One tsp. At bedtime.
Intervention:
This physical incompatibility is due to the selective preference of the potassium bromide on the
water present in the elixir and chloral to that of the alcohol. When recently compounded the
solution is clear, but later on turbidity develops and ultimately two layers are formed. The lower
layer contains all the potassium bromide and water with portion of the alcohol while the upper
layer contains all the chloral hydrate and the remainder of the alcohol. The danger is that the
patient may take an over dose of chloral.
This may be remedied by diluting the elixir with an equal volume of water; thus, the prescription
may be doubled in bulk by farther addition of water and the dose is corresponding increased. Or
the aromatic elixir may be replaced by an aromatic water, or by one of the elixirs of the National
Formulary of low alcoholic strength.
Whichever procedure is adopted, the physician should be notified and proper notations should be
made upon the original prescription to insure uniformity in case of refill.
 
5. Emulsification or suspension.
Rx
Olei Morrhuae …..................................ii foz
Syrupi ..................................................iv foz
Aquae Anisi ..........................................ii foz
M.
Sig. Tsp. t.i.d
Intervention:
There will be two layers formed, the oil forming the upper layer. The addition of some emulsifying
agent will improve the preparation. The general procedure for the preparation of emulsion
(Continental, English or a combination of the two) should be followed and provide with a “shake
well” label. To be placed in a wide-mouth bottle preferably amber-colored.
 
6. Changing the order of mixing the ingredients.
Rx
Cod Liver Oil ….................................15cc
Acacia ................................................4 cc
Syr. Of Tolu …...................................15cc
Dist. Water, qs ...................................60cc
M.
Sig. Tsp. t.i.d.
Intervention:
If the oil is emulsified and then the borax previously dissolved in water is added, there will be
formation of a tough solid mass, but if borax is dissolved in the syrup with a little water and then
added to the emulsion, the formation of tough mass is prevented. The sugar prevents the
gelatinizing effect of the borax of the acacia.
 
7. Changing the bulk of the preparation.
Rx
Potassium Bromide …..................v oz
Peppermint water .........................i foz
M.ft. Sol.
Sig. Tsp. At bedtime.
Intervention:
The oil present in the peppermint water will be thrown out of solution and will float on the surface.
This is due to the salting out action of the Potassium bromide. This may be remedied by filtering or
by substituting ½ of the peppermint water with distilled water. The bulk may also be doubled by
addition of an equal volume of water, and with the permission of the physician the dose is also
increased accordingly.
 
8. Use of a different form of the same ingredient.
Rx
Cocaine Muriate ….....................x gr
Liquid Petrolatum, qs ….............i foz
M.
Sig. Use as directed.
Intervention:
Cocaine muriate is insoluble in the liquid petrolatum. With the permission of the physician, cocaine
may be substituted and a clear solution will be produced.
In cases where alkaloidal salts are to be dissolved in liquid petrolatum or mineral oils. The
substitutions of the free alkaloid, prevent the incompatibility, since the free alkaloid is soluble while
alkaloidal salts are not.
 
9.  Addition of stiffening agents as in ointments and suppositories.
Rx
Phenol ..........................................xx gr
Cacao Butter ................................iii oz
M. ft. supp. #x
Sig. One at bedtime.
Intervention:
Phenol, salol, or chloral hydrate when mixed with cacao butter produces a lowering in the melting
point of the cacao butter and the resulting suppositories would be too soft. In this case, the
addition of some hardening agent, like wax or stearic acid is indicated. Care should be taken
however that the resulting melting point should not exceed 37°C, that is the melting point must
remain approximately 1°C below body temperature.
 
10. The addition of an ingredient which promotes solubility.
Rx
Iodi …..............................v gr
Adipis Lanae ...................i oz
Petrolati, qs ad. ................i oz
M. ft. Unguentum
Intervention:
It is practically impossible to reduce iodine to a state of subdivision sufficiently fine to permit its
satisfactory incorporation into an ointment. However, it is easily soluble in a concentrated solution
of potassium iodide, and the resultant solution can then be taken up in an absorption base. In this
case a solution of 10 grains potassium iodide in 15 minims of water can be used to dissolve the
iodine; the product then being taken up by the wool fat and incorporated into petrolatum.

M4-Lesson 2: Chemical Incompatibilities

Whenever the ingredients in the prescription undergo chemical reaction whereby their original
composition is altered, chemical incompatibility is said to take place. The diagram below shows
the different chemical incompatibilities.
 M4- Lesson
2.1: Remedies for Chemical Incompatibilities

Chemical incompatibilities may be remedied by any of the following:

1. Prevent the precipitation by the addition of glycerin, syrup or honey to the incompatible
ingredients before mixing, as in the following prescription.
Rx
Codeine Sulfate …......................................0.13g
Aromatic syrup of eriodyctiol, qs …..............30 cc
M. ft. solution
Intervention:
When prepared as it is, slight turbidity is developed, due partly to the separation of the resinous
matter from the aromatic syrup, when the acid-reacting codeine salt is dissolved therein, and also
due to the formation of codeine tannate. However, clear solution will be obtained when the
codeine salt is triturated with a vehicle made up of an equal volume of glycerin and aromatic syrup
of eriodyctiol.
 
2. If the precipitate is harmless, suspend and provide the container with a “shake well”
label, as in the
Rx
Tr. Myrrh .......................................ii foz
Morphine acetate...........................ii gr
Tannic acid….................................ss oz
Ginger syrup.. ...............................iss foz
M. ft. sol.
Sig. Tsp. t.i.d.
Intervention:
The resinous matter of the tincture will be precipitated by the syrup (physical). By adding the
tincture to the syrup in small portions and shaking well after each addition, the resin comes down
in a form in which it can be more readily suspended in the liquid. Tannic acid combines with
morphine to form a compound insoluble in water. On standing the precipitate may be converted
into masses, which will render an even dosage difficult.
However, by adding about 10cc of honey directly to the tincture in place of much syrup, it will help
to keep the precipitation matter finely divided and suspended.
 
3. Dilute before mixing.
Rx
Iodine …..............................2.5 g
Alcohol …............................25 ml
Oil of Turpentine, qs …........50ml
M. ft. sol.
Sig. Apply as directed.
Intervention:
If iodine is added directly to the oil of turpentine a violent reaction takes place, much heat is
evolved that the mixture may even catch fire. However, if the iodine is first diluted by dissolving in
alcohol and then added gradually to the oil of turpentine, the reaction will be very much moderated
although some heat may be developed. The mixing is preferably done in an open container.
 
4. When chemical incompatibility is dangerous or undesirable the physician should be
notified and make arrangement for a practical solution, like omission or substitution:
a) Omission:
Rx
Quinine Sulfate …..........................2 g
Dilute Sulfuric Acid …...................2ml
Sodium acetate ...............................4g
Syrup …..........................................30ml
Dist. Water, qs ................................120ml
M.S.A
Sig. Tsp. t.i.d.
If the quinine sulfate is dissolved by the use of sulfuric acid and mixed with the solution of sodium
acetate, a bulky white precipitate of quinine acetate will be formed. The sodium acetate is also
partly converted to sodium sulfate and acetic acid. However, if the acid is omitted a fine
suspension of quinine sulfate is produced, this should be provided with a “shake well” label.
b) Substitutes:
Rx
Zinc sulfate…...............................ss gr
Sodium borate / aa ......................iv gr
Boric acid/ Rose water, qs ......i foz
M. ft. collyrium
This prescription when first compounded is clear, but sooner or later, there may occur a
precipitation of the slightly soluble basic zinc borate, which is objectionable for eye application. By
replacing sodium borate with boric acid, precipitation will be avoided.
 
Note: In a survey conducted in the different drugstores in the United States, the following ten
individual ingredients arranged in the order of their frequency, were found responsible for most of
the incompatibilities in prescription.

1. Distilled water
2. Sodium bicarbonate
3. Acetylsalicylic acid
4. Liquid petrolatum
5. Sodium phenobarbital
6. Compound pepsin elixir
7. Sodium salicylate
8. Aminopyrine
9. Syrup of Wild Cherry
10. Glycerin

Therefore, greater care in compounding should be observed any of the above ingredients are
present in a prescription.

M4-Lesson 3: Therapeutic Incompatibilities

Therapeutic Incompatibility is that form of disagreement whereby ingredients of antagonistic

medicinal activity are prescribed together. It includes other changes which take place after a drug
is administered. Below is a diagram showing the different types of therapeutic incompatibility.

Therapeutic incompatibility is not always undesirable. Where an agent affects several organs,
another agent may be employed with it that modifies or counteracts its effect upon one or more of
these parts and leaves its action on the others more or less uninfluenced. When an agent has two
or more different actions, another agent may be employed with it that will modify or counteract one
or more of these effects without materially interfering with its other action.
Therapeutic incompatibility, which occurs when an undesirable pharmacological reaction occurs
within the patient as a result of two or more incompatible medications concurrently. These
medications do not necessarily have to be given via the same route. It is imperative that the
pharmacy be aware of ALL medications, dietary supplements, and over the counter medications
that a patient has been taking in order to prevent known therapeutic incompatibilities.
To prevent incompatibilities, it is important to consider all the ways in which medications may
interact outside of or inside the body. If you must mix a medication, always follow manufacturer’s
instructions as to the correct volume and type of diluent; which solutions it may be added to for
"piggy back" administration; and what flush solutions must be used in between administrations to
prevent events like precipitation within the patient’s access device (for example, never
administering phenytoin into an intravenous line containing dextrose, or never allowing
amphotericin B to come into contact with saline solutions).
Other issues to consider are the presences of electrolytes (e.g. potassium chloride) mixing into
continuous infusions, such as in a piggyback situation. If mixing medications in a syringe for bolus
administration (IV pushes), assure that they are compatible when combined in a syringe. If
consulting a drug reference is not helpful, contact the pharmacy, which has access to additional
compatibility information.
Be on alert for medications with a known history of frequent incompatibilities when they come into
contact with other drugs. Among the drugs most often incriminated in incompatibilities are
furosemide, phenytoin, heparin, midazolam, and diazepam when used in IV admixtures.

I. PHARMACOKINETIC INTERACTIONS
Pharmacokinetics
- processes of absorption, distribution, metabolism & excretion (ADME) of drugs
- "what the body does to the drug"
- ADME is altered by the precipitant drug
Manifestations of Pharmacokinetic interactions:

Alterations in Absorption (A) (majority of the drug orally administered required to be dissolved and
absorbed. The gastric pH range in 2.5 and 3, so therefore drugs are able to increase gastric pH)
a drug to be absorbed must be nonionized and lipophilic
Acidic drug is best absorbed in the stomach; Basic drug is best absorbed in the intestine

 Alteration of pH
(those who increase gastric pH are antacid, anticholinergics, proton-pump inhibitors-PPIs, H2
antagonists/blockers. Increase gastric pH = decrease effect of some drugs)
⎯ Antacid + Bisacodyl: premature liberation of Bisacodyl (API; cannot be crushed) 
⎯ Antacid + Ketoconazole: Ketoconazole A (decrease effect)
⎯ Antacid + Salicylates: Salicylate A (decrease effect)

 Complex Formation/Complexation
-involves the formation of complexes which are insoluble form and large compounds that are
difficult to absorbed (no absorption = no or decreased effect)
Metal ions= calcium, magnesium, aluminum, iron  form complexes that are poorly absorbed
⎯ Tetracycline + Metal-containing drugs:
Tetracycline A
⎯ Fluoroquinolones + Metal-containing drugs: Fluoroquinolone A
⎯ Cholestyramine + Digoxin:  Digoxin A
⎯ Cholestyramine + Warfarin:  Warfarin A
⎯ Penicillamine + Metal-containing drugs:
 Penicillamine A)
⎯ Sucralfate + Levothyroxine: Thyroxine A

Gastric emptying time (GET) refers to the time for the stomach contents to be transported to the intestine.
(Motility disorder is a factor for absorption) Cathartics increased GET
 Decreased Gastric Emptying Rate ( GE Time) if low GET =increased motility =
decrease absorption
⎯ Atropine + Antacid ( antacid A)
Example: Atropine + Amphetamine

 Increased Gastric Emptying Rate ( GE Time) if high GET = decrease motility =

increase absorption
⎯ Nicotine + Antacid ( antacid A)

 Increased GI Motility
⎯ Cathartic + Any Drug ( drug A)
  Adsorption of the Drug
-adsorbents usually bind with substances concurrently administered with them
-leads to the formation of large compounds that are hard to absorbed
- can be beneficial if there is toxicity
⎯ Adsorbent + Any Drug ( drug A)
Examples:
Cholestyramine + Digoxin
Cholestyramine + Warfarin
Colestipol + Vitamin K
*cholestyramine and colestipol bind bile acid and prevent their absorption in the digestive tract but they
can also bind other drugs especially acidic drugs such as warfarin, Acetylsalicylic acid, sulfonamides,
phenytoin, ferocites. To correct cholestyramine and colestipol binding or what they do = administer the
medications preferably 4 hours layo/between the drugs combined to the said drugs
 Interruption of Enterohepatic Circulation

⎯ Antibiotics + OCP ( OCP A)

 Inhibition of GI Microbial Flora
- Changes in the GI flora of the gastrointestinal tract may affect the metabolism of some drugs
- Increase GI Flora = increase metabolism = decrease absorption
- Decrease GI Flora = decrease metabolism = increase absorption
- Antibiotics (decreased Gi flora because they target good and bad antibiotics) + Digoxin (increased
Digoxin A)= Decrease GI Flora = decrease metabolism = increase absorption = leads to toxicity
⎯ Erytromycin ⬇ bacterial in activation Digoxin
Alterations in Distribution (D)
- Distribution is a process by which a drug is delivered to body tissues and fluids
- The distribution of unabsorbed drug within the body depends on several factors (it could be
blood flow, solubility, or protein-binding). Protein binding = if high protein binding  lesser
efficacy; if lower/low protein binding  increase efficacy
- Main mechanism = Displacement
 Displacement from Protein Binding Sites
⎯ Warfarin + Phenylbutazone (Hemorrhage)
⎯ Glibenclamide + Phenylbutazone (Hypoglycemia)
⎯ OHA + ASA (Hypoglycemia)
⎯ Bilirubin + Salicylates (Kernicterus)
Alterations in Metabolism (M)
- Decrease GI Flora = decrease metabolism = increase absorption
-
Enzyme Inducers = decrease absorption = Enzyme Inhibitors = increase absorption = drug
therapeutic failure toxicity
 Carbamazepine Cimetidine
Phenobarbital Chloramphenicol
Phenytoin Clarithromycin
Rifampicin Disulfiram
Tolbutamide Erythromycin
Smoking Grapefruit juice
Chronic alcoholism Isoniazid
Estrogen Ketoconazole
Itraconazole
Metronidazole
Miconazole
Valproic acid
Acute alcoholism
Alterations in Excretion (E)
- Excretion refers to the elimination of drugs from the body
- For a drug to be excreted, it has to be in hydrophilic form and ionized form or else it will only be
reabsorbed

 Alteration of Urinary pH
⎯ ASA + NaHCO3  renal excretion of ASA
-Acidic drug is best excreted in a basic urine; basic drug is best excreted in a acidic urine

II. PHARMACODYNAMIC INTERACTIONS Pharmacodynamics

 explainthe mechanism of actions & pharmacologic effects of drugs
 "what the drug does to the body"
Additive Effects
 1+1=2
 response is equal to the combined effects of individual drugs
⎯ Alcohol + Barbiturates: sedation
⎯ Alcohol + Antihistamines: sedation
⎯ Alcohol + CNS Depressants: sedation
⎯ Alcohol + Chloral hydrate: sedation
⎯ Alcohol + Chlorpropamide:
hypoglycemic effects
⎯ Flecainide + Verapamil: negative inotropic & chronotropic effects
Synergistic Effect
 Synergism: 1+1>2
 response is greater than the combined effects of the individual drugs
⎯ Sulfamethoxazole + Trimethoprim (Bactericidal effect)

Potentiation
 0+1=2
 a drug with no inherent activity will enhance the effect of another drug
⎯ Amoxicillin + Clavulanic acid: 
Amoxicillin’s antibiotic effect)
⎯ Ampicillin + Sulbactam: Ampicillin’s
antibiotic effect
⎯ Piperacillin + Tazobactam: 
Piperacillin’s antibiotic effect
⎯ Levodopa + Carbidopa:  Levodopa’s
effect
Antagonism
 (1+1=0)
 drug inhibits the effect of the other
⎯ Phenoxybenzamine + Catecholamines: (management of pheochromocytoma)
⎯ Warfarin + Vitamin K: (antidote for Warfarin toxicity)
⎯ Heparin + Protamine SO4: (antidote for Heparin toxicity)
⎯ Opioids + Naloxone (antidote for opioid toxicity)
⎯ Benzodiazepine + Flumazenil: (antidote for Benzodiazepine toxicity)
⎯ Atropine + Physostigmine: (antidote for Atropine toxicity)
 ⎯ Procaine + Sulfonamides: (antagonism
of Sulfonamide’s antibacterial activity)

Other Pharmacodynamic Interactions

⎯ Aminoglycoside + Loop diuretic: 

nephrotoxicity & ototoxicity
⎯ Aminoglycoside + Neuromuscular blocker:
 muscle relaxation or paralysis
⎯ Diuretic + Neuromuscular blocker:
hypokalemia causing increased muscle relaxation or paralysis
⎯ Diuretic + Digitalis:  hypokalemia causing digitalis toxicity
⎯ Diuretic + Tetracycline: BUN levels
1. Prescription 1

Cod liver
oil Water
M.ft.sol.

Comment: Cod liver oil will not mixed with water.

 Manifestation: Immiscibility
 Ingredient/s: Cod liver oil and water
 Type: Physical
 Correction: Addition of therapeutically inactive ingredient like emulsifier. Change of dosage form from solution to emulsion.
2. Prescription 2

Thymol 1 part
Camphor 1
part M.ft.cap.

Comment: Both are eutectic compounds.

 Manifestation: Liquefaction
 Ingredient/s: Thymol and camphor
 Type: Physical
 Correction: Dispense separately [in separate capsules or by embedding] or Addition of therapeutically inactive ingredient
like starch [diluents].
3. Prescription 3
Lime water
Store above room temperature.

Comment: Exothermic solutions when stored above room temperature causes the separation of solid substances.

Constant opening of the container will allow entry of carbon dioxide which will react with the calcium hydroxide
causing the formation of insoluble carbonates.
Ca(OH)2 + CO2 → CaCO3 ppt + H2O

 Manifestation: Separation of solid

 Ingredient/s: Lime water
 Type: Physical
 Correction: Proper storage
4. Prescription 4
Sodium
Phenobarbital
Aluminum
hydroxide Water
M.ft.sol.

Comment: Sodium Phenobarbital forms precipitate with calcium, magnesium and aluminum.

 Manifestation: Precipitation [Al+3phenobarbital]

 Ingredient/s: Sodium Phenobarbital and aluminum hydroxide
 Type: Chemical
 Correction: Dispense separately
5. Prescription 5
Benzoic acid 0.5g
Water qs.ad. 100
mL M.ft.sol.

Comment: Solubility of benzoic acid to water is 0.4:100.

 Manifestation: Insolubility
 Ingredient/s: Benzoic acid and water
 Type: Physical
 Correction: Adjustment of the volume of the prescription. From 100 mL it should be adjusted to 125 mL, check for the dose.
 DIPSENSING AND MEDICATION SAFETY

Why do we need a care plan?  The purpose of the care plan is to organize all of the work agreed upon the practitioner
and the patient to achieve the cause of therapy. This required interventions to resolved drug therapy problems, to meet
these goals and to prevent new drug therapy problems developing. Thereby, optimizing the patient’s medication
experience.
PHARMACEUTICAL CARE PLAN-a written, individualized, comprehensive medication therapy plan based on clearly
therapeutic goals. A care plan is a systematic ongoing process of planning action and documentation.

CREATION OF A PATIENT CARE PLAN

 Resolve all existing drug therapy problems (such as ADR, SE)
 Achieve the goals of therapy intended for each active medical problem
 Prevent future drug therapy problems

PURPOSE, ACTIVITY AND RESPONSIBILITIES:

1. Establish goals of therapy

 Determine appropriate interventions to:

- Resolve drug therapy problems
- Achieve goals of therapy
- Prevent new problems
2. Schedule follow-up evaluations (encourage the patient to have an evaluation after taking the medication)

Development of Goals of Therapy: (informed also the patient about the goals of therapy)
1. Goals of therapy are established for each indication managed with drug therapy.
2. Desired goals of therapy are described in terms of the observable or measurable clinical and/or laboratory
parameters to be used to evaluate effectiveness and safety of drug therapy
3. Goals of therapy are mutually negotiated with the patient and other health care practitioners when appropriate.
4. Goals of therapy are realistic in relation to the patient's present and potential capabilities.
5. Goals of therapy include a time frame for achievement

ELEMENTS OF CARE PLAN

 Medical condition- list of diseases that the patient has
 Drugs related problem- state the drug therapy problems including the patient’s problem or condition, the drug
therapy involved and the correlation between the drugs and the patient conditions
 Goals of therapy- state the goals in future tense; goals should be realistic, measurable and observable, specific and
associated within the definite time frame
 Intervention- in collaboration with the patient, the practitioner develops and prioritizes a list of activities to
address the patient’s current needs
 Follow up plans- this is also an important element because it determines when the patient should return to follow
up and what will occur at the subsequent pc.

SAMPLE CARE PLAN

Patient: Juan Dela Cruz (a 75 year-old man, who underwent CABG in two months ago and started simvastatin 10 mg daily
for six weeks ago for dyslipidemia. Fasting cholesterol reveals 230 mg/dL and LDL is 141 mg/dL and HDL 45 mg/dL and the
triglycerides is 220 mg/dL (Increase LDL; Decrease HDL; Increase triglycerides)
Drug therapy problems: Simvastatin 10 mg
Medical Condition: Dyslipidemia  unfortunately, it is treated with adequate dose of lipid lowering agent (patient not
responsive to the dose of simvastatin 10 mg
Smoker/smoking (he continues smoking of 1.5 packs of cigarettes a day
Goals of Therapy: Decrease LDL (less than 100 mg/dL)  since the patient has CAD, the LDL goal is 100 mg/dL
Interventions: increase simvastatin 10 mg to 20 mg daily for 1 month (maximum dose for simvastatin is 80 mg); review
possible effects such as constipation, muscle weakness or rhabdomyolysis and monitor the liver because it could cause
liver injury
Follow up plan:
 Repeat Fasting, Lipid Profile (to check if the goal is achieved)
 Assess Adverse Drug Reaction (because the dose is increased)
 Smoking Cessation

Purpose of Follow up Evaluation:

 Positive/ Negative impact to the patient
 Uncover drug therapy problems
 Take appropriate action to address problems

Action taken for ff evaluation:

 Resolved- therapeutic goals achieved for acute condition (discontinue therapy)
  Stable- therapeutic goals achieved BUT continue same therapy for chronic diseases management
 Improved- progress is being made in achieving goals continue same therapy (more time is required)
 Partial improvement- progress is being made but minor adjustments in therapy are required to fully achieved the
therapeutic goals
 Unimproved- little or no progress has been but continue the same therapy to allow additional time for benefit to
be observed
 Worsened- decline in health is observed despite an adequate duration using the optimal drug (with this case,
modify the drug therapy  such as increase dose)
 Failure- therapeutic goals have not been achieved despite an adequate those and the duration of therapy (with
this case, discontinue the medications
 Expired- the patient dies while receiving the therapy

Example of Care Plan Documentation

Action taken for ff evaluation:

Pharmaceutical Care Patient Record
Dean Dong dantes is a 77 year old man and asian man with osteoarthritis is currently treated with celecoxib. He has been
diagnosed with hypertension and hyperlipidemia on blood tests. Both HTN and hyperlipidemia are treated with losartan
and simvastatin respectively

Patient Name: Dean Dong Dantes (patient’s identification) Gender: Male

Address: 123 GMA, Metro Manila Actual Weight: 140 lbs
Telephone: 8-7000 Age: 77 Ideal Height: 5’5’’
Insurance: n/a Allergies: Shellfish and Aspirin
Medical Condition: Hypertension, Hyperlipidemia
Tobacco/ Alcohol /Substance Use: smokes 1 pack of cigarette, occasionally drinking alcohol.

*allergies is immune-mediated reaction that often prelude future use of the medication except in rare cases in which the
benefit of using the drug outweighs the risks of reaction. While side effects may sometimes be self-limiting with continued
use or it may be successfully managed with adjustments in dose regimen or dosage administration (example: a drug taken
once daily causes drowsiness may be taken at bedtime)

Medication Record

- Each step in patient care process should be

documented.
- Documentation should take place on an
ongoing basis to provide an updated
record of the patient’s current and
changing needs.
- The document provides a means of
communication among health care
providers and is now required for
accreditation
 -Patient takes nabumetone 750 mg by mouth daily
-a stuff that should be recorded for medications that have been
discontinued and relevant clinical impressions or comments can also be
recorded
-The patient stop ibuprofen due to dyspepsia. For anti-hypertensive
regimen which was initiated because the patient is not responsive to the
nabumetone, the patient was initiated with hydrochlorothiazide 25 mg and
subsequently changed to triamterene and hydrochlorothiazide. Atenolol
was also given because only partial improvement in hypertension was
achieved with the diuretic activity.

ASSESSMENT, PLAN and FOLLOW-UP EVALUATION

-this section provides a record of the therapeutic intervention and patient’s responses to them. Information is documented
and events occur providing a flow chart of the patient’s progress to date the historical information contained in the chart is
important to incorporate in therapeutic decision-making