INCOMPATIBILITIES IN PRESCRIPTIONS
Definition
When two or
more ingredients of a prescription are
mixed together the undesired change that may take place in the physical,
chemical or therapeutic properties of the medicament is termed as incompatibility.
Classification
Incompatibilities are of three types:
1.
Therapeutic incompatibility
2.
Physical incompatibility
3.
Chemical incompatibility
THERAPEUTIC INCOMPATIBILITY
Usually
this incompatibility arises when one or more drugs produces response or
intensity different from that intended in the patients.
Classification
A)
Over doses
B)
Under doses
C)
Improper consumption by the patient
D)
Contra-indicated drugs
A) Over doses: This can be subgrouped as follows:
Excessive single dose
Sometimes
a single dose may become overdose depending on the health of the patient e.g. a
normal dose (taking body weight as 70 kg for an adult male) may be overdose for
a lowly built person. However it should not be more than 2 to 3 normal dose.
Remedy: The pharmacist
should consult the physician and clarify the dose.
e.g. 1 Rx
Atropine
sulphate 6 mg
Phenobarbital 360 mg
Make
capsules.
Label: One capsule
to be taken three times a day before meals.
Comments: In this prescription the doses of both atropine sulphate
and phenobarbital are 12 times the normal doses. The physician intended for 12
capsules to be dispensed but he has mistaken or may be it is an incomplete
prescription. Hence, before dispensing the pharmacist should consult the
physician again.
Correct prescription
Rx
Atropine
sulphate 6 mg
Phenobarbital 360 mg
Make
capsules. Supply 12 capsules.
Label: One capsule
to be taken three times a day before meals.
e.g. 2 Rx
Strychnine
sulphate 20 mg
Iron
and ammonium citrate 500 mg
Prepare capsules. Supply 12
capsules.
Label: One capsule to be taken three times a day after meals.
Comment: 10 times
overdose of strychnine hydrochloride than that of normal. The pharmacist should
consult the physician and obtain the permission to change the dose.
Corrected prescription
Strychnine
sulphate 2 mg
Iron
and ammonium citrate 500 mg
Prepare
capsules. Supply 12 capsules.
Label: One capsule
to be taken three times a day after meals.
Excessive daily dose
In
this case the daily dose of drug is exceeded .
e.g.1 Rx
Codeine
phosphate 15 mg
Ammonium
chloride 500 mg
Prepare capsules and supply 24
capsules.
Label: Two capsules to be taken every hour for cough.
Comment: The U.S.P. recommends that the prescribed dose should be
taken after every four hours and not every hour. Hence the physician should be
consulted.
Additive and synergistic combinations:
There are certain drugs
possessing similar pharmacological activity. If these drugs are combined
together, they may produce additive or
synergistic action. In such case advice of the physician is necessary.
e.g. Rx
Amphetamine
sulphate 20 mg
Ephedrine
sulphate 50 mg
Syrup
q.s. 100 ml
Let
a mixture be made
Label: Take 25 ml every four hours.
Comment: Both of the drugs are sympathetic stimulants and they are
prescribed in their full dose. The formulation will produce additive overdose
effect. Hence, The dose of individual drug should be reduced.
(B) Under dose In this
type of incompatibility, effect of one drug is lessen or antagonised by the
presence of another drug. This can be exemplified by combination of following
types of drugs:
1. Stimulants like nux-vomica, strychnine
sulphate, caffeine etc. with sedatives
like barbiturates, paraldehyde etc.
2. Sympathomimetic or adrenergic like ephedrine, nor-adrenaline with sympatholytic drugs like ergotamine.
3. Sympathetic stimulants like
methamphetamine with parasympathetic
stimulants like pilocarpine.
4. Purgatives like castor oil, liquid
paraffin etc with antidiarrheal agents
like bismuth carbonates.
5. Acidifiers like dilute hydrochloric acid
and alkalisers like sodium
bicarbonate, magnesium carbonate.
e.g. Rx
Aspirin 300 mg
Probenecid 500 mg
Prepare capsules.
Label: One capsule a day for gout.
Aspirin is an NSAID given to
reduce the pain and swelling in case of gout attack. Probenecid blocks the
active reabsorption of uric acid from the lumen of nephron, but salicylates
(aspirin) blocks this action of probenecid. Hence, both of the drugs are antagonistic
to each other, so its combination is therapeutically useless.
(C) Improper consumption by the patient:
In certain prescription some
special directions should be written. If the patients are nor advised the drugs
may not produce the desired action due to low bioavailability.
e.g. Rx
Tetracycline
hydrochloride 250 mg
Prepare
capsules. Supply 10 capsules.
Label: Take one capsule every six hourly.
Comments: Calcium present in milk inactivates the tetracycline,
hence a patient may not get any therapeutic effect if he/she takes the capsule
with milk.
Remedy: The pharmacist should advise the patient to take the
capsule with water and not with milk. The patient should not take antacid
containing calcium salts.
(D) Contra-indicated drugs
Certain
drugs should not be given in particular disease condition
e.g.
(i) corticosteroids
are contraindicated in patients with peptic ulcer.
(ii) Vasoconstrictors
are contraindicated in hypertensive patients
(iii)Some drugs should not be given in asthmatic
patients e.g. barbiturates, morphine etc.
(iv)If a person is allergic to a drug (e.g. penicillin
injection) then it should not be given to the patient.
(v) Certain
combination of drugs are contraindicate:
Rx
Sulphadiazine 0.25 g
Sulphamerazine 0.25 g
Ammonium
chloride 0.50 g
Prepare capsules
Label: Take two
capsules six hourly for cough.
Comment: In this
prescription ammonium chloride is a urinary acidifier and it could cause
deposition of sulphonamide crystals in the kidney.
PHYSICAL INCOMPATIBILITY
Usually, this is due to
immiscibility or insolubility. It can cause unsightly, non-uniform products
from which removal of an accurate dose is very difficult.
Classification:
(A) Immiscibility
(B) Insolubility
(C)Liquefaction
(A) Immiscibility
1) Oils are immiscible with water and hence combination of oily
drugs with water produces a product possessing two separate layers.
Remedy: This problem
can be overcome by emulsification or solubilization.
2) Care must be taken when concentrated hydroalcoholic solutions
of volatile oils such as spirits and
concentrated waters, are used as adjuncts (e.g. as flavouring agents) in
aqueous preparations. Large globules of oils may be separated.
Remedy: To prevent the formation of large globules, the
hydroalcoholic solution should either be gradually diluted with the vehicle
before admixture with the remaining ingredients or poured into the vehicle with
constant stirring.
3) Addition of high concentrations of electrolytes to mixture in
which the vehicle is a saturated aqueous solution of a volatile oil causes the oil
to separate and collect as a surface layer.
e.g. This happens
in Potassium Citrate Mixture B.P.C.
in which large quantity of soluble solids salts out the lemon oil.
Remedy: To
disperse the droplets evenly, quillaia tincture is added as a wetting agent.
(B) Insolubility
1) Liquid
preparations containing indiffusible solids such as chalk, aromatic chalk
powder, succinyl sulfathiazole and sulphadimidine (in mixtures) and calamine
and zinc oxide (in lotions) - a thickening agent is necessary to obtain a
uniform product from which uniform doses can be removed.
2) Some insoluble
powders such as sulphur and certain corticosteroids (hydrocortisone acetate) and antibiotics are difficult to wet with
water.
Remedy: Wetting
agents
e.g.
saponins for sulphur containing lotions
and
polysorbates in parenteral
suspensions of corticosteroids and antibiotics are used to distribute the
powder and prevent formation of a slowly dispersing, solid stabilised foam on
shaking.
3) When a resinous tincture is added to water the water
insoluble resin agglomerate forming indiffusible clots.
Remedy: This is prevented by slowly adding the undiluted dispersion
of protective colloid (Tragacanth
mucilage).
e.g. Lobelia & Stramonium
tincture which should be mixed with tragacanth mucilage and stirred constantly.
This will produce a stable preparation.
4) high concentrations of electrolytes cause cracking of soap
emulsions (ionic) by salting out the emulsifiers.
C) Liquefaction
When
certain low melting point solids are powdered together a liquid or soft mass is
produced due to lowering of the melting point of the mixture to below room
temperature. Thus an eutectic mixture
is formed
Any
two of the following exhibits this type of behaviour, camphor, menthol, phenol,
thymol and chloral hydrate, also sodium salicylate with phenazone.
e.g. Rx
Thymol 250 mg
Camphor 2 mg
Menthol 2 mg
Make
powder.
Comments: If these ingredients are triturated together, they will
form an eutectic mixture.
Method-I:
All the ingredients are triturated.
An eutectic mixture (liquid) will
be formed. The liquid is triturated with enough absorbent powder e.g. light
kaolin or light magnesium carbonate, to give a free flowing powder.
Method-II:
Each ingredient is triturated
separately with small amount of adsorbent or diluent and then these powders are
lightly mixed by tumbling action) and packed.
The diluent largely prevents
contact between the ingredients and adsorbs any liquid that may be produced.
e.g. Rx
Chloral hydrate 250 mg
Prepare
capsules. Supply 10 capsules.
Label: Take the capsules at night time.
Comment: Chloral hydrate is hygroscopic in nature. It will absorb moisture
and soften the hard gelatin capsule shells and the shape of the capsule may
change physically.
Remedy: An equal quantity of light magneisum oxide should be mixed
with chloral hydrate.
Other
adsorbents those may be used are kaolin, talc, starch etc.
e.g. Rx
Aminopyrine 0.3 g
Acetyl
salicylic acid 0.2 g
Codeine
sulphate 0.015 g
Belladonna
extract 0.010 g
Prepare
capsules.
Comment: In this prescription aminopyrine and acetyl salicylic acid
form eutectic mixture and wetting of
belladonna extract give green colour.
Remedy: Light magnesium oxide (approximately 65 mg) may be added.
The half quantity of magnesium oxide is mixed with aminopyrine and the other
half with acetyl salicylic acid separately. The two are mixed gently and then
other ingredients are added and mixed gently.