Dispensing RA 6675 – Generics Law

- Pharmacist’s function of TPD - September 13, 1988

o Taking prescription order - “An act to [PRE] promote, require, and
o Preparing the drugs acc to the ensure the drugs and medicines identified
instructions of a physician/dentist by their generic names – PDUA –
o Delivering it to the patient or client o production of an adequate supply,
with proper instructions o distribution,
Prescription o use, and
- Written order and instruction from a licensed o acceptance.”
prescriber to the pharmacist for the – UIA
o Use of drug product/s for a specific Incorrect prescription
pt 3 types of Rx based on general prescribing
o Identifies the medication/s to be - Erroneous Rx
dispensed - Violative Rx
o Accompanied by directions on its - Impossible Rx
proper use Erroneous Rx
Medication orders - Brand name precedes the generic name
- Requests for medications by a licensed - Generic name in parenthesis
prescriber - Brand name not in parenthesis
- Intended for use in the institutional setting
A.O. No. 90, s. 1990
Subject: Amendment to A.O. No. 62 s. 1989 RE:
Rules and Regulations to Implement Prescribing
Requirements
- “Permits the writing of the generic names of
more than one drug in one prescription form”
- A Rx form with more than one drug product
is no longer regarded as erroneous

Violative Rx
- Generic name is not written, legible and a
brand that is legible is written
- Brand name is indicated and instructions
such as “no substitution” that tend to
obstruct, hinder, or prevent generic
dispensing
Impossible Rx
Superscription - Only generic name is written but not legible
- Rx symbol meaning “take or give” - Generic name does not correspond to the
- Beginning of the direct order to fill the order brand name
and dispense the prescription - Both generic and brand names are not
Inscription legible
- Principal/most important part of the - Drug product required is not registered with
prescription FDA
- Name, dose per unit, quantity of each, and Record Books
dosage forms of the medicine/s or drugs - Poison book = 5 years
Subscription - Prescription book = 2
- Instructions to the pharmacist - Dangerous drugs book = 1
- Preparation of drugs which requires
compounding Two broad classification of medications
Signa - Prescription or Ethical Drugs
- Directions to the pt on how to use the - Non-prescription or OTC Drugs
medicine
- Repeat verbally and clearly to the pt
instructions on
o When to the take the medicines
o Precautions
o Simple instructions
Prescription or Ethical Drugs Regulated Drugs
- Dispensed upon written order of a validly- - Sleep-inducing sedatives
registered licensed physician/dentist/vet o Barbital
- For the mgt or tx of a condition or disease o Seco, pheno, amobarbital
1. All antibiotics except some ointments - Other drugs containing salt or derivative of a
2. All injectables (amp or vials) salt of barbituric acid
3. Cough syrups containing any amt of - Any salt, isomer, or salt of isomer of
narcotics (except DM) amphetamine
4. Vit products with > 10,000 U Vit A o Benzedrine or Dexedrine
5. Highly potent drugs for special medication o Any drug which produces a
(ex: steroids, digitoxin) pharmacologic effect similar to
6. Paregoric Elixir (in emergency cases, 1 dose amphetamine
may be dispensed without Rx) - Hypnotic drugs
7. All drugs bearing the Rx symbols on their o Methaqualone or any other
labels compound producing similar
Paregoric Elixir pharmacologic effects
- Camphorated tincture of opium Requirements in the disp & compounding of DD
- Tinctura opii camphorate - Prescribed in special Rx forms issued by DDB
- Medication known to be antidiarrheal, - Record them in the DD book
antitussive, and analgesic Pharmacist must
Non-Prescription or OTC Drugs - Check all required data
- Can be dispensed without written order of a o Opium license no. of the physician
validly-registered licensed o Professional license no.
physician/dentist/vet o Residence certificate of the buyer
- Prevention or symptomatic relief of minor or - Keep these DD in a locked cabinet
self-limiting ailments - Keep and file the original Rx
1. Multivit products of low dosage - Quarterly report of all transactions (copy of 2 to
2. Anti-TB drugs except injectables be submitted to the municipal health officer wihin
3. Cough syrup containing DM 15 d following last day of every quarter
4. Household remedies except paregoric
5. Simple analgesics (ASA, APAP 500 mg, The Dispensing Process
>600 mg requires Rx) Steps in processing of Rx order
Dangerous Drugs (List A Drugs) 1. Receive the prescription
Refer to: 1) Prohibited Drugs, 2) Regulated Drugs 2. Read and check/analyze the prescription
- Require a special Rx form 3. Number and date of the prescription
- Use is monitored by DDB 4. Prepare the label
Prohibited Drugs 5. Prepare/compound and package the drug
- Opium and its active components & product
derivatives: heroin & morphine 6. Recheck the label of the product vs. the Rx
- Cocaine leaf and its derivatives 7. Check the price of the product & inform buyer
o Cocaine alpha & beta Eucaine 8. Deliver the product
- Hallucinogenic drugs – mescaline, LSD, & 9. Provide pt counseling
others producing similar effects 10. Record and file the prescription
- Indian hemp & its derivatives Magistral Pharmacy
- All preparation made from any of the - Most important division of true pharmaceutical
foregoing practice
- Others with the physiological effects of a - Preparation or compounding & dispensing of
narcotic drug prescriptions extemporaneously or as the
Brown Mixture Tab. Morphine Sulfate H.T. occasion or physician’s needs may require
Brown Mixture Tab. Morphine Sulfate H.T. Processing of Rx order
Brown Mixture Liq. Morphine with AtropineTab - Enhances the image of pharmacist to both the
Codeine Sulfate H.T. Morphine Sulfate Amp. physician & the pt
Codeine Sulfate T.T. Morphine Sulfate Tab. - Reflects professional responsibilities
Demerol Amp. Sublimaze Inj.
Demerol Tab. Repifen Inj.
Demerol Vial Codevite Syrup
Dolo-Adamon Supplement. Deka Syrup
Dolo-Adamon Tab. Endotussin Syrup
Elixir Paregoric Raminon Syrup
Innovar Inj. Tussionex Susp.
Receiving the Rx Guidelines on Dispensing to Implement the Generics Act
- Enhances pt-pharmacist relationship of 1988
- Facilitates gathering of essential disease & drug II. Label of Unit Dose Rx or dispensing products which
info critical in providing quality phar care are not in their original containers should include:
Reading & Checking/Analyzing ▪ Small bottles; Tin cans; Boxes; Plastic
- Pharmacist should consult another pharmacist or paper envelopes
or the prescriber in case of Information required on drug outlet’s labels:
o Indistinct word/illegible phrases or 1. Name of the patient
abbrev 2. Generic name of the drug
o Omissions: 3. Brand name, if any
▪ Desired strength of 4. Manufacturer
meds/dosage form 5. Dosage strength
o Size & freq of dose be carefully noted 6. Expiry Date
and checked: 7. Directions for use
1. Age 8. Name of the Pharmacist
2. Wt and condition of pt III. In partial filling of the Rx.
3. Possible influence of other Information required to be written on the Rx:
drugs being taken 1. Date of partial filling
4. Freq of administration 2. Quantity served & balance of the Rx
- Familiar with available strengths and dosage 3. Name & address of the drugstore
forms of prefabricated drug products Additional requirements:
Numbering and Dating the Rx 1. The prescriber must have an S-2 license
- Place the same number on the label and record 2. The special DDB Rx form must be used
book as desired 3. A recording system following pertinent DDB regulation
o Identifies the bottle or package must be covered.
o Reference of the original medication
order IV. In dispensing drugs in List A and List B:
- Dating of the Rx on the date filled/compounded 1. Done by the pharmacist
to establish identity 2. Follow the order & instructions of the doctor on the Rx
Labeling 3. Partial filling of Rx for drugs in List A:
- Rx labels should be 3.1 Rx must be retained by the pharmacist
o Computerized or typewritten 3.2 The patient must asked the prescriber for
– neat, attractive, and legible another Rx to complete the total dose of the
o With aesthetic and professional medication
appearing label. 4. After the Rx is filled the original copy of the Rx shall
o Size in conformance with the size of the be retained & kept for a period of 1 year by the
prescription container. pharmacist for inspection.
- Imprinted on the label
o Name, address, tel no. of the pharmacy Preparing/Compounding the Rx
- Label of compounded Rx should include - Organize the method
1. Number of Rx - Information necessary
2. Date of filling 1. Adjuvant used
3. Name of Patient 2. Order of mixing
4. Quality and quantity of ingredients 3. Amt ot each ing
5. Directions for administration 4. Capsule size
6. Name of Physician 5. Type and size of container
- Auxiliary labels provide safety & warning 6. Name and product identification number
o Proper use of manufacturer.
o Handling - Partially filled Rx
o Storage o Returned to the buyer after recording in
o Refill status the Rx book
o Necessary warnings & precautions - Partial filling of prohibited or List A drugs
o Shall not be allowed.
Packaging
- Use appropriate containers/closures
o Colored or plastic containers
Plastic containers: Consequences of incompatibility
- Advantages: - Patient:
o Lightness of weight, resistance to o May not receive the full therapeutic
breakage, versatile design effect of the medication
- Disadvantages: o Adverse effect due to the formation of
o Permeable to atmospheric gases & toxic products
moisture vapor Physical incompatibility
o Subject to leaching - Defined as a form of disagreement in
o Deformed with extreme temperature prescriptions which do not involve chemical rxn
Rechecking - Result of
- All details of the label against the Rx order o Insolubility (most frequent cause),
o To verify directions, patient’s name, Rx o Liquefaction, or
number, date and prescriber’s name o Physical complexation
- Verify ingredients & amount - Cause:
Rx Pricing o Non-uniform
- Fair/equitable profit/pricing code o Unsightly or unpalatable mixtures
3 Methods of Pricing Rx ▪ Possess the potential danger or
- % Mark-up Method non-uniform dosage
o Prefabricated (manufactured) dosage
forms Classifications of physical incompatibility
For compounded dosage forms: INCOMPLETE SOLUTION
- % Mark-up + minimum fee method - Due to immiscibility or insolubility
- Professional Fee Method - Due to a wrong solvent
% Mark-up Method PRECIPITATION
- Dispensing price - Insolubility
= cost of ing + (cost of ing x %MU) - Mucilagenous, albuminous substances and
% Mark-up + minimum fee/compounding fee Method some metallic salts are precipitated from
- DP = cost of ing + (cost of ing. x %MU) + min. aqueous solution by the addition of alcohol.
fee or compounding fee - Camphor in Camphor water, and volatile oils are
Professional fee Method precipatated from aromatic waters when metallic
- DP = cost of ing + professional fee salts are dissolved in the liquid.
- Boric acid is precipitated when tragacanth is
Delivering the Rx added in a saturated solution.
- Personally present the Rx medication to the pt - Colloidal solutions show precipitation on addition
- If personal delivery is not possible (delivered to of electrolytes.
the patient’s home or office.) SEPARATION OF IMMISCIBLE LIQUIDS
o Appropriate instructions are provided - Oils dissolved in alcohol separate with the
o Encourage the patient to call should addition of water.
there be any questions. - Spirit of ethyl nitrite + potassium citrate =
- Finished Rx separation and layering
o correctly and skillfully compounded LIQUEFACTION OF SOLID INGREDIENTS (eutexia)
o physical appearance – indicate the pride - Formation of eutectic mixtures
and care the pharmacist has taken in his - Lowering of melting point. e.g. salol and menthol
professional work. - Liberation of water of crystallization or hydration
- Presence of deliquescent substances
Incompatibilities - Eg. Phenol, menthol, thymol, ASA
- When problems arise during: - Intentional
o Compounding o Camphor + menthol
o Dispensing o EMLA Cream – eutectic mixture of local
o Administration of pharmaceuticals anesthetic
- Problems develop as a result of: INCORRECT FORM PRESCRIBED
o Using two or more drugs - Physician may prescribe incorrect form for the
o Use of only one drug such as dosage most efficient preparation of the Rx
errors - Eg, alkaloid salt to be dissolved in liquid
- Types petrolatum
o Physical - Free alkaloid should be prescribed
o Chemical o Soluble in liquid petrolatum
o Therapeutic - Alkaloidal salts
o Combination of types o Insoluble in this solvent.
GELATINIZA TION - Delayed incompatibilities
- Solution of acacia is gelatinized by the addition o Other mixtures:
of ferric salts. o React on such a slow rate
- Collodion is gelatinized by phenol. o Occur without appreciable visible
POLYMORPHISM change/immediate physical evidence of
- Cubic: NaCl change
- Tetragonal: urea o May or may not result in loss of
- Monoclinic: sucrose therapeutic activity
- Hexagonal: iodoform o Rx is dispensed if used up before about
- Triclinic: Boric acid 10% of the therapeutic activity is lost.
- Rhombic: Iodine o Remedy - use auxiliary labels
SORPTION  “Store in a Refrigerator” label
VAPORIZATION - Decrease/slows down the rate
WATER LOSS of loss of activity/chem.
- Ointments- crumbling; reactions
- Emulsions- cracking;  “Shake well” label
- Gels-syneresis - Promote uniform dosage
 Result of a potentially
Remedies for physical incompatibilities dangerous product
1. Omission of unimportant ingredient of little - Should not be dispensed & the
therapeutic value physician be consulted
2. Dispense the ingredients separately Classification of chemical incompatibilities
3. Addition of an inert ingredient to correct the OXIDATION
difficulty - Exposure to air, temps., Light
4. Alteration in the solvents used (substituting - Excessive storage, over dilution, incorrect pH
alcohol or glycerin for water or vv) adjustment, presence of catalysts.
5. Emulsification or suspension - Undergo auto-oxidation (chain rxn oxidation):
6. Changing the order of mixing of ingredients o oils & fats, phenolic substances,
7. Changing the bulk of preparation aldehydes & vitamins
8. Use of different form of the same ingredient  E.g. Epinephrine → pinkish → brown ppt
9. Addition of stiffening agents as in ointments and REDUCTION
suppositories - Less common in Rxs although
10. The addition of an ingredient which promotes - Silver, mercury, and gold salts may be reduced
solubility by light to the metallic form
RACEMIZATION
Chemical incompatibilities - Conversion of an optically active form to an
- Occur as a result of: optically inactive form without changing chemical
o Chemical interaction among the constitution
ingredients of a Rx. - E.g. thalidomide: R or S
- Original composition is altered. - Geometric isomerism: tretinoin – iso or trans
1. Compounds considered soluble: PRECIPITATION
2. All acetates - Formation of an insoluble salt
3. All nitrates - Formation of insoluble organic salts like
4. Sulfates, except Ba; Sr; Pb and Ag tannates or iron when tannin drugs are added
5. All sodium salts with iron salts; meconate of lead when opium
6. Potassium slats except barbiturates preparations are added with lead solution;
7. Chlorides except silver and mercurous insoluble blood red iron salicylate when iron
- Compounds considered Insoluble preparations ar added with salicylates.
o Carbonates, except those of the alkalis - Precipitation of alkaloids by alkaloidal reagents
o Phosphates, except those of the alkalis (Potassium iodide or Mercuric chloride (Mayer’s
- Immediate incompatibility Reagent)
o Occurs instantaneously upon - Formation of soluble bodies. E.g. formation of
compounding green crystals of iso-nitroso-antipyrine when
o Readily apparent due to: antipyrene is treated with spirit of nitrous ether.
▪ Effervescence - Flocculent precipitates
▪ Precipitation o develop several days after a stock
▪ Color changes solution or Rx is prepared
▪ Explosion o evidence of the growth of yeasts, molds
or bacteria
EVOLUTION OF GAS IMPLOSION
- Effervescence - Weak bottles having thin spots or flaws
- Mixing of acid and carbonate or bicarbonate - May break inwardly due to the development of a
COLOR CHANGES slight vacuum
PHOTOCHEMICAL DEGRADATION - Due to removal of oxygen from the air in the
- Na2[Fe(CN) 5NO] Na Nitroprusside (potent bottle by oxidation of syrup example: Bottles of
vasodilator), a syrup
- Vit B2, OTHER TYPES OF CHEMICAL CHANGE
- Nifedifine, - Polymerization
EXPLOSIVE COMBINATION - Double decomposition
- Oxidizing agents are chemically incompatible - Substitution
with reducing agents (redox reactions) - Addition, etc.
- Serious explosions may result from certain
combinations Therapeutic incompatibilities
- All oxidizing agents such as potassium chlorate, Occur:
chromic acid, potassium permanganate, silver - When two drugs or more drugs, IV fluids or both
oxide, hydrogen peroxide, nitric acid or sodium are administered together to produce a
peroxide will explode with organic matter or response which differs in nature or intensity from
oxidizable inorganic matter like sulfur and that which was intended
carbon - Occur at the site of the drug action
- Strong nitric acid produces effervescence or - Maybe intentional or beneficial
explosion with tannins or with oil of turpentine o E.g. morphine + atropine
- Hypophosphites may explode heated above Morphine – analgesic
100oC or when combined with nitrates, Atropine to prevent the excessive
chromates or permanganates respiratory depression from morphine
- Iodine may explode when treated with ammonia o Opium + calomel
or with oil of turpentine. Opium to counteract the laxative effect
CEMENTATION of calomel used for syphilis
- Rx may set a mass of cement-like hardness. - May also increase toxicity
- Occurs when compounds from: o E.g. emetine + antimony
o Hydrates (ex. Plaster of paris) polymerize, or o Epinephrine + cocaine;
o Convert to new crystal forms o Castor oil or fixed oil + santonin or
o Acacia + Bi salts aspidium oleoresin (oil increses
SEPARATION OF IMMISCIBLE LIQUIDS solubility of santonin)
- Immiscible liquids not soluble in the Rx e.g. Combinations liable to produce therapeutic
decomposition of chloral by the alkali into incompatibilities
chloroform. 1. Sedatives + stimulants
GELATINIZA TION 2. Demulcents + irritants
- Solutions form a gel when combined with certain 3. Laxative + astringents
substances 4. Atropine + morphine
DEVELOPMENT OF HEAT OR COLD 5. Caffeine + chloral hydrate
- Chemical reactions with either 6. Strychnine +Barbital derivatives
o Liberation of heat (compounds will 7. Tannin + aloin
decompose) or Consequences
o Absorption (form stable compounds) of - Therapeutic effectiveness
considerable amounts of heat o Reduced or delayed
HYDROLYTIC CHANGES o Loss of activity
- Many substances hydrolyze in water & the o Delay in the release or absorption of
change may be hastened by heat, catalyst, drug
esters, amides, certain metals (Zn, Fe), Responsible:
glycosides - Physician rather than the pharmacist but the
INVISIBLE CHANGES pharmacist may inform the physician to
- Chem. changes occur without visible evidence eliminate:
of the reaction - Errors in Rx writing/interpretation
DEVELOPMENT OF POISONOUS SUBSTANCES - Overdose (excessive single dose/too frequent
- Chem. reaction-producing products which are administration)
more toxic than the original substances - Contraindicated drugs (steroids/peptic ulcer
- Ex. KI + Hg2Cl2 (calomel) in the presence of - Synergistic/Antagonistic effects
moisture → Hg+2 (toxic) - Alter of Rx order requires permission of presc
Factors affecting IV compatibility Side Effect
- pH - Expected and known effect of a drug that is not
o Occurs when the components of an IV the intended therapeutic outcome.
solution differ significantly in pH - Common, reproducible, predictable, dose-
- Temperature dependent, rationalizable through drugs’
o Increased storage temperature speeds pharmacology.
up drug degradation. Medication Error
o Drug storage in a refrigerator or freezer - Any preventable event that may cause or lead to
as appropriate preserves drug stability inappropriate medication use or patient harm
- Degree of dilution while the medication is in the control of the
o The more diluted the drugs are in a health care professional, patient, or consumer.
solution, lessens ion Pharmacovigillance
o Interaction leading to incompatibility. - Science and activities relating to the detection,
- Length of time in solution assessment, understanding and prevention of
o Incompatibility increases with the length adverse effects or any other drug-related
of time that drugs are in contact with problem.
each other. ‘SIGNAL’
- Order of mixing - Consists of reported information on a possible
o Ex.: Calcium phosphate, should not be causal relationship between an adverse event
added consecutively when an IV and a drug, the relationship being unknown or
admixture is being prepared. incompletely documented previously.
o This keeps these substances from
pooling or forming a layer on top of the Adverse Drug Reactions
IV fluid, decreasing the chance of Classification by Severity (Karch and Lasagna)
incomp. 1. Minor: No antidote, therapy or prolongation of
o Thorough mixing after each addition is hospitalization is required in response to the
essential ADR. Ex: H1 blockers: N&V; opioids:
Drug interactions constipation
Frequently applied to those situations: 2. Moderate: The management of the ADR
- Effects of one drug are altered by the prior or requires a change in drug therapy, specific
concurrent administration of another treatment, or an increase in hospitalization by at
- Dietary item influences the activity of a drug least 1 day. Ex: Combination Oral
(e.g., cheese & monoamine oxidase inhibitors) contraceptives: venous thrombosis; NSAIDs: GI
- A drug causes alterations of laboratory test problems
values 3. Severe: The ADR is potentially life threatening,
- A drug essentially interacts with itself (e.g. by causing permanent damage, or requiring
stimulating its own metabolism) intensive medical care. Ex: ACE inhibitors:
May either be: angioedema; Phenothiazines: arrhythmia
- Adverse Drug Interaction 4. Lethal: The ADR directly or indirectly contributes
- Beneficial Drug Interaction to the death of the patient. Ex: Anticoagulant:
bleeding
Terminologies Risk factors for ADRs
Adverse Event 1. Age
- Any undesirable experience associated with the 2. Gender
use of a medical product in a patient 3. Comorbidities
Adverse Drug Event 4. Polypharmacy/ concurrent medications
- Injury resulting from the use of a drug. 5. Duration of theraphy
- Includes harm caused by the drug (adverse drug 6. Narrow therapeutic index
reactions and overdoses) and harm from the use 7. Ethnicity and Genetics
of the drug (including dose reductions and
discontinuations of drug therapy). a) Genetic polymorphism – N-acetyltransferase
- May result from medication errors but most do (NAT). The slow acetylator phenotype
not. experiences toxicity from isoniazid,
Adverse Drug Reaction sulfonamides, procainamide, and hydralazine
- Noxious & unintended (HIPS). The fast acetylator phenotype may not
- Occurs at doses normally used in man for p, d, t respond to isoniazid and hydralazine in the
of disease or modification of physiologic function management of tuberculosis and hypertension,
- Harm directly caused by drug at normal dose respectively. NAT, a phase-II conjugating liver
and normal use enzyme
 Asians: fast acetylators; Caucasians: slow Type C (Continuous)
acetylators; Eskimos: fast; Afro-Americans: slow - Long term effects usually related to the dose
and duration of treatment.
b) Idiosyncrasies – G6PD Deficiency - hemolytic 1. Ethambutol – optic neuropathy
anemia may be triggered by sulfonamides or 2. NSAIDS – neuropathy
fava beans. G6PD is needed for regeneration of 3. Prednisone – Iatrogenic Cushing
reduced glutathione syndrome
4. Anthracyclines – cardiotonic
Classifications of ADR 5. Phenothiazine tranquilizers – Tardive
Type A (Augmented) dyskinesia
- Actions related to the pharmacological activity of 6. Laxative – colonic dysfunction
the drug 7. Narcotics and caffeine – addiction
- Extension effects - Tolerance
1. Dose related responses arising from an o Requires increasing dosages of a drug
extension of therapeutic effect to achieve similar effects, dependence
Prevention is adjustment of dosage is defined as the compulsive need of an
regimen. individual to use a drug to function
1. Anti HTN – hypotension normally.
2. Sedative-hypnotics – daytime - Tachyphylaxis
somnolence o Rapid diminution in responsiveness
3. B-blockers – bradycardia following administration of a drug
4. Insulin – hypoglycemia Type D (Delayed)
5. Sulfonylureas – hypoglycemia - Carcinogenesis (hormonal/gene toxicity)
- Adverse effects - Adverse effects associated with reproduction
1. Reactions unrelated to the goal of (teratogens)
therapy 1. Thalidomide – phocomelia;
1. NSAIDS - 2. Diethylstilbestrol – vaginal adenocarcinoma;
2. Anti-neoplastic - 3. Isotretinoin – craniofacial abnormality
3. Antidepressants - Type E (Ending of use/Withdrawal syndromes)
4. TCA’s - 1. Alcohol – delirium tremens (disorientation and
Type B (Bizarre) visual hallucinations)
- Totally abnormal effects, unrelated from the 2. Barbiturates – restlessness, mental confusion,
drug’s known pharmacological action convulsions
- Very small doses may elicit the reaction once 3. Steroids – adrenal insufficiency; chronic
allergy or idiosyncrasy is established. Addison’s Disease
1. Sulfonamides – SJS 4. B-blockers – rebound HTN or rebound
2. Halothane – acute hepatic necrosis tachycardia
3. Vancomycin – Red man syndrome with 5. Narcotics – withdrawal
flushing and hypotension. Red man Type F (Failure of efficacy/therapeutic failure)
syndrome is an infusion-related reaction - Lack of efficacy of drug products
peculiar to vancomycin. It typically consists - Result of imperfect or counterfeit manufacture of
of pruritus, an erythematous rash that the product
involves the face, neck, and upper torso. - Examples:
4. Anesthetic Drugs – malignant hyperthermia o Failure to control infection/apparent
antimicrobial resistance;
o uncontrolled hypertension
Factors:
1. Resistance
2. Patient tolerance
3. Poor compliance
4. Toxic excipients/ manufacturing errors
5. Inappropriate route of administration
6. Underdosing
7. Substandard medicine
8. Expired
Causes of ADR
✓ Pharmaceutical causes – altering the quantity of
drug (particle size, nature and quantity of
excipients and coating materials) available for
systemic absorption; influencing release rates
✓ Pharmacokinetic causes – the way a drug is
handle by the body during ADME may affect
humans in as adverse manner; ototoxicity with
aminoglycosides when used in patients with
renal failure.
✓ Pharmacodynamic causes – increased Beneficial drug interaction
sensitivity of target organs in the body to drugs - Desired & intended, when a combination of
medications produces:
Predisposing/influencing factors in ADR o Improved therapy
- Pt related factors o Greater margin of safety
o Presence of renal, hepatic, and cardiac o More appropriate onset or duration of
disease action
o Age o Lowered toxicity
o Previous ADR or drug allergy o Enhanced potency with diminished side
o Sex/gender effects
o Genetic influence Multiple drug therapy is justified if it provides
o Miscellaneous (diet, smoking, alcohol, - Greater efficacy
environmental exposures) - Greater margin of safety
- Drug-related - More satisfactory onset or duration of effect
o Pharmaceutical properties Clinical factors in DI
o Pharmacokinetic properties - Diagnostic errors
o Pharmacodynamic effects - Prescribing errors
1. Insufficient study of the patient
2. Contraindicated drugs
3. Excessive single dose
4. Excessive daily dose
5. Additive and synergistic combination
6. Antagonistic combination
7. Rx writing errors
8. Nomenclature error
9. Dosage form error
- Drug Administration and Patient Care
o Placebo and psychosomatic factors
o Unpalatability
- Combination of Factors
Drug interactions - Metabolism
Types of drug-drug interactions Enzyme inducer Enzyme inhibitor
Pharmacodynamic interactions 1. Carbamazepine 1. Metronidazole
- Addition: 1+1 = 2 2. Rifampicin 2. Erythromycin
o E.g. Prazosin + B-blocker 3. Omeprazole (macrolides except
= orthostatic hypotension 4. Phenytoin Azithromycin)
o Non-Dihydropyridine CCB + B-Blocker 5. Griseofulvin 3. Disulfiram
= blockade of AV node 6. Phenobarbital 4. Diphenhydramine
o Antidepressant + Azithromycin 7. St. John’s Wort 5. Verapamil
8. Cigarette smoking 6. Valproic acid
= cardiac arrhytmias
9. Chronic alcoholism 7. INH
- Synergism: 1+1 = 3
8. Cimetidine
o Sulfamethoxazole (SMX) and 9. Ciprofloxacin
trimethoprim (TMP) 10. Chloramphenicol
o Sulfadoxine and Pyrimethamine 11. Ketoconazole
- Antagonism: 1+1 = 0 12. Grape fruit
o Propranolol + Albuterol 13. Acute alcoholism
o OHA + Glycocorticoids
o L-Dopa + Neuroleptics Drug-medicinal herbs interactions
o Tetracycline + Penicillin Dietary supplements or food supplements
- Potentiation: 1+0 = 2 - Alternative therapy most commonly used,
o Amoxicillin + Clavulanic acid includes:
o Loop Diuretic + Silver → ear fluid - Medicinal herbs or herbal drugs
imbalance ototoxicity - Nutraceuticals
- Electrolyte Concentration o Natural substances that include certain
o Digoxin + Non-potassium sparing herbs, such products as cholesterol-
Diuretics lowering margarines, psyllium-fortified
▪ K depletion → digoxin toxicity products
→ tachycardia o Therapeutic claims not scientifically
o Lithium + diuretics studied & evaluated by the FDA
Pharmacokinetic interactions Interactions
- Absorption - May intensify or reduce the efficacy of a drug or
o Altered pH cause a serious side effect.
▪ Ketoconazole + antacid - Avoided by consulting the doctor before taking
→ ↓ bioavailability of supplements
ketoconazole
▪ Bisacodyl + antacid
o Complexation
▪ Quinolones/ tetracycline + Fe,
Ca, Mg, Al, Bi, Zn
o Alteration of motility / GER
▪ Cathartic/laxatives ↑motility
▪ Anticholinergic – ↓ motility
o Alteration of GI Flora
▪ Antibiotic + Digoxin = ↑ Digoxin
level
▪ Antibiotic + Warfarin = ↑
anticoagulation
▪ Antibiotic + OCP = alters
enterohepatic circulation of
estrogen leading → decrease in
concentration of OCP
- Distribution
o Displacement from protein binding site
o Phenytoin + warfarin = ↑ free phenytoin
→gingival hyperplasia
o Tolbutamide + Sulfonamide →hypogly
o Hypoalbuminemia = ↑ conc of free drug
o Epinephrine + Lidocaine →
vasoconstrict
Drug-food interactions
May result in any of the following:
✓ Delayed/reduced absorption of the food
nutrients or the drug
✓ Enzyme inhibition or induction resulting in
delayed or hastened drug elimination
✓ Reduced plasma concentration of the food
nutrient or the drug resulting in decreased
therapeutic effect
✓ Increased or decreased action of the medication
or inactivation of the medication
Pharmacist should give proper advice, to avoid the
potential adverse drug reaction on whether to:
✓ Eliminate the interacting food altogether
✓ Adjust the time of intake
Examples of food that should not be taken with drugs as
general rule
- Alcohol
o Increases the risk of liver damage,
increase drowsiness &/or sedation, or
cause nausea.
- Caffeine
o CNS stimulant alters the action of many
drugs affecting CNS depending on
whether the drug is sympathetic or
parasympathetic.
- Grapefruit
o Enzyme induction whereby the
biotransformation of drugs are
hastened.
- Milk - Dairy product or any product containing
Ca, Fe, Mg, Al and other heavy metals (like
antacids & multivitamins)
o Forms a chelate with the drug rendering
both the drug & the heavy metal non-
usable by the body.
- Drug that causes gastric irritation
o Pts are advised to take the medication
with milk or crackers or with a full
stomach.
- Antibiotics
o Almost always taken with an empty
stomach unless the patient complains of
gastric irritation.
 - Difficulty in compliance
o Not following doctor’s instructions; not
taking the prescribed drug
o Risky & life-threatening

Drug-food interactions
1. Biphosphates + food → decrease BA
2. Anti-infectives – any food may decraese BA
except Penicillin and Tetracycline which shlould
be taken 2 hrs a.c.
3. Erythromycin stearate - taken before meals
4. Erythromycin ethyl succinate - before or after
5. Digoxin + oatmeal = fibers interfere with
absorption
6. MAOI’s + cheese, tyramine, yogurt, sour cream,
cured meat, liver, caviar, dried fish, avocado,
banana, red wine → HTN due to ↑catecholamine
7. Warfarin + brocoli, spinach, kale, Vit K
→decrease anticoagulant effect
8. Metonidazole + Alcohol → Disulfiram like effect
9. Griseofulvin/ Phenytoin + Fatty foods = ↑ BA

Drug-disease interactions
Refer to following:
✓ Worsening of a disease because of a drug
✓ Alteration of the effect of a drug because of a
disease
✓ Manifestation of side effects because of
interaction between the drug & a disease other
than the one for which the drug is being taken
Drug-disease interactions are caused by the ff
- Physiological changes in the elderly
o Amt of body water ↓
o Amount of fat tissue ↑
o Amount of ACh in the body ↓ with age
resulting in the older patient’s decreased
tolerance to drugs with anticholinergic
effects
- Kidney impairment – for the elderly
o Kidneys are less able to excrete drugs
into the urine
o Resulting in the prolonged stay of the
drugs in the body
o Thus prolonging its effect
- Liver impairment
o Decreases metabolism of many drugs,
prolonging its effect
- Altered drug response
o Older people, more sensitive to the
effects of many drugs.
o More dramatic effects to elder
-
 ✓ Fried’s Rule (for infants up to 2 years old)
infant’s dose(approx) = Age (mos) x adult dose
150
10 Star pharmacist
1. Pharmaceutical care giver
2. Decision maker
3. Manager
4. Leader
5. Communicator
6. Life-long learner
7. Teacher
8. Researcher
9. Entrepreneur
10. Agent of positive change

Extemporaneous compounding
Requirements for compounding
1. Consider the sources of ingredients or
chemicals – Reputable and reliable
supplier. They should be of quality to
produce a pure, safe and effective
medicine.
2. Equipment
3. Compounding area
o Separate area near the sink for
washing purposes.
o Should be away from heavy foot
Correction of incompatibilities traffic.
- Consult the physician o For parenterals use the LFH
- Use pharmaceutical knowledge 4. Source of information
- Add an ingredient o Pharmacy reference books
- Remove an ingredient o Journals for continuous
- Change the vehicle education.
- Change an ingredient Fundamental factors in Prescription Compounding
- Change the dosage form 1. Physical and Chemical properties of ingredients.
- Read the literature Incompatibilities
Preventing/minimizing incompatibilities A. Intentional
- Each drug should be mixed thoroughly after it is B. Unintentional - not to be dispensed
added to the preparation In case of unintentional incompatibilities
- Solutions should be administered promptly after 1. Determine the type of incompatibility
they are mixed to minimize the time available for (physical, Chemical or therapeutic)
a potential reaction to occur 2. Visible manifestation of the
- The number of drugs mixed together in an IV incompatibility
solution should be kept to a minimum 3. Remove and find remedies to prevent or
- If a Rx calls for unfamiliar drugs or IV fluids, correct the incompatibility.
compatibility references should be consulted 2. Order of Mixing and use of adjuvant
- Drugs.com – to check for drug incompatibilities 3. Pharmaceutical Techniques
4. Preparation and storage
Posology 5. Stability
Dose for children 6. Proper labeling – including auxiliary labels.
- Regulated according to the age or weight, a
fraction of the adult dose being given
Rules for infants’ & children’s doses
✓ Young’s Rule (children 2 years & older)
child’s dose (approx) = Age (yr) _ x adult dose
Age (yr) + 12
✓ Clark’s Rule
child’s dose (approx) = _Wt (lb) x adult dose
150
Solutions Pharmaceutical Aspects
 Liquid medications with one or more active 1. Acids and bases
ingredients dissolved in a suitable solvent or  May affect the preparation, solubility and
mixture of solvents. incompatibility
 Types  Most of the drugs are weak acid/ weak
1. Homogenous- one phase; base
thermodynamically stable  Bronsted acid- has H+ ion/ hydronium
2. Heterogenous- two-phased system; ion which is equivalent to proton donor.
thermodynamically unstable.  Bronsted Base- proton acceptor
e.g. coagulated or flocculated states 2. Buffers
Broad Classification of Solutions  Resist change in pH (maintain)
1. Micromelecular Solutions  For solubility and stability and
 Particle size is 1-10 A therapeutic effect or potency
 E.g. NaCl solution, water, alcohol, 3. Viscosity
glycerin  resistance to flow
2. Micellar  Structure makers ions – increase
 made up of aggregates or micelles viscosity of solution
 Polymolecular or polyionic aggregates  Structure breaker ions – decrease
reaching colloidal range of particle size. viscosity of the solution
 Micelles: closely resembles biological  When dissolving a solid in viscous
system; contains solubilizing power; solvent, dissolve the drug in minimum
associated with colloidal solutions. quantity of water or less viscous solvent.
3. Macromolecular  Kosmotropes (structure makers) or
 Large magnitude chaotropes (structure breakers)
 Acacia, CMC, albumin 4. Dissolution Rate
Physicochemical factors affecting solubility behavior  Rate at which the solute changes into its
1. Polarity molecular dispersion in the solvent.
2. Co-solvency  Solute may be in crystals, powder or
3. Temperature liquid form.
4. Salting-out  Stir or agitate or increase the
• Organic compound + aq soln → clear temperature to enhance dissolution.
soln + salt soln → ppt of organic  Macromolecular solutes, if dissolved in
compound water will form aggregates, so use
5. Salting-in wetting agents or add macromolecules
 Globulin + water + salt solution in increments.
→globulin soluble in water 5. Isotonicity- 0.9% NSS
6. Common ion effect  For parenteral solutions
 There is a shift in the equilibrium due to  If not isotonic, will cause cellulysis or
the addition of a compound having an irritation
ion common with the dissolved  Iso-osmotic= same osmotic pressure
substance.  PNSS, RBC and Blood Plasma: -0.52oC
 For pH determination Freezing point.; isotonic, iso-osmotic
 Determine the solubility of slightly 6. Toxicity
soluble slats.  Primary consideration when selecting
7. Particle size solvent
8. Complex formation 7. Stability of the Preparation
 I + KI/NaI → increase in solubility (I3-)  Shelf-life of the product must be taken
triiodo complex ion. into account
 The reaction or complex must be  Add preservative, antioxidant,
reversible antimicrobial agent
 It should dissociate easily  If instability is due to polymerization, add
 The active ingredient must be released. polymerization inhibitors.
9. Molecular size and shape
Considerations in compounding solns Emulsion
1. Solubility- each drug must be dissolved in a - Liquid preparations in which one liquid is
suitable solvent. dispersed in another liquid in the form of small
2. The salt form of the drug and not the free acid or droplets.
based form is used. - 2 immiscible liquids
3. Flavoring and sweetening agents must be - Oil, water and emulgent
prepared ahead of time. 2 Kinds
4. When adding a salt to a syrup, salt should be - O/W
dissolved first in a minimum amount of water. o Oil is internal - dispersed/ discontinuous
5. Proper vehicle must be selected. o Water is external - dispersion medium/
continuous
Suspensions o Creamy, white
- Liquid preparation with solid particles dispersed - W/O
throughout a liquid phase. o Water is internal
- Solid = insoluble o Oil is external
- Suspending agent = facilitates dispersion o Glassy, translucent
General characteristics of suspension
1. Some suspension should contain antimicrobial *** if yellow emulsion, emulsion is coarse
agents to serve as preservative.
2. The particles settle in all suspension even when General characteristics of emulsion
a suspending agent is added. (Shake well). The 1. The two liquids in an emulsion are immiscible
suspension must be shaken well to ensure and require the use of emulgent.
proper distribution of particle for uniform dosing. 2. Emulsions are unstable, and the following steps
3. Tight containers are necessary to ensure must be taken to prevent separation into two
stability of the product. Upon reconstitution, it layers
can be stored for 7 days at RT or 14 days when 1. The correct proportions of oil and water
refrigerated. must be used during preparation. The
4. Principles to keep in mind when compounding internal phase should represent about
suspension 40-6.0% of the total volume.
a. The insoluble powder should be small 2. The emulgent is needed for emulsion
and uniform in size to decrease rate of formation.
settling. 3. Homogenizer may be used to reduce
b. The suspension should be viscous. the size of the globules of the internal
c. Topical suspensions should have a phase.
smooth impalpable texture. 4. Preservatives should be added if the
d. Oral suspensions should have pleasant preparation is intended to last longer
odor and taste. than a few days.
Ways to minimize stability problems If a preservative must be used, it must
1. Particle size of all powders used in the be soluble in the water phase for it to be
formulation must be reduced. effective.
2. A thickening agent may be used to enhance 1. If the addition of flavor is needed to
viscosity. (Bentonite 6%, Veegum 6%, Acacia mask the taste of the oil phase, the
1%, Tragacanth 1-3%, Na alginate 1-2%, MC 1- flavor should be added to the external
7%) phase before emulsification.
- Bentonite and veegum – thixotropic 2. Shake well label must be provided
substances → forming gel like structure 3. The product should be protected from
upon standing. the light and extreme temperature.
3. A levitating agent may aid in the initial dispersion Avoid freezing and heating.
of insoluble particles. (glycerin, PG, alcohol, 4. If the addition of flavor is needed to
syrup, water) mask the taste of the oil phase, the
4. Flavoring agents and preservatives should be flavor should be added to the external
selected and added if the product is intended for phase before emulsification.
oral use.
5. The source of active ingredient must be
considered. (bulk powders/ tablets/ capsule)
Methods of preparation Methods of comminution
1. Dry Gum/ Continental method- use acacia or  Trituration
tragacanth in dry form.  Pulverization
 O:W:E = 4:2:1.  Grinding
 In a mortar, add oil and then the  Levigation
emulgent with rapid titration then add For vegetable or animal origin
water at once with rapid titration till  Beating
crackling sound  Contusion
2. Wet Gum/ English Method- use acacia and  Grating
tragacanth in mucilage form.  Slicing
 O:W:E = 4:2:1.  Chopping
 water + EA + oil in portions till crackling
sound. 2 Kinds of powders
3. Forbes/ Bottle Method 1. Bulk powders
 O:W:E = 3:2:1 or 2:1:1 2. Divided powders
 For volatile ingredients  How to measure powder
4. Nascent Soap Method  Block and Divide
 O:W = 1:1  Weighing – most accurate
 The formed soap will act as the  Powder measures
emulgent.  Use: parchment paper/ glassine paper
 Oil must have an adequate quantity of  Characteristics of Powder Paper
free acid.  Folds readily
Ways to identify type of emulsion  No springing back
1. Drop Dilution Test  Impermeable to atmospheric
 Emulsion + water condition
 Principle: the emulsion is miscible with  Water repellant
external phase.  Pharmaceutically elegant
 The water added is readily dispersed =  Remains clean during handling
o/w Problems with powders
2. Dye Solubility Test 1. Hygroscopic – absorbs moisture
 Add water soluble dye = o/w 2. Deliquescent – absorbs moisture then liquefy
 Add oil soluble dye = w/o 3. Efflorescent – crystalline substances, which
3. Direction of Creaming when liberate the water of crystallization or
 Creaming – process of sedimentation of hydration are converted to powder like
internal phase substances.
 Based on differences in density 4. Eutectic Mixtures – lowering of the melting point
 Upwards = o/w of the two substances upon admixture
 Downwards = w/o Remedies
4. Electric Conductivity Test 1. Hygroscopic – use moisture tight container;
 Conduction of electricity = o/w granulate
5. Fluorescence = w/o 2. Deliquescent – use adsorbent; double wrap the
powder
Powders 3. Efflorescent – use anhydrous form of the drug
 Intimate mixtures of dry finely divided drugs and 4. Eutexia – dispense separately; add adsorbent
or chemicals intended for internal or external 5. Incorporation of liquid- see that no pasty mass
administration. and liquefaction; evaporate until syrupy
 Problems in Compounding Powders consistency, add the carrier and evaporate
1. Formation of aggregates completely to dryness.
 Remedy: trituration 6. Addition of explosive mixture – strong oxidizing
2. Stratification – formation of two layers and reducing agents.
due to difference in particle size or Special powders
densities of the powders. 1. Effervescent salts/ powders
 Size – triturate  Bubble formation due to evolution of gas
 Density – tumbling (CO2)
2. Dusting Powder
3. Dentrifice – powders intended to be placed in
the teeth
4. Insufflation – for application in body cavities
5. Powder aerosols