Comprehensive Study Notes on Dispensing and Adverse Drug Reactions

Fundamentals of Pharmaceutical Prescriptions

Etymology and Definition:

- \* Derived from the Latin term "Praescriptus".

- \* Prefix "Prae" means "before".

- \* Root "Scribere / Scribo" means "to write / I write".

- \* Literal translation: "To write before".

- \* Definition: An order for medication for use by a patient issued by authorized practitioners (physicians, dentists, and veterinarians).

Nomenclature by Setting: * Prescription: Refers to orders for outpatients. * Medication Order: Refers to orders for inpatients within a hospital or institutional setting.

Classification of Drugs Based on Prescription Requirements

Non-Prescription / Over-the-Counter (OTC): * Drugs that do not require a prescription for purchase. * Used for minor or self-limiting ailments.
Prescription / Legend / Ethical Drugs: * Drugs that require a valid medical prescription. * Often carry a label "Rx" or a legend stating federal law prohibits dispensing without a prescription.
Dangerous Drugs: * Strictly regulated substances with potential for abuse.
Exempted Dangerous Drugs (EDD): * Substances that contain dangerous drugs but in combinations or concentrations that reduce the risk of abuse, requiring an Rx but under different monitoring protocols (e.g., Oral benzodiazepines).

Specific Prescription Requirements and Controls

Philippine Schedule of Dangerous Drugs

Schedule 1: * Accepted Philippine medical use: None. * Abuse potential: Extremely high. * Dependence: Lack of accepted safety for use. * Examples: Heroin, LSD, Peyote, Ecstasy, GHB, Shabu.
Schedule 2: * Accepted Philippine medical use: Yes. * Abuse potential: High ( $1 > 2$ ). * Dependence: Severe (both physical and psychological). * Examples: Opium, Methadone, Morphine, Oxycodone, PCP, Fentanyl, Methylphenidate (Ritalin®), Amphetamine (Adderall®), Meperidine (Demerol®).
Schedule 3: * Accepted Philippine medical use: Yes. * Abuse potential: Moderate ( $1 > 2 > 3$ ). * Dependence: Physical (Moderate–Low), Psychological (High). * Examples: Anabolic steroids, Hydrocodone (Lorcet® or Vicodin®), Buprenorphine, Pentobarbital.
Schedule 4: * Accepted Philippine medical use: Yes. * Abuse potential: Low ( $3 > 4$ ). * Dependence: Limited. * Examples: Diazepam, Alprazolam, Clonazepam, Meprobamate, Phenobarbital, Zolpidem, Phentermine.
Schedule 5: * Accepted Philippine medical use: Yes. * Abuse potential: Very low ( $4 > 5$ ). * Dependence: Low to High. * Examples: Ketamine, Ephedrine, Nalbuphine.

Anatomy of a Prescription: The Nine Core Parts

Prescriber’s Information: * Includes the name of the prescriber, clinic address, clinic hours, and contact information.
Patient’s Information: * Name, Age, Weight, Sex, and Address.
Date of the Prescription: * Crucial for determining the validity of the Rx.
Superscription: * Represented by the symbol "Rx". * Comes from the Latin "recipe", meaning "take thou".
Inscription: * The principal part of the prescription. * Contains the name(s), strength, and quantity of the drugs.
Subscription: * Directions intended for the Pharmacist (RPh) regarding compounding or dispensing.
Transcription / Signatura / Signa: * Directions intended for the Patient (Px) on how to take the medication.
Refill Information: * Indicates if the prescription can be refilled and how many times.
Prescriber’s Signature and License Numbers: * Must include the MD License number and PTR No. * For Dangerous Drugs, an S2 License is specifically required.

Handling Prescription Errors

Erroneous Prescription: * Conditions: Brand name precedes generic name; generic name in parenthesis; brand name not in parenthesis. * Action: Fill the prescription, keep the original, and report to the DOH within 3 months.
Violative Prescription: * Conditions: Brand name only; brand name is legible while generic name is not; contains "No substitution" instruction. * Action: Do not fill; keep the original; report to the DOH.
Impossible Prescription: * Conditions: Generic name is not legible; drug is not FDA registered; generic name does not correspond with the brand name. * Action: Do not fill; keep the original; report to the DOH.

Pharmaceutical Abbreviations and Medical Terminology

Compounding and Quantities: * aa: Of each * ad: To make (or Right Ear depending on context: ROA) * disp: Dispense * ft: Mix * qs: Sufficient quantity * dtd: Give such doses * M: Make * qs ad: Sufficient quantity to make * IU: International Units * gtt: Drop
Timing of Administration: * ac: Before meals * ic: Between meals * pc: After meals * AM: Morning; PM: Afternoon * hs: At bedtime * noct: Night * m&n: Morning and night * PRN: As needed * ATC: Around the clock * OD: Once daily; BID: Twice daily; TID: Thrice daily; QID: Four times daily * q_h: Every _ hours; QOD: Every other day * STAT: Immediately
Routes and Sites: * PO: Orally; NPO: Nothing by mouth * NGT: Nasogastric tube * IVB: IV Bolus; IVP: IV Push; IVPB: IV Piggyback * ad: Right ear; as: Left ear; au: Both ears * od: Right eye; os: Left eye; ou: Both eyes
Miscellaneous Clinical Notes: * non rep: Do not repeat (No refill) * DC: Discontinue * c: With; d: Day; et: And; h: Hour * ad lib: Freely; aq: Water * NV: Nausea and vomiting; HA: Headache; SOB: Shortness of breath * ASA: Aspirin; APAP: Paracetamol * IOP: Intraocular pressure * ung: Ointment; pulv: Powder

Safety: Dangerous Abbreviations and Tall-Man Lettering

Dangerous Abbreviations to Avoid: * "<" and ">": Usually interchanged; write "Less than" or "Greater than". * cc: Mistaken as zero (0); use "mL". * $\mu g$ : Mistaken as "mg"; use "mcg". * U (unit): Mistaken as 0, 4, or 6; write "Unit". * IU: Mistaken as IV or cc; write "International unit". * QD / QOD: Mistaken as QID; write "Daily" or "Every other day". * MS / MSO4 / MgSO4: Confusing between Morphine sulfate and Magnesium sulfate; write full names. * HCT: Could mean Hydrocortisone or Hydrochlorothiazide. * HCl: Could mean Hydrochloric acid or Potassium chloride (KCl).
Tall-Man Lettering for SALAD / LASA (Sound Alike Look Alike Drugs): * DOPamine vs. DOBUTamine * predniSONE vs. predniSOLONE * vinCRIStine vs. vinBLAStine * niCARdipine vs. niFEdipine * glipiZIDE vs. glyBURIDE

Pharmaceutical Incompatibility

Definition: Arises when two or more drugs/chemicals are combined, leading to undesirable changes.
Types: * Physical Incompatibility: Conflicting physical properties. * Chemical Incompatibility: Reaction alters chemical composition. * Therapeutic / Drug Interactions: Altered pharmacological response.

Physical Incompatibilities

Volatilization / Vaporization: Loss of substance to gas for compounds with high vapor pressure (VP). Examples: Alcohol ( $ROH$ ), Aldehydes ( $RCHO$ ), Ketones ( $RCOR$ ), Volatile oils, Nitroglycerin (NTG).
Loss of Water / Dehydration / Desiccation: Reverse of liquefaction. * Emulsions: Manifests as "cracking". * Gels: Manifests as "syneresis". * Ointments: Manifests as "crumbling".
Liquefaction (Solid to Liquid): * Efflorescence: Loss of water of hydration/crystallization (e.g., $CuSO_4 \cdot 5H_2O \rightarrow CuSO_4$ ; Citric acid). * Hygroscopicity: Absorption of moisture without liquefying (e.g., Silica, Methanol, Honey). * Deliquescence: Absorption of moisture leading to liquefaction (e.g., Hydroxides $OH^-$ , Nitrates $NO_3^-$ , Chlorides $Cl^-$ ). * Eutexia: Lowering of a solid's melting point (MP) upon contact with another solid at room temperature (RT). Example: EMLA (Lidocaine + Prilocaine).
Insolubility: (Solid + Liquid) e.g., Camphor + Water; Gum + Alcohol.
Immiscibility: (Liquid + Liquid) e.g., Oil + Water.
Polymorphism: Ability of a substance to exist in different crystalline forms. * Cocoa Butter Polymorphs: * $\gamma$ (Gamma): $18^oC$ * $\alpha$ (Alpha - metastable): $22^oC$ * $\beta'$ (Beta-prime): $28^oC$ * $\beta$ (Beta - stable): $34.5^oC$ * Crystal Systems and Examples: * Cubic: $NaCl$ (Mnemonic: CubiCle / NaCu). * Monoclinic: Sucrose (Mnemonic: SuMo). * Triclinic: $H_3BO_3$ (Mnemonic: TriBo). * Rhombic: Iodine (Mnemonic: RhomIo). * Tetragonal: Urea (Mnemonic: T → U; 4 sides). * Hexagonal: Iodoform (6 syllables).
Types of Precipitation: * Change of Solvent: Camphor + Alcohol + Water → Camphor precipitates. * Change in pH: Phenobarbital Sodium (basic) + Orange syrup (acidic) → Phenobarbital precipitates. * Change in temperature: * Endothermic: Temp increase = solubility increase. * Exothermic: Temp increase = solubility decrease. * Salting Out: Salt + Aromatic water → Volatile oil evaporates / precipitates; Salt + Acacia mucilage → Acacia precipitates.

Chemical Incompatibilities

Photolysis: Degradation due to light. Examples: Dacarbazine (yellow to pink), Metronidazole (darkening), Doxorubicin, Nifedipine, Vitamin $B_2$ , Sodium nitroprusside, Cisplatin.
Racemization: Conversion of an optically active drug to an inactive form (mix of 2 enantiomers). Example: Atropine, Thalidomide. * Eutomer (Good isomer): Provides activity (R-Thalidomide for morning sickness/leprosy). * Distomer (Bad isomer): Responsible for toxicity (S-Thalidomide causing Phocomelia).
Polymerization: Formation of polymers. Example: Formaldehyde to Paraformaldehyde (Prevention: add Methanol).
Explosive Mixture: Oxidizing Agent (OA) + Reducing Agent (RA). Example: $KMnO_4$ + Glycerin/Sugar.
Oxidation / Dehydrogenation: Change in color. Examples: Ascorbic acid (white to brown), Epinephrine (colorless to pink).
Reduction / Hydrogenation: Example: $AgNO_3 \rightarrow Ag$ (Tollen's silver test; metallic silver precipitates).
Gelatinization: Acacia + Ferrous salts.
Cementation / Caking: Acacia + Bismuth salts.
Acid-Base Reactions: * Effervescence: Release of $CO_2$ . Example: $NaHCO_3$ + Citric/Tartaric acid → $CO_2$ (used to mask taste). * Precipitation: Chemical formation of a new product. Example: $CO_2$ (Acid) + $Ca(OH)_2$ (Base) → $CaCO_3$ (Solid) + $H_2O$ .
Solvolysis: Solvent-induced decomposition. * Hydrolysis: Water is the solvent. Most common cause of degradation (e.g., Aspirin ( $ASA$ ) + $H_2O \rightarrow$ Acetic acid + Salicylic acid).

Drug Interactions

Classification of Evidence: * Established: Well-known. * Probable: Very likely but not proven (Mnemonic: ProVe). * Suspected: Might occur, needs study (Mnemonic: SuMo). * Possible: Could occur, limited data (Mnemonic: PoCo). * Unlikely: Doubtful.
Components: * Precipitant: The cause of the interaction. * Object: The drug being affected.
Pharmacokinetic Interactions (ADME): * Absorption: * pH Alteration: Antacids + Enteric Coated Tablets (ECT) like Bisacodyl, ASA, or Ketoconazole. * Complexation/Chelation: Multivalent metals + Tetracyclines (TCN) or Fluoroquinolones. * GI Motility: Anticholinergics decrease Gastric Emptying Rate (GER); Laxatives increase GER. * GI Flora: Broad-spectrum antibiotics + Digoxin, Estrogens, or Warfarin. * Adsorption: Bile Acid Resins (BARs) + Digoxin, Warfarin, or Vitamins A, D, E, K. * Distribution (Protein Binding): * Acidic drugs bind to Albumin. * Basic drugs bind to $\alpha_1$ -acid glycoprotein. * Free drug is active and well-distributed. * Bound drug is inactive and cannot be metabolized/excreted until dissociation. * Examples: Valproic Acid + Phenytoin → CNS depression; Oral Hypoglycemic Agents (OHA) + Sulfonamides → Hypoglycemia; Warfarin + Phenylbutazone → Bleeding. * Metabolism: * Enzyme Induction: Warfarin + Phenobarbital → Thrombosis (due to decreased effect of warfarin). * Enzyme Inhibition: Warfarin + Cimetidine → Profuse bleeding (due to increased drug levels).
Pharmacodynamic Interactions: * Addition ( $1 + 1 = 2$ ): Alcohol + Antihistamine; Ampalaya + OHAs. * Synergism ( $1 + 1 > 2$ ): Anti-TB drug cocktails; Cotrimoxazole; Sulfadoxine + Pyrimethamine (Fansidar®). * Potentiation ( $1 + 0 = 2$ ): Levodopa + Carbidopa; Co-amoxiclav. * Antagonism ( $1 + 1 = 0$ ): Vitamin K + Warfarin; Histamine + Epinephrine.

Environmental and Dietary Interactions

Drug-Food Examples: * CNS Depressants + Caffeine (Stimulant antagonism). * TCN / Fluoroquinolones + Dairy (Chelation). * Griseofulvin + Fatty meals (Increased absorption). * MAOIs + Tyramine-rich foods (Hypertensive crisis). * Warfarin + Green leafy vegetables (Vitamin K antagonism). * Metronidazole + Wine/Beer (Disulfiram-like reaction).
Drug-Herb Examples: * Antihypertensives (Anti-HTN) + Licorice. * ASA + Garlic / Ginkgo biloba (Bleeding risk). * CNS depressants + Valerian / St. John’s Wort. * MAOIs + Ma-Huang.
Drug-Laboratory Interactions: * Rifampicin + Urinalysis → False positive. * Vitamin C + Glucose test → False positive.

Adverse Drug Events (ADE) and Reactions (ADR)

ADE: Untoward incident related or unrelated to drug use.
ADR: Noxious, unintended response at normal doses; generally unpredictable.
Medication Error: Controllable and preventable errors in the medication use process.
Type A (Augmented): Common, dose-dependent, related to pharmacology. * Extension Effects: Exaggeration of primary mechanism (e.g., Hypoglycemia by OHAs; Bradycardia by Beta-blockers; Serotonin syndrome by SSRIs). * Side Effects: Action on non-target sites (e.g., Dry cough by ACEIs; Endocrine effects like gynecomastia by Cimetidine; Kernicterus by Sulfonamides; Cholestatic hepatitis by Erythromycin estolate).
Type B (Bizarre): Rare, unpredictable. * Idiosyncratic: Genetically determined (e.g., SJS by Carbamazepine/Phenytoin). * Hypersensitivity (Allergic): * Type I (Anaphylaxis): Mediator: IgE. Examples: penicillin/cephalosporin allergies. * Type II (Cytotoxic): Mediator: IgG/M. Examples: Hemolytic anemia, ITP. * Type III (Immune complex): Example: SLE. * Type IV (Delayed): Mediator: T-cells. Examples: Contact dermatitis, Tuberculin test.
Type C (Continuous): Long-term use issues (Addiction, Dependence, Tolerance).
Type D (Delayed): Carcinogenicity and Teratogenicity.
Type E (End of Use): Withdrawal effects (e.g., Steroids → Addison’s Disease; Clonidine → Rebound HTN; Opioid withdrawal).
Type F (Failure of Therapy): Caused by resistance (AMR), counterfeit drugs, or wrong route (e.g., Potassium supplements must not be given IV bolus/push).

Teratogenicity and Pregnancy Categories

FDA Pregnancy Categories: * A: Safe for humans and animals. * B: Animal studies show no risk; human data unavailable. * C: Animal studies show risk; human data unavailable (Benefits may outweigh risk). * D: Clear evidence of human fetal risk (Benefits > Risk). * X: Proven fetal abnormalities (Risk > Benefits). Examples: Retinoids, Thalidomide, Statins, Warfarin.
Specific Teratogenic Effects: * ACEIs/ARBs: Renal dysgenesis. * Alcohol: Fetal alcohol syndrome. * Carbamazepine/Valproic acid: Neural tube defects. * Lithium: Ebstein’s anomaly. * Methimazole: Aplasia cutis. * Phenytoin: Fetal hydantoin syndrome. * Tetracycline: Tooth discoloration and bone problems. * Thalidomide: Phocomelia (seal-like limbs).

Medication Error Classifications

Causes: Commission (Doing the wrong thing) vs. Omission (Failure to do the right thing).
Patient Outcomes (Harm Index): * A: No patient involved (Mnemonic: Ala pa naman). * B: Error occurred but did not reach the patient (Mnemonic: Buti nalang). * C: Error reached patient, no harm (Mnemonic: Chamba). * D: Reached patient, requires monitoring to prevent harm (Mnemonic: Dapat i-monitor). * E: Harm occurred, intervention required. * F: Harm occurred, prolonged hospitalization required. * G: Permanent damage (Mnemonic: GG / Grabe). * H: Near death (Mnemonic: Hingalo). * I: Death (Mnemonic: Iyak / rIp).

Pharmacy Management and Alternative Care

Pricing Methods: * Dispensing Fee Method: Acquisition cost + fixed fee. * Percentage Mark-Up Method: Costly drugs pay a proportionally larger part of service costs. * Per Diem Method: Single daily charge derived from average drug/service costs.
CAM Terms: * Nutraceutical: Food providing medical benefits. * Phytochemical: Edible plant components modulating metabolism for cancer prevention. * Homeopathy: Applies "Law of Similar" using weak doses of active substances. * Iridology: Correlating iris color/texture with mental and physical disorders.