PARENTERALS-notes-2010 - Parenteral Medications and Sterile...

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Unformatted text preview: Parenteral Medications and Sterile Fluids Sterile small- and large- volume injectable preparations (SVP, LPS), irrigation fluids intended to bathe body wounds or surgical openings, dialysis solutions, biologicals (vaccines, toxoids, anti-toxins) and blood replenishment products. Parenteral routes of adm inistration 1. INTRAVENOUS or I.V. • Used in emergencies: rapid action because there is no absorption. • Optimum blood levels are achieved with accuracy and immediacy. • Useful to treat unconscious, uncooperative patients. • Drug cannot be removed once injected (if toxic effect or inadvertent overdose). • Absolute sterility requirements (aseptic handling of syringe, needles, solutions, point of entrance). • Most expensive dosage forms. • Requires specialized personnel for administration. • Small (up to 100 ml) and large-volumes (>100 ml - 1000 ml) can be used peripherally (e.g. veins of the antecubital area) or centrally (e.g. subclavian vein). • Only aqueous solutions are used (exception: fat emulsion in parenteral nutrition solutions). • Main hazards: i. THROMBUS (thrombi, thrombosis): blood clot formed within a blood vessel due to a slowing of the circulation or to an alteration of the blood or vessel wall. ii. EMBOLUS (emboli): a circulating clot that can lodge in a blood vessel and cause obstruction (pulmonary embolism, cerebral embolism, stroke). 2. INTRAMUSCULAR or I.M. • Less rapid, greater duration than IV. • Aqueous and oleaginous solutions and suspensions may be used: variable absorption rate. PHCY 6100- Teixeira 1 Parenteral Medications and Sterile Fluids • Administration into the skeletal muscle, avoiding nerves and blood vessels. Slight aspiration before injection will assure the drug won’t be injected into a vein. In adults, the upper outer quadrant of the gluteus maximus is preferred while in infants the best are the deltoid muscles of the upper arm or the midlateral muscles of the thigh (gluteal area is small and has very little muscle, also close to the sciatic nerve). • Volumes administered: 5 ml if in gluteal area and 2 ml in the deltoid. • Site of injection should be rotated in a series (avoid abscess, induration) 3. SUBCUTANEOUS or Sub-Q, S.C., S.Q., Hypodermic, “Hypo” • Administration into the loose interstitial tissue, underneath the surface of the skin. • Small amounts: 1.3 ml max (larger amounts cause painful pressure). • Usual sites: outer surface of the upper arm, anterior surface of the thigh, and lower portion of the abdomen. • Largely used for administration of Insulin and vaccines (MMR, DPT, rubella, tetanus toxoid, etc). • Not suitable for irritating drugs or thick suspensions. 4. INTRADERMAL or I.D. or INTRACUTANEOUS • Administration into the dermis (connective tissue), the more vascular layer of the skin, just underneath the epidermis (when bevel of needle disappears into the skin). • Usual site: anterior surface of the forearm. • Very little volumes applied (0.1 ml ) with very short and thin needles. • Used for diagnostic determinations (tuberculin, diphtheria toxin) and immunizations (BCG vaccine). I NJECTI ONS Characteristics 1. Sterility: absence of all living organisms and their spores a) Methods of Sterilization: i. STEAM UNDER PRESSURE (Autoclave): • Method of choice if product is thermostable. PHCY 6100- Teixeira 2 Parenteral Medications and Sterile Fluids Higher temperatures of steam are obtained by increasing the pressure (under atmospheric conditions steam temperature is 100_ C). It is the high temperature that kills the microorganisms, not the pressure. • The mixture moisture + heat denatures and coagulates some of the microbe’s essential proteins. • A standard load is autoclaved for 15 min at 121°C. In general the time required depends on the nature of the load (dry x wet materials). • Not suited for oils, oleaginous preparations and exposed powders. ii. DRY HEAT (Sterilizing oven): • Very high temperatures and longer periods of exposure are used (160-170° C for 2 hr. minimum). If higher temperatures are used, shorter exposure time can be used. • High temperature will kill microbes by dehydration of cells followed by slow burning or oxidative processes. • Applicable to all products not penetrated by moisture such as oils, glycerin, petroleum products (petrolatum, mineral oil, paraffin), heat-stable powders (e.g. zinc oxide). • Also used for glassware and surgical instruments. iii. FILTRATION: • Microorganisms are removed by adsorption to a filter medium or by a sieving mechanism. • Bacterial filters (old fashioned) and pore-size specified filters (membranes of cellulosic esters with pores of extremely uniform size). Membrane filters with pore-size of 0.2 µ are considered sterilizing filters). • Useful for heat-sensitive (thermo-labile) products. Very useful for small volumes of liquids (e.g. compounding of ophthalmics in community pharmacy). • Advantages: speed, low cost, complete removal of microorganisms and particulate matter. • Disadvantages: effectiveness of filtrate is determined by microbial load; adsorption of certain materials to the membrane; defective filter; long time needed if filtration of large volumes. iv. GAS (Ethylene oxide or Propylene oxide): • These gases are extremely flammable and are used in a mixture with an inert gas (CO 2 ). • Gas will interfere with the metabolism of the bacterial cell. • Requires specialized equipment • Longer exposure time is necessary: 4 -16 hours. • Useful for heat-sensitive and moisture-sensitive materials (enzymes, antibiotics). • Largely used for sterilization of medical and surgical supplies and appliances. • Bag method v. IONIZING RADIATION (Gamma rays and Cathode rays): • Rays will induce microorganisms to form deleterious products, which will destroy the cells, and/or chromosomal nucleoproteins of microbes will become disoriented or destroyed. • PHCY 6100- Teixeira 3 Parenteral Medications and Sterile Fluids • Limited use due to highly specialized equipment and unknown effects of irradiation on products. b) Validation of Sterility: confirmation of absence of microorganisms and spores. BIOLOGIC INDICATORS (U.S.P.) are defined as specific spores of microorganisms particularly resistant to a certain sterilization process that are added to a carrier (strip of filter paper) or to one sample of the load being sterilized. i. For STEAM: spores of bacillus stearothermophilus ii. For DRY HEAT/GAS: spores of bacillus subtilis iii. For IONIZING RADIATION: spores of bacillus pumilus 2. Pyrogen-free: absence of fever-producing organic substances from microbial contamination (lipopolysaccharide from the outer cell wall of the bacteria and endotoxins). a) Pyrogens: relatively thermostable products that remain after regular sterilization processes, such as autoclaving (125°C), dry heat (170°C) and filtration with filter >0.2µm pore size. Pyrogens can be destroyed with high heat by oxidation or “burning up”: oxidizing agents (potassium permanganate, peroxides, alkali, acids) or 250°C for 30-45 minutes. Parenteral preparations are generally made with pyrogen-free water and chemicals. b) Validation of Pyrogen-free: i. RABBIT TEST: change in rectal temperature of 0.5° C in one rabbit or a sum of 1.4 °C in 5 rabbits. ii. LAL TEST (Limulus Amebocyte Lysate): based on the coagulation of an enzymeprotein complex from red blood cells of the horseshoe crab in presence of lipopolysaccharides (pyrogens). This test is more sensitive to endotoxins than the rabbit test. 3. Particulate-free: a) Particulate matter refers to mobile, undissolved substances unintentionally present in parenteral products. b) Standards related to the number and dimensions of particles in LPS and SVP are established by USP, depending on the risk level: i. LPS: not more than 50 particles/ ml that are ≥ 10 µm (50,000/L) OR not more than 5 particles/ml that are ≥ 25 µm (5,000/L). ii. SVP: not more than 10,000 particles/container that are ≥ 10 µm and/or 1,000 particles/container ≥ 25 µm. c) Control and detection of particulate matter: i. Electronic liquid-borne particle counter with a light-obscuration sensor. ii. Clarity test: the swirling of the contents of a container against a light and dark background under light. • Particles of lint, rubber, other debris: float or settle to the bottom • Air bubbles: rise to the surface and dissipate • Normal human vision: detects particles > 50 µm; also reflective particles (glass) of 25 µm. PHCY 6100- Teixeira 4 Parenteral Medications and Sterile Fluids d) Origins: i. The solution itself and chemicals comprising it; ii. The manufacturing process; iii. The packaging components; iv. The devices used for administration; v. The manipulations during preparation. 4. Stability: parenterals regularly have added substances a) Buffers to keep the pH; b) EDTA, citric acid, tartaric acid to prevent oxidative processes; c) Benzyl alcohol, chlorobutanol, benzoates to prevent from microbial and fungal growth; d) Special packaging components, lyophilization (freeze-dry method), spray-drying. PR EPAR ATION OF INJECTIONS 1. Methods: same used for oral solutions, suspensions and emulsions but with some specific characteristics • Special purity of solvents and drugs • Buffers, stabilizers and preservatives are restricted • Coloring agents are prohibited • Products must be sterile, pyrogen-free and particulate-free (compendial standards for particulate matter must be used to avoid thrombus formation and embolism) • Prepared in controlled areas (strict sanitation, personnel especially trained and clothed) • Packaged in hermetic containers as single-dose or multiple-dose • Volume in slight excess • Specific labeling • Powders for reconstitution packaged as lyophilized forms. 2. Solvents And Vehicles: a) AQUEOUS: • • • • Water for injection, USP (WFI): same as purified water, USP; not required to be sterile; must be pyrogen-free; no antimicrobial agent; used for manufacturing of parenterals that will undergo final sterilization. Sterile Water for injection, USP (SWFI): sterile; pyrogen-free; packaged in singledose containers; no antimicrobial agent; used as diluent for reconstitution of powders or in parenteral admixture (aseptically added). Sodium Chloride injection or Normal Saline injection, USP (NS, 0.9% NaCl): sterile; pyrogen-free; isotonic solution (0.9% NaCl, ~154 mEq of sodium and chloride ion/liter); no antimicrobial agent. Bacteriostatic water for injection, USP (BWFI): sterile; pyrogen-free; contain bacteriostatic agents; packaged in containers of not more than 30 ml; used only when small volumes are administered due to toxicity of antimicrobial agents (benzyl alcohol, etc); “Not for use in newborns”. PHCY 6100- Teixeira 5 Parenteral Medications and Sterile Fluids • • • • Bacteriostatic Sodium chloride injection, USP: 0.9% NaCl; same characteristics as BWFI. Ringer’s injection, USP: sterile solution of NaCl + KCl + CaCl 2 in concentration similar to physiologic fluids; used as vehicle or electrolyte replenisher. Lactated Ringer’s or Ringer’s lactated: same as Ringer’s injection + Lactate. Dextrose 5% in Water, USP (D5W): sterile; isotonic solution of dextrose; used to hydrate patients without addition of salts. b) NONAQUEOUS: • • USP grade glycerin, polyethylene glycol, propylene glycol, alcohol: used as solvents for drugs with limited water solubility or susceptible to hydrolysis; must be nonirritating, nontoxic, non-sensitizing; should allow “syringeability” (not very viscous). Fixed vegetable oils, USP: corn oil, cottonseed oil, peanut oil, canola oil, sesame oil; must remain clear when stored under refrigeration; must not contain mineral oil or paraffin; label must list specific oil; used mostly for intramuscular injections. 3. Added substances: a) Only if necessary to increase stability or effectiveness (buffers, preservatives, solubilizers, antioxidants, etc). b) Within a vial of an injectable product the air is customarily replaced with an inert gas (Nitrogen) to prevent chemical reaction with oxygen. PACK AGING, LABELING, STOR AGE OF PARENTERALS 1. Containers: a) Permeability b) Leaching of constituents c) Sorption of drugs d) Transmission of light e) Alteration during storage f) Closures g) Clarity and absence of color (only amber color for light-sensitive drugs) h) Types: i. GLASS: Types I, II, or III. NP type not permitted; heavy, easy to break, bulky for storage, leaching of alkali from soda-lime glass (Types II and III). ii. PLASTIC: low and medium density polymers of polyethylene; allows more variety of shapes and sizes, more resistant to impact, may leach polymer from plastic additives (plasticizers); more prone to cause binding of drug molecules to polymer materials; can be used for packaging as well as for supplies; polypropylene can be autoclaved; polyvinyl chloride (PVC) allows more rigidity and good clarity but cannot be autoclaved. i) Single-dose containers: ampuls, bottles, pre-filled syringes; cannot be resealed; may be packaged as small-volumes or large-volumes. PHCY 6100- Teixeira 6 Parenteral Medications and Sterile Fluids j) Multiple-dose containers: bottles, bags; contain antibacterial preservatives; allow withdrawal of several doses; can be resealed; packaged as small-volumes only (~30 ml to limit number of penetrations and excess of antibacterial agent). 2. Labels: very strict rules apply a) Placement: must leave sufficient area of container free for inspection of particulate matter. b) Labeled volume: a slight excess in volume of the contents of ampuls and vials over the labeled “size” or volume of package is permitted and common practice because it is impossible in practice to transfer the entire volume of a single-dose container or the last dose of a multiple-dose container into a syringe. 3. Storage: RT for chemically pure agents; refrigeration for biological products, vaccines, insulin, some antibiotics, cytotoxic and biotechnology products. DOSAGE FOR M S FOR PAR ENTERAL USE 1. Official Types: defined by USP __________________ Injection, USP: solutions, fat emulsion. Sterile ________________, USP: dry solid or liquid concentrate, need to be reconstituted or diluted, contain no other substance than the drug. _____________ for Injection, USP: same as previous + other substances. Sterile ____________ Suspension: solids suspended in vehicle, not for IV and spinal injection. Sterile _________for Suspension: dry powders, which need addition of suitable vehicles, not for IV and spinal injection. 2. Injections and Other Sterile Fluids: a) SVP (Small Volume Parenterals): preparations for direct injection into vein, muscle, subcutaneous tissue, etc (e.g. insulin, antibiotics, analgesics). b) LVP (Large Volume Parenterals): solutions (except fat emulsion) for intravenous infusion only; contain no antibacterial; used for replenishment of body fluids and electrolytes or to provide nutrition; single-dose containers with volumes varying from 150 ml - 1000 ml. i. Types of LPS: • Maintenance Therapy: for patients entering or recovering from surgery or unconscious. • Replacement Therapy: patients with heavy loss of fluid and /or electrolyte (severe diarrhea, vomiting). • Water Requirement: water is administered in a solution with Dextrose or electrolytes (avoids hemolysis). PHCY 6100- Teixeira 7 Parenteral Medications and Sterile Fluids • Electrolyte Requirement: potassium (cardiac and skeletal muscle function) is used for Hypokalemia during severe burns, GI diseases, acute alcoholism, poor nutrition; sodium (principal extracellular cation) is used for Hyponatremia during excessive sweating, diarrhea, use of some diuretics; chloride (principal extracellular anion, necessary for muscle contraction and to maintain acid-base balance); • Calcium, Magnesium, Iron are also lost but not replaced during short-term parenteral therapy. • Caloric Requirement: D5W is used to maintain basal caloric requirements, reduce caloric deficit and minimizes breakdown of proteins (a 70 Kg fasting patient loses ~80 g/day of protein). • Parenteral Nutrition (Hyperalimentation): infusion of large amounts of basic nutrients (amino acids, high concentration of dextrose, electrolytes, vitamins, fat ) for patients unable to get oral or enteral nutrition. • Enteral Nutrition: nasogastric, gastrostomy or transpyloric routes useful for bedridden patients who are not physically active, post-surgical patients or cancer patients with very poor appetite. • Blood Replenishment: whole blood, red blood cells, serum albumin, plasma protein fraction, etc. • Pellets or Implants: sterile small solids implanted subcutaneously (thigh or abdomen) with especial injectors or by surgical incision; has long-lasting effect (50x - 100x the usual dose used by other routes); some hormones are used as implants (corticosteroids, estrogens, testosterone). • Irrigation Solutions: not used by injection, these solutions are used during surgical procedures to wash blood and debris or to wash wounds. • Dialysis solutions: used for peritoneal dialysis or hemodialysis for removal of toxic substances (poisoning, kidney failure, before renal transplants) from blood or peritoneal cavity. PHCY 6100- Teixeira 8 ...
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