Parenterals Flashcards
1
Q
Parenteral
A
- Intended to be placed in direct contact with the internal body fluids or tissues (injections)
- Must be sterile and pyrogen-free
2
Q
Sterile
A
Absence of viable microorganisms
3
Q
Sterilization
A
Process by which all viable microorganisms are removed or destroyed
4
Q
Pyrogens
A
- Bacterial endotoxins
- Organic substances resulting microbial growth or breakdown
- Produces fevers, chills, malaise, shock when injected into humans
5
Q
Injectables
A
Any dosage form placed beneath the skin of the body using a needle, catheter, or cannula
6
Q
Thrombus
A
Blood clot formed within a blood vessel
7
Q
Embolus
A
Thrombus that is circulating in blood stream
8
Q
Embolism
A
Embolus lodges in a blood vessel and blocks or occludes blood flow
9
Q
When to Use Parenterals
A
- Rapid onset of action (general)
- Patient is uncooperative
- Patient is unconscious
- Drug not absorbed through biological membranes (compare oral tablets)
10
Q
Routes of Parenteral Administration
A
- Intramuscular - 90 degrees
- Subcutaneous - 45 degrees (subcutaneous tissue)
- Intravenous - 25 degrees (dermis)
- Intradermal - 10-15 degrees (epidermis)
11
Q
IV Advantages
A
- Rapid onset of action - no absorption step
- Accurate blood levels can be achieved and maintained by continuous infusion of drug
- Useful in emergency situations because of the rapid circulation of the drug
12
Q
IV Disadvantages
A
- Once administered, drug cannot be retrieved
- Potential for thrombosis or embolism - most common if needle touches wall of vein
- More common when drug solution is irritating to body tissue
13
Q
Bevel
A
- Inject with needle facing upwards at an angle
- Ensure direction of flow is in flow with the blood
- Ensure that lumen is unobstructed
14
Q
Flashback/Back Flow
A
Pulling back on syringe to ensure entrance into vein, blood should enter syringe if in vein
15
Q
Aseptic Precaution
A
- Used to avoid risk of infection
- IV solution, syringe, and needle are sterile
- Swab skin area to clean prior to injection
16
Q
Vessels
A
- Differ in size and closeness to surface
- Differ with age, type of illness, gender
- Men’s are closer to surface than womens’
17
Q
Are injections more or less painful near fingers?
A
More
18
Q
Should you administer irritating drugs in larger or smaller veins?
A
Larger - want the maximum chance of immediate dilution
19
Q
What can be administered by IV?
A
- Large and small volume parenterals (no volume restriction)
- Drugs must be in solution - water or water-miscible solvent, emulsions (NO SUSPENSIONS OR OIL SOLUTIONS)
- Can use almost any size needle depending on injection site
20
Q
IM Advantages
A
-Prolonged drug action compared to IV (depot effect)
21
Q
IM Disadvantages
A
- Longer/larger needles needed
- Less rapid onset
- Absorption steps - muscle to blood stream which can be fast or slow depending on formulation
22
Q
IM Route - Sites
A
- Avoid major nerves and blood vessels
- Upper quadrant of butt
- Thigh (vastus lateralis) or deltoid of arm are also good sites
- Thigh or deltoid are best for infants/small children (not enough muscle in gluteus maximus)
23
Q
Should there be flashback/backflow of blood with IM?
A
No
24
Q
What can be administered by IM?
A
- Aqueous solutions/suspensions
- Oleaginous solutions/suspensions
- Chemical/physical properties of drug and anticipated biological response determines which prep to use
- Solutions with water-miscible solvents are rarely used IM since they tend to cause irritation/damage
- Volume restrictions - 2 mL for deltoid; 5 mL for butt
25
SC Info
- Injection just under skin - loose interstitial tissue of upper arm, anterior thigh, or lower abdomen
- Shorter, more narrow gauge needles used
- No flashback/backflow
- Absorption step - rates can be rapid depending on formulation
- Aqueous solutions and suspensions
- Volume restriction - ~1.3 mL
26
ID (Intradermal) Info
- Injection just beneath epidermis
- Least common
- Typically for immunizations, diagnostics (TB), or anesthetics for pain during stitching procedures
- Short needles or narrow gauges
- VERY small injection volumes
27
ID Sites
- Upper pectorals
- Back near shoulder blades
- In the bends of elbows
28
Other Routes of Admin
1. Intra-articular (joints)
2. Intrasynovial (joint fluid area)
3. Intraspinal (spinal column)
4. Intrathercal (spincal fluid)
5. Intra-arterial (arteries)
6. Intracardiac (heart)
7. Central venous catheters (ports) - used when repeated IVs are required like in chemo patients or TPN solutions
29
Parenteral Formulaiton Requirements
- Solvents/vehicles must be of highest purity
- Added substances must be of highest purity
- Inclusion of each material MUST be justified
- ALWAYS sterile and pyrogen-free
- Stricter compendial standards for the limits of particulate matter
- Prepared STRICTLY in controlled environments by trained personnel
- Packaged in HERMETICALLY sealed containers of high quality
- Filled to a volume that is in excess of the labeled size
- Restrictions limit the volume of the product which can be sealed into a container
- Specific label requirements
30
Parenteral Solvent Vehicles
Aqueous Vehicles
1. Water for injection
2. Sterile water for injection
3. Bacteriostatic water for injection
4. Sodium chloride injection
5. Bacteriostatic sodium chloride injection
6. Ringer and lactated ringer injected
Non-Aqueous Vehicles
31
Water for Injection, USP
- Purified by distillation or reverse osmosis
- Total solids <1mg/100 mL
- May contain added substances
- Must be pyrogen-free (not required to be sterile)
- Intended to be used in the manufacture or injectable products`
32
Sterile Water for Injection, USP
- Packaged in single-dose containers, no larger than 1 L
- Must be pyrogen-free (and sterile)
- Cannot contain any antimicrobial agents or other substances
- Intended to be used a solvent, vehicle, or diluent for already sterilized and packaged injectables
- 1 L bottle cannot be administered intravenously due to lack of ISOTONICITY
33
Bacteriostatic Water for Injection, USP
- Sterile water for injection containing one or more antimicrobial agents
- Packaged in prefilled syringes or vials (=< 30 mL)
- Used as a sterile vehicle in preparation of small volume parenterals (< 5mL of solvent is needed)
- Labeled "not for use in neonates"
34
Sodium Chloride Injection
- Sterile isotonic solution of sodium chloride in water for injection
- No antimicrobial agents
- Used as sterile vehicle in solutions or suspension of drugs for parenteral admin. (reconstitution)
- Also used to flush catheter/IV line
35
Bacteriostatic Sodium Chloride for Injection
- Sterile isotonic solution of sodium chloride in water for injection + one or more antimicrobial agents
- Packaged in vials =< 30 mL
- Used for reconstitution and to flush catheter/IV line
- Not for use in neonates
36
Ringers Injection
- Sterile solution of sodium chloride, potassium chloride, calcium chloride, and sodium bicarbonate in water for injection
- Concentration of electrolytes similar to physiologic fluids
- Used as vehicle for other drugs or alone as an electrolyte replenisher and plasma volume expander
37
Lactated Ringers Injection
- Different concentrations of the 3 salts plus sodium lactate instead of sodium bicarbonate
- Used as a fluid and electrolyte replenisher and a system alkalizer
38
Non-Aqueous Vehicles
- Used when physical and chemical characteristics of drugs preclude the use of water
- Solvents include water-miscible and not water-miscible
- No single "miracle" non-aqueous solvent
39
Water-Miscible Solvent Examples
- Propylene glycol
- Polyethylene glycol
- Glycerin
- Alcohols
40
Not Water-Miscible Solvent Examples
- Peanut oil
- Cottonseed oil
- Sesame oil
- Castor oil
DO NOT USE MINERAL OIL
41
Other Substances
- Only included if they increase stability or usefulness of preparation
- For some drugs, which substances CAN NOT be included are in their monograph
- Typical additives: buffers, preservatives, solubilizers, and antioxidants
42
Possible Ingredient List
- Drug
- Solvent
- Osmotic pressure adjuster
- Bacteriostatic agent(s)
- Buffers
- pH Adjusters
- Antioxidants
- Chelating Agents (EDTA)
- Solubilizing Agents
- Viscosity Building Agent
43
Osmotic Pressure Adjusters
- Added if needing to achieve a desired osmotic pressure
| - EX: NaCl, Mannitol, dextrose
44
Bacteriostatic Agent(s)
- Used if multi-dose product
| - EX: benzyl alcohol, phenol
45
Buffering Agents
- Only added if pH range is necessary to maintain
| - EX: phosphate salts, acetates, citrates
46
pH Adjusters
- If product requires specific pH
| - EX: NaOH, HCl
47
Antioxidants
- If drug is prone to oxidation
| - EX: Bisulfate, ascorbate
48
Solubilizing Agent
-If needed to get desired concentration of drug
| EX: surfactants like polysorbate 80
49
Viscosity Building Agent
- IF suspension product used
- Thickener
- EX: NaCMC
50
Sterility and Pyrogens
- Complete destruction or removal of all living organisms and their spores form a preparation
- Several sterilization methods utilized
- Method Used depends on ingredients/prudct
51
Sterilization Methods
1. Steam Sterilization
2. Dry-heat sterilization
3. Sterilization by filtration
4. Gas sterilization
5. Sterilization by ionizing radiation
52
Steam Sterilization
- Requires an autoclave (similar to pressure cooker)
- Bacteria and spored are killed by high pressure steam, permeates everything
- Sealed vials or ampules (flass) or an aqueous solution will generate their own steam at high temperatures and sterilize inner contents
- Destruction of the protein in the cell kills microorganisms
- Higher pressures allow for higher temperatures to be achieved and therefore less exposure periods to be necessary
53
Dry-Heat Sterilization
-Form of sterilization that uses ONLY heat
-Kills bacteria/spores by dehydration
-Requires higher temperatures and longer exposures than steam sterilization
(160-170C for at least 2 hours)
-Many drugs/products can't handle these temperatures
-Dosage forms that can handle it: oil-based suspensions/solutions, petrolatum products, bulk powders
54
Filtration Sterilization
- Physical removal of microorganisms by passing solutions through specialized filters
- Cellulose is the most common, or nylon
- High number of narrow pores through a tortuous path
- Primarily used for heat sensitive products
- Cannot be used for suspensions
- Filters used in multiple places during manufacturing
- Often used in clinics/hospitals when small amount of solution needs sterilization
- Can be fast/efficient with small volumes but takes more time with larger volumes or highly viscous products
- Prepackaged filter/filter holders can be used for single use
- Suitable for thermo-labile drugs
- Possibility of active drug absorbing to the membrane filter
55
Filter Sizes
- Generally 0.22 and 0.45 micron
- 0.45 - gives clean particulate-free solution but only when starting with sterile solution
- 0.22 when combined with clean, top-quality ingredients and sterile water is usually considered to produce a sterile solution
- CANNOT STERILIZE SOLUTIONS WITH VIRAL EXPOSURE
56
Gas Filtration
- Exposure of product to ethylene oxide or propylene oxide gas
- Gases interfere with metabolism of microorganisms
- Method requires a chamber (like an autoclave)
- Product exposed to gas, humidity, and heat
- Exposure time: 4-16 hours depending on product/conditions
- Primarily used to sterilize surgical instruments, needles, syringes, and disposable plastics
57
Ionizing Radiation Sterilization
- High energy, penetrating gamma radiation
- Can sterile even densely packaged products
- Microorganisms die and can no longer grow due to DNA damage
- Cold process with no heat
- Time of exposure is the only variable
- Can be used with devices, syringes, ointments, raw ingredients, heat-sensitive drugs
58
How to know a process worked?
- Validation of process - like manufacturing the active and drug product
- Test methods defined by USP
- Aerobic and anaerobic organisms killed is tested
- Tests are also performed routinely to confirm equipment's functionality (autoclave tape for example)
59
Pyrogen-Free Establishment
- Ideally use pyrogen-free water, top ingredients, ensure no times for microorganism growth
- Pyrogen Test - inject healthy rabbits with 10 mL/kg of product and if <0.5 temperature increase is achieved then considered pyrogen free
- Bacterial Endotoxins Test - aka 'LAL' test (limulus amebocyte lysate), enzyme from horseshoe crab that will coagulate in the presence of bacterial endotoxins
60
Parenteral Storage/Packaging
- Compatibility of container with formulation
- Type of glass for storage may be indicated in the drug's monographo
- Amber and clear glass - inspection of contents allowed
- Single dose: cannot be re-sealed
- Multi-dose: allows to remove some product while maintaining purity
61
Single-Dose Containers
- Ampules: sealed by fusion of glass container under aseptic conditions, break top, use filter needles
- Vials: liquids or powders for reconstitution
- Single-use, disposable, pre-filled syringes
62
Multiple Dose Containers
- Vials with rubber closures
- Holds =< 30 mL (~10 doses)
- Use needle to penetrate closure and remove desired volume, closure reseals upon removal of needle
- Sterility maintained as long as need is sterile
- Prefilled syringes also exist for multiple dosing
- Typically contain antibacterial preservatices
- Liquids or powders for reconstitution
63
Parenteral Labeling Requirements
- Name of prep
- Strength - liquids = % strength and amount/volume. powder = amount of active present
- Route of admin
- Storage conditions
- Lot number and expiration
- Name of manufacturer/distributor
- Label on container must allow for visual inspection
64
Small Volume Parenterals: Insulin
- Hormone secreted by pancreas-glucose metabolism
- Patient produces no insulin
- Insulin does not respond to body glucose
- Very high MW protein from pig/cow pancreas, also some human sources
- Primarily administered SC - too large to be absorbed orally and degraded by stomach acid/enzymes
65
Insulin Formulations
- Multiple dose vials or prefilled syringes
- Strength = units/mL
- Insulin differs by onset, time to peak, and duration of action
66
Insulin Injection
- Regular insulin ('R')
- Solution made form dissolved zinc-insulin crystals
- Near neutral pH
- Contains phenol or cresol as a preservative
- Rapid onset of action (immediate)
- Stored in fridge
- Should not be frozen (damages proteins)
- Don't inject cold product
67
Isophane Insulin Suspension
- 'NPH' insulin
- eutral Protamine Hagedorn
- Aqueous, buffered suspension containing crystals of zinc-insulin-protamine
- Suspended particles ~30 microns in size
- Human or animal sources
- Intermediate acting
68
Mixtures of NPH/Regular Insulin
- Fast onset of action
- Longer duration
- Mixed together in syringe and injected
- Available in premixed vials
- 70/30 or 50/50 (NPH/Regular)
- SC only
69
Prompt Insulin Zinc Suspension
- Semilente
- Amorphous insulin zinc suspension
- Dissolves rapidly after SC injection
70
Extended Insulin Zinc Suspension
- Ultralente
- Crystals of insulin zinc suspension
- Dissolves slowly upon SC injection
71
Insulin Zinc Suspension
- Lente
- 70/30 mixture of ultralente and semilente
- Fairly rapid onset, intermediate duration -Still possibly available for use in dogs and cats
72
Insulin Lispro Injection
- Differs by a few amino acids
- Very rapid onset of action and short duration (multiple injections)
- Intended for injection just prior to a meal
- Lispro mixtures: complex with NPH to make it long acting in 75/25 or 50/50 mix
73
Insulin Aspart
- Novolog
- Differs by a few amino acids
- Very rapid onset and short duration
74
Insulin Glargine
- Lantus
- Rearrangement of amino acids (long duration)
- Intended to provide basal coverage
- Very fine dispersion of microspheres
75
Insuline Glulisine
- Apidra
- Another manipulation of insulin protein
- Rapid onset of action, short duration
- Admin prior to meal
- Intended to use in patients that also use a long acting insulin
76
Insulin Detemir
- Levemir
- Another insulin analog
- No peak activity but long acting
- Provides basal levels of insulin
- Other rapid acting/short duration insulin used to provide extra activity for meals
77
Insulin Infusion Pumps
- Infusion of SC insulin to maintain normal levels - strict control at 70-140 mg/dL
- Small, lightweight pumps
- Delivers either short-acting or rapid-acting insulin
- Patients still need to monitor glucose levels
- Potential infusion-site reactions
- Can be used in conjunction with artificial pancreas
78
Administering Insulin Pen
- Pen holds multiple doses of insulin
- Small disposable needle tips attached
- Inject SC
- Can be pre-filled that are discarded when empty or reusable by adding new cartridges
79
Large Volume Parenterals
- 100-2000 mL
- Glass bottles or plastic bags
- Lack of preservatives so single use
- Not necessarily drug-containing solutions
- If adding a drug there is a possible incompatibility
- Given by IV
- Same quality criteria as small volume parenterals - sterile and pyrogen-free
80
Use of Large Volume Parenterals
- Maintenance
- Replacement therapy (water, electrolytes)
- Deliver calories
- Enable slow infusion of drug solutions - contrast to single bolus
- Parenteral nutrition
81
Parenteral Special Considerations
- Potential for med errors from calculation mistakes or wrong drugs
- Adsorption of drugs in the IV lines, glassware, or tubing
- Contamination of IV lines and tubing
- Handling and disposal of chemotherapeutics
82
Implantable Pellets
- Alternative injectable
- EX: Levonorgestrel implants
- Subdermal implantation
- Provides long-term reversible contraception
- Must be sterile and pyrogen-free
83
Irrigation Solutions
- Alternative injectable
- Bathe/wash wounds, surgical incisions, body tissues
- Must be sterile and pyrogen-free
84
Dialysis Solutions
- Alternative injectable
- Remove toxins from blood (hemodialysis)
- Removes toxins from peritoneal cavity (peritoneal dialysis)
- Must be sterile and pyrogen-free
