Exam 2 (Polymers, Parenterals 1-6) Flashcards
What are the two types of polymer synthesis? What are examples of each?
Condensation polymerization - Two or more monomers that have different reactive functional groups interact with each other. Ex. Nylon
Addition polymerization - aka Free-radical polymerization. This involves initiation, propagation, and termination of the radical. Ex. polyacrylate, polystyrene.
What is the difference between Mn and Mw?
Mn - Number average. This is when you add the molecular weight of the compound, then divide by the number of monomers.
Mw - Weight average. Here, you divide by the molecular weight.
What is polydispersity?
Polydispersity is when the monomers are not homogenous.
If Mw»_space; Mn, then polydispersity (Mw/Mn)»_space; 1.
This means if it’s more homogenous, the polydispersity will be closer to 1.
What are these properties of polymers: glass transition temperature, structure, mechanical properties (stiffness, toughness, viscoelasticity, molten)
Glass transition temperature - The temp range where a polymer changes from a hard, rigid, or “glassy” state to a more pliable, compliant or “rubbery” state.
- T «_space;Tg = polymer is glass-like and rigid
- T»_space; Tg = polymer is rubbery and soft
Mechanical properties -
- Stiffness: this can be determined by stress/strain (slope), so the more stress needed to break the polymer, the stiffer it is. The more elongation at break, the less stiff it is.
- Toughness: this can be determined by the AUC. Higher AUC means it’s tougher.
- Viscoelastic: When polymers for neither purely elastic or fluid. These polymers show elastic and viscous behaviors
- Molten polymers or concentrates solutions can show Non-Newtonian flow (plastic, pseudoplastic, and dilatant).
What are some factors that affect Tg?
- Polymer length: Longer polymer, higher Tg
- Side chains: More side chains (bulkier), higher Tg
- Cross linking: More crosslinking, higher Tg
- Plasticizer: Lowers Tg
What is the definition of plasticizer and what is the function of them?
Plasticizer - molecules that increase the entropy and mobility of the polymer chains, thus lowering Tg.
ex. Water
What are some features of hydrogels?
Hydrogels - Crosslinked networks of hydrophilic polymers. These are essentially water soluble polymers (ex. jello).
- Chemical gels (covalently crosslinked)
- Physical gels (crosslinked via H-bonds, hydrophobic interactions, or complexations)
These swell rapidly when they are placed in water due to chain-water interactions, electrostatic repulsion, and osmotic forces. They retain a large amount of water in their structures.
What are the reasons for concern when it comes to biologics?
Inadequate controls increase the incidence of medication errors (incorrect ingredients, strengths of ingredients, contamination with pathogens, contamination with pyrogens).
What new law was imposed in 2004 in the USP 797?
A practice standard for compounding sterile preparations in pharmacy was imposed.
What was the idea behind the 2012 article, “Avastin Doesn’t Blind People, People Blind People”
The doctor used the medication left over from the first patient for the second patient, which caused infection that resulted in blinding people.
Humans are the ones making the mistake when it comes to biologic infection risk.
Why is the pharmacist so important when it comes to sterile products?
The pharmacist is THE health care professional that is responsible for doing the last check when approving or rejecting biologic formulas.
What is the distinction between USP chapters > 1000 or < 1000?
Chapters > than 1000 is just a recommendation (nice to have but you don’t have to)
Chapters < 1000 are enforceable.
What is the USP 797?
The law of compounding sterile preparations. Every pharmacist needs to know it and use it for any/all parenteral products.
What is a parenteral product in terms of pharmacy practice?
Products administered by injection. AKA all injectable products.
What are some considerations about parenteral products?
- Administration of the therapeutic agent requires an injury to the body
- Administration bypasses the body’s natural defense barriers
- Administration makes the body vulnerable
- Products must meet some stringent requirements
What are the 3 main requirements specifically for parenterals?
- Sterile
- Particle free
- Pyrogen free
(Pyrogen = bacteria endotoxins that produce fever)
What are the 5 risks when it comes to parenterals?
- Microbial contamination
- Excessive bacterial endotoxins
- Variability in the intended strength of correct ingredients
- Unintended chemical and physical contaminants
- Ingredients of inappropriate quality
What does it mean for something to be sterile and how do we achieve sterilization?
Sterile - Free of microbial organisms
Achieved by -
- Steam (autoclave)
- Filtration (bacteria retentive membrane)
- Dry heat (oven; used to make vial sterile)
- Gas (ethylene oxide)
- Irradiation (gamma rays; used to sterilize clothes/gloves/equipment)
T or F: Sterilization gets rid of pyrogens
False;
Why do we want parenterals to be particle free?
Foreign particles can trigger immune responses that can produce damage to the lungs and kidneys. Particles have killed people.
What’s the difference between septicemia and septic shock?
Septicemia - Infection of the blood
Septic shock - Acute reaction to bacterial endotoxins
What does the preposition,”for,” mean in terms of parenterals. Ex. Purduemycin for injection
“for” - don’t use it as is; you have to do something to it before injecting
Why do we worry about the size of the preparation? How many mL does something need to be in order to be considered a large volume parenteral?
If something goes wrong, and the volume is large, then that’s a large problem.
LVP - Large volume parenteral. Single dose injections packages in a container containing more than 100mL.
What is the preferred vehicle in parenterals?
Water
More specifically, there are 3 types of water used in parenteral products:
- WFI - Water for injection: Pyrogen free, non sterile, single use sealed container.
- SWFI - Sterile water for injection USP: Pyrogen free, sterile, packed in sealed containers not larger than 1000mL
- BWFI - Bacteriostatic water for injection USP: Pyrogen free, sterile with antimicrobial agent added
What is important about SWFI?
Although it is pharmacologically safe, sterile, particle and pyrogen free, we can never inject plain water directly into the blood stream (it will produce lysis of the cells).
What are 4 traits of the IV ROA?
- Very rapid
- Straight to the blood
- Good for irritant drugs (because it gets diluted in the blood immediately)
- Suitable for large volumes (careful of mistakes)
If something is good for IV, it can almost always be used for all other types of injections.
What’s the difference between requirements for parenteral v. intra-spinal injections?
Parenteral requirements: sterile, particle free, pyrogen free. (isotonic and phys. pH is recommended)
Intra-spinal injection: sterile, particle free, pyrogen free, isotonic, physiological pH, no preservatives.
Intra-spinal injections have much stricter requirements
What are the common aqueous isotonic vehicles?
0.9% (w/v) NaCl solution - AKA normal saline (NS) or saline
5% (w/v) Dextrose Solution - AKA D5W
- These are usually interchangeable, but sometimes they aren’t, so we need to be cautious of that.
Also bacteriostatic sodium chloride injection (NS with antimicrobial preservatives) & Ringer’s solution (NS with K+ and Ca2+ in physiological conc.)
What are the 3 common water miscible solvents used as vehicles for parenterals?
Ethyl alcohol, polyethylene glycol (PEG), propylene glycol (PG)
- These are used to solubilize drugs and can also slow down hydrolysis. (Often used in IM but can also be used in IV)
- Due to their hemolytic potential, we can only have a certain concentration of the cosolvent in parenterals.
T or F: oil can never be injected into the blood stream.
False, an oil emulsion is okay for IV injection, but straight liquid oil can’t (acts like an embolus).
ex. Flour vs. cake
What are the common antimicrobials, what preparations are they used for, and when are they not as effective?
Benzyl alcohol 0.9% (most common), parabens (like methyl 0.18%, propyl 0.02%-parabens), and Cresol.
- Used for multi-dose purpose (NOT single use)
- Antimicrobials are not very effective in non-aqueous formulations.
What are 3 important components of using preservatives in parenterals?
- Some people are allergic to preservatives
- Do not use preservatives (especially benzyl alcohol) in neonates, because it can produce gasping syndrome
- No preservatives in intra-spinal route administration
Why do we use buffers and what are the 3 common buffers?
The buffer is there to protect the drug over time (help shelf life, preserve product). Once we are going to inject the drug, we want the drug as close to physiological pH as possible to reduce irritation.
Common buffers:
- Citrates: Safe by IV, irritating by IM or SC routes
- Acetates
- Phosphates - potentially fatal danger (phosphate + calcium combined have strong tendency to precipitate and can be fatal)
Common antioxidants (4) and chelating agent (most common)?
Antioxidants -
- Metabisulfite salts (low pH)
- Bisulfate (intermediate pH)
- Sulfite (high pH)
- Ascorbic acid
Chelating agents - catalyze oxidation reactions
- Sodium EDTA (most common)
What do we do if the preparation doesn’t match phys. pH?
Inject in small volumes
Inject slowly
Inject into central vein
What type of glass should be used as a container for parenterals?
Use type 1 glass to minimize problems
What does the drop number for IV bags tell you?
Ex. 15 is drop number - 15 drops = 1cc (mL)
Things that actually affect drops/mL
- Viscosity of the CSP
- Surface tension
- Density
What are the two types of tips of syringes? Which one is required for hazardous drugs?
Leur tip and Leur Lok
Leur Lok is required for hazardous drugs.
Why do filter needles need to be used when using ampules?
To filter out the microscopic shards of glass that are in the drug due to breaking the ampule.
What does it mean that the IV route of administration is the least forgiving?
There is immediate distribution, so there’s no line of defense if something goes wrong.
In general, if it can go into IV, it can be used in other routes of admin.
But there are some things that can go in IM that cannot go into IV.
What are the 3 common venous complications for IVs?
Phlebitis - Inflammation from irritation of the tunica intima of the vein. Involves moderate to severe discomfort, may take days-months to subside, limits veins available for future therapy.
Thrombosis - Formation of a blood clot in the vein. Involves pain, swelling, and pulmonary embolism.
Thrombophlebitis - A little bit of both
Why should we worry about infusion rates?
Small injection volumes can give very high injection rates that are not dangers, but large volumes can give very “reasonably looking” infusion rates that are in fact dangerous (ex. person has kidney deficiency).
The body can void ~3000 mL/day (about 100-150 mL/hr)
Ex. pt lost arms and legs because they were given too much IV fluid
What are the max volumes of IM injection we can give at the deltoid, thigh, and gluteal muscles?
Deltoid - 2mL
Thigh - 5mL
Gluteal - 5mL
IM injections still need to get absorbed, so it’s not always faster than oral drugs.
What’s the max admin volume for SUBQ?
Is IM or SUBQ faster?
What’s infusion by subcutaneous route called?
How do the formulation considerations of SUBQ vs IM compare?
- Admin volume can’t be more than 1.5mL
- Absorption tends to be slower than IM due to lower vascularization of the tissue
- Hypodermoclysis - infusion by subcutaneous route
- Formulation considerations are similar to those for IM route
What are the 2 intraspinal ROAs?
Intrathecal - into the subarachnoid space and cerebral fluid (brain); Bolus admin directly into the CSF; Meds have higher potency than epidural for intrathecal.
Epidural - Into the space at the thoracic or lumbar level between the dura mater and the vertebral canal (epidural space); Bolus or continuous admin; In neonates, it’s at the caudal level.
What is the special care for intra-spinal injections?
Must be isotonic
Must have physiological pH
Cannot have preservatives
What is “first air,” and why is it so imporant?
First air - the air exiting the HEPA filter in a unidirectional air stream that is essentially particle free. All items required for the preparation of the CSP are to maintain a clear, uninterrupted path of HEPA filtered air the entire time.
If we violate this, we could harm the patient.
What are the sources of contamination of CSPs?
There are 3 sources of contamination:
- People
- Equipment
- Environment
What are the quantitative parameters associated with the air quality required for aseptic technique?
In the critical area, the air is HEPA filtered (ISO Class 5) - no more than 100 particles > 0.5 micron per cubic foot (3520 particles/cubic meter)
What is the difference between the two types of air flow used in PECs for CSPs?
Horizonal
Vertical - hardest; must be used for hazardous (cytotoxic and vesicant) products
What are the different regions/locations associated with proper aseptic technique and inside the LAFW?
Critical site - Any point where microorganisms or other contamination could enter a parenteral product during compounding
Critical area - ISO Class 5 environment; The space between the HEPA filter and the critical site. Must keep first air laminar air flow in this area
Direct compounding area (DCA) - Area within the LAFW where critical sites are exposed to HEPA filtered air
What do these stand for: PEC, LAFW
PEC - Primary engineering control
LAFW - Laminar air flow workbench
What parts of IV administration sets are most frequently used in hospitals?
There’s a basic set with one Y site and an add-a-line set with more than 1 Y-site.
Macrodrip - Delivers large quantities at faster rates. 10, 15, 20 drops/mL
Microdrip - When pt needs small or closely regulated amount of IV solution; 60 drops/mL
Volume-control sets - Use when precision is needed.
ADD-Vantage system - The vial with the drug is attached to the bag and the separation is removed, thus mixing the contents in the bag.
What parameters affect (by facilitating or by presenting resistance) IV fluid flow during infusion to patients?
rate = Driving Force/Resistance
- Tubing (macrobore vs. microbore)
- In-line filter
- Viscosity of IV fluid
- Length of tubing
- Venous backpressure
What’s the difference between peripheral and central vein access devices?
Peripheral
- Butterfly needle - Used to reduce movement of the needle
- Over-the-Needle catheter - Use needle only to pierce the vein, then put a catheter that can move without causing damage (this is preferred)
Central - more expensive, requires more skill than peripheral, can get larger volumes
- PICC
- Surgically implanted
What are the different central vein devices we’ve seen?
PICC - through the arm
through the jugular is also an option
CVC - surgically implanted
Hickman - central line; requires surgical insertion, dacron cuff prevents excess motion.
Broviac - central line
Vascular access port - the port and catheter is under the skin; uses a noncoring needle
What conditions warrant central vein therapy?
For pts that need repeated administration of large volumes of fluid. This is for long-term infusion therapy. Also for irritating medications like potassium and fluids with high osmolarity. Ex. total parenteral nutrition (TPN).
What are the advantages and risks associated with central vein therapy?
Advantages -
- Access to central veins
- Rapid infusion of large amounts of fluid
- Can draw blood and measure CV pressure
- Reduces the need for repeated venipunctures
- Reduces risk of vein irritation from infusing irritating substances due to quick dilution
Risks -
- Sepsis
- Thrombus formation
- Perforation of vessel and adjacent organs
- Air embolism
Complications from damage to inner lining of the vein:
- Stenosis
- Thrombus
- Venous occlusion
- Phlebitis and pain
What are the main types of flow control devices utilized in infusion therapy?
Controllers - Uses gravity
Pumps - Powered devices. Provides a pressure between 2-12 psi. High pressure is used for intra-arterial infusion.
- Use of excessive infusion pressures can be a hazard with respect to infiltration at the site of injection.
- Syringe pumps: for small volume infusion, useful for intermittent IV meds, it’s a smart machine, useful for pediatric patients
What do these terms mean: PICC, LVP, CVC, VAP, PCA
PICC - Peripherally-inserted central catheter
LVP - Large volume parenteral
CVC - Central vein catheter
VAP - Vascular access port
PCA - patient-controlled analgesia
What are some features of infusion pumps?
- Volumetric delivery regardless of back pressure, tubing resistance, position of patient, etc.
- Safety features (alarm for things like occlusion of line, air in line, empty container, flow rate error, etc)
- Pumps are getting smarter
- The pump doesn’t need the drip chamber
ex. Symbiq, Omni-Flow
What are three other parenteral pumps?
Patient controlled analgesia - Pain relief is generally obtained at a lower total dose of drug
Ambulatory pumps - Refers to size and weight of the pump, as well as ability to operate without an external power source.
Implantable pumps - Usually with reservoirs of ~50mL. Used for IV, intraspinal, and intra-arterial routes. These can deliver as low as 1 uL/hr.
What is isotonicity? What is iso-osmolarity? What’s the difference?
Isotonicity - Uniform tension or tone between the membrane of living cells & their surrounding environments
Iso-osmolarity - Solutions containing the same concentration of particles
In what situations are iso-osmotic solutions also isotonic, and what situations are iso-osmotic solutions not isotonic?
Osmolarity is a number measured by an instrument. Tonicity refers to the effect on living cells. For example, if a solution of sulfuric acid gives the same osmolarity value as NS, the two solutions are iso-osmotic, but only the NS is isotonic (bc it’s compatible with living cells).
So if it’s not compatible with living cells, it’s not isotonic.
Side note, also NS and D5W are both isotonic, they are not always interchangeable.
What is the relationship between osmolarity and tonicity in the context of cell lysis?
- The solution can’t be isotonic if the cell breaks open.
Blood cells will lyse if SWFI is injected to the the water rapidly entering the cell due to osmosis.
How do we measure the risk of any given preparation?
By knowing the osmolarity or the osmolality of the preparation.
We measure this using an osmometer (adds up the total concentration of solutes dissolved, including the drug).
- This uses properties like freezing point depression, lowering or vapor pressure, osmotic pressure, and elevation of boiling point.
What is the equation for molarity and what is the equation for osmolarity?
Molarity = # moles of solute / Liter of solution
Osmolarity = # Osmoles of solute / Liter of solution
Osmolarity = [# moles of solute / Liter of solution] x [# m-particles / 1 molecule]
What’s the difference between the equations for osmolarity and osmolality?
Osmolarity = [# osmoles of solute / (volume of solvent + solute)]
Osmolality = [# osmoles of solute / weight (kg) of only the solvent]
