brunetti parenterals 2

why the parenteral route?

- rapid onset of drug action in emergency situations

- patients who are nil per os; nothing by mouth for medical reasons

- unconscious

- for drugs, like proteins, that cannot be absorbed effectively from the GI

practical considerations for parenteral administration

- intradermal almost never used for treatment

- IM and SQ used fairly often, but they must be absorbed into systemic circulation

- more volume in IM than SQ

- more delayed drug delivery with IM; allows for oil formulations to sit and slowly release over time

cleansing the injection site

- 70% isopropyl alcohol

- povidone iodine [Betadine]

- chlorhexidine-alcohol

choosing the appropriate needle gauge and length

- length is based on route of administration

- gauge of needle is thickness; lower is thicker and higher is thinner

- tend to use higher gauge

general characteristics of IV preparations

- provides rapid onset action

- bioavailability 100% in IV because no absorption phase

IV bolus vs infusion

- bolus with 21 g needle

- bolus undiluted directly in systemic circulation

- infusion for patient safety with diluted drug slowly administered over time to minimize toxicity

- bolus achieves effective Cp immediately, followed by IV infusion to sustain Cp level

- some drugs can never be given bolus, but some drugs must be given low doses as bolus

nurses often dilute IV push meds

- nurses do this to diminish pain and irritation at injection site and to avoid drug reactions

- sometimes they do this because undiluted solution too viscous or more concentrated solution is too difficult to measure the appropriate dose in the syringe

- because usually nurses perform this dilution outside of a laminar flow workstation, possible that sterility of injectable solution may be compromised

- very quick process, so do not have to worry about class sterility

1 liter=

1 kg

IV preps in large volumes

- LVPs up to 1000 mL are administered via infusion via an indwelling catheter (needle)

- infusion flow rates

- there are risks associated with IV administration and indwelling catheters

infusion flow rates

- can be up to 150 mL/hr or greater, unless KVO/keep vein open the slower

- rate also depends on the specific drug. once determined, the rate is accurately controlled with infusion pumps

common structure of catheter

- one spike in you, splits off into y or w shape

- multiple entry points, so you can infuse multiple drugs at once

risks associated with IV administration and indwelling catheters

- infection

- thrombophlebitis

- extravasation

- central line associated blood stream infections (CLABSIs)

extravasation

- could have devastating consequences depending on the physiochemical characteristics of the drug

- drug that is caustic leaks out into dermal area and causes necrosis

CLABSIs and venous thromboembolisms

- there are 2 adverse complications that are associated with IV infusions, indwelling catheters and central venous catheters

- there are problems that become life-threatening

- when there products occur, it detracts from the hospital's quality index ratings

infiltration

- leakage to surrounding tissue if non-vesicant solution

Vesicants

- something that causes tissue necrosis

- ex: many therapeutic agents

- may need surgical intervention

how to handle extravasated drug

- antidote preferred over saline

peripheral IV

- inserted into peripheral veins, but do not terminate in central veins

- may feel burning

- regular peripheral IVs can cause fewer events compared to central, but regular peripheral IVs are short term

Central Venous catheters (CVC)

- for patients who need longer-term venous access

- also to minimize pain and risk of harm for some patients

- are catheters that are inserted directly into central veins

- usually inserted by physicians into a vein in the neck and are often reserved the ICU

- the lines eventually reach the superior vena cava

CVC increase the risk of

- CLABSI

- venous thromboembolisms

PICC line (peripherally inserted central catheter)

- a more commonly used variation of CVC line

- can be inserted by physicians or specially trained nurse

- are inserted into peripheral veins but terminate in central veins live CVCs

- not limited to the ICU

- may require heparinization or KVO slow infusion with isotonic LVPs to prevent thrombus formation

advantage of PICC lines

- can be kept in longer that peripheral IVs

disadvantages of PICC line

- poses greater risk of infection and embolism than ordinary peripherally venous catheters

intra-arterial

- less common form of the intravascular route

- for targeting a drug to a specific region or tissue

- high risk of injury

onset for IM

- more slowly absorbed and slow onset

- effects of the drug will be prolonged

IM needle

- lower gauge, around 20, so that you can draw up the formulation

drugs you can only use with IM

- Benzathine Penicillin G

- an aqueous suspension, so it can never be administered IV

- the preferred treatment for syphilis

where can you inject IM

- deltoid muscle for smaller volume up to 2 mL

- gluteus maximus for larger volume up to 5 mL

- MUST avoid hitting nerves or blood vessels

SQ needles

- 21g

- shorter than IV bolus or IM

SQ injection volume

- limited to 2 mL, but usually lower

other names of SQ injection

- hypodermic injections

SQ injection sites

- upper arm or the anterior thigh

- need to rotate the site of injection for frequently administered SC injections, as with insulin, to reduce risk of lipoatrophy

- "pinch and inch"

what is SQ not suitable for

- irritating drugs

intradermal points

- 23g needles

- shorter needle length

- often used for diagnostic tests and some immunizations

- not as common as IV, IM, or SQ

- limited to less than 2 mL

- not intended for producing systemic effects

safe injection practices

- use new needle and syringe each time you reuse MDV

- make sure to wipe the rubber top before each use every time with alcohol swab

Safe syringe and assistance for substance abuse issues

- hypodermic syringes and needles may be sold from the pharmacy department behind the counter in NJ pharmacies under the supervision of a licensed pharmacist

- the purchaser needs to show proof of 18 years of age, and then purchase is limited to a maximum of 10 units at a time

- the pharmacy must provide the purchaser with a state-approved info sheet on proper disposal, including locations, as per the NJ department of health and human services

industrial manufacture or large-scale compounding of parenteral dosage forms

- as enforced by FDA for all US manufacturing facilities

industrial general compounding considerations

- adhere to all applicable cGMPs/current good manufacturing practices

- subject to FDA inspections which could result in recalls or closures if violations are found

Hospital/infusion pharmacy general considerations of parenteral compounding

- requirements are enforced by the state board of pharmacy

- monitored by the joint commission, the hospital accrediting agency

similarities between industry and healthcare facilities

- environmental controls: ISO class 5 environmental control in Direct compounding areas

- aseptic technique/processing: there must be no obstruction between HEPA filter's "first air" and any "critical sites"

- have only essential objects on the working surface of the Hood/direct compounding area to avoid the creation of dead spaces that obstruct laminar air flow

- training programs required by all involved personnel, with periodic recertification

- overall process validation to be conducted at the end of each batch preparation. more routine in industrial manufacturing or in 503b outsourcing compounding pharmacies

- policy and procedures manual required in industry, hospitals, and 503b facilities

- industrial processing involves adherence to similar requirements as in hospital CSP work. USP chapter 797 and 800 requirements apply

lyophilized powder

- cake does not only have the drug; it also has excipients

- a powder

- has longer stability and shelf life, but once you mix it, it needs to be refrigerated and used quick

- reconstitute with sterile water for injection SWFI

- once powder in solution, it must be further diluted before injected into patient

- most go into solution rapidly, except for daptomycin

common excipients in lyophilized powder

- mannitol and lactose as fillers

- phosphate, citrate, and acetate salts as buffers to adjust pH for solubility and stability

Lyophilization

- an industrial process; not an extemporaneous process in hospitals or compounding pharmacies

- requires low pressure vacuum technology

- does no require or usually involve high temperatures, so many drugs, including biologics, that are thermolabile can be formulated into lyophilates

- a relatively expensive industrial manufacturing process

water for injection

- not sterile, but must be pyrogen free

- do not typically use this in hospital setting

- its method of preparation and ultimate quality depend on the original water source

- employed in industrial operations to manufacture products that are then sterilized by a terminal method of sterilization like autoclaving

treatments that water for injection undergoes if impure

- classic distillation to remove pyrogens

- filtration

- reverse osmosis

- de-ionization

technical requirements for water for injection

- limits on total solids upon evaporation

- must be stored in well-closed containers at controlled low temperature to limit bacterial growth that will lead to pyrogen formation

- must be used within 24 hours to limit possibility of pyrogen formation

sterile water for injection

- cannot be used for IV infusion of large volumes

- hemolysis of patients RBCs lead to death if given plain sterile water infusion because hypotonic

- discard unused portion, because it is single use

- must be pyrogen free

bacteriostatic water for injection

- has preservative Benzyl Alcohol

- 30 mL volume limitation to prevent the patient from receiving big dose of preservative

- name and concentration of bacteriostatic agent must be stated on the label

- useful vehicle in MDVs

- not more than 5 mL can be injected into patient

never use bacteriostatic water for injection in infant

- they can't metabolize benzyl alcohol

- causes gasping syndrome, which is a CS toxicity

sodium chloride injections

- if patient has high sodium don't use this

- when there is specific chemical or physical incompatibility between Na+ and API as indicated on package insert of product

- the diluting vehicle of choice for large volume parenteral infusion for drug administration and also for hydration, electrolyte replenishment therapy and for "keep vein open" purposes

sodium chloride injection concentrations

- normal saline or isotonic saline is 0.9% NaCl solution

- 3 is hypertonic, and used in hyponatremic patients

- 23.4 used to make other concentrations of sodium chloride injection, but never directly injected

dextrose for injection

- refers to 5% dextrose solution, of D5W, which is approximately isotonic

- becomes the diluting vehicle of choice for large volume infusions when NaCl injection not available or contraindicated

don't use dextrose for injection when...

1. The patient needs to avoid a glucose spike - as in patients with diabetes.

2. The Active Pharmaceutical Ingredient (API) is not compatible with dextrose

(usually indicated on the package insert)

3. The patient is hyponatremic

ringer's injection/lactated ringer's injection

- more physiologic because it has electrolytes that aren't just sodium and dextrose

- has NaCl, KCl, CaCl2

- bounce back and forth between the preferred fluid historically, but we prefer Lactated Ringer's right now

slide 30 image

- dextrose and normal saline are approximately isotonic

non-aqueous vehicles

- could be toxic at large volumes

- must be diluted further so that body can clear it before it becomes toxin

- sterile glycerin may also be administered IV for osmotic diuresis to remove fluid form the brain as in treating Reyes syndrome

- vegetable oils, olive oil, sesame oil, substitutions if it doesn't work for the person unless TPN; only works for IM

total parenteral nutrition

- microemulsion so that body is able to handle lipids and this special formulation can not be exchanged with other oils

preservatives

- benzyl alcohol 1% is most used

- benzalkonium Cl 0.01%

- thimerosal 0.01%, which was suspected to have caused autism in children who got vaccines but hasn't been proved yet

- methyl and propyl parabens 0.01% to 0.3%

terminal methods of sterilization

- want to achieve probability of less that 1/10^6

- involves the application of a lethal process to sealed containers

dry heat sterilization

- a terminal sterilization method not used for drugs

- 150-170 degrees centigrade for 2 hours or more

- sterilization and depyrogenization of surgical instruments and glassware

- sterilization of non-aqueous materials like glycerin and liquid petrolatum/mineral oil

pressurized steam sterilization

- terminal

- autoclave

- steam acts as sterilant

- higher pressure and higher temperature means less time to sterilize

- the preferred method of sterilization for aqueous CSPs

- closed systems, like solutions in flexible plastic bags, that are sterilized by this method must contain water in order to generate the steam that acts as the sterilizing agent

- method of choice for sterilizing most parenteral drug products unless the API is easily destroyed by heat

radiation sterilization

- terminal

- employs ionizing radiation, usually limited to industrialized applications to sterilize gauze, bandages, possible some drugs

- UV radiation, a wavelength of 253.7 um is not actually classified as a method of sterilization and is a special case

UV radiation

- can be used to reduce bacterial counts in a room where sterile products are prepared and stored

- used more often in industrial settings

- use is limited because personnel need to wear protective eye covering to avoid harm to the eyes

ethylene oxide sterilization

- terminal

- strictly industrial

- sterilizes disposable syringes, needles, and membrane filtration devices

- ethylene oxide gas penetrates sealed pouches to sterilize the contents

- 2 weeks to de-sorb the ethylene oxide gas residue which is toxic if in contact with human skin

filtration sterilization

- not a terminal method

- used very often in clinical setting

- use filters to filter out what you think is sitting in the fluid

- USP 797: passage of solution through a sterilizing grade membrane to produce a sterile effluent

membrane filters

- 0.22 and 0.45 um are most common sizes

- screen or sieve filters

- the ones used today are much smaller compared to older depth-style sterilizing filters

- commercially available in wrapped disposable pouches

USP 797 definition of sterilizing membranes

- Membranes that are documented to retain 100% of a culture of a strain of Brevundimonas (Pseudomonas) diminuta [diameter 0.3μm] per cm2 of membrane surface under a pressure of not less than 30 psi. Such filter membranes are usually 0.22 μm (or 0.2 μm)

nominal pore size, depending on the manufacturer

0.45 microns

- for more viscous fluids

sterilizing membrane filters

- remove but don't kill bacteria

- produce a sterile effluent(filtrate) with very low particulate matter counts

- commercially available in wrapped disposable pouches

types of membrane filters

- polymers and cellulose

polymers for membrane

- cellulosic esters, polyvinylidene fluoride, polytetrafluoroethylene

cellulose ester nitrate or acetate for membrane filter

- most commonly used for routine sterilizations

- could be problematic for sterilizing solutions containing proteins that might bind to the membrane.

- The other types of membranes mentioned above are appropriate for dealing with solutions of extreme pH values or for non-aqueous solutions.

positive vs negative pressure on filters

- filtration sterilization using a disposable syringe with a mounted filter for positive pressure AFTER you have initially draw up the solution, so that when you push the liquid out the dirty stuff gets left in the syringe

- never reuse filter because the crud is stuck

- positive pressure u are left with dirty in the filter

- negative is when u draw up clean drug in the filter

when is vacuum pressure/negative used

- for filtering larger volumes and has industrial applications

in-line filters

- frequently attached to administration sets to ensure that solutions being transfused into the veins of high-risk patients do not contain any bacteria

- filter built within the tubing

6 inch rule

- when you are in the hood, you have a 6 inch frame to work into so that the HEPA filter can work and can constantly clear particulate matter

- do not work at the edge of the hood