The main idea is the incompatibilities that accrue between the IV drug with drug, solution, container and IV set .
Simple study of incompatibilities of drug admixtures in Iraq , that accrue heavily in pharmacy and hospitals, it incorrect because the compliance of patient not a reason for admixture and we didn't found any study on this admixtures that confirm it safety. At last it very important to avoid it because the great risk .
hospital formulary is developed under the guidance of pharmacy and therapeutic commitee of the hospital.pharmacist working in a hospital should play an important role in the preparation of the hospital formulary
Drug distribution is one of the basic service provided by the hospital pharmacy.
Drug distribution system falls in to 3 categories -
1)Ward – controlled system
2)Pharmacy controlled imprest based system
3)Pharmacy controlled patient issue system
COMMUNITY PHARMACY AND MANAGEMENT – CHAPTER -1................... (1).pptSumit Tiwari
A community pharmacy, often referred to as retail pharmacy or retail drug outlets, is places where medicines are stored and dispensed, supplied or sold
hospital formulary is developed under the guidance of pharmacy and therapeutic commitee of the hospital.pharmacist working in a hospital should play an important role in the preparation of the hospital formulary
Drug distribution is one of the basic service provided by the hospital pharmacy.
Drug distribution system falls in to 3 categories -
1)Ward – controlled system
2)Pharmacy controlled imprest based system
3)Pharmacy controlled patient issue system
COMMUNITY PHARMACY AND MANAGEMENT – CHAPTER -1................... (1).pptSumit Tiwari
A community pharmacy, often referred to as retail pharmacy or retail drug outlets, is places where medicines are stored and dispensed, supplied or sold
One of lectures given during our Port said fifth neonatology conference, 23-24 October 2014 given by dr Dr El Sayed Khalaf MD Pediatrics,Consultant Pediatric and Neonatology
Pediatric fever can be a benign symptom of common childhood illness. But what about when it isn't? When bacterial or viral infection triggers Systemic Inflammatory Disease Syndrome (SIRS) it's known as pediatric sepsis. In the United States each year there are approximately 430,000 cases of pediatric sepsis, approximately 10% of which are considered pediatric severe sepsis. Of these, approximately 4,300 children die each year, often due to missed or delayed diagnosis. But today EMS plays a decisive role in the identi-fication and early treatment of these critically ill children. This program will show advanced EMS providers how to assess, treatment, and coordinate care for these very sickest children. Take home the knowledge of how you can make the biggest difference for our lit-tlest patients. www.Romduck.com www.RescueDigest.com
Acute anaphylaxis and anaphylactic reactionsdani raad
this presentation speak about Acute anaphylaxis and anaphylactic reactions and their definitions , symptoms , diagnosis , treatment , all informations are in brief
This presentation discusses about the etiology, clinical features, complications and management of Septic Shock.
The information compiled in this presentation (from medical textbooks and internet sources) does not belong to me, but has been done so for educational purposes
History
3 year old boy.
Taken to Pediatrician with fever and cough.
Started on Paracetamol and oral antibiotics.
One week later still low grade fever, tachypnea.
Referred to hospital.
A 12-year old girl presents to your office with a sore throat and fever. You diagnose her with pharyngitis caused by group A beta hemolytic streptococcus. She is given an IM injection of penicillin. Approximately 5 minutes later , she is found to be in respiratory distress and audibly wheezing. Her skin is mottled and cool. She is tachycardiac, and her BP has fallen to 70/20 mm hg. You immediately diagnose her as having an anphylactic reaction to the penicillin and give an IM injection of epinephrine.
McKesson Case Study: Pharmacy Systems & AutomationForgeRock
Patrick Stromberg, Architect, Pharmacy Systems and Automation, McKesson
Alexey Shmelkin, CISSP, Senior Security Architect, Information Security
Architecture and Services, McKesson
Following a brief update on the usage of ForgeRock products within McKesson, this session will
provide an overview of the integration between EnterpriseRx, a pharmacy management system, and
ForgeRock products. We will cover the challenges specific to the business domain along with a look
at how we got here and where we’re going. The challenges are interesting in that they deal with a
large number of customers, a native (non-browser) client and limited information about end-users.
Bulk compounding is defined by the FDA as the combination, mixing or alteration of drug ingredients to create medications to fulfil the need of patient.
Drug interaction is defined as the pharmacological activity of one drug is altered by the concomitant use of another drug or by the presence of some other substance
The Drug whose Activity is effected by such an Interaction is called as a “Object drug.”
The agent which precipitates such an interaction is referred as the “Precipitant”.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
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Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
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2. OBJECTIVES :
• What is Incompatibility ?
• Why I in need to mix parental injection
• What are the guidelines for parental drug admixtures?
• When I can mix them ?
• When I can’t & why ? What happen if I give them ?
• How can I minimize risk of incompatibilities
• What are the most common admixture in Iraq todays ?
• Are they pharmaceutically compatible
3. WHAT IS INCOMPATIBILITY ?
• Incompatibility is defined as “ a phenomenon which occurs when one drug
is mixed with others and produces an unsuitable product/s by some
physicochemical means that are no longer safe or effective for the patient.
Drug stability and compatibility are critically important in the provision of safe and effective drug
therapy
Multiple drugs may be administered simultaneously to a critically ill patient and determining the
compatibility of those agents is of great importance.
It is estimated that over 30% of the commonly utilized drugs are incompatible or unstable when
added or combined with usual fluids or agents.
4. TYPES OF INCOMPATIBILITIES
1. Therapeutic Incompatibility
2. Physical Incompatibility
3. Chemical Incompatibility
4. Drug IV Container Incompatibilities
• Will be discussed later in more details
5. WHY I IN NEED TO MIX PARENTAL DRUGS ?
• Difficulties with venous access limiting the number of intravenous lines
available for continuous administration of multiple drugs
• Multiple drugs requiring parenteral administration within a short time
frame such as in a home visit by a general practitioner
• Patients at home requiring many drugs by simultaneous continuous
infusion where multiple intravenous lines are not feasible, for example,
use of a syringe driver during palliative care.
6. WHAT ARE THE GUIDELINES FOR PARENTAL
DRUG ADMIXTURES?
In the UK they are the following
• Only be undertaken in the best interests of the patient;
• Be avoided where possible;
• Only be done by a person who is competent and willing to do so;
• Take place in a pharmacy (where possible).
7. THERAPEUTIC INCOMPATIBILITY
• The result of pharmacological effects of several drugs in one patient (a.k.a.
drug interactions).
• Ex: Aminophylline administered with Cimetidine. Cimetidine inhibits
degradation of Aminophylline through cytochrome P450 system thereby
increasing the Aminophylline levels.
8. PHYSICAL INCOMPATIBILITY:
• Interaction between two or more substances which lead to change in color, odor, taste, viscosity and morphology. A visible
physical change takes place
Types of physical incompatibility:
1. Insolubility and immiscibility(Alcohol or lipid solvents vs. water )
2. Change of concentration
3. The creation of gas
4. Ion reaction
5. Fat emulsion
6. Adsorption and leaching
7. precipitatation upon dilution
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9. Concentration change :
Drugs that are compatible at lower concentrations can become incompatible at higher concentrations
• Cimetidine hydrochloride compatibility.
The stability of cimetidine hydrochloride mixed in intravenous solutions individually with 37 additives was
investigated. Recommended doses of cimetidine hydrochloride injection and the other additives were diluted
aseptically in varying concentrations in compatible intravenous solutions
The results of this investigation suggest that incompatibility may be expected when cimetidine hydrochloride is
combined with some antibiotics, and cimetidine incompatibilities may be concentration dependent.
Alcohol and lipid solvent :
When the formulated product is diluted in an aqueous solution, the drug may precipitate out until
enough solution is added to enable dissolution without the need for a solvent.
Diazepam lorazepam in ethanol, PG , glycerin , PEG
• digoxin is formulated with propylene glycol 40% and ethanol 10%. It needs to be administered diluted at
least fourfold to prevent precipitation.
10. ION REACTION :
• The salts of monovalent cations, such as sodium and potassium, are generally more soluble than those of
divalent cations, such as calcium and magnesium. Mixing solutions containing calcium or magnesium ions has
a substantial risk of forming an insoluble calcium or magnesium salt.
• Mixing magnesium sulfate 50% and calcium chloride 10% results in precipitation of insoluble calcium sulfate.
• The mixing of drug salts of calcium, and to a lesser extent magnesium, with phosphates, carbonates,
bicarbonates, tartrates or sulfates should also be avoided.
• A recent warning has been issued about mixing calcium-containing solutions, including ringer 's solution, with
ceftriaxone causing the formation of the insoluble ceftriaxone calcium salt.
• The ceftriaxone-calcium compound may form a precipitate in blood, which may damage kidneys, lungs, or
gallbladder.
• Cisplatin (Platinol-AQ) ,Interacts with aluminum to cause a blackish colored precipitate that results in loss of
potency. Cisplatin molecule is being forced out of solution. Use stainless steel needles to avoid this.
11. Creation of gas :
the creation of extensive amounts of gas can be hazardous.
• Metoclopramide formulated as its hydrochloride salt is incompatible with sodium bicarbonate for this reason .
• Control solutions were cloxacillin in NS for injection, vancomycin in NS, and NS alone. Incompatibility was defined
as any visible particulate matter, substantial haze or change in turbidity relative to the controls, change in colour,
or evolution of gas.
Fat emulsion :
• such as Intralipid, TPN and some drug formulations (e.g.
Diazemuls), can easily be destabilised, cracked or separated
when they are mixed with solutions containing highly positively
charged ions.
• electrolytes should only ever be added to TPN in a specialist
pharmacy aseptic unit where the stability of the final product
can be checked before use.
12. TOTAL PARENTERAL NUTRITION (TPN) AND DRUG COMPATIBILITY
• The co-infusion of drugs and PN should be avoided
• . PN solutions are diverse in their composition and compatibilities with drugs can never be guaranteed.
• Drugs administered to patients receiving PN should be given through a separate IV site or catheter
lumen. If a separate site is not available, the drug may be given through a separate line that has a Y-connection to the PN line as close to the patient as possible. The PN
should not be running and the common tubing must be adequately flushed before and after drug administration
• The following drugs are INCOMPATIBLE with PN and MUST NOT be run concurrently with PN solutions
under any circumstances. These drugs may be administered through a Y-connection provided the PN solution is stopped, the line clamped immediately above
the Y and the line adequately flushed.
• acetazolamide calcium doxorubicin phenytoin acyclovir cefazolin etoposide phosphate amphotericin
ceftriaxone furosemide sodium bicarbonate ampicillin cisplatin mannitol ATG( Anti-thymocyte globulin)
deferoxamine paraldehyde
• PARENTERAL NUTRITION (PN) AND BLOOD PRODUCT COMPATIBILITY
• No blood products are to be co-infused with PN.
• Furosemide injection is permitted with Albumin for Renal Dialysis patients only.
14. ADSORPTION
• Non-polar, sparingly soluble drugs stored in plastic containers tend to partition into the plastic container wall.
A classical example is nitroglycerin.
• Nitroglycerin has low water solubility, approximately 0.1%, which suggests that it has high non-polar solubility.
• Indeed, if nitroglycerin in aqueous solution is placed in a polyvinylchloride IV bag (non-polar medium) or is
delivered through a polyvinylchloride IV set, the drug will be lost by adsorption to the plastic. Since the dosing
of nitroglycerin is critical, it should be dispensed in glass IV bottles and infused with a special, non-adsorbing
infusion set , Polyolefin (semi-rigid) and Polyethylene plastics are acceptable.
• Large polymeric drugs (e.g. paclitaxel), proteins (e.g. insulin) and highly lipid-soluble drugs, the flow rate,
concentration of drug and pH can all affect the extent to which adsorption occurs.
15. LEACHING
• Leaching is the release of DEHP from PVC containers into the IV bag medication. DEHP
has been shown to produce a wide range of toxic effects, particularly in male neonates
where the infant’s reproductive system can be compromised.
• Products that exacerbate leaching: Chlordiazepoxide HCl, Cyclosporine, Dosetaxel,
Etoposide Lipid Emulsions, Paclitaxel, Teniposide
• susceptible populations: critically ill male neonates, pregnant and lactating
women, pediatric patients, adolescent boys, and chemotherapy patients. Animal
toxicity studies indicate that PVC and DEHP target the testes, liver and kidneys.
16. DRUGS THAT PRECIPITATE UPON DILUTION
Precipitation of a drug from its concentrated injection solution when it is diluted with water or
saline is counter-intuitive.
• Diazepam is very poorly water soluble so it is formulated as an injection solution in a vehicle
comprising 50% propylene glycol and 10% ethanol.
• At first, dilution produces a slight turbidity which clears upon mixing, but dilution beyond
fourfold produces an opaque white precipitate which does not clear until substantial further
dilution.
• Other drugs which demonstrate solubility problems and which are formulated in injection
vehicles other than simple aqueous solutions include digoxin, clonazepam, phenytoin,
amiodarone and phytomenadione
17. CHEMICAL INCOMPATIBILITY
Reaction between two or more substances which lead to change in chemical properties of pharmaceutical dosage form.
• Types of chemical changes:
1. Oxidation-reduction and hydrolysis
2. PH change
• Acid and base drug
3. Denaturation
4. Formation of insoluble complexes
• Chemical incompatibility is two types:
• Tolerated
• Adjusted
AS
18. CHANGE PH :
Can cause drugs to precipitate out of solution.
Most medicines are small chemical organic molecules that are often formulated as weak acid or weak base salts.
EXAMPLE// Furosemide & Phenytoin & daptomycin can precipitate if mixed with a solution that lowers its ph like glucose
5% morphine sulphate precipitate out of solution in an alkaline environment.
Physical precipitation of
Midazolam as a result of
an unfavorable pH
medium5
19.
20.
21.
22. OXIDATION, REDUCTION AND HYDROLYSIS
• Can cause the chemical degradation of a drug, resulting in a loss of
potency or the formation of toxic by-products.
• Erythromycin is reconstituted, it is degraded by hydrolysis and will lose
potency after eight hours. This reaction is accelerated by a change in pH and
therefore erythromycin should not be diluted with glucose or combined with
acidic drugs, such as linezolid. Most stable in pH= 6-8. Buffer each 100 mL of
D5W with 1 mL of sterile 4% NaHCO3 solution (24 hour stability under
refrigeration).
• Ampicillin Sodium , Dextrose solution exhibits a catalytic effect on the
hydrolysis of Ampicillin.
23. MECHANISM OF CHEMICAL INCOMPATIBLITY OF
AMINOGLYCOSIDES WITH BETA-LACTAMS
N-Acylation of aminocyclitol portion by the beta-lactam(nucleophilic addition of the
NH2 to the carbonyl group of b-lactam ring-- N-acylation) leading to inactive
complex
24. Denaturation
Denaturation can occur when biological compounds — large, complex
molecules that are extremely sensitive to being denatured — are mixed with
other drugs, particularly if they are exposed to extremes of pH, or if they are
agitated for a prolonged period.
• Biologics, such as blood products and monoclonal antibodies, should never
be mixed with other drug compounds and should always be administered
through separate lines.
• Many proteins are stable only at specific pH values and ionic strengths
(filgrastim, for instance, is unstable in normal saline).
25.
26.
27.
28. WHAT HAPPENS IF WE ADMINISTERED INCOMPATIBLE
INJECTION :
• Damage from toxic products
• Particulate emboli from crystallization and separation
• Tissue irritation due to major pH changes
• Therapeutic failure
TK
29. PREVENTIVE STRATEGIES :
• Plausibility check strict indications for each drug preparation
• Separation of drug doses by time and place This can include the rinsing of the infusion
system with a neutral IV solution prior to the application of another drug
• Consistent check of alternative modes of administration
• Usage of multi-lumen catheters Protection of particle
• Infusion use appropriate in-line filters.
• Mix thoroughly when a drug is added to the preparation
• Minimize the number of drugs mixed together in an IV solution.
• Solutions should be administered promptly after mixing so that occurrence potential
reactions can be minimized.
• Always refer to compatibility references.
30. WHERE TO LOOK FOR COMPATIBILITY DATA
• Must use professional judgment when evaluating different reference sources.
Instability is defined as “a phenomenon which occurs when LVP or LVP drug product (IV admixture) is modified due to storage conditions (time, temp., light, sorption). An unsuitable product may be formed.
NOT all incompatibilities are dangerous, some are just normal.
Color Change
Imipenem-cilastatin or dobutamine may show some color change but NOT a sign of incompatibility.
Hazy Appearance
When ceftazidime is reconstituted, carbon dioxide gas is released and can cause a hazy appearance.
Precipitation
The precipitate that forms when paclitaxel is refrigerated dissolves again at room temperature.
Our main concern is the last three types which we will try to discuss as much as possible .
Therapeutic Incompatibility:
The result of pharmacological effects of several drugs in one patient (a.k.a. drug interactions).
Mechanisms
Pharmacokinetic: absorption, distribution, metabolism, excretion (e.g. Ciprofloxacin and Maalox).
Pharmacodynamic: antagonism/ synergism (e.g. Coumadin and Vitamin K)
Example// Best to avoid mixing heparin with IV antibiotics since heparin can affect the stability of certain antibiotics (e.g. aminoglycosides)
Main causes of incompatibilities in standard IV therapy
Incompatibilities of drugs can occur between
drugs and inappropriate IV solutions as diluent
two drugs (drug-drug incompatibility) when they are
- mixed together, e.g. within the same infusion line (simultaneous infusion) and/or IV container
- administered one after the other, but within the same infusion line
drugs and adjuvants (preservative, buffer, stabilizer, solvent)
drugs and materials of IV containers (e.g. PVC) or medical devices, which can concern the nature of the material used and/or reactions at the inner surface (e.g. adsorption)
Areas of Concern with admixture
Drugs admixed in the same syringe.
Drugs administered by the same IV administration set.
Drugs admixed in the same IV solution.
Drug interaction with the IV container.
Drug interaction with administration devices.
Drug stability after admixture.
Physical incompatibility of cloxacillin and vancomycin, visible to the unaided eye, was dramatic and immediate at certain concentrations. The incompatibility occurred at concentrations of vancomycin 2 mg/mL and cloxacillin 1.25 mg/mL and above, a range that includes many of the concentrations recommended for administration of these 2 drugs. Cloxacillin and vancomycin are not compatible for concurrent Y-site administration and are likely incompatible for sequential administration separated by a fluid bolus flush through lines and administration sets.
Adsorption of insulin to infusion containers
10-33% of insulin in solution was adsorbed in infusion bottles and tubing. This adsorption decreased with increasing concentrations of insulin.
Adsorption of insulin to glassware and tubing depends on:
Concentration of insulin
Contact time of insulin in glass and tubing
Flow-rate of infusion solution
Presence of negatively charged protein such as human serum albumin (HSA)
The use of in-line filters and PVC bags resulted in greater loss of insulin
Insulin binds to peritoneal dialysis solution and this binding was an instantaneous phenomenon not influenced by time.
Insulin adsorption is greater in an electrolyte solution than in dextrose.
Insulin was found to be more readily adsorbed to glass surfaces than to plastic surfaces.
Addition of HSA and gelatin to the parenteral solutions reduced adsorption.
Flushing the infusion set with 50 ml of insulin solution reduced the adsorption.
“The type of insulin did not influence adsorption. Half of the 32 IU added to soda-glass and siliconized bottles were adsorbed, while plastic containers adsorbed less. Neither the type of infusion solution (except for 60% glucose), nor the type of infusion set infuenced adsorption. Human serum albumin prevented adsorption only incompletely.”
In 1983 another study stated that “this adsorption phenomenon can be neglected if a minimal insulin concentration in the infused solution has been reached.” above
Leaching is the loss or extraction of certain materials from a carrier into a liquid (usually, but not always a solvent).
In fact, the California EPA has identified DEHP as a reproductive toxin
The pH-value and the buffer capacity (pKa value) of the IV solutions and the drugs used are major factors responsible for physical interactions [Newton 2009]. The situation in an infusion regimen is specific to the combination of drugs and solution used. Usually, the drug has the greatest influence and therefore defines the pH-value of the solution infused. Many drugs are weak bases, present as the water soluble salts of the corresponding acids. Changes in pH-value in the infusion tubing, e.g. from simultaneous addition of another drug, may release the bases from their salts. Because of the low aqueous solubility of such bases, particles may precipitate (Fig.1). The process of precipitation is influenced by the relative quantity of the drugs added, as well as their buffering capacity. These Ph dependent precipitation reactions are usually very rapid and can be identified within a few centimeters in the infusion tubing system.
They can visibly be observed as crystals, haziness or turbidity (Fig.1+2) [Newton 2009]. Precipitations based on drug incompatibilities are responsible for the most common particle formation seen in complex ICU infusion lines [Schröder 1994].
adsorption process is generally classified as physisorption (characteristic of weak van der Waals forces) or chemisorption (characteristic of covalent bonding). It may also occur due to electrostatic attraction.(wiki)
Co-administration of drugs and blood products.
“The addition of a drug to a blood product intravenous line raises the question of physical and chemical compatibility of the drug with the blood and any preservatives or additives in the blood product. This clinical scenario is encountered frequently, however the practice has not been well studied. Protocols at most institutions prohibit the addition of drugs to blood products. We investigated the addition of analgesic drugs used for patient-controlled analgesia (morphine 1 mg/ml, pethidine 10 mg/ml and ketamine 1 mg/ml) to a standard red cell concentrate, resuspended red blood cells. The red cells were analysed by a Blood Transfusion Service Haematologist and subjected to standard quality control tests. The morphology of the red cells in resuspended red blood cell preparations was unchanged by the addition of these drugs at any stage during storage. The drug concentration in the resuspended red blood cell serum was measured at 0 and at 20 minutes and there was no decrease in concentration which showed that there was no loss of free drug in the resuspended red blood cell serum. This study demonstrates that the concern regarding injury to red cells in standard red cell concentrates by addition of these drugs is unjustified.”
Another study
“The physical stability of an immunoglobulin G4 monoclonal antibody (mAb) upon dilution into intravenous (i.v.) bags containing 0.9% saline was examined. Soluble aggregates and subvisible particles were observed by size-exclusion high-performance liquid chromatography (SE-HPLC) and light obscuration when formulated with suboptimal levels of polysorbate 20. With sufficient PS20 levels, particle formation was minimized. Intravenous bags composed of polyvinyl chloride caused more protein particle formation than polyolefin bags. Differences between bag types were affected by removing headspace and by transferring the saline solution into glass vials.”
The unintended presence of precipitation and toxic products can cause various negative consequences for the patient. This can range from thrombophlebitis up to multi-organ failure. The reduction or elimination of the active drug can lead to a therapeutic failure. The extent of the damage mainly depends on the patient’s condition (age, weight, nature, severity of the disease etc.) and on the type of drug administered. Consequences of physicochemical drug incompatibilities are particularly severe in neonate and pediatric patients [Höpner 2007]
There is little published scientific information about the frequency of drug incompatibility reactions.
In one study, incompatibility was investigated in a pediatric intensive care ward showing that 3.4 % of drug combinations were incompatible and thus potentially dangerous [Gikic et al. 2000].
A life threatening nature was found for 26 % of incompatibilities in an intensive care unit (ICU) by Tissot et al. [2004].
Another survey collected 78 different medication regimes and found 15 % with incompatibility reactions [Vogel Kahmann et al. 2003].
Taxis and Barber [2004] reported that in the ICU clinical incompatibilities can contribute to 25 % of medication errors.
Further publications showed that, depending on the ward type, up to 80 % of IV drug doses were prepared with the wrong diluent [Cousins et al. 2005, Hoppe-Tichy et al. 2002]
Literature Resources
Drug Facts and Comparisons
Handbook on Injectable Drugs (Trissel)
Calcium & Phosphate Compatibility in Parenteral Nutrition (Trissel)
Stability of Compounded Formulations (Trissel)
Extended Stability for Parenteral Drugs (Bing)
King Guide to Parenteral Admixtures (King)
American Journal of Health-System Pharmacy
Hospital Pharmacy
International Journal of Pharmaceutical Compounding
Drug package inserts
Compatibility charts