Lecture 1 part 2: pharmaceutical aspects of infections drug therapy Flashcards
What infection characteristics influence drug delivery? (8 points)
- site of infection
- patient condition
- acute vs. chronic infection
- required dosage schedule
- multi drug therapy
- drug and dosage form availability
- orphan drugs for rare diseases
- drug resistance
Which two infection characteristics that influence drug delivery dictate the choice of administration?
- site of infection
2. patient condition
What causes super bugs?
-antibiotic resistance due to insufficient/excessive use
What are the possible causes of superbugs? (6 points)
- self medication
- uncontrolled availability of antibiotics
- in appropriate prescribing
- incomplete therapy (education, cost)
- international travel (hard to control)
- lower R&D investment -> few new antibiotics
What are the different formulation requirements for antibiotics that should be considered? (7 points)
- short/long term therapy
- systemic/targeted delivery
- route of administration
- patient acceptability
- side effects
- dose requirements
- physicochemical characteristics of the active compound
What are the differences between benzylpenicillin, phenoxymethyl penicillin and procaine penicillin?
- benzyl = administered IV due to instability in GIT
- phenoxymethyl = can be adminsitered orally, but only achieves low blood concentrations. Not enough for systemic use, so used for local infections in stomach.
- Procaine= salt form of benzylpenicillin. Given IM to avoid pain at site of injection. Also provides SR release. Used for veterinary purposes.
What is OPAT?
outpatient parenteral antimicrobial therapy.
-parenteral antimicrobial therapy conducted in the community
What are the advantages of OPAT? (3 points)
- reduces costs associated with in-patient stay
- empowers patients
- decreases morbidity
What is special about the formulation of antimicrobials used in OPAT?
They are extemporaneously compounded and placed in infusors. These are self administered by the patient.
What antibiotics are commonly used in OPAT? (7 points)
- amoxicillin
- vancomycin
- ceftriaxone
- flucloxacillin
- benzylpenicillin
- cefazolin
- meropenem
what is amoxicillin?
-broad spectrum bacterialcidic beta lactam antibtiotic
How can amoxicillin be administered?
- in bolus doses or as a continuous infusion
- pharmaceutical companies recommend administering as multiple bolus doses throughout the day
How do patients with severe infections achieve better outcomes with amoxicillin?
-if it is given as a continuous infusion
What is the stability data on amoxicillin like?
There is a lack of data on formulations packed in infusors
-some references say there is a significant concentration dependent degradation after 7 days
What are examples of novel drug deliver systems? (6 points)
- micelles
- vesicles
- multifunctional dendritic polymers
- nanospheres
- nanocapsules
- liquid crystals
What is Atrigel?
- Patented drug delivery technology which enables site-specific and systemic drug delivery
- consists of biodegradeable polymers dissolved in biocompatible carriers
- forms solid implant upon contact with aqueous bodily fluids
WHat is Atridox?
- a sustained release formulation of doxycyline hyclate 10% using Atrigel delivery system
- used to treat peridontal disease
- available as 2 separate solutions of drug and polymer which are mixed before injection
- liquid flows around infected tooth area and adapts to local morphology, hardening to waxy substance
- Slow release of doxycycline up to 21 days
What is Vitrasert?
- Polymer based intravitreal implant formulation containing ganciclovir
- for patients with AIDS related cytomegalovirus retinitis.
- Consists of tablet coated with poly vinyl alcohol and ethylene vinyl acetate polymer
- adminstration, removal or replacement requires surgery
- releases drug over 5-8 months in slow release fashion.
What is amphotericin B?
- antifungal antibiotic that is administered by IV
- pure drug is yellow/orange powder insoluble in water
- initial formulations marketed as powder for injection
- may cause nephrotoxicity
What is Abelcet?
- Amphotericin B liquid complex
- has lipid conjugates ranging from 500-5000nm with 33% drug loading
- ribbon like particles
- uses DMPG and DMPC as carrier lipids
What is Amphotec?
- Amphtericon B formulated as sulfate complex colloidal dispersion.
- carrier lipids include cholestryl sulfate
- particles are disk shaped
- approx 125nm in size with 50% drug loading.
What is Ambisome?
- liposomal amphotericin B formulation
- various carrier lipids.
- 100nm diameter spheres
- liposomes hold drug in bilayer membrane
- lower levels of side effects
- offers highest plasma concentration and low clearance rates.
What are examples of future novel formulations?
- Aciclovir available as 200, 400, and 800mg dispersible tablets have complex dosing regimen
- associated with GIT side effects such as nausea
- poorly absorbed from the GIT
What is Amikacin?
- water soluble aminoglycoside
- ribosomal protein synthesis inhibitor
- used to treat pulmonary infections like CF
