Antimicrobials 2 Flashcards
What are bacteriocidal antibiotics?
they kill bacteria dead
Give examples of bacteriocidal antibiotics
penicillin
cephalosporins
metronidazole
What are bacteriostatic antibiotics?
they make bacteria stop working
bacteria are then cleared by the immune system
Give examples of bacteriostatic antibiotics
macrolides
lincosamides
tetracyclines
fusidic acid
How is the in-vitro antimicrobial activity of drugs assessed?
determining minimum inhibitory concentration (MIC) and minumum bactericidal concentration (MBC)
What is the minimum inhibitory concentration?
the lowest concentration of a chemical that prevents visible growth (bacteriostatic)
What is the minimum bactericidal concentration?
lowest concentration of a chemical that results in death (bactericidal)
Practically, how is the antimicrobial activity of a chemical assessed?
overnight aerobic incubation of a standard size inoculum of bacteria in a low protein liquid medium at pH 7.2
Why may the antimicrobial activity of a chemical differ in vivo?
conditions in vivo will be different from incubation conditions thus antimicrobial activity will change
If a drugs has a MBC 4x greater than the MIC then the drug is classed as …
bactericidal
What are broad spectrum antibiotics?
they act against both gram positive and gram negative bacteria
When are broad spectrum antibiotics used?
prior to formal identification of the (specific) disease causing bacteria
Give examples of broad spectrum antibiotics
amoxicillin
co-amoxiclav
tetracyclines
What are narrow spectrum antibiotics?
they act against a specific family of bacteria
When are narrow spectrum antibiotics used?
best when used with culture sensitivity and testing
Give examples of narrow spectrum antibiotics
Macrolides
Clindamycin
What is pharmacokinetics?
This is what the body does to the drug
ADME
What does absorption refer to ?
bioavailability of the drug
What does distribution refer to ?
the process by which a drug diffuses from intravascular fluid space to extravascular fluid spaces
Elimination of the drug after administration usually occurs from …
liver or kidney
What is pharmacodynamics?
this is what the drug does to the body
Regarding pharmacodynamics, the antimicrobial effects of the drug at the site of infection is…
concentration dependent
time dependent
What are the clinical functions of pharmacodynamics?
-used to predict drug efficacy in patients
-provide a rational basis for determining the optimal dosing regimens
The pharmacodynamics of an antimicrobial drug relates its pharmacokinetics to the _________ of the antimicrobial effects at the site of action.
time course
What is the most common side effect of antibiotics ?
allergic reactions
How are allergic reactions to antibiotics typically avoided?
by avoiding the drug
What is an option for patients with an allergy to a specific antibiotic who have no other antibiotic options?
desensitisation
(may be possible)
What serious allergic reactions can arise from antibiotic use?
Stevens Johnson Syndrome (SJS)
Toxic Epidermal Necrolysis (TEN)
SJS and TEN can present as
serious skin and mucous membrane disorders
rashes, skin peeling and sores on mucous membranes
What antibiotics can be implicated in SJS and TEN?
penicillin
cephalosporins
Antibiotic associated colitis a side effect of antibiotic use due to …
disruption of the normal balance of the gut flora
eradication of the normal gut flora by antibiotic which results in an overgrowth of other microbes which include clostridium difficile
____% of patients may develop anti-biotic associated diarrhoea
5-25%
What kind of antibiotics are often implicated in antibiotic-associated colitis ?
broad spectrum antibiotics
Clindamycin (this is a narrow spectrum antibiotic)
cephalosporin
coamoxiclav
amoxicillin (to a lesser extent?)
What is pseudomembranous colitis ?
medical condition in which the colon gets inflamed in association with excessive intake of antibiotics
What are the symptoms of pseudomembranous colitis?
watery diarrhoea
abdominal pain along with cramping
fever
mucousy stools
nausea
dehydration
Another side effects of antibiotic induce/mediated flora change is _________.
opportunistic candidal infections which may occur in mouth or vagina
overgrowth of fungal species
Candida albicans may take over where there is limited competition from bacteria due to antibiotic treatment
What is the effect of antibacterial on typhoid vaccine?
antibacterials inactivate typhoid vaccine
Miconazole (antifungal) interacts with what drugs?
Alfacalcidol- miconazole reduces effects of alfacalcidol
Calcitriol- miconazole possibly reduces effects of calcitriol
ciclosporin- miconazole possibly inhibits metabolism of ciclosporin which increases its plasma concentration
Coumarins- miconazole enhances the anticoagulant effect of coumarins; avoid concomitant use if possible
(coumarins include warfarin)
Miconazole (antifungal) interacts with what drugs?
Alfacalcidol- miconazole reduces effects of alfacalcidol
Calcitriol- miconazole possibly reduces effects of calcitriol
ciclosporin- miconazole possibly inhibits metabolism of ciclosporin which increases its plasma concentration
Coumarins- miconazole enhances the anticoagulant effect of coumarins; avoid concomitant use if possible
(coumarins include warfarin)
MHRA (Medicines and healthcare products regulatory agency) employs the use of _________ and __________ to monitor adverse effects observed due to drugs/medication
Yellow card schemes
Medical alerts
In 2012, a medical alert for the potential reminder of hypersensitivity for which drug was announced by the MHRA?
chlorhexidine
In 2016, a medical alert for the potential reminder of serious interaction with warfarin for which drug was issued by the MHRA?
topical miconazole, including oral gel
What is the Yellow Card scheme used for ?
used to report suspected side effects or adverse drug reactions to any medicines, vaccines and even medical devices
medical devices e.g. implants
What are components of a typical bacterial cell?
cell wall
plasma membrane
chromosome
cytoplasm
ribosome
Whats is the MOA of penicillin?
beta-lactams present in penicilln interfere with the crosslinking of peptidoglycan protein in the bacterial cell wall
(bacterial cell wall- peptidoglycan crosslinks present)
Penicillin (beta lactam) binds to the transpeptidase enzyme which is responsible for peptidoglycan cross-links
this weakens the strength of the cell wall
Penicillin have a ______ dependent bactericidal action
time dependent
What adverse drug reaction is associated with penicillin?
allergy
What is a contraindication of penicillin use ?
methotrexate (immunomodulatory) - dihydrofolate reductase enzyme inhibitor
probencid (kidney disease)
What is the purpose of a beta-lactam ring
disrupt peptidoglycan cell wall- prevent cross-links from forming
What enzyme is responsible for the formation of the peptidoglycan crosslinks?
bacterial DD-transpeptidase enzyme
What is a requirement for penicillin to work?
the bacteria must be growing for it to work
Briefly compare the bioavailability of oral dose amoxicillin and penicillin V
amoxicillin has a greater oral bioavailability (74-92%) compared to penicillin v
How is penicillin G administered and why is this?
Penicillin G is administered intravenously
it is not acid stable thus cannot be delivered orally
Amoxicillin is equally well absorbed with food or in the fasting state. True or false
True
When is co-amoxiclav better taken (for better absorption)?
it is better taken at the start of a meal
When is penicillin V better taken (for better absorption)?
it is better absorbed in the fasting state
Is penicillin able to cross the BBB?
no it is not because it is poorly lipid soluble
How is penicillin eliminated after drug administration?
excreted unchanged by tubular secretion in the kidneys
Penicillin excretion/elimination can be blocked by…
probencid (used in kidney disease)
Penicillin excretion/elimination can be blocked by…
probencid (used in kidney disease)
Why is a dose reduction of penicillin necessary for patient with kidney disease on probencid?
this is because probencid can block tubular excretion of penicillin
Amoxicilling is a __________ spectrum antibiotic which can be used to treat … (name the conditions)
broad
Dental abscesses
otitis media
bronchitis
pneumonia
urinary tract infections
gonorrheoa
Phenomethylpenicillin (Pen V) is a _______ spectrum antibiotic for use as amoxicillin. How is it dosed?
narrow spectrum
dosed QDS (4x daily) on an empty stomach
What is the benefit of co-amoxiclav?
(as amoxicillin)
reduced resistance due to clavulanic acid which inhibits beta-lactamase enzyme
((beta-lactamase enzyme developed to increase resistance to beta-lactam which interferes with cell wall synthesis)
Co amoxiclav side effects can include …
pseudomembranous colitis?
risk of c. difficle
When should co-amoxiclav be used?
after consultation with secondary care
When antibiotics are under the antibiotic class “penicillins”
penicillin
amoxicillin
coamoxiclav
What are the most common side effects of penicillins?
rash
diarrhoea
abdominal pain
nausea/vomiting
drug fever
hypersensitivity
allergic reactions
When should you contact a health care provider immediately when using penicillins?
bloody stool
anaphylaxis
severe skin reaction
fever
What is the MOA of metronidazole (broad spectrum antibiotic)?
inhibits DNA synthesis once converted into an active form by anaerobic bacteria
Metronidazole is active against… (name the microorganisms)
anaerbobic bacteria
Protozoa
Metronidazole has _________ dependent bactericidal action
dose/concentration dependent
What adverse reactions are associated with metronidazole?
Di-sulfiram reaction where there is an acute sensitivity to alcohol
- immediate feeling of a hangover
should NOT be taken with alcohol.
What are the contraindications for metronidazole?
interacts with coumarin anticoagulants like warfarin
What is the clinical use of metronidazole?
dental abscess and NUG (necrotising ulcerative gingivitis)
also used to treat pseudomembranous colitis (C.difficile)
Briefly describe bioavailability of metronidazole?
excellent bioavailability after oral administration
food has no effect on bioavailability of metronidazole
Briefly describe distribution of metronidazole
lipid soluble drug thus has wide distribution throughout the body
When is the peak serum concentration of metronidazole reached?
after one hour of administration
How is metronidazole eliminated from the body?
eliminated unchanged in the urine
Disulfiram reaction associated with metronidazole is more unpleasant than serious. What must you warn you patients of?
NO alcohol
When it occurs- tachycardia and flushing can occur
Disulfiram reaction can occur up to _______ after stopping metronidazole
up to 72 hours after stopping metronidazole
What is the effect of metronidazole on warfarin (coumarin)?
the anticoagulant effects of warfarin increases
this has cause bleeding in some cases
What should you do if metronidazole is prescribed to a patient on warfarin?
monitor INR (international normalised ratio)
What are the most common side effects of metronidazole?
nausea/vomiting
dizziness
headache
vaginal candidiasis
metallic taste
Combined use of alcohol and metronidazoe may lead to…
cramps
nausea/vomiting
flushing
headache
red-brown urine discoloration
What is the MOA of macrolides (bacteriostatic)?
they inhibit protein synthesis by acting on bacterial ribosomes
Macrolides have the same site of action as ___________ antibiotics. Considering this, how should they be administered?
clindamycin
they should not be administered concurrently as they will compete for the same site of action
What are adverse reactions associated with macrolides?
GI disturbances are common and unpleasant
Macrolides have a __________ post anti-biotic effect
prolonged
What are the clinical uses of macrolides?
used if a patient is allergic to penicillin and metronidazole
What are the members of the macrolide class of antibiotics ?
erythromycin
clarithromycin
azithromycin