Overview Of Antimicrobials Flashcards
Antimicrobials
Agents useful in treatment of infections by _______
microbes
Antibiotics are _______ which ________ or ______
substances got from a microorganism
suppresses the growth of another organism or eradicates another organism
Mechanism of action of penicillin
inhibit synthesisb of bacterial cell wall
Mechanism of action of cephalosporines
inhibit synthesisb of bacterial cell wall
Mechanism of action of cycloserine
inhibit synthesisb of bacterial cell wall
Mechanism of action of vancomycin
inhibit synthesisb of bacterial cell wall
Mechanism of action of bacitracin
inhibit synthesisb of bacterial cell wall
Mechanism of action of asole antifungals
inhibit synthesisb of bacterial cell wall
Mechanism of action of polymyxin
Fucks up bacterial cell membrane by increasing its permeability
Mechanism of action of polyene anti fungal nystatin
Fucks up bacterial cell membrane by increasing its permeability
Agents that affect function of 30S or 50s ribosomal subunit to cause (reversible or irreversible ?) inhibition of protein synthesis; these are bacterio___
Reversible
static
agents that affect bacterial nucleic acid metabolism, such as ______ e.g. rifampin which inhibit _____ and the _____ which inhibit ________________
rifamycins
RNA polymerase
quinolones
topoisomerase and DNA gyrase
the antimetabolites which block essential enzymes of folate metabolism such as ———- and the _______
trimethoprine
sulphonamides
antivirals: several classes exist.
a) nucleic acid analogues- ______ or ____ that selectively inhibit viral _______, and ______ or ______ , which inhibit ________
acyclovir; ganciclovir; DNA polymerase
zidovudine or lamivudine; reverse transcriptase
antivirals: several classes exist.
b) Nonnucleoside reverse transcriptase inhibitors, such as _______,_______
© inhibitors of HIV _______ or influenza ________
nevirapine, efavirence
protease; nuraminidase
Bacteriocidal agent: it _______________
kills the bacteria
Bacteriostatic agent: it _______________ so that the __________________
supresses the growth or replication of the bacteria
patient’s immune system eliminates it.
FACTORS THAT DETERMINE SUCEPTIBILITY TO ANTIMICROBIAL THERAPY
____________, as even bacteriocidal drugs will only _________ and the __________ will then _________
Intact host immune system
eliminate some bacteria
host’s immunity
eliminate the rest.
Hence when patient’s immune system is low, there is need for _______ or ______
more potent antibacterial or greater dose
High protein conc at the site (Pus)
May aid or limit drug action ?
Limit
High pH may limit drug action.
T/F
F
Low PH
Location of infection may limit drug action
T/F
T
BACTERIAL RESISTANCE TO ANTIMICROBIAL AGENTS
It can be ________ or _______
Common mechanisms is by _______,________,_________, or _______
primary or secondary
mutation, transduction, transformation, conjugation
______________________(m/c/s) is the ideal method of selecting antibacterials, this is combined with __________
However,
________ choice may be necessary :
MICROSCOPY, CULTURE AND SENSITIVITY
clinical impression
Empherical
Empherical choice may be necessary to prevent drug resistance
T/F
T
When could Empherical choice be necessary despite the m/c/s?
In serious infections
Complications Of combination OF Anti microbial agents includes superinfection
T/F
T
ANTI-TB drugs
_______________ is the causative organism
Mycobacterium tuberculosisis
ANTI-TB drugs
Drugs: 1st line drugs below have ______ level of efficiency with _______ degree of toxicity. _____ of them are combined
List them
greatest; an acceptable
Four
Isoniazid, rifampin, ethambutol, streptomycin or pyrazinamide.
ANTI-TB drugs
2nd line drugs can be used if there is _________ to first line drugs or _________
– list them
microbial resistance
patient related factors(unacceptable ADRs)
Capreomycin
Cycloserine
Amikacin
Aminosalucyclic acid
Kanamycin
Ethionamide
_________ is the primary antiTB Drug
Isoniazid
ISONIAZID
all patients with dx caused by isoniazid- sensitive strains of the _____ bacillus should receive the drug if they can tolerate it
tubercle
Isoniazid is related to _______, it is a ______ derivative.
nicotinamide
pyridine
Isoniazid
It is bacteriostatic for ______ but bactericidal for __________
resting bacilli
rapidly dividing micro- organisms.
Isoniazid
If ___________ is not given along with isoniazid ,___________ may occur.
pyridoxine (vitamin B6)
Peripheral neuritis
Which ANTI TB drug colors the urine orange
Rifampin
Rifampin:
This drug colours urine _______
Untoward effect- Not common. Rashes, fever, nausea, vomiting, _____ is most notable, _______ is not common.
orange
Jandice
Hepatitis
Ethanbutol: The most important reaction is ________ with decrease in ______ and inability to differentiate colour ——- from ______
optic neuritis
visual acuity
red from green.
Adverse drug reactions to ethanbutol are few .
T/F
T
STREPTOMYCIN
It is bacter_____ for tubercle bacilli .
Icidal
Bacterial resistance has developed to streptomycin over the years.
T/F
T
ADRs of streptomycin : features of ________ effect such as _____,______,______
vestibule-cochlear
tinictus, deafness, distortion of balance.
Pyrazmanide – synthetic pyrazine analog of _________
nicotinamide
AMINOGLYCOSIDE ANTIBIOTICS
List 7
Gentamicin, tobramycin, amikacin, netilmicin, kanamycin, streptomycin and neomycin.
AMINOGLYCOSIDE ANTIBIOTICS
They all contain ______ in _____ linkage.
The aminoglycosides are used primarily to treat infections caused by gram-________ bacteria.
amino sugars in glycosidic
negative
Aminoglycosides
They are _____, and their polarity is a part responsible for their pharmacokinetic properties e.g. None is ____________, _______ conc found in CSF, and all are relatively ________ by the normal kidney.
polycations
adequately absorbed after oral administration
inadequate
rapidly excreted
AMINOGLYCOSIDE ANTIBIOTICS
They act to interfere with _______ in susceptible microorganisms.
protein synthesis
Aminoglycosides
Mutations affecting _________, the target for these drugs can rapidly confer marked resistance to their action.
proteins in the bacterial ribosome
Aminoglycosides
______ acquisition leading to elaboration of drug metabolizing enzymes can also result in resistance.
Plasmid
There can’t be cross resistance to Aminoglycosides
T/F
F
There can
Serious toxicity is a major limitation to the usefulness of aminoglycosides: ————— and__________
ototoxicity( auditory& vestibular)
serious nephrotoxicity.
History: The dev of streptomycin was the result of a well planned scientific search for antibact substances. In 1943, a strain of _________ was isolated that elaborated a potent antimicrobial substance, streptomycin.
streptomyces griseus
________ and _____ are both broad-spectrum derived from species of the actinomycete micromonospora.
Gentamicin and netilmicin
Aminoglycosides MECH OF ACTION:
They are rapidly bacter_____.
They act at the ______, where they inhibit ____________ and decrease the fidelity of translation of mRNA
icidal; ribosome
protein synthesis
Aminoglycosides MECH OF ACTION:
Aminoglycosides diffuse readily through _________ in the outer memb of gran- negative bacteria and thereby enter the __________
aqueous channel formed by porin proteins
periplasmic space
Aminoglycosides MECH OF ACTION:
transport of aminoglycosides across cytoplasmic (inner) membrane is dependent on transport, partly because of a requirement of a ____________ to drive permeation of these antibiotics.
This is the ________ phase __, and it can be blocked or inhibited by ____ cations e.g ca2+), _________ , a ______ease in pH, and (aerobic or anaerobic ?) environment.
membrane potential (interior negative)
energy – dependent;1
divalent; hyperosmolality
decr; anaerobic
The pH and anaerobiasis impair the ability of the bacteria to ___________________
maintain the driving force necessary for transport (members potential).
Following transport across the cytoplasmic membrane, the aminoglycosides bind to _____ and inhibit the ___________.
This phase termed ______ phase II (EDP2), is thought to be liked with disruption of the structure of the cytoplasmic membrane.
polysomes
synthesis of proteins
energy dependent
The 10 intra cellular site of action of the aminoglycosides is the ___ ribosomal subunit which consists of 21 proteins & a single 165 molecule of RNA, alteration of at least ___ of these proteins markedly affect the action of _______.
30s; 3; Streptomycin
The other aminoglycosides(besides streptomycin) apart from binding to the _____ ribosomal subunit appear to bind to several sites on the _____ ribosomal subunit as well.
30S
50s
Aminoglycosides disrupt the normal cycle of ribosomal function by interfaring at least in part with the ___________ that occurs at the ribosome (intuition).
1st step of protein synthesis
MICROBIAL RESSITANCE TO THE AMINOGLYCOSIDES
Factors responsible are
a) failure of ________ of the antibiotic
b)______ of the drug for the bacterial ribosome
c) most importantly, ________ of the drug by microbial enzymes.
permeation
low affinity
inactivation
The metabolites of the aminoglycosides may compete with the unaltered drug for —————- but they are incapable of ___________ and _________.
intra cellular transport
binding effectively to ribosomes and interfering with protein synthesis
Strictly anaerobic bacteria are (susceptible or resistant?) to the aminoglycosides
With reason
Resistant
since their transport across the cytoplasmic (inner) membrane is oxygen – dependent
ANTIBACTERIAL ACTIVITY of aminoglycosides is Mainly towards gram- ______bacilli
negative
_______ and _______ are active in vitro against more than 95% of strains of staphylococcus aureus and most strains of staph. but they should not be used alone in their infections because the clinical efficacy has not been documented
Getamicin and tobramycin
sensitive microorganisms are defined as those inhibited by ___________ but that are not associated with a high incidence of ______
this value is _____ ml for gent, tobra, netilmicin and ______ for amikacin and kanamycin .
peak conc that can be achieved clinically in plasma
toxicity
4 to 8 ; 8 to 16
Amikacin and netilmicin have retained their activity against nosocromial infections because of ________________
resistance to the aminoglycoside metabolizing Enzymes.
ABSORPTION of aminoglycosides
They are highly polar cautions hence (well or poorly?) absorbed from GIT >1% is absorbed ff oral or rectal admin
Poorly
Aminoglycosides are inactivated in the GIT
T/F
F
They are not inactivated in GIT
Aminoglycosides are eliminated quantitatively in feces.
T/F
T
Absorption of Aminoglycosides is ___eased when there is bacillary dysentery but that of _____ is not altered in the presence of inflammatory disease of the bowel.
Decr
neomycin
Repeated oral or rectal admin of Aminoglycosides may result in accumulation to toxic concentrations in patients with ____ impairment.
Instillation into body cavities with ____ surfaces may result in rapid absorption and unexpected toxicity.
renal
serosa
Aminoglycosides
Intoxication may also occur when applied topically to large wounds, or cutaneous ulcers particular with renal insufficiency.
T/F
T
Rapid absorption of aminoglycosides from _____ and _____ injection (Pick Plasma Conc 30 to 90 minutes similar to the peak after 30 minutes of completion of I.V. infusion of an equal dose over a 30 min period).
I/M and SC
DISTRIBUTION of aminoglycosides :
Because of their ____ nature they are largely excluded from most cells, from ____ and the ___.
Inflamation ____eases penetration into peritoneal and pericardial cavities.
Intrathecal or intraventricular Admin is necessary in cases of gram-_______ bacillary ______ in adults as opposed to neonates who have in-mature _____.
polar; CNS; eye
incr
negative; meningitis
BBB
ELIMATION of Aminoglycosides
Excretion almost entirely by ___________________ of 50 to 200 ml are achieved.
A large fraction of (eneterally or parenterally?) admin dose is excreted unchanged during 1st 24 hours with most of this appearing in 1st 12 hours.
glomerular filtration & conc in urine
parenterally
The t 1⁄2 of Aminoglycosides is ____ in plasma.
2 – 3 hours
Renal clearance of Aminoglycosides is approx 2/3 of the simultaneous creatinine clearance (this suggest some tubular ________).
resorption
UNTOWARD EFFECTS of Aminoglycosides
Reversible & irreversible ______,________,and _______.
vestibular, cochlear & renal toxicity
UNTOWARD EFFECTS of Aminoglycosides
Accumulation in the ___________ of the inner ear
Sustained exposure leads to permanent dysfucntiond effects.
(Younger or Older ?) patients more susceptible to ototoxicity.
perilymph & endolymph
Older
UNTOWARD EFFECTS of Aminoglycosides
________ and _________ have more predominant vestibular effects while
_____,_______, and _______ lmpact auditory function more.
__________ both equally
other notable ADRs include
__________ – renal cortex
. Dysfunction of ______ nerve
Peripheral neuritis
streptomycin and gentimicin
amikacin, kanamycin and neomycin
Tobramycin
Nephotoxicity
optic
_________ Aminoglycoside is used in Combination therapy in UTI especially when seirous untio sensitivity results are out.
Gentamicin
tobramycin has Antimicrobial activity & pharmacokinetics similar to gentimicin
T/F
T
________ Aminoglycoside has the Broadest antimicrobial activity
Amikacin
Amikacin is also has resistance to aminoglycoside – inactivating enzymes hence special role in hospitals where gentimicin and tobramycin resistant microorganisms are prevalent.
T/F
T
NET ILMICIN is metabolized by majority of the aminoglycoside – metabolizing enzymes
T/F
F
It’s not
Mention 4 adverse effects of using Aminoglycosides
Ototoxicity
Nephrotoxicity
Paralysis
Skin rash
Acyclovir- ________
Zidovudine-_________
Rifampicin-_______
Quinolones-______
DNA polymerase
Reverse transcriptase
Rna polymerase
Topoisomerase and dna gyrase
Pristinamycins
Bactericidal or bacteriostatic
bacteriostatic
Chloramphenicol
Bactericidal or bacteriostatic
bacteriostatic
Broad spectrum Aminoglycosides- ______, _____, ______, and _____
gentamicin
netilmicin
Amikacin
Neomycin
Aminoglycosides
High or Low therapeutic index?
Low
TOBRAMYCIN
Antimicrobial activity & pharmacokinetics similar to ______ but superior In treating ______
gentimicin
Pseudo aerguernosa
Aminoglycosides can undergoe cross resistance
Tetracyclines can undergoe cross resistance
T/F
T
T
Aminoglycosides are well absorbed orally
T/F
Why?
F
Are polar cations
Aminoglycosides administration = all are ____ EXCEPT ______ and ______
IV
KANA and NEO
Aminoglycosides administration = Poor absorption and distribution but loves ____,______,_______.
skeletal muscle, kidney, and inner ear
neomycin can also be given topically
T/F
T
________ Aminoglycoside is also used clear the git before surgery
Neomycin
Good for nosocomial-___,______
Similar activity- _____,_______
For UTI- _______
Amikacin, netilmicin
gentamicin and Tobramycin
gentamicin
