Antibiotics Flashcards
(153 cards)
1
Q
Mechanism of action of penecillin
A
Interferes with last step of bacterial cell wall synthses: cross linkage via acting on transpeptidase enz
Acts on PBS(cell memb proteins :synthsis and maintaince of cell wall) out of which transpeptidase is one
Continuous action of autolysin(degradative enz for cell wall remodelling) even in the abscens of cell wall synthsis
Results in osmotically less stable memb
2
Q
Cephalosporin moa
A
Same as penecillin
3
Q
Doc for gas gangrene/C.perforinges
A
Penecillin
4
Q
Doc for syphilis
A
Penecillin
5
Q
Diff penecillin V and G
A
G: parenteral
V: more stable so orally
6
Q
All B lactams are excreted via urine except
A
Nafcillin
Oxacillin
7
Q
Penecillin G used for
A
Gp and GN cocci
GP baciili
Spirichets
8
Q
Adverse effect of methicillin
A
Intersitial nephritis,Hematuria,albuminuria
9
Q
Extended spectrum penecillins work against
A
Same as penecillinG but more for GNB
10
Q
Classification of penecillins
A
PenecillinV/G
B lactamase resistant:methicillin etc
Extended spectrum:amoxi, ampi,piperacillin
etc
11
Q
Doc for listeria
A
Ampicillin
12
Q
Egs of antipseudomonal penecillins
A
Ticarcillin
Piperacillin
13
Q
piper/ticarcillin ___ to pencillase producing organism
A
Senisitive
So given along with tazobactam and clavulinic acid respectively
Tt not together
14
Q
piper/ticarcillin ___ to pencillase producing organism
A
Senisitive
So given along with tazobactam and clavulinic acid respectively
Tt not together
15
Q
Extended spectrum penicillins are _____ to B lactamase producing org
A
Sensitive
Amoxi clavulinic acid
Ampi-sulbactum
16
Q
Depot forms of penecillins
A
Absorbed slowly into circulation and persist at low levels over a long period
Given IM
Eg: procaine Penicillin G, benzathine P G
17
Q
Method of Excretion of penicillins from kidney
A
.Organic acid (tubular) secretory system
.filteration
18
Q
Effect of probenecid on penicillin level
A
Increase P levels
Competes for active tubular secretion via organic acid transporter so inhibits P secretion.
19
Q
Route of penecillin G
A
Iv, Im
20
Q
Can penecillin penetrate CNS
A
Until they are inflamed (inflammation disrupts BBB leading to increased permeability)
21
Q
Spectrum of cephalosporins with respect to staph
A
All generations scan work against MSSA not MRSA
EXCEPT newer 5th generation cephalosporin: ceftaroline
22
Q
5th generatiom cephalosporin
A
Ceftaroline
I.v.
23
Q
No B lactam is effective against MRSA except__
A
5 th generation cephalosporin
24
Q
All cephalosprins are excreted via urine except
A
Ceftriaxone
Cefoperazone (both 3 rd gen)
25
Which cephalosprins penetrate BBB
All 3 rd gen : except cefoperazone
| Only one of 2 nd gen : cefuroxime
26
Ist generation cephalosprins drugs
Dro-zo-le
Cepha/cefa except cefaclor (2 nd gen)
Cefadroxil
Cephazolin
Cephalexin
27
Cephalosprins spectrum
1 gen : GP high , GN weak (like penecillin G)
2 gen :GN high ,GP and anaerobes weak
3gen: GN high + few pseudo , GP and anaerobes weak
4th gen:same as 3 rd
28
Why is cilastatin combined with imipenem
To protect it from metabolism by renal dehyropeptidase (brush border of proximal tubule) which converts into a NEPHROTOXIC metabolite
29
Most cephalosporins do not penetrate CSF except
Third gen cephalosporins
30
Carbapenems spectrum
GP (B lactamase producing)
GN
Anaerobes
PSEUDOMONAS
31
Peculiar side effect of imepenem
Seizures
32
3 rd gen cephalosporin active against pseudomonas
Ceftazidime
33
Monobactam spectrum
Aerobic GNB only
(Not against GP and anaerobes)
Same as aminoglycosides
34
______ may offer a safe alternative for treating patients who are allergic to pencillins, cephalosprins, carbepenems
AZTREONAM because of less cross reactivity
35
B lactams
Penicillins
Cephalosporins
Monobactams
Carbepenems
36
Vancomycin use
(Maily GP)
MRSA
C.difficile( 2nd choice to metronidazole)
37
Moa of vancomycin
Prevents release of peptidoglycan units release from carrier
38
Red man syndrome seen with
Vancomycin
Infusion related
Due to release of histamine
39
Daptomycin moa
Act on cell membrane
Produces membrame channel and membrane leakage
This causes rapid depolarization, resulting in a loss of membrane potential leading to inhibition of protein, DNA, and RNA synthesis, which results in bacterial cell death.
40
Daptomycin use
GP(including MRSA) for complicated skin infections and bacterimia
Cannot be used in Rx of pneumonia because inactivated by surfactant
41
vancomycin
Daptomycin
Telavancin
Spectrum?
GP
MRSA
Strepto(including penecillin resistant)
Enterococci (including susceptible to vancomycin)
All IV except vanco i.e. oral too
42
Televancin moa
Inhibitss both bacterial cell wall synthseis
| and cell memb
43
SE of vancomycin
Red man syndrome
| Oto and nephrotoxic
44
Fosfomycin moa
Inhibits a transferase enz which catalyses first step in peptidogylcan sythesis
(P last step- transpeptidase- cross linking)
45
Fosfomycin use
UTI caused by E.coli/faecalis/ fecium
46
Polymxins moa
GN
Binds to phospholipids of GN cell membrane
47
Use of polymxins
For GN bacteria
Includes
1.Polymxin B- PE, oph,otic, topical
2.Colistin/polymxin E- I.V , inhaled
Se: nephro and neurotoxicity when given systemically
48
Moa of tetracylines
Inhibit protien synthesis by binding to 30S ribosome & inh. aminoacyl tRNA attachment to 'A' site
Static
49
Tetracyline spectrum
Broad s -GN & GP
Highly R-entero, myco, pseudo
Highly S-spiroch, rickettsia, chlamydia
50
Absorption of tetracylines
Administration with dairy products or other substances that contain divalent and trivalent cations (for example, magnesium and aluminum antacids or iron supplements) decreases absorption, particularly for tetracycline , due to the formation of nonabsorbable chelates
Tetracyline drug should be taken empty stomach rest are absorbed irrespective of food (but take care of above point)
51
Ecxretion of tetracyclines
Urine except doxycyline(bile)
52
______ are theTetracylines achirving therapeutic comcentration in CSF
Doxy
| Mino
53
Drugs causing phototoxicity
Tetracylines
Sulfonamides
FQs
54
Drug causing pseudotumor cerebrii
Tetracylines
Benign, intracranial hypertension characterized by headache and blurred vision may occur rarely in adults.
55
Side effects of tetracylines
Gastric discomfort , esophagitis- mucosal irritation
Effects on calcified tissues-
Teeth :Brown dis, ill formed, prone to caries.
Bone:deformity and reduction in height
(Child and pregnancy)
Hepatotoxicity
Phototoxicity
Ototoxic
Pseudotumor cerebrii
56
Tigecycline
Act ag bac. that had dev resist to ttc
Also broad S
Not active ag. Pseudo and proteus
Active ag. Enterobacteriacae
Moa- same
Lack of cross resist. Bw ttc and it
Route- i.v
Ex: bile mainly
57
Contraindications of teyracycline
Children and pregnancy
58
Ototoxic antimicrobials drugs
vancomycin
Tetracycline
Aminogycoside
Macrolide
59
Concurrent administration of AG with neuromuscular blockade should be avoided.
why?
interfere with calcium ions movements through the calcium channels of the membrane of the motor nerve-endings inhibiting acetylcholine release at the synaptic cleft.
60
AGs moa
Binds to 30S subunit, distorting its structure and causing misreading of the mRNA
61
Antibiotics that disrupt protein synthesis are generally ___ however, aminoglycosides are unique in that they are _____
Bacteriostatic
Bacterocidal
62
extended interval dosing (a single large dose given once daily) is now more commonly utilized than divided daily doses in case of AGs .Why?
The bactericidal effect of aminoglycosides is concentration dependent; that is, efficacy is dependent on the maximum concentration (Cmax) of drug above the minimum inhibitory concentration (MIC) of the organism.
The larger the dose, the longer the PAE
PAE (post Ab effect) is continued bacterial suppression after drug levels fall below the MIC.
reduces the risk of nephrotoxicity and ototoxicity
increases convenience.
63
AGs spectrum
Aerobic GN bacilli including pseudomonas
64
Route of administration of AGs
Parentral-i.v , i.m. itrathecal
The highly polar, polycationic structure of the aminoglycosides prevents adequate absorption after oral administration.(except neomycin)
65
AGs does/ not penetrate CSF
Does not
Even when inflamed
So intrathecal
66
SE of AGs
Ototoxicity
Nephrotoxicity
Neuromuscular blockade
Allergic
67
AGs excretion
All via urine
68
Neomycin
Against GNB
Topical: skin infn
Oral :Prep of bowel before surgery to reduce PO infn
Hepatic coma-dec NH3 by inh bacterial flora(lactulose)
69
Neomycin
Against GNB
Topical: skin infn
Oral :Prep of bowel before surgery to reduce PO infn
Hepatic coma-dec NH3 by inh bacterial flora(lactulose)
70
Triple ointment
Neomycin+polymyxin+bacitracin
Out of the above neo cause contact dermatitis
Polymixin,neomycin=GN
Bacitracin=GP
71
Moa of macrolides
Bind to 50S rib, prevent translocation of peptide chain from A to P site
72
csf penetration of macrolides
Does not penetrate
73
_____macrolides is eff against many of the same org as penicillin G
Erthryomycin
74
RX of M.pneumonae
Azithromycin or doxycyline
75
Rx of chlamydia
Azithromycin or doxyxline
76
Macrolide used in MAC
Azithromycin
77
Rx of MAC
Erthyromycin , rifampin , ethambutol
78
spectrum of macrolides
```
Gpc (not MRSA)
Clamydia
Mycoplasma
Mycobacteria
Spirochete
h.pylori
C. Jejuni
Legionella
H.influenza
```
79
Excretion of macrolide
All bile (azith/eryth/telithro) except clarthromycin , urine
80
Se of macrolide
.Git-epigastric pain
+motilin R -promotes int motility without affecting colon
Used in diabetic gastroparesis and postop ileus
But tolerance develops and flora eff :not used as prokinetic
Ototoxic:high dose
Hypersenstivity
Hepatitis:estolate
81
Drug interaction of macrolide with CYP450
.All are enz inhibitors(cla/erythro/telith) except AZITHROMYCIN
82
Moa of macrolide
.Bind to 50S rib, prevent translocation of peptide chain from A to P site
83
Fidaxamycin moa, spectrum and use
Similar to macrolide
Binds RNA polymerase and inhibits transcription
GP aerobe and anaerobe only
C.difficile(minimal systemic abspn)
84
Chloramphenicol moa
chloamp
50s-inh peptidyl transferase
*macrolides & clinda:
50s-prevents translocatn from a to p site
85
50S ribosomal subunit is the target of
Macrolides,Clindamycin
Chloramphenicol
Quinupristin/dalfopristin
Linezolid
86
Excretion of chloamphenicol
Metabolised by liver via glucuronidation and in urine
Dose reductions are necessary in patients with liver dysfunction or cirrhosis.
87
CSF penetration of chloramphenicol
Yes
"Phen"-lipid solubility
88
SE of chloramphenicol
ANEMIA
- hemolytic anemia(in G6PD def)
- aplastic (BM suppression Due to some similarity of mammalian mitochondrial ribosomes to those of bacteria)
GRAY BABY
ENZ INHIBITOR
89
Grey baby syn caused by
CHLORAMPHENICOL
Neonates have a low capacity to glucuronidate the antibiotic, and they have underdeveloped renal function. Therefore, neonates have a decreased ability to excrete the drug, which accumulates to levels that interfere with the function of mitochondrial ribosomes. This leads to poor feeding, depressed breathing, cardiovascular collapse, cyanosis (hence the term “gray baby”), and death.
90
Chloramphenicol spectrum
GP and GN (Broad like teyracycline and macrolides)
91
GP and GN
```
Chloramphenicol
Tetracycline
Macrolides
Sulfonamides
Carbepenems
```
92
Clindamycin spectrum
GP (including MRSA, strepto, ANAEROBES)
93
Clindamycin adr
Pseudomembranous colitis by C.difficile
94
Quinupristin/dalfopristin
Mixture
Moa- binds to separate sites on 50S
Use: E.faecium including VRE vamcomycin resistant enteroccoci
95
Linezolid spectrum
GP mainly
VRSA and VRE
96
Linezolid moa
Binds to P site of 50S rib and distorts tRNA binding site -inh formn of initiation complex
97
Linezolid adr
Bm depression , thrombocytopenia
N, v, headache,git upset , rash
Optic neuritis , peripheral neuropathy (>28days)
Not to be given with MAO inh, SSRI,dietry tyramine.( nonselective monoamine oxidase inhibitor activity and may lead to serotonin syndrome)
98
MRSA antibiotics
```
ORAL
TMP-SMX
Doxy,minocyline
Clindamycin
Linezolid
```
```
IV
Vancomycin
Linezolid
Clindamycin
Daptomycin
Telavancin
```
99
Moa of FQs
Cidal
INHIBITS TOPOISOMERASE II/DNA GYRASE
relieves strain while double stranded DNA is being unwound by helicase.The enzyme causes negative supercoiling of the DNA or relaxes positive supercoils.
TOPOISOMERASE IV
First, it is responsible for unlinking, or decatenating, DNA following DNA replication. The double-helical nature of DNA and its semiconservative mode of replication causes the two newly replicated DNA strands to be interlinked. These links must be removed in order for the chromosome (and plasmids) to segregate into daughter cells so that cell division can complete.
Topoisomerase IV's second function in the cell is to relax positive supercoils. It shares this role with DNA gyrase, which is also able to relax positive supercoils. Together, gyrase and topoisomerase IV remove the positive supercoils that accumulate ahead of a translocating DNA polymerase, allowing DNA replication to continue unhindered by topological strain.
100
Respiratory FQs
Levofloxacin and moxifloxacin
101
FQs spectrum
4 generations
GN mainly but As the gen increase more action against GP
1-naldixic acid
2- GN and atypical :norfloxacin , cipro
3- inc GP,GN: levofloxacin
4-GP and anaerobic: moxifloxacin
102
FQs which is highly efficacious in dirrhoeal diseases
Ciprofloxacin
103
FQ with Anaerobic activity
Moxifloxacin
104
FQ used for UTIs
Ciprofloxacin
| Levofloxacin
105
Uses of FQs
```
Respiratory-levo, moxi
Git infections-cipro
Anthrax-cipro
UTIs-cipro , levo
Anaerobic - moxi
Cystic fibrosis for psedomonas- cipro
Typhoid- cipro
TB
Prostitis
```
106
Excretion of FQs
Via urine except MOXIFLOXACIN which is excreted primarily by liver
107
Csf penetration of FQs
No
108
Absorption of FQs
Ingestion of fluoroquinolones with sucralfate,
aluminum- or magnesium- containing antacids,
dietary supplements containing iron or zinc
Calcium and other divalent cations also interfere with the absorption of these agents
109
FQs adr
N/c/d
Headache, dizziness,lightheadedess ( caution in CNS disorder)
Phototoxicity
Arthropathy/ articular cartilage erosion in animals
Tendinitis/tendin rupture
QT prolongation - moxifloxacin
Drug interaction?
110
Sulfonamides spectrum
Bacteriostatic
GN+GP
Not anaerobic
111
Sulfonamides moa
Structural analogue of PABA, inh de novo folate synthsis in bacteria , so folic acid is not formed
112
What is cotrimoxazole
Sulfmethoxazole (sulfonamide) + pyimethamine
The sulfonamides (sulfa drugs) are a family of antibiotics that inhibit de novo synthesis of folate : PABA analogue and inhibits dihydo pteroate synthase.
A second type of folate antagonist—trimethoprim—prevents microorganisms from converting dihydrofolic acid to tetrahydrofolic acid, with minimal effect on the ability of human cells to make this conversion by inhibiting dihydrofolate reductase.
113
Sulfonamide for toxoplasmosis
Sulfadiazine + pyrimethamine
114
sulfasalazine use
Not absorbed after oral administration
INFLAMMATORY BOWEL DS
Local intestinal flora split sulfasalazine into sulfapyridine and 5-aminosalicylate, with the latter exerting the anti-inflammatory effect. Absorption of sulfapyridine can lead to toxicity in patients who are slow acetylators.
115
Silver sulfadiazine
Topical
Burns to prevent colonisation
Silver sulfadiazine is preferred because mafenide produces pain on application and its absorption may contribute to acid–base disturbances.
116
What is Significance of sulfonamides being highly bound to albumin?
KERNICTERUS- displace bilirubin from albumin , inc free bilirubin which can pass through immature BBB
WARFARIN:Transient potentiation of the anticoagulant effect
METHOTREXATE: inc
117
Drug interactions of FQs
Only Ciprofloxacin inhibits CYP450
Inc theophylline , warfarin , cyclosporine
118
CSF penetration of sulfonamides
Yes
119
Excretion of sulfonamides
Unchanged drug + acetylated metabolite( acetylation done by LIVER) appear in urine
120
Sulfonamides adr
CRYSTALLURIA- by acetylated metabolite
HYPERSENITIVITY- rash , angioedema , SJS
HEMATOPOITIC DISTURBANCE- hemolysis in G6PD def. , granulocytopenia , thrombocytopenia.
KERNICTERUS
DRUG POTENTIATION of the ones bound to albumin
121
CI of sulfonamide
Allergy
Newborns and infants
Pregnant women at term(due to kernicterus)
122
Trimethoprim moa
Prevents formation of tetrahydrofolic acid from dihydrofoloc acid by inhibiting dihydrofolate reductase
123
Why trimethoprim does not effect mammilian enzymes
. The bacterial reductase has a much stronger affinity for trimethoprim than does the mammalian enzyme, which accounts for the selective toxicity of the drug.
124
Trimethoprim spectrum
Similar to sulfonamides
125
Trimethoprim adr
Folic acid deficiency especially in preg and those having poor diet
126
Why trimoprim amd sulfamethoxazole are combined
Synergistic activity by inhibition of 2 sequential steps in the formation of folic acid.
Same half life
Both can cross CSF
Spectrum becomes broader
Both distribute throughout the body and can cross BBB
127
Antibacterial spectrum of cotrimoxazole
respiratory tract infections- Pneumocystis jerovicii, H .influenza, Legionella
Toxoplasmosos
Git infections-shigellosis , nontyphoid salmonella,Salmonella carriers
MRSA
Nocardia
Cross BBB
Listeria(ampicillin)
UTI and Prostatic inf ( trimethoprim concentrates in prostatic and vaginal fluid)
128
Excretion of cotimoxazole
Parent drugs and metabolites excreted in urine
129
Csf penetration of cotrimoxazole
Yes by both the components
130
Adr of cotrimoxazole
Git -n ,v
Skin rash
Hematologic - anemia , leucopenia , thrombocytopenia(REVERSED BY CONCURENT ADMINISTRATION OF FOLINIC ACID: protects patient but does not enter org because they are impermeable to it)
Hemolytic anemia in G6PD def- sulfamethoxazole
Displacement of albumin bound drugs' sulfamethoxazole
131
UTIs drugs used
Cotrimoxazole
| FQs
132
Methenamine moa
Methenamine decomposes at an acidic pH of 5.5 or less in the urine, thus producing formaldehyde, which acts locally and is toxic to most bacteria .
Methenamine is frequently formulated with a weak acid (for example, mandelic acid or hippuric acid) to keep the urine acidic.
The urinary pH should be maintained below 6. Antacids, such as sodium bicarbonate, should be avoided.
133
Methenamine use
Lower UTI
Not upper UTI(eg: pyleonephritis) because of alkalinzation of urine by urea splitting org eg: proteus
134
Why methenamine is CI on hepatic inficiency and renal insufficiency?
Methenamine is broken down into formaldehyde and NH3 in bladder .
NH3 has to be converted into urea by liver but in hepatic insufficiency NH3 accumulates.
Methenamine mandelate is contraindicated in patients with renal insufficiency, because mandelic acid may precipitate.
135
Why sytemic toxicity of methenamine does not occur
No decompostion of the drug to its active metabolite occur in ph 7.4
136
Methenamine adr
Git
Higher doses: albuminuria, hematuria
137
Why sufonamodes and methenamine should not be given concurrently
1. S react with formaldehyde and mitual antagonism
| 2. Inc crystalluria
138
Abs which do not penetrate at all
Macrolides
FQs
Aminoglycosides
139
Enz inhibitors
Ciprofloxacin only
All amcrolides except azithromycin
Chloramphenicol
140
Antibiotics whose absorption is effected by cations in food
FQs
| Tetracylines
141
Spectrum of
1. Vancomycin
2. Daptomycin
3. Telavancin
```
COMMON:GP
Staph aureus( MRSA)
Stepto.pyogenes , agalactiae
Strepto.pneum (penecillin resistant)
E.fecalis, fecium (vacomycin susceptible)
```
UNIQUE
1.C.difficile
2. VRE(gecium/ fecalis)
3. some VRE
142
Fosfomycin
| Fadaxamycin
UTI
C.difficile
143
Lincosamides
Clindamycin drugs
144
Pseudotumor cerebrii
Isotretinoin
| Tetracylines
145
Doc for legionella infection
Macrolides (especially azithromycin)
&
Respiratory floroquinolones
146
Doc for H.influenzae
Cephalosporins( eg: ceftriaxone , cefotaxime)
147
Doc for gonococcal infection involving cervix , urethra , pharynx , rectum
Ceftriaxone IM single dose + (Rx for Chlamydia if its infection is not ruled out) azithromycin PO OR doxycycline PO
148
Doc for meningoccocal infections
Third gen cephalosporins
149
Doc for pertussis
Macrolides
150
Doc for gas gangrene
Penecillin + clindamycin
151
Doc for tetanus
Metronidazole or penecillin
| Not used in botulism
152
Doc for listeria
Ampicillin
153
Doc for diphtheria
IM PenecillinG then oral penecillin V
Or
Erythromycin
