Pharmacology Flashcards
1
Q
Name 2 classes of bacterial cell wall synthesis inhibitors.
A
Beta-lactams, Glycopeptide
2
Q
Beta lactams bind to the active side of which enzyme?
A
Transpeptidase (penicillin binding protein)
3
Q
Name 4 types of beta lactams
A
Penicillins, cephalosporins, carbapenems, monobactam
4
Q
Name the 4 classes of penicillins
A
- natural penicillins (Pen G and Pen V),
- penicillinase resistant penicillins (cloxacillin, flucloxacillin),
- aminopenicillins (amoxicillin, ampicillin),
- antipseudomonal penicillins (piperacillin)
5
Q
Which natural penicillin is administered parenterally?
A
Penicillin G
6
Q
Syphilis caused by Treponema pallidum can be treated with which penicillin?
A
Penicillin G
7
Q
Are natural penicillins commonly used against Staphylococcus aureus?
A
No
8
Q
Which class of penicillin is commonly used against methicillin sensitive Staphylococcus aureus?
A
Penicillinase resistant penicillins
9
Q
How does methicillin sensitive Staphylococcus aureus acquire resistance against the natural penicillins?
A
They produce penicillinases
10
Q
Which bacteria is cloxacillin effective against?
A
Methicillin Sensitive Staphylococcus aureus (MSSA)
11
Q
How are the penicillins mainly cleared?
A
Renal clearance
12
Q
Name the 2 aminopenicillins
A
Ampicillin, amoxicillin
13
Q
Are aminopenicillins effective against beta lactamase producing strains of bacteria?
A
No
14
Q
Which of the aminopenicillins (amoxicillin or ampicillin) has better oral absorption?
A
Amoxicillin
15
Q
Does aminopenicillins sufficiently cover Pseudomonas and Klebsiella?
A
No
16
Q
How are aminopenicillins cleared?
A
Renal
17
Q
How is piperacillin administered?
A
IV
18
Q
Which class of penicillins has coverage against Pseudomonas, Proteus and Klebsiella?
A
Anti-pseudomonal penicillins (piperacillin)
19
Q
Name 3 beta lactams-beta-lactamase inhibitor combination drugs.
A
- Augmentin (Amoxicillin + clavulanic acid)
- Unasyn (ampicillin + sulbactam)
- Zosyn (piperacillin + tazobactam)
20
Q
How do beta-lactamase inhibitors work?
A
They either covalently bind at or near the active site of the β-lactamase and restructures it, permanently inactivating. In doing so, they protects other beta-lactam antibiotics from beta-lactamase catalysis.
21
Q
Name a microbe that commonly causes nosocomial infections and is resistant to all penicillins.
A
MRSA (methicillin resistant Staphylococcus aureus)
22
Q
Name at least 2 penicillins related life-threatening allergic reactions.
A
- Anaphylaxis
- Stevens Johnson syndrome
- Toxic epidermal necrolysis
23
Q
Which generation of cephalosporins does cefazolin and cephalexin belong to?
A
First Generation
24
Q
Which generation of cephalosporins are primarily administered orally?
A
First and second generation cehalosporins. Cefazolin (first generation) is an exception.
25
How are the 3rd, 4th and 5th generation cephalosporins administered?
Parenterally
26
Name at least 3 types of microbes against which first and second generation cephalosporins are ineffective?
Pseudomonas aeruginosa and
(LAME species)
- Listeria monocytogenes,
- Atypicals (Mycoplasma, Chlamydia, Legionella spp.),
- MRSA, and
- Enterococcus species
27
Ceftriaxone belongs to which generation of cephalosporins?
Third Gen
28
Name one cephalosporin from the third and fourth generation each which is effective against Pseudomonas aeruginosa.
Third generation – Ceftazidime
Fourth generation - Cefepime
29
Which generation of cephalosporins has coverage against MRSA?
Fifth generation (ceftobiprole, ceftaroline)
30
How are most cephalosporins cleared?
Renal
31
How is ceftriaxone cleared?
Hepatic
32
Explain the mechanism of resistance underlying MRSA.
MRSA expresses an altered penicillin binding protein (PBP2a) with reduced affinity for the penicillins
33
Name 3 advantages the third generation and fourth generation cephalosporins have over the first and second generations.
1. Higher activity against Gram-negative bacteria
2. Greater resistance against the beta-lactamase producing strains
3. Greater CSF penetration
34
Does cephalosporin have cross reactivity with penicillins?
Yes
35
Does cephalosporin have cross reactivity with penicillins?
Yes
36
Name the class of antibiotics that are commonly used against extended spectrum beta-lactamase (ESBL) producing bacteria?
Carbapenems
37
Name 3 carbapenems.
1. Imipenem,
2. meropenem,
3. ertapenem
38
How are carbapenems administered?
Parenterally
39
Imipenem is combined with __________, which works by __________.
cilastatin,
inhibiting dehydropeptidase 1 (DHP1) found in the brush border of the proximal renal tubule. (DHP1 is necessary for the hydrolysis of imipenem. It is not a beta lactamase inhibitor.)
40
Can carbapenems be used to treat MRSA?
No
41
Which carbapenem has good CSF penetration?
Meropenem
42
Which of the following carbapenems is not effective against Pseudomonas aeruginosa?
Ertapenem
43
Which drug classes of beta lactams have cross reactivity with penicillins?
Cephalosporins, carbapenem
44
Which drug class does aztreonam belong to?
Monobactam
45
Aztreonam is effective against Gram-
negative bacteria (no activity against Gram positive and anaerobic microbes)
46
Does aztreonam have cross-sensitivity to penicillin?
No
47
What are some adverse effects related to the use of penicillins, cephalosporins and carbapenems?
GIT related symptoms (vomiting diarrhea), hypersensitivity (Symptoms range in severity, from a minor rash to life-threatening conditions like anaphylaxis)
48
Vancomycin is useful against Gram ___________
Positives
49
How is vancomycin commonly administered?
IV
50
When is oral vancomycin preferred?
Clostridium difficile-associated diarrhea (CDAD) or the more severe antibiotic-associated pseudo-membranous colitis
51
What is the first line of antibiotics for CDAD?
Vancomycin
52
Vancomycin interferes with cell wall synthesis by inhibiting ___________
transglycosylation
53
Name 3 antibiotics that work by inhibiting bacterial cell wall synthesis, and are effective against MRSA?
1. ceftobiprole (Fifth generation cephalosporins)
2. ceftaroline (Fifth generation cephalosporins)
3. Vancomycin
54
How is vancomycin cleared?
Renal
55
Name 3 adverse effects related to vancomycin
1. Nephrotoxicity,
2. Ototoxicity,
3. Red man syndrome
56
Name 2 key targets of antimicrobials that work by inhibiting bacterial protein synthesis?
50S, 30S bacteria ribosomal subunits
57
Name at least 2 classes of antibiotics which are 30S protein synthesis inhibitors
tetracyclines, glycylcycline, aminoglycosides
58
Name 3 examples of tetracyclines
tetracycline, doxycycline, minocycline
59
Tetracycline prevents binding of ___________ to the A site of mRNA-ribosome complex
tRNA
60
Tetracyclines should not be administered with dairy products or substances that contain divalent and trivalent cations as this would lead to the formation of ___________, which would ___________ the absorption of the drugs.
non-absorbable chelates,
reduce
61
Comment on tetracycline’s antimicrobial coverage
It has broad spectrum activity against many Gram-negative and Gram-positive bacteria. It also has coverage against atypical bacteria. It does not have adequate coverage against Pseudomonas aeruginosa and Proteus
62
How is tigecycine administered?
Intravenously (It has poor oral bioavailability unlike the tetracyclines.)
63
Glycylcyclines (tigecycline) were designed to overcome which two mechanisms of tetracycline resistance?
Expression of efflux pumps, and ribosomal protection
64
Tigecycline is useful in targeting some of the resistant microbes including
1. Methicillin resistant staphylococci (MRSA),
2. Multidrug-resistant streptococci,
3. Vancomycin-resistant enterococci (VRE),
4. useful against carbapenem resistant strains of Extended-spectrum β-lactamase–producing gram-negative bacteria
65
Name at least 4 adverse effects associated with the use of tetracyclines
1. Gastrointestinal distress (To reduce ulceration, drink plenty of fluids and do not take it before sleep)
2. Phototoxicity (Like fluoroquinolones)
3. Superinfection like thrush
4. Deposition in bone/primary dentition and may cause discoloration of teeth
66
The use of tetracyline and tigecycline is contraindicated in which populations of patients?
Pregnant women,
Breastfeeding women
Children less than 8 years of age
67
Aminoglycosides are transported across the inner membrane of Gram-negative bacteria by ___________ , which is an energy dependent process.
Active transport
68
Aminoglycosides are particularly effective against _______ Gram-negative bacteria
Aerobic
69
Name 5 examples aminoglycosides
gentamicin, streptomycin, tobramycin, amikacin, neomycin
70
Aminoglycosides demonstrate synergism when combined with which class of antibiotics? Name one class.
Beta lactams (e.g. gentamicin and ceftriaxone for the management of staphylococcus endocarditis)
71
How are aminoglycosides commonly administered?
Parenterally (They have poor oral bioavailability)
72
Name an aminoglycoside that is used in the management of tuberculosis
Streptomycin (administered IM)
73
How are aminoglycosides cleared?
Renal
74
Name at least 2 adverse effects associated with aminoglycosides
1. Ototoxicity
2. Nephrotoxicity (Do not combine with other nephrotoxicity)
3. Neuromuscular paralysis (Especially when used with neuromuscular blockers)
75
Name an aminoglycoside that is administered orally
Neomycin (bowel prep)
76
Name 2 groups of patients in whom aminoglycosides would be contraindicated
1. Pregnant women,
2. Patients suffering from myasthenia gravis because of the risk of prolonged neuromuscular blockade
3. Patients with severe renal Impairment
77
What are the 6 “NOs” in relation to aminoglycosides?
1. No to protein synthesis
2. Particularly active against aerobic Gram-Negative Organisms
3. No to use during pregnancy
4. No to oral administration
5. No to CSF penetration
6. Nephro- and Oto- toxicities
78
Name 3 types of 50S protein synthesis inhibitors
Macrolides, clindamycin, linezolid
79
Name 3 macrolides
Erythromycin, clarithromycin, azithromycin
80
Are macrolides bacteriostatic or bactericidal antibiotics?
Bacteriostatic
81
How can macrolides be administered?
Oral and IV
82
Name some of the microbial infections that the macrolides are useful against
Respiratory infections caused by S.pneumoniae, H. influenzae and Moraxella catarrhalis and those caused by atypical bacteria such as Legionella pneumophilia, Mycoplasma and Chlamydia
STDs caused by Chlamydia trachomatis and Neisseria gonorrhoea
H.pylori infections
83
Name 2 adverse effects associated with macrolides
1. Gastric Distress
2. Hepatotoxicity
3. Ototoxicity
4. May prolong QT interval
84
How are macrolides cleared?
Erythromycin and clarithromycin undergoes hepatic clearance
Azithromycin – is mainly eliminated unchanged in faeces
85
Which of the macrolides cause the most GI distress?
Eythromycin
86
Name 2 mechanisms via which bacteria may acquire macrolide resistance
ERM gene expression, efflux pumps
87
Which drug(s) can exhibit cross resistance with macrolides?
Clindamycin (if the microbes acquire resistance by expressing erm methylases)
88
Linezolid works by ___________
It binds the bacterial 23S ribosomal RNA of the 50S subunit and inhibits the formation of the initiation complex needed for protein synthesis.
89
Clindamycin is primarily used to treat _________ infections
anaerobic
90
Can clindamycin be used to treat MRSA?
Yes
90
How is clindamycin administered?
Oral / IV
91
Name an adverse effect associated with the use of clindamycin
Clostridium difficile associated diarrhoea
92
What is linezolid’s mechanism of action?
It binds the bacterial 23S ribosomal RNA of the 50S subunit and inhibits the formation of the initiation complex needed for protein synthesis.
93
Linezolid is effective against Gram _________ bacteria?
Positive
94
Linezolid binds to bacterial _________ ribosomal RNA of 50S subunit
23S
95
Name 3 antibiotics that only covers Gram positives?
Vancomycin, penicillinase resistant penicillin, linezolid
96
How is linezolid administered?
Oral / IV
97
What does linezolid cover?
Many of the resistant Gram-positive strains such as MRSA, VRE, VRSA
98
Name at least 2 key adverse effects associated with prolonged use of linezolid
1. Irreversible peripheral neuropathies
2. Optic neuritis
3. Bone marrow suppression
99
Linezolid can cause _________ if administered concomitantly with SSRI or MAO inhibitors?
serotonin syndrome
100
Can linezolid be used for the treatment of catheter-related bloodstream infections?
No, it is not approved. (Based on FDA recommendation)
101
Name 2 antibiotics that can be administered orally for MRSA
Linezolid and clindamycin
102
Which of the protein synthesis inhibitors are safe for use in pregnant women?
Macrolides, clindamycin
103
Fluoroquinolone targets _________ in Gram negatives and _________ in Gram positive bacteria
DNA gyrase, topoisomerase IV
104
Name 3 fluoroquinolones
ciprofloxacin, levofloxacin, moxifloxacin
105
Fluroquinolones should be administered at least _________ hours before consumption of dairy products or substances that contain divalent cations
2 hours
Best on empty stomach
106
Name the two respiratory quinolones
Levofloxacin and moxifloxacin
107
Name at least 3 adverse effects associated with the use of fluroquinolones.
1. Phototoxicity
2. Tendinitis or tendon rupture
3. Prolong QT interval
4. Peripheral Neuropathy
5. GI distress
6. Arthropathy
108
Which antibiotics are known to cause phototoxicity?
Tetracyclines, fluoroquinolones
109
Fluoroquinolones are contraindicated in _________
1. Children < 18 years old
2. Pregnant women
110
Can fluoroquinolones be used when breastfeeding?
No
111
Name 3 folate synthesis inhibitors
Sulfonamides, trimethoprim, cotrimoxazole
112
Folic acid is vitamin B9 that is needed in humans to produce healthy ___________
Red Blood Cells
113
Which enzyme does sulfonamide inhibit?
Dihydropteroate synthase
114
Sulfonamides are only effective in bacteria that synthesize their own __________?
Folic acid
115
Sulfonamides can cause nephrotoxicity as a result of __________?
crystalluria
116
G6PD deficient patients using sulfonamides can suffer from __________
hemolytic anemia
117
Usage of sulfonamides in last trimester can cause __________ in newborns
kernicterus
118
Which enzyme does trimethoprim inhibit?
Dihydrofolate reductase
119
Folic acid deficiency caused by trimethoprim can be managed by giving the patients _____________ .
Folinic acid
120
Trimethoprim can cause __________ deficiency in humans
folic acid
121
Cotrimoxazole is a combination of which 2 antibiotics, and in what ratio?
Trimethoprim and sulfamethoxazole, 1:5 respectively
122
Name an antibiotic which is used as the choice of drug for the management of pneumocystis pneumonia
Cotrimoxazole
123
Cotrimoxazole is contraindicated in which trimester(s) of pregnancy?
First and last
124
Name at LEAST two indications for cotrimoxazole
1. Uncomplicated UTI
2. Pneumocystis pneumonia
125
Name at LEAST 3 adverse effects related to the use of cotrimoxazole
1. Glossitis
2. Rash
3. Photosensitivity
4. Blood disorders including megaloblastic anemia, leukopenia, and thrombocytopenia
126
What is nitrofurantoin’s mechanism of action?
It is converted by the bacteria to a highly active intermediate, which disrupts the synthesis of DNA, RNA and metabolic processes.
127
Nitrofurantoin is effective in treatment of _________ .
Lower UTI
128
Nitrofurantoin can cause urine colour to turn _________ .
brown
129
How is nitrofurantoin cleared?
Renal
130
G6PD deficient patients using nitrofurantoin are susceptible to ___________ .
Hematologic disturbances such as hemolytic anemia, leukopenia
131
What is G6PD, and why is it important in red blood cells?
The glucose-6-phosphate dehydrogenase (G6PD) enzyme is the central factor of the antioxidant defense system in red blood cells, which helps maintain high levels of reduced glutathione (GSH) and nicotine adenine dinucleotide phosphate (NADPH), to protect the RBC from oxidative damage caused by reactive oxygen species.
132
Name 3 groups of patients in whom nitrofurantoin may be contraindicated.
1. Patients with impaired renal function
2. Pregnant women (at term > 37 weeks)
3. Infants <1 mth of age
133
What would be examples of recommended treatment options for simple UTI in healthy women of reproductive age?
1. Cotrimoxazole
2. Nitrofurantoin
134
Name 2 polyenes antifungal
1. Amphotericin B
2. Nystatin
135
Name the 2 categories of azole antifungals
1. Triazole
2. Imidazole
136
What is the mechanism of action polyene antifungals?
They bind to ergosterol in the plasma membranes of sensitive fungal cells to forms pores (channels). These pores disrupt membrane function, allowing electrolytes and other small molecules to leak from the cell, resulting in cell death.
137
How is amphotericin B commonly administered?
IV (poor oral bioavailability)
138
What advantage does the liposomal formulation of amphotericin B has over the conventional deoxycholate formulation?
Liposomal formulation has reduced renal toxicity
139
State 2 adverse effects associated with amphotericin B deoxycholate formulation
1. Fever and chills
2. Nephrotoxicity
140
Name 2 clinical indications for amphotericin B
Candidiasis
Aspergilliosis
Cryptococcal meningitis
141
Name an anti-fungal, which is relatively safe for use in pregnancy despite systemic exposure.
Amphotericin B
142
What is the mechanism of action for 5-Flucytosine?
5-flucytosine is converted, by cytosine deaminase, to its metabolically active form 5-fluorouracil (5-FU), which inhibits protein synthesis and inhibits thymidylate synthase hence inhibiting DNA synthesis.
143
How is 5-Flucytosine commonly administered?
Oral (good oral bioavailability)
144
State at least 2 adverse effects associated with the use of 5 flucytosine
Bone marrow suppression
Hepatotoxicity
GI related effects
145
State one clinical indication for 5-flucytosine
Cryptococcal meningitis (usually in combination with amphotericin B, rarely used as single agent due to resistance)
146
Name 3 echinocandins
Caspofungin
Micafungin
Anidulafungin
147
State the mechanism of action of the echinocandins
Echinocandins inhibit the activity of the glucan synthase complex, resulting in loss of the structural integrity of the cell wall
148
How are echinocandins commonly administered?
IV
149
Name 2 fungal species against which Echinocandins have potent activity
1. Candida
2. Aspergillus
150
What is the mechanism of action of azoles?
They inhibit C-14 α-demethylase (CYP450 enzyme), thereby blocking the demethylation of lanosterol to ergosterol. This inhibition of ergosterol biosynthesis disrupts membrane structure and function and inhibits fungal cell growth.
151
Do the triazoles have good oral bioavailability?
Yes
152
State 3 adverse effects common to the triazoles
QT prolongation
Hepatotoxicity
GI side effects
153
Name a triazole which is associated with the adverse effect of cardiotoxicity
Itraconazole
154
Name a triazole which is associated with the adverse effect of neurotoxicity
Voriconazole
155
Name one class of anti-fungals, which is significantly associated with CYP450 enzymes related drug-drug interactions?
Azoles
156
Which azole should not be taken with antacids?
Itraconazole (low pH improves absorption)
157
Which azole is the treatment of choice for the management of aspergillosis?
Voriconazole
158
How are the imidazoles commonly administered?
Topical (minimally absorbed)
159
Name 2 anti-fungal drugs that can be used in the management of vuvlovaginal candidiasis and describe how it is administered
clotrimazole (cream)
fluconazole (oral)
miconazole (vaginal suppository)
nystatin (vaginal suppository)
160
Is nystatin administered parenterally?
No
161
State a clinical indication for nystatin, and how it is administered.
1. oropharyngeal candidiasis (oral agent; swish and swallow or swish and spit)
2. vulvovaginal candidiasis (vaginal suppository)
162
What is terbinafine’s mechanism of action?
It inhibits squalene epoxidase, thereby blocking its conversion to lanosterol and biosynthesis of ergosterol, an essential component of the fungal cell membrane.
163
How is terbinafine administered for the management of tinea capitis?
Oral (Topical application cannot be used for the management of tinea capitis)
164
What are the first line drugs against tuberculosis?
(RIPES)
Rifampicin
Isoniazid
Pyrazinamide
Ethambutol
Streptomycin
165
What is the mechanism of action of rifampicin?
Rifampicin inhibits gene transcription of mycobacteria by blocking the DNA-dependent RNA polymerase, which prevents the bacillus from synthesizing messenger RNA and protein, causing cell death.
166
State 2 clinical indications for rifampicin
1. Latent / Active tuberculosis
2. Leprosy, against Mycobacterium leprae
167
Which organism causes tuberculosis?
Mycobacterium tuberculosis
168
Which of the 4 standard first line anti-tuberculosis drugs are safe for use in patients with kidney failure?
Rifampicin and Isoniazid
169
Name 3 adverse effects associated with rifampicin
Hepatitis
Cutaneous reactions
Gastrointestinal symptoms
170
What is the mechanism of action of isoniazid?
Isoniazid is activated by the catalase-peroxidase enzyme of M. tuberculosis. The activation of isoniazid produces oxygen-derived free radicals that can inhibit the formation of mycolic acids of the bacterial cell wall, cause DNA damage and, subsequently, the death of the bacillus.
171
Which enzyme is involved in the metabolism of isoniazid, and presents with wide variation in activity in the community due to genetic polymorphisms?
N-acetyl transferase (rapid acetylator vs slow acetylator phenotypes are found in the population due to the genetic polymorphism
172
State 2 adverse effects related to isoniazid
1. Peripheral Neuropathy
2. Hepatitis
173
Patients on isoniazid are often co-administered _________ to help overcome ________ deficiency to avoid peripheral ________ .
pyridoxine, vitamin B6, neuropathy
174
What food – food interactions must patients taking isoniazid be aware for?
They should avoid food rich in tyramine and histamine (certain types of fish, cheese and red wine).
175
What is the mechanism of action of pyrazinamide?
Pyrazinamide is converted to its active form, pyrazinoic acid, by the microbial enzymes. The accumulation of pyrazinoic acid decreases the intracellular pH to levels that cause the inactivation of critical pathways necessary for the survival of the bacteria.
176
Which of the first line anti-tuberculosis drugs is highly effective against the persistent bacilli
Pyrazinamide
177
Which of the 4 standard first line anti-tuberculosis drugs must be avoided or used with caution if the patient suffers from liver disease?
(RIP)
Rifampicin
Isoniazid
Pyrazinamide
178
Which of the 4 standard first line anti-tuberculosis drugs (R.I.P.E) is/are highly associated with causing gout like symptoms?
1. Pyrazinamide (More common with pyrazinamide then ethambutol)
2. Ethambutol
179
Which of the 4 standard first line anti-tuberculosis drugs must be avoided or used with caution if the patient suffers from kidney impairment?
1. Pyrazinamide
2. Ethambutol
180
What is the mechanism of action ethambutol?
Ethambutol inhibits the arabinosyltransferase enzyme and interferes with the polymerization of arabinose into arabinogalactan, the principal polysaccharide on the mycobacterial cell wall.
181
Which of the 4 standard first line anti-tuberculosis drugs (R.I.P.E) is/are highly associated with causing visual toxicity?
Ethambutol
182
Which class of antibiotics does streptomycin belong to?
Aminoglycoside
183
How is streptomycin administered?
Intramuscular injection
184
In which groups of individuals would physicians have a high index of suspicion for multi drug-resistant tuberculosis?
Individuals
1. who were previously treated for TB,
2. who have failed TB treatment,
3. who are known contacts of patients with MDR-TB, or
4. who come from countries with high prevalence of drug resistant tuberculosis
