Antimicrobial, antiviral and antifungal

Question 1

Sulphonamides are a structural analogues of which of the following?

A Folic acid
B PABA
C Tetrahydrofolate
D Dihydrofolate

Answer 1

B

Explanation
Sulphonamides: “Folate Antagonist”, a DNA synthesis inhibitors. -Competitive inhibitor of Di-hyrdopteroate synthase -Structurally similar to PABA (Para-amino-benzoid acid), a precursor required by di-hydropteroate synthase for production of di-hydropteroic acid and subsequent folate synthesis. -A synergistic effect with Trimethoprim, another “Folate Antagonist” which inhibits Di-hydrofolate reductase.

Question 2

Regarding amphotericin B, which of the following statements is correct?

A Its dose needs to be reduced in mild renal impairment
B It can be given orally to treat systemic illness
C Liver toxicity is the most significant toxic side effect
D It can cause fever, headache and confusion

Answer 2

D

Explanation
Amphotericin is only given orally to treat a fungal infection in the gut. The immediate side effects seen are due to an infusion related toxicity which can be ameliorated by slowing down the infusion rate or decreasing the daily dose. Hepatic and renal impairment have little or no effect on drug concentrations. Renal damage is the most significant toxic reaction.

Note: amphotericin needs dose modification in extreme renal dysfunction

Question 3

Regarding zidovudine (AZT), which of the following statements is correct?

A It has a similar mechanism of action to amantadine
B It has a short half life
C It is not used to treat retroviruses
D It blocks thymidine kinase

Answer 3

B

Explanation
AZT is used to treat retroviral infections. AZT inhibits reverse transcriptase of HIV1/HIV2. Amantadine blocks the M2 proton ion channel of the virus particle and inhibits uncoating of the viral RNA within infected host cells, thus preventing its replication. AZT is well absorbed from the gut (63%) and widely distributed to body tissues and fluids including CSF.

Note: Although AZT has a serum half life of 1.1hrs (a short half life), the intracellular half life of the phosphorylatedcompound is 3-4hrs hrs, allowing twice daily dosing.

Question 4

Regarding cephalosporins, which of the following statements is incorrect?

A They are not as sensitive to beta-lactamase as penicillins
B Ceftazadime has activity against pseudomonas
C Third generation cephalosporins have greater gram negative cover than first generation cephalosporins
D Cefaclor is a first generation cephalosporin

Answer 4

D

Explanation
Cefaclor is a second generation Cephalosporin. Other 2nd generation cephalosporins include: cefoxitin, cefotetan, cefuroxime, cefprozil, cefmetazole, loracarbef and cefonicid

Extra:

Why cephalosporins are more stable than penicillins? Like penicillins, they inhibit cell wall synthesis by preventing cross-linking of peptidoglycan. However, unlike many penicillins, cephalosporins are resistant to β-lactamase produced by Staphylococcus spp.

Question 5

Regarding metronidazole, which of the following statements is correct?

A It has a low bioavailability
B It is highly protein bound
C It increases the anticoagulant effects of warfarin
D It poorly penetrates the CSF

Answer 5

C

Explanation
Metronidazole is an antiprotozoal drug with antibacterial activity against anaerobes. It is the treatment of choice for trichomonas-2g stat. It is well absorbed after oral administration and has a bioavailability of over 90% and readily penetrates the CSF. It has a low protein binding (10-20%). It produces a disulfiram like effect- the inhibition of acetaldehyde dehydrogenase and the accumulation of acetaldehyde and an increased “hangover effect”. It inhibits CYP 3A4 (the P450 associated with metabolism of 50% of all drugs) and therefore potentiates the effect of warfarin.

Question 6

A patient with impetigo would be most likely to respond to which of the following drugs?

A Phenoxymethylpenicillin
B Streptomycin
C Cephalexin
D Metronidazole

Answer 6

C

Explanation
Impetigo is an acute, highly contagious gram-positive bacterial infection of the superficial layers of the epidermis. Its classified as non-bullous(70% of cases) or bullous Impetigo is caused by bacterial infection. Both Group A beta hemolytic streptococci and S aureus cause nonbullous impetigo, whereas bullous impetigo is caused almost exclusively by S aureus. For antibiotic therapy, the chosen agent must provide coverage against both Staphylococcus aureus and Streptococcus pyogenes. Topical mupirocin is adequate treatment for single lesions of nonbullous impetigo or small areas of involvement. It is applied to the affected area 2 to 3 times daily. A 7-day course is usually standard, although few large studies have been performed to verify this as the most effective approach. Systemic antibiotics are indicated for extensive involvement or for bullous impetigo. A cephalosporin, semisynthetic penicillin, or beta-lactam/beta-lactamase inhibitor combination is generally suitable for first-line therapy. Phenoxymethylpenicillin above does not cover staph. Streptomycin and Metronidazole are clearly not indicated.

Question 7

Which of the following vaccines is a live virus vaccine?

A Measles
B Typhoid
C Rabies
D HBV

Answer 7

A

Explanation
Typhoid vaccine-live bacteria,

HBV-inactive viral antigen,

Rabies-inactive virus

Extra: Actually there are 2 types of Typhoid vaccines:
1. Killed vaccine- Given as a shot
2. Live (attenuated) vaccine- Given orally

LISTS

Live-attenuated:
- Measles, mumps, rubella
- Chickenpox
- Zoster
- Rotavirus
- Yellow fever
- Oral typhoid
- Bacillus Calmette-Guerin

Inactivated
- Hepatitis A & B
- Diptheria, pertussis and tetanus
- Tetanus toxoid
- Influenza
- Pneumococcal conjugate and polysaccharide
- Meningococcal conjugate and polysaccharide
- HPV
- Rabies
- Salk (inactivated polio)
- Japanese B encephalitis

Question 8

Regarding macrolide antibiotics, which of the following statements is correct?

A They enhance metabolism by cytochrome pathways
B They are usually active against neisseria species
C They bind at the 30 s ribosome sub-unit
D They are bacteriostatic but not bactericidal

Answer 8

B

Explanation
Macrolides bind to the 50s subunit of the ribosome, they are both bactericidal and bacteriostatic. They inhibit the p450 system and thus increase the concentration of multiple drugs. Resistance to the macrolide is achieved by the reduction of the permeability of the bacterial cell wall, efflux pumps, production of esterases and modification of the ribosomal binding site. Macrolides are effective against both gram positive and negative bacterial

Question 9

Which of the following is a second generation cephalosporin?

A Cephalothin
B Cefoxitin
C Cephalexin
D Ceftazidime

Answer 9

B

Explanation
Other 2nd generation: cefaclor, cefotetan, cefuroxime, cefprozil, cefmetazole, loracarbef and cefonicid

Extra:
1st Gen: Cefadroxil, Cephalexin, Cephradine,Cephapirin, Cephalothin, Cefazolin. Cefazolin is the only parenteral 1st Gen ceph in general use. It is the drug of choice for surgical prophylaxis. It penetrates well into most tissues. It does not penetrate CNS. It is an alternative to antistaphylococcal penicillin for patients who are allergic to penicillins.

3rd Gen: Cefoperazone, Cefotaxime, Ceftazidime, Ceftizoxime, Ceftriaxone, Cefixime, Cepodoxime proxetil, Cefdinir, Cefditoren pivoxil, Ceftibuten and Moxalactam

4th Gen: Cefepime Generally Cephalosporins are not active against enterococci and L monocytogenes. Cephalosporins similar to penicillins, but more stable to many bacterial beta lactamses.

1st Gen- Most active against Gram positives

2nd Gen- Gram +ves and gram -ves

3rd Gen- have expanded gram neg coverage compared to 2nd gen.

Extra:

A useful tool for people to remember them by:
1st gen - Have ‘FA/PHA’ - CeFAzolin - CeFAlothin - CeFAloridine - CeFAdroxil - CePHAlexin - CePHRAdine Exception to this is cefaclor (2nd gen)

3rd gen - “IME or ONE” - CefexIME - CeftazidIME - CefotaxIME - CefizoxIME - CefpodoxIME - CeftriaxONE - CefoperazONE Exceptions - cefibuten, cefdinir, moxalactam - cefuroxime (2nd gen)

4th gen - “PI” - CefePIme - CefPIrome

5th gen - “ROL” - CeftobipROLe - CeftaROLine

2nd gen - everything else + the 2 exceptions from earlier - Cefoxitin - Cefprozil - Cefotitan - Cefmetazole

Question 10

The cephalosporin with the highest activity against gram positive bacteria is?

A Cefuroxime
B Cephalothin
C Cefaclor
D Cefipime

Answer 10

B

Explanation
Cephalothin is a first generation cephalosporin. First generation cephalosporins are very active against gram-positive cocci, such as pneumococci, streptococci and staphylococci.

Fourth generation cepahlosporins-cefepime is active against Streptococcus pneumoniae, Groups A and B streptococci. Though active against methicillin-susceptible Staphylococcus aureus (first generation cephalosporins have minimal activity against MRSA), it is less potent than the 1st and 2nd generation agents.

Cefepime is active against P aeruginosa, enterobacteriaceae, Haemophilus and Nisseria

Cefaclor and cefuroxime are second generation cephalosporins have gram positive and gram-negative spectrums

Nice way to remember the first generation cephalosporins is they almost all have spelling with “ceph” whereas the rest have “cef”

Note: apparently the TGA has decided to name them all with “cef” -Can no longer use the recall tip that first gen cephalosporins start with ceph while the rest have cef. But will still leave the question as is.

Extra: Remember first generation cephalosporins as all having spelling “cephAL” or cefAL”

Question 11

Which class of antibiotics listed below does not possess a beta-lactam ring?

A Monobactams
B Cephalosporins
C Carbapenams
D Fluoroquinolones

Answer 11

D

Explanation
Fluroquinolones are synthetic fluorinated analogs of naladixic acid

Question 12

Which of the following antibiotics does not exert its action by inhibiting cell wall synthesis?

A Imipenem
B Vancomycin
C Ceftriaxone
D Erythromycin

Answer 12

D

Explanation
Ceftriaxone: Third generation cephalosporin which is a structural analog of the D-Ala-D-Ala substrate which inhibits peptidoglycan synthesis, cross linking, resulting in cell death

Vancomycin = Glycopeptide. MOA same as penicillins

Imipenem = Carbapenem. Structurally related to beta-lactam antibiotics

Erythromycin = Macrolide. Binds to 50S ribosomal RNA + inhibits formation of 50S ribosomal subunit. Inhibitory at low concentrations and bactericidal at higher concentrations.

Question 13

Regarding erythromycin, which of the following statements is correct?

A It binds to the 50 s sub-unit of the bacterial ribosome
B It has a large cross-reactivity with the penicillins
C It is inactivated by beta-lactamases
D It is bacteriostatic only

Answer 13

A

Explanation
Macrolides bind to the 50s subunit of the ribosome, they are both bactericidal and bacteriostatic. They inhibit the p450 system and thus increase the concentration of multiple drugs. Resistance to the macrolide is achieved by the reduction of the permeability of the bacterial cell wall, efflux pumps, production of esterases and modification of the ribosomal binding site. Macrolides are effective against both gram positive and negative bacterial

Question 14

Penicillins reach high concentrations in which of the following?

A Breast milk
B Vitreous humour
C Tubular fluid in kidneys
D CSF with normal meninges

Answer 14

C

Explanation
Penicillin is excreted into sputum and milk to levels 3-15 % of those in serum. penetration into eye, prostate, CNS is poor. However, with active inflammation much higher levels can be achieved.. Penicillin is rapidly excreted in the kidneys. 10% by glomerular filtration, 90% by tubular excretion

Question 15

Regarding Zidovudine ( AZT), which of the following statements is correct?

A It is not well absorbed from the gut
B It has a half life of 1-3 hrs
C It has no activity against retroviruses
D It inhibits viral thymidine kinase

Answer 15

B

Explanation
AZT is used to treat retroviral infections. It has a half-life of 1-3hrs. The serum half-life averages 1 hour and the intracellular half-life of the phosphorylated compound is 3.3 hours. AZT inhibits reverse transcriptase of HIV1/HIV2. AZT is well absorbed from the gut (63%) and widely distributed to body tissues and fluids including CSF. Plasma protein binding is 35%. AZT is eliminated primarily via the kidney following glucoronidation by the liver

Question 16

Of the antiviral drugs listed, which one acts on reverse transcriptase?

A Vidarabine
B Acyclovir
C Ganciclovir
D Zidovudine

Answer 16

D

Explanation
Ganciclovir, acyclovir, and vidarabine are all nucleoside analogues and all inhibit viral DNA polymerase after being activated by viral kinase phosphorylation.

Question 17

Regarding metronidazole which of the following statements is NOT true?

A It is useful against trichomonas vaginalis
B It inhibits alcohol dehydrogenase
C It is used to treat Gardnerella (vaginalis)
D It causes a metallic taste in the mouth

Answer 17

B

Explanation
Metronidazole is an antiprotozoal drug with antibacterial activity against anaerobes. It is well absorbed after oral administration and readily penetrates the CSF. It produces a disulfiram like effect- the inhibition of aldehyde dehydrogenase and the accumulation of acetaldehyde

Exta:

One of the stems may say: metronidazole turns urine into a green colour.

Medication that may turn urine green: Some medications that have been implicated include promethazine, cimetidine, amitriptyline, metoclopramide, and indomethacin.

Question 18

Acyclovir has therapeutic action against all of the following viruses, except?

A VZV
B HSV 1
C HSV2
D CMV

Answer 18

D

Explanation
In vitro testing shows some weak activity against CMV, EBV and HHV-6.

The agents used to treat CMV infections are: Valganciclovir Ganciclovir Foscarnet and Cidofovir

VZV: varicella zoster virus causing herpes zoster infections (shingles)

Question 19

Regarding acyclovir, which of the following statements is correct?

A It acts to inhibit viral entry into cells
B It is commonly given in doses of 10-20 mg TDS
C It is a guanosine analogue
D It is used to treat CMV

Answer 19

C

Explanation
Acyclovir is given in doses of 10-20mg/kg. It is not useful against CMV in vivo. It inhibits viral DNA synthesis and is administered via an oral or intravenous route. Oral bioavailability is low (15-20%) and is unaffected by food. Half life 2-3 hrs and excreted primarily by glomerular filtration and tubular secretion.

Question 20

Regarding amantadine, which of the following statements is correct?

A All of the above
B It is an antiviral drug
C It potentiates dopaminergic function
D It causes acute psychosis

Answer 20

A

Explanation
Amantadine blocks the M2 proton ion channel of the virus particle and inhibits uncoating of the viral RNA within infected host cells, thus preventing its replication. One of the side effects is that it produces insomnia and not sedation. It is active against influenza A only. Clinical manifestations of anticholinergic activity tend to be present in acute amantadine overdose. It is an antiviral drug that was by chance found to have antiparkinsonism properties; it may potentiate dopaminergic function by influencing the synthesis, release or uptake of dopamine

Question 21

All of the following antibiotics inhibit nucleic acid synthesis except?

A Chloramphenicol
B Sulfadiazine
C Rifampicin
D Norfloxacin

Answer 21

A

Explanation
Norfloxacin inhibits DNA replication, trimethoprim blocks purine production-(Trimethoprim interferes with the conversion of dihydrofolate to tetrahydrofolate, the precursor of folinic acid and ultimately of purine and DNA synthesis).Rifampicin blocks production of RNA and sulfasalazine is involved DNA blocking activities-although the process is not well understood.

Chloramphenicol is a bacteriostatic drug that stops bacterial growth by inhibiting protein synthesis. Chloramphenicol prevents protein chain elongation by inhibiting the peptidyl transferase activity of the bacterial ribosome. (Chloramphenicol diffuses through the bacterial cell wall and reversibly binds to the bacterial 50S ribosomal subunit. The binding interferes with peptidyl transferase activity, thereby prevents transfer of amino acids to the growing peptide chains and blocks peptide bond formation. As a result bacterial protein synthesis is blocked and impede bacterial cell proliferation)

Source:https://pubchem.ncbi.nlm.nih.gov/

Question 22

Regarding trimethoprim, which of the following statements is incorrect?

A It is bacteriocidal
B It is synergistic with sulphonamides
C It is less toxic to humans than bacteria
D It causes folate synthesis disruption

Answer 22

A

Explanation
Trimethoprim and sulphonamides block sequential steps in bacteria folate synthesis, and when used in combination have a synergistic effect that is often bactericidal. Alone, each agent is generally only bacteriostatic

Question 22

Regarding gentamicin, which of the following statements is correct?

A It has a large theraputic index
B It is not nephrotoxic
C It enters cells by an oxygen dependent influx
D It decreases the effect of neuromuscular junction blocking drugs

Answer 22

C

Explanation
Gentamycin is effective against gram positive and gram-negative bacteria but not against anaerobes. It prevents protein synthesis of the bacteria. The drug is transported actively across the cell membrane into the cytoplasm by an oxygen dependent process. Many bacteria are resistant to gentamycin owing to the inability of gentamicin to penetrate the cell wall. This is overcome when a penicillin or vancomycin is added in combination. These inhibit cell wall synthesis allowing gentamicin to enter the bacteria; it is a bactericidal combination. Gram-negative resistance is due to plasmid encoding aminoglycoside-modifying enzymes. It is both ototoxic and nephrotoxic. Gentamicin increases the effect of the neuromuscular blocking agents (including suxamethonium). Gentamicin has both a concentration dependent killing and post antibiotic properties and a narrow therapeutic index.

Question 23

Which of the following drugs listed below is a cell wall inhibitor?

A Gentamicin
B Cephalosporin
C Ciprofloxacin
D Tetracycline

Answer 23

B

Explanation
Tetracyclines— Inhibit Protein synthesis

Gentamicin (Aminoglycoside) — Inhibit Protein synthesis

Ciprofloxacin (Fluoroquinolone) - DNA gyrase inhibition, thereby inhibiting cell division.

Question 24

Which of the following antibiotics is resistant to staphlococcal beta-lactamase?

A Penicillin
B Piperacillin
C Amoxicillin
D Cloxacillin

Answer 24

D

Explanation
Methicillin, nafcillin and isoxazolyl penicillins are resistant to staphlococcal beta lactamase. The isoxazolyl penicillins include oxacillin, cloxacillin and dicloxacillin. Methicillin is no longer used due to its nephrotoxicity.

Question 25

Question 26
Which of the following statements is true regarding penicillins?

A Food does not impair absorption of penicillins
B Penicilllins do not cause hypernatremia
C 50% of people with a previous reaction to penicillin will have another reaction
D Penicillin can cause seizures.

Answer 25

D

Explanation

Hypernatraemia can occur if penicillin is given in very high doses and patients have renal or cardiovascular diseases. Seizures occur in patients with renal failure who are given high dose penicillin. A history of penicillin reaction is not reliable, about 5-8% of people claim such a history, but only a small number of these will have a serious reaction when given penicillin. Less than 1% of persons who previously received penicillin without incident will have a serious reaction when given penicillin. Only amoxicillin can be given with food. Most of the other penicillins absorption is impaired by food and the drugs should be administered at least 1-2hrs before or after a meal.

Question 26

Of the drugs listed, which inhibits cell membrane function?

A Vancomycin
B Amikacin
C Amphotericin B
D Erythromycin

Answer 26

A

Explanation
Amikacin inhibits the 30s ribosome subunit (protein synthesis). Erythromycin inhibits protein synthesis.

Vancomycin inhibits cell wall synthesis. Although direct form the textbook:

Vancomycin inhibits cell wall synthesis by binding firmly to the D-Ala-D-Ala terminus of nascent peptidoglycan pentapeptide. This inhibits the transglycosylase, preventing further elongation of peptidoglycan and cross-linking. The peptidoglycan is thus weakened, and the cell becomes susceptible to lysis. The cell membrane also is damaged, which contributes to the antibacterial effect. (Indirect mechanism)

Amphotericin B binds to ergosterol (a component of fungal cell walls), and alters the permeability of the cell membrane by forming pores, allowing leakage of intracellular ions, which leads to cell death

Question 27

Regarding cephalosporins, which of the following options is incorrect?

A Generally they have a wider spectrum of activity compared to pencillins due to beta-lactmase resistance
B Cefaclor is a second generation cephalosporin
C ceftriaxone has anti-pseudomonal activity
D 2nd generation cephalosporins have greater gram negative activity than first generation cephalosporins

Answer 27

C

Explanation
Ceftazidime (3rd gen), Cefoperazone (3rd gen) and Cefepime (4th gen) have anti-pseudomonal activity.

Question 28

Which antibiotic is a cell wall inhibitor?

A Gentamycin
B Erythromycin
C Vancomycin
D Streptomycin

Answer 28

C

Explanation
Cephalosporins and penicillins are also cell wall inhibitors

Question 29

Question 30
Regarding pentamidine, which of the following statements is correct?

A It should be avoided in HIV patients
B It is an antiretroviral agent
C It can cause iatrogenic diabetes
D It is a protease inhibitor

Answer 29

C

Explanation
Pentamidine is an antirprotozoal drug. It interferes with nuclear metabolism. It can be toxic to the beta cells of the pancreas and cause diabetes. It is used as an agent for prophylaxis against pneumocystosis in immune compromised patients e.g. HIV patients

Question 30

Regarding Penicillin G, which of the following statements is correct?

A 50% of people who claim allergy will have an allergic reaction on further exposure
B Hypernatraemia is not reported
C 100,000u intrathecally can cause seizures
D It has good penetration to the eye

Answer 30

C

Explanation
Hypernatraemia can occur if penicillin is given in very high doses and patients have renal or cardiovascular diseases. Seizures occur in patients with renal failure who are given high dose penicillin. A history of penicillin reaction is not reliable, about 5-8% of people claim such a history, but only a small number of these will have a serious reaction when given penicillin. Less than 1% of persons who previously received penicillin without incident will have a serious reaction when given penicillin. Only amoxicillin can be given with food to prevent the drug binding with the food and not being absorbed or gastric acid neutralizing the drug

Note: Penicillin can be given intrathecally but this route is not recommended as it can cause encephalopathy, seizures and death. If intrathecal penicillin is necessary the dose should be halved. The IV route is safe due to the protective features of the blood brain barrier.

100000U of Penicillin is roughly 100mg. Doses >12mg intrathecal or in patients with severe renal failure can produce seizures and should be avoided

Question 31

Which of the following drugs causes hypoprothrombinaemia & bleeding disorders?

A cefoxitin
B Cefuroxime
C Cefotetan
D Cefaclor

Answer 31

C

Explanation
Cephalosporins containing a methylthiotetrazole group can frequently cause hypoprothrombinaemia and bleeding disorders preventable by administration of vitamin K twice weekly (10mg). Such cephalosporins include cefamandole, cefmetazole, cefotetan and cefoperazone. These dugs can also cause a severe disulfiram like reaction thus alcohol should be avoided during treatment with these cephalosporins. All the above are second generation cephalsporins. Cefuroxime, cefaclor and cefoxitin do not contain a methylthiotetrazole (MTT) group.

Question 32

Regarding erythromycin, which of the following statements is correct?

A It is effective against Campylobacter jejuni
B It is predominantly renally excreted
C It is bacteriostatic only
D It is a cell wall inhibitor

Answer 32

A

Explanation
Erythromycin is excreted mostly in bile and feces. Only 5% is excreted in the urine. It inhibits protein synthesis. It has bacteriostatic activity against susceptible bacteria and at higher concentrations it is bactericidal.

Inhibition of protein synthesis occurs via the binding to the 50S ribosomal RNA.

Question 33

A patient taking isoniazid for the a TB infection can become susceptible to the following vitamin deficiency

A V-B12
B V-B6
C V-B3
D V-B1

Answer 33

B

Explanation
Miscellaneous reactions to isoniazid (INH) include haematological abnormalities, provocation of a vitamin B6 deficiency (pyridoxine), and tinnitus and GIT discomfort. INH can reduce the metabolism of phenytoin, increasing its blood levels and toxicity

Vitamin B6 is involved in the process of making serotonin and norepinephrine. Vitamin B6 is also involved in the formation of myelin.

Note:

Pellagra-vit B3 deficiency: the FOUR Ds of deficiency

Dermatitis, diarrhoea, dementia and death

Question 34

Which antibiotic-mechanism of action pairing is correct

A Aminoglycosides-inhibition of protein synthesis via the 50s ribosomal subunit

B Vancomycin-inhibition of cell wall synthesis

C Chloramphenicol-Inhibition of DNA synthesis

D Azithromycin-inhibition of the 30s ribosome

Answer 34

B

Vancomycin inhibits cell wall synthesis by binding to the D-Ala-D-Ala terminus of nascent peptidoglycan pentapeptide. The cell membrane is also damaged, which contributes to the antibacterial effect. It is active only against gram positive bacteria

Azithromycin-inhibition of the 50s ribosome

Chloramphenicol-Inhibition of protein synthesis

Aminoglycosides-inhibition of the 30s ribosome

Note: Inhibition of the ribosome at the 30s and 50s subunits lead to an inhibition of protein synthesis

A way to remember (from a user: It is based on house selling.
Buy AT 30(s Ribosome)
A = Aminoglycosides (“TANG” = Tobramycin, Amikacin, Neomycin, Gentamicin)
T = Tetracycline (“MDTT” = Minocycline, Doxycycline, Tetracycline, Tigecycline)

CELL at 50(s Ribosome)
C - Chloramphenicol
E - Erythromycin (Macrolides)
L - Lincosamide
L - Linezolid

Question 35

A man returns from South Africa with a Plasmodium Vivax infection. Which of the following statements is correct?

A Artemisinins is the new treatment of choice
B Treatment with chloroquine alone is satisfactory
C Primaquine should be avoided in G6PD defeciency
D Treatment with doxycycline and quinine is satisfactory

Answer 35

C

Explanation
Chloroquine is the drug of choice in treatment of non falciparum and sensitive falciparum malaria. Chloroquine does not eliminate dormant liver forms of P. vivax and P. ovale and therefore primaquine must be added for the radical cure of these species. Artemisinin based therapy is now standard for the treatment of uncomplicated F. malaria. New trials suggest good effect even in complicated F. malaria. Both quinine and choloquine can induce haemolysis in patients who are G6PD defecient. Doxycyline together with quinine is used for the treatemnt of P. falciparum

From the CTG guidelines

Treatment for uncomplicated malaria caused by Plasmodium falciparum and Plasmodium knowlesi should be initiated in hospital because a small proportion of patients deteriorate after starting therapy.

Artemether+lumefantrine (an artemisinin-based combination) is the treatment of choice for uncomplicated malaria. Chloroquine is no longer recommended for the treatment of malaria because high-grade chloroquine-resistant P. falciparum malaria has spread to most malaria-endemic areas of the world, and high-grade chloroquine-resistant Plasmodium vivax malaria occurs in several areas of the Asia-Pacific region.

For patients with malaria caused by P. falciparum (either alone or with other species) acquired from this region and who respond slowly to artemether+lumefantrine (i.e. persisting parasitaemia after 72 hours of therapy), switch to oral quinine sulfate plus either doxycycline or clindamycin as above, for 7 days. P. vivax and Plasmodium ovale can exist as dormant parasites (hypnozoites) in the liver, which can reactivate to cause relapsed malaria. The regimens for the blood-stage of uncomplicated malaria (see above) do not eliminate hypnozoites, so concurrent treatment with primaquine is required for malaria caused by these species to eliminate dormant liver parasites.

Primaquine can cause severe haemolysis in patients who are glucose-6-phosphate dehydrogenase (G6PD) deficient. If the patient is G6PD deficient, seek expert advice. For P. vivax infection, once G6PD deficiency has been excluded, use concurrently: primaquine 30 mg (child: 0.5 mg/kg up to 30 mg) orally, daily For P. ovale infection, once G6PD deficiency has been excluded, use concurrently: primaquine 15 mg (child: 0.25 mg/kg up to 15 mg) orally, daily for 14 days.

Severe malaria caused especially by plasmodium falciparum but can be caused by other malaria species. Artesunate IVI or quinine dihydrochloride if artesunate is not immediately available.

Question 36

Which of the following best describes the mechanism of action of ciprofloxacin?

A Irreversible inhibitors of protein synthesis
B Inhibition of dihydropteroate synthase
C DNA gyrase inhibitor
D Ribosomal translocation inhibition

Answer 36

C

Explanation
Fluroquinolones are active against a variety of gram + and gram - bacteria. They block bacterial DNA synthesis by inhibiting bacterial topoismerase (DNA gyrase). Inhibition of DNA gyrase prevents the relaxation of supercoiled DNA that is required for normal transcription and replication. Fluorinated derivatives- ciprofloxacin, levofloxacin and norfloxacin have improved antibacterial activity compared with nalidixic acid and also achieve bactericidal levels in blood and tissues

Inhibition of dihydropteroate synthase= sulfonamides

Irreversible inhibitors of protein synthesis= aminoglycosides

Ribosomal translocation inhibition= macrolides

Question 37

Regarding the penicillins, which is INCORRECT?

A Concentration is most tissues are equal to serum
B Can be used for enterococcal meningitis.
C Mostly excreted by tubular secretion
D Does not need to be adjusted in renal failure

Answer 37

D

Explanation
Penicillin concentration in most tissues is equal to those in serum. Penicillins also excreted into sputum and milk. Penicillin is rapidly excreted by the kidneys. About 10% is by glomerular filtration and 90% by tubular secretion. The normal half life of penicillin G is 30m. Ampicillin and extended spectrum penicillins have half lives of 1 hour. For penicillins that are cleared by the kidney, the dose MUST be adjusted in renal failure. Nafcillin is biliary excreted. Oxacillin, dicloxacillin and cloxacillin are renally and biliary excreted and thus the dose does not need to be adjusted. They are effective against enterococcal meningitis as they are able to cross the inflamed meninges. High doses are required (and with aminoglycosides)

Question 38

Administration of tetanus toxoid provides what type of immunity?

A Natural active
B Artificial passive
C Natural passive
D Artificial active

Answer 38

D

Explanation
Tetanus toxoid is a form of tetanus toxin which has been damaged by heat or formalin so that it is not dangerous, but is still immunogenic. It can be administered to the patient, who then develops anti-toxin antibodies. Since the patient develops his/her own antibodies, this is an example of active immunity. As the antibodies are produced against a manufactured substance,(such as a toxoid or a vaccine) and not the organism itself, it is artificial. In passive immunity, antibodies are formed in another person or organism and transferred to the affected individual. An example of natural, passive immunity is antibodies transferred from mother to child across the placenta. An example of artificial passive immunity is tetanus anti-toxin, antibodies formed by other individuals and transferred to a person following tetanus exposure. Note that tetanus toxoid and tetanus antitoxin are two different substances, the first causing antibody production, and the second giving passive immunity from disease.

Question 39

Erythromycin increases which of the following drug serum concentration by increasing its oral bioavailability?

A Warfarin
B Digoxin
C Cyclosporine
D Prednisolone

Answer 39

B

Explanation
Macrolides including erythromycin and clarithromycin (but not azithromycin-and is therefore free of drug interactions that occur with other macrolides) inhibit the P450 enzymes and thus increase the serum concentrations of numerous drugs e.g. theophylline, oral anticoagulants, cyclosporine and methylprednisolone. Erythromycin increases the serum concentration of oral digoxin by increasing its bioavailability.

Note: The above statements are referring to two separate ideas (I think)

1-Oral bioavailability will be affected by the first pass of the liver and its enzymes. However, warfarin has 100% bioavailability. Its serum concentration rises due to the fact that macrolides inhibit the p450 enzymes inhibiting warfarin’s metabolism, thus increasing its serum concentration. Theophylline is similar (bioavailability is 100%)

2-There is evidence that erythromycin increases digoxin’s oral bioavailability. The mechanism is unclear but it may be related to the destruction of intestinal flora, which plays a role in digoxin’s metabolism. Removal of this flora by erythromycin and more digoxin will be absorbed.

Extra: Digoxin levels are increased by antibiotics that alter gut flora to increase bioavailability eg. erythromycin. 10% of the population have enteric commensal bacteria that reduce the oral bioavailability of digoxin.

Question 40

Which of the following drugs is the treatment of choice for Trichomoniasis?

A Tetracycline
B Metronidazole
C Trimethoprim-sulfamethoxazole
D Albendazole

Answer 40

B

Explanation
Metronidazole is the treatment of choice. A single dose of 2g is effective. Tinidazole may be effective in metronidazole resistant infections. Metronidazole is also the treatment of choice for Giardiasis and Entamoeba Histolytica

Question 41

Which of the following cephalosporins do not cause hypoprothrombinaemia?

A Cefoxitin
B Cefamandole
C Cefoperazone
D Cefotetan

Answer 41

A

Explanation
Hypoprothrombinaemia and bleeding disorders can be caused by cephalosporins that contain a methylthiotetrazole group. These include: cefamandole, cefmetazole, cefotetan and cefoperazone.

Extra:

According to the journal article

Use of Hypoprothrombinemia-Inducing Cephalosporins and the Risk of Haemorrhagic Events: A Nationwide Nested Case-Control Study. Li-ju Chen etal

It reports the following: In addition, cefoxitin, which is without any heterocyclic side chains attached to 3-position of cephem nucleus, has been reported to cause hypoprothrombinemia.

Hypoprothrombinemia-inducing cephalosporins

• Flomoxef
• Cefamandole
• Cefmetazole
• Cefoxitin
• Cefotetan
• Cefoperazone
• Cefotaxime
• Cefuroxime
• Ceftriaxone

I am going to leave the question as is.

Question 42

A patient is taking Rifampicin, what should you tell them about the drug?

A It reduces the effects of a patient’s anticoagulant drugs

B Rifampicin cause harmless greenish discolouration of tear, sweat and urine

C It is not well absorbed orally and therefore should be taken on an empty stomach

D Rifampicin can cause a flu like illness despite the correct dose ingestion

Answer 42

A

Explanation
Rifampicin is an antibiotic produced by Strep mediterranei. It is active against gram positive and negative bacteria, mycobacteria and chlamydiae. There is no cross resistance to other class of antimicrobial agents.

Rifampicin inhibits the B subunit of bacterial DNA dependent RNA polymerase and thereby inhibits RNA synthesis.

Rifampicin is well absorbed orally and excreted mainly through the liver into bile. It undergoes enterohepatic circulation

Indications:

Acute tuberculosis. (It must be administered with other agents to prevent multidrug resistant strains). An oral 600mg dose twice daily can eliminate meningococcal carriage. It can be used as prophylaxis in contact of children with Haemophilus influenza b. It is also used to eradicate staphylococcal diseases such as osteomyelitis and prosthetic valve endocarditis

Adverse reactions:

Harmless orange colour to urine, sweat and tears. It can cause cholestatic jaundice and hepatitis. It induces the p450 system that increase the elimination of drugs including methadone, anticoagulants and some anticonvulsants. If administered less often than twice weekly, it may cause a flu like syndrome characterized by fever, chills, myalgis, anaemia and thormbocytopaenia. It has been associated with acute tubular necrosis

Dosing schedule

Active TB: daily dose. (if follow intermittent dosing- it is recommended 2-3 times a week (6m)

Latent TB: daily dose (4m)

Question 43

An elderly patient with chronic renal impairment develops a lower respiratory tract infection. Which antibiotic as a single agent is best suited for her?

A Clarithromycin
B Penicillin
C Moxifloxacin
D Ciprofloxacin

Answer 43

C

Explanation
Fluoroquinolones are generally well tolerated. Most fluoroquinolones are eliminated by renal mechanisms-tubular secretion or glomerular filtration. Dosage adjustment is required for patients with low creatinine clearance. However, dosage adjustment for renal failure is NOT required for moxifloxacin. It is non renally cleared and therefore contraindicated in patients with hepatic failure.

Penicillin is rapidly excreted by the kidneys. Dose adjustment is required according to the kidney function.

Clarithromycin is metabolized in the liver. The drug and its active metabolite is excreted in the urine. Dose adjustment is required in patients with low creatinine clearance.

Question 44

Which of the following antibiotics has Pseudomonas cover?

A Cefepime
B Cefuroxime
C Ceftriaxone
D Cephalexin

Answer 44

A

Explanation
Cefepime is a fourth generation cephalosporin with pseudomonas cover. Other cephalosporins with pseudomonas cover include third generation cephalosporins ceftazidime and cefoperazone. Ceftriaxone is a third generation cephalosporin that does not have pseudomonas cover. Cephalexin is a first generation cephalosporin with predominately gram positive cover. Cefuroxime is a second generation cephalosporin with predominately gram positive cover and some cover against gram negative species such as Haemophilus influenzae and Neisseria gonorrhoea.

Question 45

What is the mechanism of action of tetracycline antibiotics?

A Irreversible binding to peptidoglycan pentapeptide

B Reversible binding to the 30S ribosomal subunit inhibiting protein synthesis

C DNA gyrase inhibitor

D Reversible binding to the 50S ribosomal subunit inhibiting protein synthesis

Answer 45

B

Explanation
Pharmacodynamics
Long-acting tetracycline antibiotic
Broad spectrum
Bacteriostatic
Inhibits protein synthesis by binding reversibly to the 30S ribosomal subunit

Question 46

What is the main mechanism of penicillin resistance?

A Increased antibiotic efflux
B Inactivation by beta-lactamases
C Decreased antibiotic influx
D Alteration of penicillin-binding proteins

Answer 46

B

Explanation
Resistance mechanisms of penicillin:
- Inactivation by beta lactamase (main mechanism) - Modification of target PBPs
- Impaired penetration of drug to target PBPs (gram negative)
- Antibiotic efflux (gram negative)

Question 47

Gentamicin does not have anti-microbial activity against which of the following?

A Anaerobes
B Pseudomonas Aeruginosa
C Beta-lactamase producing strains of H. influenzae
D S. aureus

Answer 47

A

Explanation
Gentamicin has good coverage against aerobic gram negative bacteria, including pseudomonas; gram positive bacteria including Staph and Strep; but no activity against anaerobes.

Source: https://litfl.com/pharm-101-gentamicin/

Question 48

A healthcare worker suffers a needlestick injury from an HIV+ patient and requires prophylaxis. Which of the following is an appropriate choice of drug?

A Diphenoxylate
B Zidovudine
C Amantadine
D Ribavirin

Answer 48

B

Explanation
Zidovudine is an NRTI (nucleoside/nucleotide reverse transcriptase inhibitor) anti-retroviral agent that causes competitive inhibition of HIV-1 reverse transcriptase. Incorporation into the growing viral DNA chain causes premature chain termination.

Question 48

Azithromycin has been reported to cause which of the following cardiac arrhythmias?

A Supraventricular tachycardia
B Sinus bradycardia
C Atrial fibrillation
D Ventricular tachycardia

Answer 48

D

Explanation
Macrolide antibiotics prolong the QT interval due to an effect on K ion channels. Prolongation of the QT interval can lead to torsades de pointes arrhythmia.

Question 48

What is an appropriate antibiotic choice to treatment mycobacterial infections?

A Probenecid
B Erythromycin
C Cefuroxime
D Penicillin G

Answer 48

B

Explanation
Macrolide antibiotics have good cover against mycobacterial infections. Penicillin G is active primarily against susceptible gram positive bacteria and gram negative cocci. Cefuroxime is a second-generation cephalosporin with similar activity to first generation cephalosporins but additional gram negative coverage. Probenecid inhibits renal tubular secretion of penicillin thus prolonging half-life and duration of action.

Extra:

Antimicrobial activity
Gram positive organisms e.g. pneumococci, strep, staph
Mycoplasma pneumoniae, L pneumophila, Chlamydophila pneumoniae, Listeria monocytogenes
Gram negative organisms e.g. neisseria, bordatella pertussis, campylobacter
Treponema pallidum

Question 49

Which medication can be used as a one-off dose for treatment of chlamydia trachomatis?

A Azithromycin
B Ciprofloxacin
C Doxycycline
D Ceftriaxone

Answer 49

A

Explanation
Azithromycin is highly active against Chlamydia species. The drug penetrates most tissues and is slowly released from tissues producing an elimination half-life of 2-4 days. This allows a single dose of 1g Azithromycin to be as effective as 7 days of doxycycline for chlamydial cervicitis and urethritis

ETG guidelines advise only a single dose of Azithromycin (1g) for the treatment of asymptomatic chlamydia infections. For symptomatic infections, a repeat dose of Azithromycin (1g) a week later is advised.

Question 50

Which class of UTI antibiotics affects the P450 sytem

A Nitrofurantoin
B Fluoroquinolones
C Sulfonamides
D Trimethoprim

Answer 50

B

Explanation
According to a web search, fluoroquinolones antibiotics inhibit cytochrome p450

The TB does not seem to directly state this about fluoroquinolones