PMCOL 344 Exam Questions With
Correct Answers
Gout
what is it?
characteristics? - answer-metabolic disorder leading to raised plasma uric acid levels
-painful attacks of acute arthritis produced by deposition of sodium urate crystals in joints (big
toe)
urate crystals and immune response - a...
characteristics? - answer✔-metabolic disorder leading to raised plasma uric acid levels
-painful attacks of acute arthritis produced by deposition of sodium urate crystals in joints (big
toe)
urate crystals and immune response - answer✔activate PRRs (toll like receptors) to trigger
innate immune response. activation of kinin, complement, generation of cytokines and
accumulation of neutrophils. neutrophils engulf crystals and cause tissue damage by releasing
ROS and proteases.
acute treatment of gout
prophylaxis treatment - answer✔- NSAIDS and glucocorticoids
- Inhibitors of uric acid synthesis (allopurinol) and Uricosuric drugs (probenecid)
Allopurinol - answer✔acute treatment of gout. inhibits uric acid synthesis
Allopurinol mechanism - answer✔analogue of hypoxanthine, converted to alloxanthine by XO
and then irreversibly inhibits XO (product inhibition)
reduces levels of urate and uric acid in plasma, tissues and urine
formation of uric acid - answer✔DNA breakdown produces hypoxanthine. converted by
xanthine oxidase into xanthine. converted by xanthine oxidase into uric acid.
Probenecid - answer✔- increases excretion of urate by inhibiting reabsorption by URAT-1 in
proximal tubule.
- competes with urate for binding.
infections - answer✔invasion and multiplication of organisms
colonization (commensals) - answer✔gut bacteria break down food remains, produce vitamins
(vit K), control growth of potentially pathogenic organisms (antimicrobials cause secondary
infections due to decreased normal flora)
classification of bacteria - answer✔shape (spheres=cocci, rods=bacilli, spirals)
aerobes and anaerobes
gram positive, gram negative
gram positive bacteria - answer✔one plasma membrane. up to 40 layers of peptidoglycan
layers. purple stain sticks to mesh
gram negative bacteria - answer✔2 plasma membrane layers, makes it harder for drugs to get
into cell. peptidoglycan layers between membranes.
bactericidal - answer✔kills bacteria
bacteriostatic - answer✔stop bacteria from reproducing or inhibit growth (not kill)
must have active immune system (critical in helping body control and eliminate infections) no
decline in bacteria, can increase once drug removed
antibiotic targets - answer✔- biochemical reactions: affect formation of cell wall, protein
synthesis
- structural targets: affect membrane, intracellular organelles
classes of potential biochemical reactions (targets) - answer✔Class 1: generation of ATP and
simple carbon compounds (similar in humans therefore poor targets)
Class 2: energy dependent synthesis of amino acids, nucleotides, phospholipids, etc
Class 3: formation of macromolecules RNA, DNA, peptidoglycans
(2 + 3 most important)
Folate in humans vs bacteria - answer✔Class 2 reaction.
Folate (FH4) required for DNA synthesis, humans can only get folate from diet, bacteria cannot
take up folate so need de novo synthesis.
folate synthesis - answer✔PABA (p-amino benzoic acid) converted into folate by
dihydropteroate synthetase. folate then converted into tetrahydrofolate (FH4) by dihydrofolate
reductase. FH4 then involved in DNA synthesis (thymidylate).
sulfamethoxazole - answer✔analogue of PABA, compete for binding to dihydropteroate
synthetase.
broad spectrum, effective against gram - and + bacteria
bacteriostatic (suppress division, no killing)
sulfonamides negative aspects - answer✔-occurrence of adverse reactions and resistance
(synthesis of dihydropteroate enzyme that is insensitive to drug)
-effects reduced in presence of tissue breakdown (presence of purines and thymidine can be used
directly by bacteria for DNA synthesis and bypass need for folic acid
human vs bacterial dihydrofolate reductase - answer✔differential sensitivity to enzyme
antagonists
trimethoprim - answer✔inhibitor of folate synthesis
-very high affinity for bacterial vs human
-bacteriostatic
-given with sulfamethoxazole as co-trimoxazole
-resistance to trimethoprim due to altered dihydrofolate reductase
methotrexate - answer✔inhibits both human and bacterial enzyme but bacteria cannot take it up
so it is not effective as an antibiotic
class 3 reactions - answer✔bacterial cell wall synthesis
peptidoglycan - answer✔-major component of bacterial cell wall, not found in eukaryotic cells
(good drug targets)
-backbone of amino sugars (N-acetyl muramic acid and N-acetylglucosamine
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