95 - Selective Toxicity of Drugs

Question 1

Examples of selectivity
1
2
3

Answer 1

Species-level toxicity
Cell-level selectivity
Organ-level selectivity

Question 2

Examples of antimicrobials against bacterial ribosomes

Answer 2

Tetracyclines, aminoglycosides

Question 3

Sulfonamides

Answer 3

Target bacterial folic acid metabolism.

Resembles para-amino benzoic acid (part of folic acid)

Question 4

Bacterial folate metabolism
1
2
3

Answer 4

PABA (para-amino benzoic acid) converted to folate.
Folate converted to tetrahydrofolate.
Tetrahydrofolate converted to precursors to nucleotides.

Question 5

Example of syndergy between antimicrobials

Answer 5

Sulfonamides (inhibit PABA -> folate), trimethoprim (inhibit folate -> tetrahydrofolate)

Question 6

Example of synergy between antimicrobials

Answer 6

Sulfonamides (inhibit PABA -> folate), trimethoprim (inhibit folate -> tetrahydrofolate)

Question 7

Enzyme that sulfonamides interfere with

Answer 7

Dihyropteroate synthase

Question 8

Enzyme that trimethoprim interferes with

Answer 8

Dihyrofolate reductase

Question 9

What does methotrexate resemble?

Answer 9

Folic acid

Question 10

Effects of methotrexate

Answer 10

Inhibits purine synthesis.
Inhibits DTMP synthesis.
Anti-cancer agent.

Question 11

Human folic acid metabolism

Answer 11

Folate to tetrahydrofolate (through dihydrofolate reductase)

Tetrahydrofolate to precursors of nucleotides (EG: thymidylate).

Question 12

What does methotrexate inhibit?

Answer 12

Dihydrofolate reductase.

Question 13

Functions of methotrexate
1
2
3

Answer 13

✦ Inhibits human dihydrofolate reductase
(inactive in bacteria)
✦ Cytotoxic anticancer agent (large doses)
✦ Cytotoxic immunosuppressant (lower doses,
rheumatoid arthritis)

Question 14

Functions of methotrexate
1
2
3

Answer 14

✦ Inhibits human dihydrofolate reductase
(inactive in bacteria)
✦ Cytotoxic anticancer agent (large doses)
✦ Cytotoxic immunosuppressant (lower doses,
rheumatoid arthritis)

Question 15

Risk of methotrexate

Answer 15

Known teratogen

Question 16

When is methotrexate prescribed in pregnant women?

Answer 16

To terminate an ectopic pregnancy (can abort)

Question 17

How often is methotrexate taken?

Answer 17

Once per week (high risk of overdose, overdose is nasty)

Question 18

*Kidney ion transfer

Answer 18

KIDNEY ION

Question 19

*Kidney ion transfer

Answer 19

KIDNEY ION

Question 20

Active driver of ion transport in the kidneys

Answer 20

Na/K ATPase

Question 21

Active driver of ion transport in the kidneys

Answer 21

Na/K ATPase

Question 22

How is renal architecture unconventional?

Answer 22

Transfer of oxygen from arteries to veins via countercurrent exchange

Question 23

Why are the testicular arteries arranged in an unconventional manner?

Answer 23

Countercurrent exchange of testosterone.

Reduces the amount of testosterone released into the body, so that it is easier to regulate.

Question 24

How is most testosterone released into the body

Answer 24

Through the lymphatics, bound to albumin proteins.
Test released into the venous blood is mostly transferred to the arterial blood, back to the testes (via countercurrent exchange)

Question 25

Outcome of renal unconventional blood supply

Answer 25

Relative hypoxia in the kidneys. | Not absolute hypoxia (as kidneys function normally), but is at a risk of hypoxia.

Question 26

Countercurrent exchange of kidneys

Answer 26

Arteries of one nephron are beside the veins of an adjacent nephron.

Question 27

What can lead to kidney damage?

Answer 27

Conditions leading to low renal perfusion (kidneys already in a state of relative hypoxia)

Question 28

Triple whammy

Answer 28

Combination of a diuretic and an ACE inhibitor (or AT1 receptor antagonist) is effective treatment for hypertension. Add in NSAID leads to acute renal failure.

Question 29

Why can NSAID lead to renal failure?

Answer 29

Prostaglandin-mediated vasodilation preserves renal blood flow when diuretic and ACE-I are administered.

Question 30

Safe hypertension treatment

Answer 30

Diuretic + ACE inhibitor.

Question 31

Safe hypertension treatment

Answer 31

Diuretic + ACE inhibitor.

Question 32

Danger with diuretic and ACE inhibitor hypertension treatment

Answer 32

Patients can self-prescribe NSAID, which leads to renal failure when co-administered with ACEI and diuretic

Question 33

Example of a nephrotoxic antibiotic

Answer 33

Gentamycin

Question 34

Class of antimicrobial that gentamycin is

Answer 34

Aminoglycoside

Question 35

Side effects of gentamycin

Answer 35

Nephrotoxic, ototoxic (leads to deafness, vertigo)

Question 36

Advised length of gentamycin treatment

Answer 36

No more than 48 hours. | Once per day (one bolus)

Question 37

Advised length of gentamycin treatment

Answer 37

No more than 48 hours. | Once per day (one bolus)

Question 38

How is gentamycin excreted?

Answer 38

Entirely through kidneys

Question 39

Why might gentamycin be ototoxic?

Answer 39

Selectively taken up by hair cells in the ear. Gets into the fluid area of the cochlea (slow clearance area). Not known how it gets into hair cells

Question 40

Why is gentamycin administered once per day?

Answer 40

Equally effective if administered once per day. Less toxic to ear, kidney. Need to get through trough period, where gentamycin enters cochlea, leaks out slowly.

Question 41

Patients who are at higher risk of ototoxicity with gentamycin treatment

Answer 41

Those exposed to continuous loud sound during treatment, those with tinnitus.

Question 42

Paraquat

Answer 42

Herbicide.

Question 43

Paraquat

Answer 43

Herbicide.

Question 44

How does paraquat work? 1 2 3

Answer 44

Activated into a radical form by getting electrons from electron transport chains. Radical form oxidises anything it can tough, makes ROS. Destroys cell membranes, DNA, proteins, etc.

Question 45

What activates paraquat in a plant?

Answer 45

e- in chloroplasts

Question 46

How does paraquat get activated in mammalian cells?

Answer 46

Accepts electrons from NADPH.

Question 47

Effect of paraquat on mammals

Answer 47

Activated by accepting e- from NADPH. | Accumulates in lung epithelial cells via active transport.

Question 48

Effect of paraquat on mammals 1 2

Answer 48

Activated by accepting e- from NADPH. | Accumulates in lung epithelial cells via active transport.

Question 49

Effect of paraquat on mammals 1 2

Answer 49

Activated by accepting e- from NADPH. Accumulates in lung epithelial cells via active transport. Lung epithelium exposed to very high concentrations

Question 50

Dose difference of paraquat for mammals

Answer 50

Low dose selectively kills lung epithelial cells. | High doses destroy tissues systemically.

Question 51

Dose difference of paraquat for mammals

Answer 51

Low dose selectively kills lung epithelial cells. | High doses destroy tissues systemically.