Drugs

Question 1

What is a natural painkiller that is administered intravenously?

Answer 1

Morphine

Question 2

Is aspirin a natural or synthetic drug?

Answer 2

Synthetic

Question 3

Is aspirin a prodrug or active drug?

Answer 3

Prodrug

Question 4

What was heroin originally marketed for?

Answer 4

Coughing (is a sedative)

Question 5

Is heroin a natural or synthetic drug?

Answer 5

Synthetic- optimized from morphine and crosses the blood brain barrier more effectively

Question 6

What was the synthetic antibiotic developed to treat syphilis and how does it work?

Answer 6

Salvarsan: is an antagonist prodrug, contains a thiol (cysteine) in the active site which does a nucleophilic attack on As

Question 7

What was aspirin developed from and how?

Answer 7

Esterified salicyclic acid

Question 8

What is the pharmacophore of Prontosiil Red and its mode of action?

Answer 8

Sulfonamide, antagonist antibiotic that mimics folate and inhibits folate synthesis enzymes; without folic acid bacteria die

Question 9

What was the first natural antibiotic and how was is it administered?

Answer 9

Penicillin, intravenously

Question 10

What is the mode of action of penicillin?

Answer 10

Active antagonist, mimics D-Ala-D-Ala and blocks the CROSSLINKING TRANSPEPTIDASE ENZYME (CTE) active site; no crosslinking so bacteria die

Question 11

What are three synthetic antibiotics developed from penicillin and how are they administered?

Answer 11

Amoxicillin, ampicillin and methicillin; oral

Question 12

Are penicillin and its derivatives active or prodrugs?

Answer 12

Active drugs

Question 13

Name 4 last resort antibiotics and describe their modes of action

Answer 13

Vancomycin: active antagonist which BINDS to D-Ala-D-Ala (rather than mimic it) hence stops binding to CTE, therefore no crosslinking so bacteria die. Intravenous

Daptomycin: introduces curvature in the cell wall, bacteria die. Intravenous

Tigecycline: inhibits specific bacterial protein synthesis. Intravenous

Linezolid: stops protein production. ORAL

Question 14

What is Acyclovir ad what was it developed to treat?

Answer 14

Synthetic, broad spectrum antiviral developed to treat herpes

Question 15

What is the mode of action of Acyclovir?

Answer 15

Antagonist targeting DNA synthesis; mimics a DNA base, gets incorporated into DNA and acts as a chain terminator hence stopping DNA replication

Question 16

What does AZT stand for and what does it target (and treat)?

Answer 16

Azidothymidine (anti-nucleoside); synthetic antagonist targeting reverse transcriptase enzyme to treat HIV/AIDS. Mimics a DNA base, gets incorporated into DNA and acts as a chain terminator hence stopping DNA replication

Question 17

What is another drug to treat HIV/AIDS with a different mode of action to AZT?

Answer 17

A protease inhibitor saquinavir; contains a peptide bond mimic which binds to HIV-protease 1, preventing the hydrolysis of proteins for assembly (antagonist)

Question 18

What is Clavulanic acid and how does it work?

Answer 18

Antibiotic containing a beta-lactam with an O instead of S (better leaving group), allowing CL to react with a nucleophile twice on a beta-lactam, DEACTIVATING THE ENZYME

Question 19

Name two antiviral drugs used to treat flu and describe how they work (similarities and differences)

Answer 19

Relenza and tamiflu. Both are active antagonists targeting the neuraminidase enzyme by binding non-covalently, preventing transmission of the virus. Relenza is delivered by inhalation (diskhaler) as a powder and tamiflu is delivered orally.

Question 20

How does Salbutamol work and how does Salmeterol differ?

Answer 20

Both synthetic, anti-asthma drugs; they are active agonists which bind to the beta2 receptors in the lungs . Salbutamol gives short-term relief whereas Salmeterol has a longer half life as adheres to membranes and fatty tissues.

Question 21

Describe 2 natural narcotic drugs which target neurological receptors

Answer 21

Mescaline (hallucinogen) and ephedrine (stimulant)- both agonists which mimic neurotransmitters, acting on receptors to stimulate a change in mood. NB: pseudo-ephedrine, a slight stimulant (isomer) used in cold and flu medication.

Question 22

How does amphetamine work?

Answer 22

A synthetic stimulant used to improve performance by mimicking neurotransmitters, acting on receptors to stimulate a chance in the heart (targets circulation).

Question 23

Name and explain a narcotic drug which targets serotonin receptors

Answer 23

Ecstasy- mood altering agonist drug. Mimics serotonin to stimulate receptors, eventually leads to ‘burn out’.

Question 24

Why was Fenfluramine marketed as a diet drug and why was it discontinued?

Answer 24

Intended to stimulate adrenaline receptors (agonist) to burn energy, but caused changes in the heart leading to cardiotoxicity.

Question 25

What is Tamoxifen?

Answer 25

A synthetic anticancer drug (hormone therapy) targeting estrogen receptors, particularly effective for use against breast cancer. Is an antagonist in breast cancer by blocking binding of estrogen therefore stopping the supply of key proteins for proliferation. Is an agonist in the uterus. Can be used prophylactically.

Question 26

Name and describe a synthetic anticancer prodrug

Answer 26

Cyclophosphamide: converted to active form by cytochrome P450. Antagonist crosslinks DNA by binding to nucleophilic guanine bases preventing the helix from unwinding, hence DNA can’t replicate.

Question 27

What is Doxorubicin?

Answer 27

A synthetic anticancer treatment targeting Leukaemia and Hodgkin’s lymphoma, not currently on the market. Is a DNA intercalator; sits between bases (non-covalent binding), altering the helical structure hence stopping division.

Question 28

What enzyme does the anticancer drug methotrexate target and how does this give rise to its therapeutic effects?

Answer 28

Hydroxymethyl transferase (HMT); binds to HMT (antagonist), blocking folate thus preventing the biosynthesis of DNA bases, particularly thymine.

Question 29

Name and explain a topical skin cancer treatment

Answer 29

5-fluorouracil; active synthetic antagonist which irreversibly inhibits thymidylate synthase by binding (similar structure to uracil) but preventing elimination due to the F.

Question 30

What is vincristine/vinblastine?

Answer 30

A NATURAL antagonist anticancer drug targeting tubulin polymerisation. Prevents polymerisation of tubulin to form microtubules which constitute the mitotic spindle, thus preventing cell division and preventing the cancer from growing and metastasizing..

Question 31

What is taxol?

Answer 31

Originally a natural anticancer drug, now made by semi-synthesis, used to various cancers and melanoma. Targets tubulin polymers; prevents cell division by stabilizing the microtubules and protecting them from disassembly.

Question 32

What metal ion is used to treat Cd2+ toxicity and is it an agonist or antagonist?

Answer 32

Ca2+; antagonist- competes for sites to alleviate symptoms.

Question 33

Name 4 chelating ligands, describe how they work and what metal ions they are used against (metal ion toxicity)

Answer 33

Dimercaptol (BAL), synthetic, Hg2+/Cd2+/ As3+/ Ni2+
D-penicillamine (not L), synthetic, Hg2+/Cd2+/ Pd2+/ Cu2+
EDTA, synthetic, Ca2+/ Pb2+
Desferal, natural, Fe3+/ Al3+

Detoxify by coordinating competitively to the metal ion thus making the complex safe and excretable. Chelating causes a favourable entropic change, increasing kinetic stability.

Question 34

What drug is used to treat thallium (Tl) poisoning?

Answer 34

Colloidal Prussian blue, synthetic, Tl+ replaces K+ in the lattice so it becomes insoluble and is excreted (ion exchange adsorbent).

Question 35

What synthetic chelating ligand drugs are used to treat iron overload, and what are the isoelectronic/structural to?

Answer 35

3,4-HPOs (ORAL), catechols (ie enterobactin). Coordinate to the metal competitively thus removing the metal from the blood.

Question 36

What metal poisoning is 3,4,3-LlHOPO used for?

Answer 36

Used to treat plutonium poisoning (Pu4+), chelating octadentate ligand (don’t want binding to Fe3+).

Question 37

What is Clioquinol and why can it be used for neurodegenerative diseases?

Answer 37

A synthetic, chelating ligand drug targeting Cu2+/ Zn2+. Is a small, lipophillic molecule so can cross the blood-brain barrier and chelate metal ions connected to protein misfolding and production of free radicals in the brain (which leads to some neurodegenerative diseases). NB: not on the market!!!

Question 38

Describe the prodrug mechanism of deferiprone for the treatment of neurodegenerative diseases

Answer 38

Synthetic chelating ligand and antioxidant that can be taken orally (Fe3+, amyloid fibrils). Carried to brain by glucuronidation on metabolism, only a siderophore once reaches the brain (Fe elsewhere is protected).

Question 39

Describe the prodrug mechanisms of albomycin and cefidericol

Answer 39

Both antibiotics, albomycin= natural, cefidericol= synthetic; targets Fe uptake channels (albomycin = E coli). Trojan horse style drug; taken up by bacteria as essential iron, but antibiotic is linked to the siderophore which kills the bacterium, or it dies if efflux occurs because no Fe.

Question 40

Describe the mechanism of cisplatin and its development to carboplatin/oxaliplatin and picoplatin/quinoplatin/phenanthriplatin

Answer 40

Synthetic, antagonist, anticancer prodrugs used to treat testicular and ovarian cancers.
Cisplatin enters the cell by diffusion, Cl- dissociates due to lower conc in cell, is hydrolysed to [PtCl(NH3)2(H2O)]+ which approaches negatively charged DNA and crosslinks it (1,2- intrastrand) forming a coordinate bond to the N7 of guanine, no replication/translation, cytotoxic
Carboplatin/oxaliplatin: same effectivity as cisplatin but lower dosage= reduced side effects. Bidentate ligand falls off less easily than Cl-.
Picoplatin/quinoplatin/phenanthriplatin: same effectivity as cisplatin but lower dosage and avoids problems of tumour resistance. Pt is coordinatively shielded from attack by steric bulk.

Question 41

What is auranofin used to treat and what is it’s mechanism?

Answer 41

Synthetic, antagonist, anti-rheumatic prodrug; targets thioredoxin reductase (TR) to treat rheumatoid arthiritis. TR is in high levels at inflammation sites. Au+ inhibits it by binding to sulfur donors e.g. cysteine (or selenocysteine).