Drugs Flashcards
Learn the different drugs and their mode of action in this module
What is a natural painkiller that is administered intravenously?
Morphine
Is aspirin a natural or synthetic drug?
Synthetic
Is aspirin a prodrug or active drug?
Prodrug
What was heroin originally marketed for?
Coughing (is a sedative)
Is heroin a natural or synthetic drug?
Synthetic- optimized from morphine and crosses the blood brain barrier more effectively
What was the synthetic antibiotic developed to treat syphilis and how does it work?
Salvarsan: is an antagonist prodrug, contains a thiol (cysteine) in the active site which does a nucleophilic attack on As
What was aspirin developed from and how?
Esterified salicyclic acid
What is the pharmacophore of Prontosiil Red and its mode of action?
Sulfonamide, antagonist antibiotic that mimics folate and inhibits folate synthesis enzymes; without folic acid bacteria die
What was the first natural antibiotic and how was is it administered?
Penicillin, intravenously
What is the mode of action of penicillin?
Active antagonist, mimics D-Ala-D-Ala and blocks the CROSSLINKING TRANSPEPTIDASE ENZYME (CTE) active site; no crosslinking so bacteria die
What are three synthetic antibiotics developed from penicillin and how are they administered?
Amoxicillin, ampicillin and methicillin; oral
Are penicillin and its derivatives active or prodrugs?
Active drugs
Name 4 last resort antibiotics and describe their modes of action
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
What is Acyclovir ad what was it developed to treat?
Synthetic, broad spectrum antiviral developed to treat herpes
What is the mode of action of Acyclovir?
Antagonist targeting DNA synthesis; mimics a DNA base, gets incorporated into DNA and acts as a chain terminator hence stopping DNA replication
What does AZT stand for and what does it target (and treat)?
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
What is another drug to treat HIV/AIDS with a different mode of action to AZT?
A protease inhibitor saquinavir; contains a peptide bond mimic which binds to HIV-protease 1, preventing the hydrolysis of proteins for assembly (antagonist)
What is Clavulanic acid and how does it work?
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
Name two antiviral drugs used to treat flu and describe how they work (similarities and differences)
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.
How does Salbutamol work and how does Salmeterol differ?
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.
Describe 2 natural narcotic drugs which target neurological receptors
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.
How does amphetamine work?
A synthetic stimulant used to improve performance by mimicking neurotransmitters, acting on receptors to stimulate a chance in the heart (targets circulation).
Name and explain a narcotic drug which targets serotonin receptors
Ecstasy- mood altering agonist drug. Mimics serotonin to stimulate receptors, eventually leads to ‘burn out’.
Why was Fenfluramine marketed as a diet drug and why was it discontinued?
Intended to stimulate adrenaline receptors (agonist) to burn energy, but caused changes in the heart leading to cardiotoxicity.
What is Tamoxifen?
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.
Name and describe a synthetic anticancer prodrug
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.
What is Doxorubicin?
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.
What enzyme does the anticancer drug methotrexate target and how does this give rise to its therapeutic effects?
Hydroxymethyl transferase (HMT); binds to HMT (antagonist), blocking folate thus preventing the biosynthesis of DNA bases, particularly thymine.
Name and explain a topical skin cancer treatment
5-fluorouracil; active synthetic antagonist which irreversibly inhibits thymidylate synthase by binding (similar structure to uracil) but preventing elimination due to the F.
What is vincristine/vinblastine?
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..
What is taxol?
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.
What metal ion is used to treat Cd2+ toxicity and is it an agonist or antagonist?
Ca2+; antagonist- competes for sites to alleviate symptoms.
Name 4 chelating ligands, describe how they work and what metal ions they are used against (metal ion toxicity)
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.
What drug is used to treat thallium (Tl) poisoning?
Colloidal Prussian blue, synthetic, Tl+ replaces K+ in the lattice so it becomes insoluble and is excreted (ion exchange adsorbent).
What synthetic chelating ligand drugs are used to treat iron overload, and what are the isoelectronic/structural to?
3,4-HPOs (ORAL), catechols (ie enterobactin). Coordinate to the metal competitively thus removing the metal from the blood.
What metal poisoning is 3,4,3-LlHOPO used for?
Used to treat plutonium poisoning (Pu4+), chelating octadentate ligand (don’t want binding to Fe3+).
What is Clioquinol and why can it be used for neurodegenerative diseases?
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!!!
Describe the prodrug mechanism of deferiprone for the treatment of neurodegenerative diseases
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).
Describe the prodrug mechanisms of albomycin and cefidericol
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.
Describe the mechanism of cisplatin and its development to carboplatin/oxaliplatin and picoplatin/quinoplatin/phenanthriplatin
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.
What is auranofin used to treat and what is it’s mechanism?
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).
