non - receptor mediated pharmacology (prodrugs and antiparacitic drugs) Flashcards
what is the parasite that causes malaria called?
P. Falciparium
how does P.Falciuparium cause malaria?
It digests the hosts Hb in the RBCs to give free soluble harm and Ferriprotoporphyrin (FP IX)
what is FPIX?
it is excreted by the parasite and converted in the parasites lysosome to non-toxic product hemazoin
what converts FPIX to hemazoin?
the enzyme Heme polymerase in the parasites lysosome
where would you find chloroquine?
it concentrates in acidic environments such as lysosomes - where it is protonated
what does chloroquine do? Result?
inhibits Heme polymerase
- FPIX builds up (toxic)
- chloroquine-haem complex forms - toxic free radical
what are the 5 targets for antimalarial drugs?
cytosolic compartment, mitochondria, apicoplast, digestive vacuole, membranes
how would antimalarial drugs target the cytosolic compartment? examples.
inhibit or antagonise folic acid metabolism - dihydrosulfate reductase inhibitors
- sulfadoxine, dapsone
how would antimalarial drugs target the mitochondria? examples
block electron transport energy production -
hydroxynapthquinolones (pyridines)
how would antimalarial drugs target the apicoplast? examples
block the protein synthesis machinery
tetracyclines - doxycycline and azithromycin
how would antimalarial drugs target the digestive vacuole? examples
inhibit the detoxification system
- quinolones (end in quine)
- aryl amino alcohols (lumefantrine)
how would antimalarial drugs target the membranes
inhibition of Ca2+ dependent ATPase
what is chelation therapy?
chelating metals, binding them together os they are easily excretable
name 5 WHO essential medicines
dimercaprol, dimercaptosuccinic acid, penicillamine, EDTA, deferoximine
what does dimercperol chelate?
acute lead, arsenic, mercury poisoning
what does dimercaptosuccinic acid chelate?
acute lead, arsenic, mercury poisoning
what does penicillamine chelate?
wilsons disease - chelation of copper
also a disease modifying anti-rheumatic drug;
non-receptor mediated
what does EDTA chelate?
acute lead poisoning
what does deferoximine chelate?
iron poising - dietary supplement
what is iron overload called?
haemachromatosis
what is a prodrug?
A compound that undergoes ‘biotransformation’ before exhibiting pharmacological effects
who won the nobel prize in 2000 for discovering a use for the prodrug L-DOPA
arvid carlsson
parkinsons disease
how does L-DOPA help to treat parkinson disease?
it crosses the BBB and increases the amount of dopamine in the substantial nigra
why is L-DOPA not an effective treatment
massiv doses (g) are required because of peripheral DOPA decarboxylase (DDC)
what does carbidopa do?
inhibits DDC so dopamine isn’t formed from L-DOPA
what is prodrug codine metabolised by?
CYP2D6
mesalazine clinical use
rheumatoid atheritis and IBS
mesalazine prodrug
azoreduction of the drug by gut bacteria to 5-ASD and sulfapyridine
sulfasalazine prodrug
reduction to sulfapyridine and mesalazine
what does CPA stand for
cyclophosphamide
what are the clinical uses for cyclophosphamide?
cancer, autoimmune disease (one of the most potent immunosuppressants)
how is the prodrug cyclophosphamide metabolised and bioactivated?
CPA is metabolised in the liver by cytochrome P450 to 4-OH-CPA (carbinolamnie) which alkylated guanidine residues in DNA.
what do alkylating agents do?
Causes intra-strand breaks on O7 and N7 on adjacent guanines
what have alkylating agents done as a treatment
Revolutionised the treatment of solid tumours of the testes and ovaries
