Peptidehormonen en neurohormonen
Diabetes
o Insuline analogen (ultrasnel) : destabilisatie hexameerkristallen in aanwezigheid van
Zn
Insuline lispro
Insuline aspart
Insuline glulisine (traag): multimeren (≠ kristallen met polymeer ipv Zn)
o Insuline analogen (vertraagd)
Insuline glargine: arginines (verhoging iso-elektrisch punt + vorming stabiele
kristallen) + glycine (kristallen minder stabiel)
Insuline detimir en degludec (vetzuur binding albumine)
Oplosbaarheid + transport
Afbraak + filtratie thv nier
Degludec : aanleiding tot filamenten die bestaan uit vele hexameren
depotwerking
o Verbetering vrijgave insuline
Sulfonylurea
Nabootsing of versterking incretines
Inhibitoren (dipeptidyl peptidase 4 (DDP4) (type 2): amide en
carbonyl interactie actieve plaats
o Vildagliptine en saxagliptine: pirolidine ring (binding DDP4)
+ nitril (ipv amide dat gehydrolyseerd wordt) + grote groep
(sterische hinder stabilisatie cis rotameer)
Saxagliptine : extra groep op pirolidine
stabilisatie trans rotameer
o Sitagliptine: triazolpiperidine (piperidine voor binding, maar
alleen slechte orale beschikbaarheid) + trifluoromethaan
(interactie katalytische serine)
o Linagliptine (non-peptidomimetics)
o Alogliptine (non-peptidomimetics)
Incretine mimetica (GLP1 agonisten) (type 2): glycine (minder
afbraak door DDP4)
o Exenatide
o Lixisenatide: lysine staart (bescherming tegen afbraak C-
terminus)
o Liraglutide : vetzuur (idem insuline)
o Semaglutide : onnatuurlijk AZ (minder afbraak door DDP4) +
extra linker in vetzuur (optimale interactie GLP1-receptor)
o Dulaglutide (antilichaam, peptibody) : glycine (minste
sterische hindering tussen ketens)
Bevordering excretie glucose
Inhibitoren Na/glucose cotransporter (SGLT2) in nieren
o Canagliflozine
o Dapagliflozine
o Empagliflozine
Vermindering opname glucose (acarbose): pseudo-oligosaccharide
, Cardiovasculair systeem
o ACE inhibitoren (metalloprotease, Zn): metaalcomplexerende groep
Captopril
Zofenopril
Enalapril
Ramipril
Lisinopril
Fosinopril
Quinapril
Perindopril
Cilazapril
o Angiotensine 1 receptor antagonisten (sartanen): vrije COOH + heterocyclische
aromatische ring + alkylketen aan ring + zuurgroep op ring + grote groep aan
heterocyclische ring
Losartan
Valsartan
Telmisartan
Irbesartan
Candesartan
Olmesartan
o Endothelinereceptor antagonisten
Bosentan
Macisentan
Ambrisentan
o Atriale natriurese factor (ANF)
Neprilysine (ANF afbraak, metalloprotease, Zn) inhibitor (sacubutril): COOH
complexeert Zn
Enkefalines, endorfines en opiaatanalgetica
N:
o Kleine substituent agonist
o Grote substituent antagonist
o Aromatische substituent agonist
o Tertiair door BH-barrière effect op CZ
o Quaternair niet door BH-barrière
Exogene opioiden (agonisten morfine receptor (mu))
o Morfinederivaten
Pijn
Hydromorfon
Oxycodon
Etorfine
Buprenorfine
Antitussivum
Codeïne
Ethylmorfine
Dihydrocodeïne
Buprenorfine
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