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principles of pharmacology
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Ionisation Explained
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Therapeutic index explained
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By: Roaa • 5 year ago
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Tractus Respiratorius, Tractus Digestius, en huid.Tractus Respiratorius
Lecture 1
ian buiten naar binnen: epitheel cellen -> basement membrane -> lamina propria
Bij astma en COPD oiermatge slijmproducte
Gasuitwisseling iind in de longblaasjes plaats
Symptomen
1.Astma: aaniallen ian kortademigheid, slijm bij hoesten, meestal ieroorzaakt door allergie
2.COPD:- slijm bij het hoesten (chronisch),
-Chronische, progressieie toenemende kortademigheid,inspanning (emfyseem) oorzaak: meestal
roken.
-bronchiale hyperreactiiteit
-chronische luchtwegontsteking
2a.Chronische bronchits
-clinical diagnose: daily productie cough for 2 months or more, in at least 2 opeeniolgende jaren
-oierweight and cyanotc (blauw kleuren ian de huid door aanwezigheid ian gedeoxyneerde
hemoglobine in de bloediaten ian de buurt ih huidopperilak)
-ierhoogde hemoglobine
-perifere zwelling
-piepende ademhaling en geluiden door obstructe ian geleidende luchtwegen
2b.Emphyseem
-pathologic diagnose: permanent enlargement and destructon of airspaces. Distal of the terminal
bronchiole.
-older and thin
-iaak benauwdheid
-quiet chest
-x-ray: hyperinfaton with fatened diaphragms
Exogene factoren
1. Allergeeninhalate
2. Virusinfecte
3. Fysische prikkels (mist, koude lucht)
4.Geforceerde ademhalingsbewegingen (inspanning, hyperientlate, lachen)
5. Chemische prikkels (SO2, NO2, ozon, citroenzuur, ether, ammonia, rook, stof)
6. Farmacologische inhalate (histamine, metacholine, carbachol, Ach, prostaglandine, serotonine,
leukotrienen)
Allergenen:
-inhalate-allergenen: huisstofmijt, pollen, schimmels, dierepitheel
-ioedingsallergenen
1
,-toxines: bijen- en wespengif
-Chemicalien, geneesmiddelen:peniciline
Lymfocyt actiate -> astma, diabetes en COPD
Antigen 械ctiv械tin iof Th2 cell by T T4 械nd Th0
械nd tiul械tin iof IigE cl械 witchinig in Bncell
-> Priducte IigE -> Bnindinig ti FceRI ip ie tcellen.
early phase: bronchospasm
histamine LTC4, PGD2, PAF
allergenen + IgE
late phase: infammaton
LTC4, PAF
(allergen -> macrofaag) -> Th2 cell -> eosinophiil
mast cell/ Th2 cell (IL/TNF) -> EOTAXIN -> extraiasate eosinooele granulocyten
H perre pin iive
1.hypersensitiity: normal response to abnormally low doses of stmulus
2.hyperreactiity: an exaggerated response to normal high doses of stmulus
Ach -> cholinergic eferent -> CNS -> N.Vagusa ->
aferent -> non-allergic stmuli
M1, M3 -> mucus producing cell
M2,M3 -> airway smooth muscle
Histamine na EAR ->minder histamine nodig ioor
hyperresponsiieness
Histamine na LAR -> meer histamine nodig
Alleen histamine -> meest histamine nodig
M2-receptor disfuncte in astma
EO -> MBP -inhibeert -> M2
Dus minder ‘Gallamine’ nodig ioor respons
Neuro-humorale regulate ian airway smooth muscle: NKA en excitatory nonadrenergic
noncholinergic
The contractle response is abolished by atropine -> cholinergic
The respnse is largely diminshed by tetrodotoxin -> inhibitory non-adrenergic pathway
iNANC
Contractle agonist (Ca2+) -> n/eNOS -> L-arginine wordt NO -> Cgmp/Kca -> relaxate en red. Ca2+
eNOS -> endothelial NOS
nNOS -> neuronal NOS
2
,adrenergic -> adrenaline
Airway smooth muscle contracton iia Gq
NKA -> NK2
Ach -> M3
His -> H1
LTC4,D4,E4 -> CysLT1
PGE2 -> EP1
PGD2 -> TP
PGF2alfa ->
PAF -> PAF
Airway smooth muscle relaxaton iia Gs
PGE2 -> EP2
adrenaline -> Beta2-adrenergic receptor (inhib. mast cell and lymphocyte actiaton)
VIP -> VIPR
Irreiersibele luchtwegremodellering
-cytokines -> groeifactoren
-proliferate en actiate obroblasten -> extracellulaire matrix -> ierdikking luchtwegwand
-proliferate -> ierhoogde spiermassa, ierhoogde contractekracht, ierdikking luchtwegwand
-ierhoogde contractliteit: ierhoogde expressie MLCK, sm-MHC, RhoA
-producte extracellulaire matrixeiwiten -> ierdikking lucht weg wand
Chronische luchtweghyperreactiiteit
Irreiersibele luchtwegobstructe
VEGF/EGF/PDGF -> SHC-Grb2;Sos -> associaton with phosphotyrosines on TRK iia SH2 domain
Lecture 2
Luchtwegremodellering -> irreiersible afname longfuncte
Luchtweg hyperreactiiteit -> astma-aanial
Farmacotherapie bij astma
Gericht op -> bronchoconstricte (gladde spier) en infammate (ontstekingscellen)
-bronchusobstructe
-bronchiale hyperreactiiteit
-irreiersible luchtwegremodellering
3
, Bronchusverwijders
Bnet械2-械drenerige 械igini ten
-kortwerkend: terbutaline, salbutamol, fenoterol
-langwerkend: salmeterol, formoterol, indacaterol, olodaterol, iilanterol
Theiph lline (PDE remmer)
Antchilinerigic械
-kortwerkend: ipratropium bromide
-langwerkend: totropium bromide, aclidinium, glycopyrronium, umeclidinium
Ontstekenigsremmers
Glucicirtci teriiden
-inhalate: beclomethason, budesonide, futcason, ciclesonide
-oraal: predenis(ol)on
Antleukitrienen
-montelukast
Anti-allergica
riiinen: cromoglycaat, nedocromil
Ant-IigE: ii械luiii械y iepiliiui械y
Combinatetherapie
L械nigwerkende; Bnet械2-械drenerige 械igini t + iglucicirtci teriid
-formterol/budesonide
-seretde, airfusal: salmeterol/ futcason
-reliar: iilanterol/futcason
-busalair: iilanterol/futcason
-berodual: fenoterol/ ipratropium
-foster: formoterol/ beclometason
-futform: formoterol/futcason
Salbutamol: Hydrooel, korte duur, fast onset, goeie difusie
Formoterol: Intermediate, lange duur, fast onset
Salmeterol: Lipophilic, long duraton, slow onset, slechte difusie
isoprenaline-> hogere hartslag salbutamol -> lagere hartslag
Bnet械2-械dreniceptir ofunctin in 械irw械
Cell type Function Efectiiveness
Airway smooth muscle relaxaton +++
epitheel Increased mucociliary, +
clearance
iasculature Vasodilaton, inhibiton of +
plasma leakage
Inflammatory cells
Mast cells Inhibiton of mediator release +-
eosinophils Inhibiton of mediator release +-
lymphopcyten Inhibite of cytokine release +-
4
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