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Pharmacology (354)
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Module 5.pdf

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Department
Pharmacology
Course
Pharmacology 2060A/B
Professor
Angela Nissen
Semester
Spring

Description
PHARMACOKINETICS.–.EXCRETION. 5.1.ROUTES.OF.DRUG.EXCRETION . Drug%Excretion% • Is%the%removal%of%parent%drug%and%drug%metabolites%from%the%body. % % . . . . . Renal%Drug%Excretion% • The%kidneys%account%for%the%majority%of%drug% excretion.% • Healthy%kidneys%serve%to%limit% the%duration%and% intensity%of%drug%effects.% • Decreased%kidney%function%prolongs%the% duration%of%action%and%intensity%of%drug%effects. % % The%Nephron% % • The%basic%structural%and%functional%unit%of%the% kidney.% • Regulates%water,%electrolyte%and%drug%excretion. % • Controls%blood%volume,%blood%pressure,%blood%pH% and%solute%(including%drug)%excretion.% % % % % 5.2.FACTORS.AFFECTING.RENAL.DRUG.EXCRETION . 1) Glomerular%Filtration % 2) Tubular%Secretion% 3) Tubular%Reabsorption%% % **Note:%gaining%a%thorough%understanding%of%the%kidney%here%will%make% Module.13%MUCH%easier.% 1) Glomerular%Filtration % % • Drugs%enter%the%kidney%from%the%renal% artery.% • Hydrostatic%pressure%within%glomerular% capillaries%forces%low%molecular%weight% drugs%into%the%renal%tubules.% • Glomerular%filtration%rate%is%~%120 % 2 ml/min/1.73%m %or%about%20%%of%total% renal%plasma%flow.% • Lipid%solubility%and%pH%do%not%affect% glomerular%filtration%of%drugs. % • Only%nonWprotein%bound%(i.e.%free)% drugs%are%filtered%at%the%glomerulus.% % % 2) Tubular%Secretion% % • Drugs%not%filtered%by%the%glomerulus%leave% the%glomerulus%by%the%efferent%arteriole. % • The%efferent%arterioles%divide%to%form% capillaries%that%surround%the%proximal% tubule.%% • Drugs%can%be%secreted%from%the%blood% surrounding%the%tubules%into%the%lumen%of% the%proximal%tubule.% • Drug%secretion%in%the%kidney%primarily%occurs% by%two%transport%systems,%one%for%weak%acids% and%one%for%weak%bases.% % 3) Tubular%Reabsorption%% % • As%drugs%move%toward%the%distal%tubule,%their% concentration%increases.% • This%is%primarily%due%to%the%actions%of%the%loop%of%henle% which%functions%to%concentrate%tubular%solutes. % • Once%in%the%distal%tubule%the%drug%concentration%often% exceeds%the%concentration%in%the%blood%that%immediately% surrounds%the%distal%tubule.% • If%the%drug%is%uncharged%or%lipid%soluble,%it’s%able%to%leave% the%tubule%and%be%reabsorbed%back%into%the%blood.% % % The%Effect%of%Age%on%Renal%Function % % • Kidney%function%is%low%in% newborn%infants.%% Typical%glomerular% filtration%rate%(GFR)%of% newborns%40% mL/min/1.73%m .%%By% two%years%old%the%GFR% reaches%that%of%a% healthy%adult%(120% 2 mL/min/1.73m ).% • As%we%age%renal%function% decreases.%% • If%renal%function%is% decreased,%renal%drug% excretion%is%decreased.% % 5.3.BILIARY.DRUG.EXCRETION . . • Some%drugs%are%eliminated%into%the%bile%and% ultimately%excreted%in%the%feces. % • Characteristics%of%drugs%eliminated%in%the%bile% include:% % %%%%%1)%%molecular%weight%>%300%Da% % 2)%have%both%polar%and%lipophilic%groups% %%% (a
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