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Excretion of Drugs
Terms in this set (26)
Excretion of drugs
The removal or clearance of the drug from the body
What are all the different routes of drug excretion from the body? (8)
2. Hepatic + biliary, feces
8. expired air
What is renal excretion dependent on?
1. glomerular filtration rate (GFR)
2. Active tubular secretion
3. Passive tubular secretion
Sum = TOTAL RENAL EXCRETION
What are the 4 factors that affect glomerular filtration?
1. Arterial blood pressure
- blood flow goes to the glomerular capillaries to the Bowman's capsule to the ultrafiltrate
2. Molecular size: smaller the size = feely filters (filtration rate is proportional to mass)
3. Molecular charge: negative charged molecules inhibited by negatively charged proteins in basement membrane and podocytes
4. Plasma protein binding because only UNBOUND drugs can be freely filtered
T/F: Each kidney has a million nephrons.
What are the factors that affect active tubular secretion?
1. Proximal Convoluted:
- organic anion transporter for secretion of organic acids
- organic cation transporter for the secretion of organic bases
- both need Na+/K+ ATPase pump in basolateral membrane (+ have diffusion step + secondary and tertiary active transport) NEED ENERGY
2. Organic cation transporters (OTCs) = transport endogenous organic bases and basic drugs (choline, dopamine, nicotine, etc.)
3. Organic anion transporters (OATs) = transport endogenous organic acids and acidic drugs (penicillin, thiazide, and loop diuretics)
What is the most important way to excrete a drug?
What are the factors that affect passive tubular reabsorption? (5)
Proximal + Distal Convoluted Tubules
= Non-ionized forms of weak acids and based
Physiochemical properties of the drug
= water soluble, ionized, polar drugs are excreted in urine bc it makes the drug less able to cross the membrane
Degree of ionization in distal tubule
= the more ionized the drug, the less reabsorption and the more the drug is excreted
Acidification of the urine pH enhances renal excretion of weak acidic drugs
= aspirin excretion is increased if patient given sodium bicarbonate increases urine pH
Fluid therapy and diuretics
= Enhance renal excretion of drugs = decrease passive reabsorption
What are the factors that affect total excretion?
Liver, Kidney, or Cardiac Disease (causes change in renal blood flow, sympathetic tone, exposure to toxins)
Age (small patients have low tubular function bc not yet developed)
Urine pH modifiers (enhance either excretion of weak acids or weak bases)
(enhance tubular flow by reducing reabsorption to increase in excretion of drug/toxin)
Plasma protein binding (decrease renal excretion)
Dose and rate of absorption
What is the second most important route of excretion?
Hepatic biliary excretion
Why might a drug end up in bile and be excreted that way instead of via renal excretion?
Drugs that are too big for globular rate filtrate so they are stuck in the bile
How can drugs enter the bile from the hepatic cells?
Passive diffusion or active transport
What are the chemical properties of drugs excreted from the bile?
Unchanged or as glucuronides
What kind of drugs can be excreted in bile via active transport?
Acidic, basic, and neutral drugs
What are examples of compounds significantly excreted in bile? (5)
- steroid hormones
- glucuronides of chloramphenicol and morphine
What is enterohepatic recirculation?
Conjugates of lipophilic compounds excreted in bile can be hydrolyzed in the intestines (via bacterial Beta-glucuronidase = local flora in gi tract) and converts the nice conjugated back into its lipid soluble free drug so now it can be reabsorbed by the intestine
What is the consequence of enterohepatic recirculation?
prolongs half-life of a drug (
need to give drug orally!!)
If a toxin is ingested that undergoes enterohepatic recirculation, what do you think we can do to prevent reabsorption and promote elimination of the drug?
What does activated charcoal do?
binds to toxins or metabolites to prevent absorption
How do drugs get excreted via feces?
Drugs that excreted in bile that are NOT reabsorbed
orally administered, non-absorbed drugs
Drugs that move from the plasma to GI tract via passive diffusion
How do drugs get excreted via milk?
Not a significant route
Basic drugs are excreted in milk in larger amounts because of ion-trapping
What are the potential issues of drugs getting excreted by milk?
- Drug residues
- Systemic or local treatment of mastitis
- adverse effects to neonates
How do drugs get secreted in semen?
treatment of prostatitis in male genital tract infections
How do drugs get excreted in saliva?
inhibition of intestinal flora in herbivores by antibiotics
Why are drugs excreted in eggs?
Drug residues in laying birds
Why do drugs get excreted via expired air?
Volatile compounds (inhalation of anesthestics like isoflurane, sevoflurane)
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