Drug Excretion

Excretion

the final LOSS of the drug substance or its metabolites from the body such as through the kidney (urine), intestines (feces), skin (sweat), saliva, and/or milk.

route of drug excretion

drug elimination

• Irreversible removal of drug from the body by all routes of elimination.

• Collective term for metabolism and excretion

nonvolatile drugs

are excreted mainly by renal excretion, into the urine

volatile drugs

gaseous anesthetics, or drugs with high volatility, are excreted via the lungs into expired air.

clearance

• the process of drug elimination from the body or from a single organ without identifying the individual processes involved.

• the volume of fluid cleared of drug from the body per unit of time

• mL/min or L/hr.

kidney

• Located in the peritoneal cavity

• most important organ for excretion

• maintain normal fluid volume

• maintain salt and water balance

• with 2 endocrine fxn

  • secretion of renin(regulates BP)

  • secretion of erythropoetin(RBC production)

regulation of renal blood flow

Blood flow to an organ is directly proportional to the arteriovenous pressure difference (perfusion pressure) across the vascular bed and indirectly proportional to the vascular resistance.

nephrons/malphigian bodies

responsible for the removal of metabolic waste and the maintenance of water and electrolyte balance.

parts of capillary part

of nephron

• glomerulus and bowman’s capsule

parts of tubular part

of nephron

• PCT

• LOH

• DCT

• CG

• Ureter

parts of nephron

3 kidney processes

GF ATS TR

1. Glomerular filtration

2. Active tubular secretion

3. Tubular reabsorption

glomerular filtration

• passive process by which small molecules & drugs are filtered through glomerulus

• filtration of LMW molecules (MW<500)

• normal GFR: 125mL/min (180 L/day)

• GFR - tells how healthy the kidney is

• ave urine: 1-1.5 L (99% are reabsorbed)

• depends on pressure

• 100 mmHg - pressure of artery

• 45-65 mmHg - pressure on glomerulus

active renal secretion

• Occurs in proximal convuluted tubule

• Reabsorption of water and active secretion of some weak electrolyte (weak acids)

• Requires carrier and energy ( against conc gradient)

• reflects the effective renal plasma flow (ERPF) - 425 to 650 mL/min

excretion

filtration - reabsorption + secretion = ?

P-amino hippuric acid (PAH) and Iodopyracet (Diodrast)

• drugs used to measure active tubular secretion

• These substances are both filtered by the glomeruli and secreted by the tubular cells

tubular reabsorption

• occurs in distal convoluted tubule

• If a drug completely reabsorbed (eg. Glucose), then the values for the clearance of the drug is approximately ZERO.

• For drugs that are partially reabsorbed, clearance values will be less than the GFR of 125 to 130 mL/min

tubular reabsorption

• Reabsorption of water and passive excretion of lipid soluble drugs

• Depends on urine pH

  • Based of Henderson-Hasselbalch equation

reabsorb

acidic urine + acidic drug = ?

excreted

acidic urine + basic drug = ?

excreted

basic urine + acidic drug = ?

reabsorb

basic urine + basic drug = ?

factors affecting excretion

• Diet rich in:

  • Carbohydrate > higher urinary pH

  • Protein > lower urinary pH

• Drugs (ascorbic acid and antacids)

  • alter urinary pH when administered in large quantity

• Intravenous fluids (solutions of bicarbonate or ammonium chloride)

  • change urinary pH and alter drug reabsorption

factors affecting excretion

1. molecular size

2. lipid solubility

3. plasma protein binding

4. urine pH

5. renal blood flow

6. disease states

7. drug interactions

molecular size

smaller molecules are filtered more easily through the glomerulus

lipid solubility

lipophilic drugs are reabsorbed more, reducing excretion

plasma protein binding

bound drugs are not filtered; only free drug is excreted

urine pH

affects ionization and reabsorption of weak acids/bases

real blood flow

igher flow increases filtration and clearance

disease states

renal impairment reduses excretion; liver disease affects metaboloism and biliary excretion

drug interactions

competing drugs may inhibit or enhance excretion pathways

tubular reabsorption

valproic acid + protein-rich diet → ?

tubular reabsorption

losartan K + vitamin C → ?

tubular excretion

aspirin + NaHCO3 → ?

tubular excretion

dipenhydramine HCl + Vitamin C

tubular excretion

methamphetamine + ammonium chloride → ?

drug clearance

• pharmacokinetic term for describing drug elimination from the body without identifying the mechanism of the process

• described in terms of volume of fluid clear of drug per time unit

• fixed volume of fluid (containing the drug) cleared of drug per unit of time

• units : volume/time (eg, mL/min, L/hr)

organ clearance

1. renal clearance

2. hepatic clearance

3. creatinine clearance

renal clearance

Vol. of plasma that is cleared of drug per unit time through the KIDNEY

hepatic clearance

Vol. of plasma that is cleared of drug per unit time through the LIVER

creatinine clearance

ratio of creatinine the urine and creatinine in the plasma

Response

refers to the therapeutic effect, sub-therapeutic effect, side effect and toxic effect

LADMER