Drug Excretion

What is the removal of drugs from the body?

Excretion

True or False: All drugs are eventually eliminated from the body

True!

Drugs may be eliminated after being —- — (—-) or they may be eliminated —-.

Chemical altered (metabolism)

Unchanged

Polar species are usually eliminated by the —- through —- and non-polar by the —- through the —-.

Kidney

Urine

Liver

Stool

Usually, the drug metabolite is (polar/nonpolar) and is eliminated by the kidneys and the stable adduct formed from the metabolite is (polar/nonpolar) and eliminated by the liver.

Polar

Nonpolar

Renal excretion is the principle route of excretion for drugs that have limited —- solubility and are ionized at —— —-.

Lipid

Physiological pH

Name the THREE major mechanisms involved in renal excretion.

Glomerular filtration of free drug

Carrier-mediated excretion of polar drugs by proximal tubular epithelial cells

Passive reabsorption

What vessels are involved in carrier-mediated renal excretion?

Efferent erterioles

True or False: Carrier-mediated renal excretion does not require energy or nonspecific carriers of organic acids and bases.

False! Carrier-mediated renal excretion DOES require energy and nonspecific carriers of organic acids and bases.

True or False: Carrier-mediated renal excretion is dose-dependent (can be saturated) and is NOT impacted by protein binding.

True!

Why is carrier-mediated renal excretion not impacted by protein binding?

Drug is free by the time this mechanism is used

What mechanism used in renal excretion often occurs if something happens while drug travels in the lumen where the ionization state changes and the drug is reabsorbed?

Passive reabsorption

Damage to what kidney unit can cause issues with renal excretion?

Nephron

True or False: Biliary excretion is reversible transfer of drug or drug metabolism from the plasma to the bile through hepatocytes.

False! Biliary excretion is IRREVERSIBLE transfer of drug or drug metabolites from the plasma to the bile through the hepatocytes.

Compounds with what TWO characteristics are conjugated in the liver hepatocytes with glucuronic acid and excreted into the bile?

High molecular weight

Polar

True or False: Biliary excretion is quantitatively less important than renal excretion.

True!

BILIARY EXCRETION PROCESS:

1. Drug is absorbed from the lumen of the small intestine and taken to the —- via the —- vein. The —- —- effect is utilized in this portion.

2. The drug undergoes —- in this new region.

3. The metabolite leaves through the —- —- and enters the intestine again.

4. The metabolite leaves as the metabolite from the body in the —-.

Liver

Portal

Glucuronidation

Bile duct

Feces

What process is described as the intestinal reabsorption of active drug (lipid soluble) in the small intestine?

Enterohepatic circulation

What impact does enterohepatic circulation have on drug half-life? What does this in turn do to the dosing interval?

Prolong

Prolong

With the biliary excretion process in mind, what role can enterohepatic circulation play in drug excretion?

Can reform drugs via glucuronidase to be processed by the liver again, ultimately increasing the time active drug is spent in the body

True or False: The dosing regimen should always take into account the enterohepatic circulation mechanism if a drug utilizes it.

True!

Name THREE drug classes that use enterohepatic circulation.

Antibiotics

NSAIDs

Hormones

Opioids

Digoxin

Renal and biliary excretion can be inhibited due to disorders of what THREE organs?

Kidney

Liver

Gallbladder

——————- secretion of the drug into the urine and bile may be competitively inhibited by other drugs or endogenous substances.

Transporter-mediated

What happens to drug clearance and dosage if transporter-mediated drug secretion is competitively inhibited?

Drug clearance is reduced and dosage regimen must be adapted

What does parenteral administration of a drug mean?

GI tract is bypassed

Name the THREE major parenteral routes of drugs.

IV

IM

SQ

(Also intrarticular, subconjunctival and epidural)

What is necessary when using a parenteral injection for patient health and safety?

Asepsis (sterility)

What parenteral drug administration gives a predictable concentration in plasma and an IMMEDIATE pharmacological response?

Intraveous

True or False: IV drugs cannot control the rate at which drugs are introduced systemically to the animal.

False! IV drugs CAN control this rate.

True or False: Drugs with hypertonic and irritating solutions should be given IV only to avoid tissue damage, while drugs in an oily vehicle should not be given IV.

True!

Continuous IV infusions are satisfactory for achieving and maintaining ———— concentration.

Additionally, a —- dose (IV bolus) can achieve this state more rapidly if needed.

Steady-state

Loading

IM and SQ administered drugs have rapid absorption when given as an —- solution (usually taking about —- minutes).

Aqueous

30

Name THREE of the FIVE factors that determine rate of absorption.

Injection site vascularity

Drug concentration in solution

Ionization degree

Lipid solubility

Area of absorbing surface where drug exposed

Name ONE major disadvantage to IM and SQ drug administration.

Drug cannot be stopped if adverse reaction encountered

True or False: Drug absorption can be altered by the addition of other drugs, and some can cause pain at the injection site. Sustained release preparations are available which are designed to give long duration of effective drug concentration.

True!

What drug absorption is described as gaseous anesthetics diffusing across the pulmonary epithelium?

Pulmonary absorption

Drugs with pulmonary absorption vary in their degree in —— —-, which affects their rate of actions, the ease at which the depth of anesthesia and speed of recovery can be changed.

Blood solubility

What drug absorption has drugs delivered across the skin for systemic distribution (transdermal)?

Percutaneous absorption

Percutaneous absorption depends on the release from drug —- and penetration of the —- layer, (stratum —-), which is the major barrier to drug absorption through the skin.

Vehicle

Keratin

Corneum

Drugs with percutaneous absorption occurs by —- diffusion and —- solubility is the most important feature.

Passive

Lipid

Give TWO examples of drug vehicles in percutaneous absoprtion and their effects.

Oil in water emulsions- enhance drug absorption

DMSO- promote absorption by rapidly carrying drugs through skin

True or False: De-epithelialized skin promotes absorption.

True!

What kind of drug administration involves supplying a medication that enters through or across a mucous membrane?

Transmucosal administration

Name FOUR regions where a drug can be given transmucosally.

Buccal

Sublingual

Intranasal

Rectal

What opioid agonist is sued to treat mild to moderate pain in dogs or cats? What trademarked version of this drug is often given transdermally? Why is it beneficial?

Buprenorphine

Zorbium

Slowly released and long-lasting

Why is buccal drug administration often used with Zorbium in cats?

Cat mouth pKa very similar to drug (50% bioavailability)

What THREE events must an orally administered drug undergo before entering the systemic circulation?

Release of drug from solid dosage form

Transport across the GI mucosal barrier

Passage through the liver

What is the ONLY drug administration route that is 100% bioavailable?

IV

Rank these drug administration routes from least to most bioavailable:

Oral/inhalation

IV

Transdermal

SQ/IM

Rectal

Oral/inhalation -> Rectal -> IM/SQ -> Transdermal -> IV