Drug Excretion, Administration

True; but they may be eliminated after being altered (metabolism) or they may be eliminated intact or unchanged

T/F - a majority of drugs look differently when they are excreted versus when they entered the body

Excretion

The removal of drugs from the body

False; all drugs are eventually eliminated from the body

T/F - not all drugs are eliminated from the body

Phase 1 (oxidation)

Cytochrome P450s are involved in what phase?

Phase 2

Conjugation and glucuronidation is involved in what phase?

Renal excretion

Principle route of excretion for drugs that have limited lipid solubility and are ionized at physiological pH

Lipid-soluble, ionized drug

What type of drug is passively reabsorbed in the distal tubule? (HINT: what type of drug is able to pass through the membrane?)

1) Glomerular filtration of free drug

2) Carrier-mediated excretion of polar drugs (water soluble) by proximal tubular epithelial cells

3) Passive reabsorption (lipid-soluble, unionized drug)

What is the step by step mechanism for renal excretion?

TRUE; it requires energy and nonspecific carriers of organic acids and bases and it can also be saturated since they are carriers that are moving these drugs

T/F - Carrier-mediated excretion of polar drugs (secretion back into proximal tubule) requires energy

TRUE

T/F - carrier-mediated excretion of polar drugs by proximal tubule is not impacted by protein binding

Because these drugs are located in the efferent arteriole which is located right next to the proximal tubule where they are secreted into

How is it possible for the drugs that are not filtered by the glomerulus able to be actively secreted into the proximal tubule?

Biliary excretion

Irreversible transfer of drug or drug metabolites from the plasma to the bile through the hepatocytes

High molecular weight and polar compounds

High/low molecular weight and polar/nonpolar compounds are conjugated in hepatocytes with glucuronic acid and excreted in bile

In small intestine

In the enterohepatic circulation, where does intestinal reabsorption of the active drug (lipid soluble) take place?

Because there is no way or a smaller chance of drug excretion so the drug will stay in the system for longer so if you give a higher dose, the clearance of the drug is reduced and therefore will stay in the system for longer

Why should you adjust drug dosage if there is renal and biliary excretion inhibition due to kidney, liver or gall bladder disorders?

TRUE; If all drugs on board need a transporter, then the transporters will eventually be saturated and the other drugs will be inhibited from binding so it is competitive

T/F - transporter-mediated secretion of the drug into urine and bile may be competitively inhibited by other drugs or endogenous substances

Parenteral administration. Examples include Intravenous, intramuscular, subcutaneous, intrarticular, subconjunctival and epidural (MUST be very aseptic when using this type of administration)

Type of administration where the GI tract is bypassed and you put the drug right into the systemic circulation? Examples?

Intravenous

Type of administration that gives a predictable concentration in plasma and an immediate pharmacological response

IV

How must hypertonic and irritating solutions be administered to avoid tissue damage?

within 30 mins when given as aqueous solutions

How fast are drugs absorbed if given IM or SQ?

-Vascularity of injection site

-Drug concentration in the solution

-Degree of ionization

-Lipid solubility

-Area of absorbing surface to which the drug is exposed

What is the rate of IM and SQ absorption determined by?

True

T/F - Drug absorption can be altered by the addition of other drugs

TRUE; example includes ketamine

T/F - Some preparations cause pain at the injection site

Drug cannot be stopped if an adverse reaction is encountered

What is the disadvantage for IM or SQ administration?

Pulmonary absorption (by diffusing across the pulmonary epithelium)

How are gaseous anesthetics absorbed?

Percutaneous/Transdermal absorption

Type of absorption that is delivered across the skin for systemic distribution

Stratum corneum (keratin layer)

What is the major barrier to drug absorption through the skin?

Passive diffusion-lipid solubility

How does absorption occur in percutaneous/transdermal absorption?

TRUE; stratum corneum is the barrier to percutaneous absorption so without this, then there is better absorption

T/F - de-epithelialized skin promotes absorption

-Oil in water emulsions

-DMSO by rapidly carrying drugs through the skin

-Heat

What can promote percutaneous/transdermal absorption?

1) Release of drug from solid dosage form (dissolution)

2) Transport across the GI mucosal barrier in the SI

3) Passage through the liver

What are the three events that a drug must undergo for oral administration before entering the systemic circulation?

Intravenous with 100 percent (then IM and SQ with 75-100%)

What route of administration gives the greatest bioavaibility?