Routes of Administration and Absorption

Question 1

What are the main enteral routes of drug administration? Parenteral?

Answer 1

oral, intrarumenal, rectal

intravenous (IV), intramuscular (IM), subcutaneous (SQ), intraperitoneal (IP), inhalation, topical (local), oral transmucosal (OTM)

Question 2

IV, dermal, SQ, IM, reservoir:

Answer 2

Question 3

What 6 things determine the choice of the route of administration of a certain drug?

Answer 3

1. physicochemical properties of the drug
2. formulation to be used
3. therapeutic indications
4. pathophysiology of the disease
5. target species
6. manufacturer’s recommendations

Question 4

How does the route of administration affect absorbance and clearance of the drug?

Answer 4

route of administration may influence the rate and extent of absorption, but it should not influence the distribution or clearance

Question 5

How is the magnitude of pharmacologic response related to drug concentration at the tissue?

Answer 5

proportionately - higher concentration = higher response

Question 6

How are drug concentrations at the tissue site approximated? Why is it approximated, rather than definitely measured?

Answer 6

measuring the plasma drug concentration (PDC)

tissue samples cannot be collected easily

Question 7

What are the 4 major movements of drugs that affect plasma drug concentration? What do these movements largely depend on?

Answer 7

1. Absorption from the sit of administration to systemic circulation
2. Distribution from systemic concentration to tissues and back again
3. Metabolism
4. Excretion

passive diffusion

Question 8

Describe the major steps a drug takes after it is administered.

Answer 8

1. absorbed into circulation
2. free drugs not bound to plasma proteins is distributed into tissue
3. the drug will either bind to the tissues/plasma proteins or is distributed back into circulation
4. drug is eliminated via hepatic metabolism and renal/biliary excretion of it or its metabolites

Question 9

What is absorption? Which routes of administration need this to occur?

Answer 9

movement of drugs from the site of administration and across one or more membranes into the bloodstream

all EXCEPT IV, where the blood is delivered directly to circulation

Question 10

What is the major obstacle related to drug GI absorption and oral route of administration across species of animals?

Answer 10

enormous interspecies diversity in comparative GI anatomy and physiology

Question 11

What does the presence of heterogeneity in morphology and physiology of the GI tract lead to?

Answer 11

regional variants in drug absorption

Question 12

Where are most drugs coming from when they reach systemic circulation?

Answer 12

small intestine (due to large surface area)

Question 13

What 6 things affect the rate and extent of drug absorption in the GI tract?

Answer 13

1. GI pH
2. surface area
3. motility
4. concentration of drug
5. permeability and thickness of mucosal epithelium
6. intestinal blood flow

Question 14

Where do drugs go after they are absorbed by the GI tract?

Answer 14

portal vein —> liver

Question 15

What is first-pass metabolism?

Answer 15

phenomenon in which a drug gets metabolized at a specific location in the body that results in a reduced concentration of the active drug upon reaching its site of action or the systemic circulation (not sufficiently high enough to cause a response)

• drugs absorbed in the intestine are metabolized in the liver as well, so it may not reach target tissue in sufficient amounts

Question 16

What are the 2 main areas for GI absorption of drugs in the mouth?

Answer 16

1. sublingual area - systemic drugs (nitroglycerin)
2. buccal mucosa - polymer patches, feline oral sprays

Question 17

Why is it difficult for drugs to be absorbed in the esophagus and cranial stomach?

Answer 17

cornified epithelium is an effective barrier that decreases chances for drug absorption

Question 18

In what way is it easy for drugs to absorb in the stomach? In what 2 ways is it difficult?

Answer 18

1. simple mucosa
2. surface mucus may act as a barrier
3. acidity and motility creates a hostile environment for drugs and promotes the absorption further down the tract

Question 19

What is the primary site for most drug absorption? Why?

Answer 19

small intestine

more alkaline pH
more simple epithelial lining
higher blood flow to the small intestine compared to the stomach
microvilli increase the surface areat

Question 20

How do dogs compare to humans in regards to drug absorption?

Answer 20

dogs have a higher permeability to many drugs

Question 21

What are the second and third first-pass effects that occur in the small intestine?

Answer 21

SECOND FIRST-PASS EFFECT: the epithelial cells of the intestine are endowed with the necessary enzymes for drug metabolism

THIRD FIRST-PASS EFFECT: resident microbial population are capable of metabolizing specific drugs

(drugs are metabolized before they reach target tissue and may not cause a drug response)

Question 22

What must occur before a drug can be absorbed across the intestinal mucosa? What are the 2 major steps?

Answer 22

drug must first be dissolved in the aqueous mucosa

1. DISINTEGRATION: solid dosage (tablet) physically disperses so that its particles can be exposed to the GI fluid
2. DISSOLUTION: drug molecules enter into solution (pharmaceutical phase)

Question 23

What are 3 important practices used for parenteral route of administration?

Answer 23

1. sterile preparations must be administered using aseptic techniques
2. dose must be accurate
3. painful reactions are a possibility

Question 24

What are the 2 primary therapeutic parenteral routes of drug administration? What is the major benefit to these routes?

Answer 24

SQ and IM

barrier to absorption is less than in oral or topical delivery - less hostile, less physical barriers (bypass the body’s defense mechanisms)

Question 25

Moderately irritating preparations can be injected IM, but what can be a possible consequence?

Answer 25

tissue reaction and necrosis

Question 26

How does the duration of drug action for IM, IV, and SQ administration compare? Rate of absorption for SQ and IM?

Answer 26

SQ > IM > IV IM > SQ

Question 27

Why is intraperitoneal (IP) administration used? What 2 things make this route unique?

Answer 27

peritoneal absorption is very efficient and there is a good mixing of the injection with the peritoneal fluid 1. large volumes can be administered 2. a majority of the drug absorbed after IP administration enters the portal vein and undergoes first-pass hepatic metabolism

Question 28

What is a common use of intraperitoneal administration?

Answer 28

toxicology in rodents

Question 29

Does intravenous administration involve an absorption phase? How much of the drug can be injected?

Answer 29

NO a large fluid volume is able to be injected

Question 30

Since IV administration is a more direct administration route, what will this result in? What types of solutions are preferred?

Answer 30

immediately high levels of the drug in the blood and rapid onset of action aqueous (irritating and nonisotonic solutions can be injected if done slowly and carefully)

Question 31

Which of the following parenteral routes of administration is not recommended for large volumes of application? a. intravenous (IV) b. intraperitoneal (IP) c. intramuscular (IM)

Answer 31

C

Question 32

How does inhalation (pulmonary route) absorb drugs? How does the size of the partlcles affect the place of absorption?

Answer 32

gases, volatile agents, and fine particles are rapidly absorbed from the airway and alveoli into the pulmonary circulation < 2μm (nebulization) = terminal ducts and alveoli < 5μm = respiratory bronchioles 5-10μm = upper respiratory tract and larger airways

Question 33

Why is response so rapid during inhalation? What happens to the drug after absorption?

Answer 33

the lungs have such a large surface area and blood supply cells lining the alveoli are very thin and profusely bathed by capillaries oxygenated pulmonary veins ---> systemic arterial circulation

Question 34

What are the main 2 ways used for topical administration? Some examples?

Answer 34

1. applied to skin and adnexa 2. variety of mucous membranes sublingual, intravaginal, intranasal, intrauterine, rectal, preputial, ocular, aural (otic)

Question 35

What is unique about drug concentration and topical administration?

Answer 35

achievement of an effective systemic concentrations is often not required for what is essentially a local therapeutic effect

Question 36

What is oral transmucosal (OTM), or buccal, drug administration? What are 2 huge advantages to this route?

Answer 36

drugs are given by mouth with the intent of absorption occurring through the mucosa of the mouth 1. avoids first-pass metabolism 2. bypasses the harsh GI environment

Question 37

The first-pass effect is most likely to occur after which one of the following routes of administration? a. IV b. IM c. SQ d. oral (PO) e. inhalation d. OTM

Answer 37

D

Question 38

What is bioavailability (F)? How is it determined?

Answer 38

percentage of an administered dose of drug that reaches systemic circulation comparing plasma levels of a drug after a particular route of administration with the levels achieved by IV administration

Question 39

Why is IV a base for calculating bioavailability (F)?

Answer 39

F for IV will always = 1 since the drug is going directly into circulation without absorption necessary, which is where drugs tend to be lost all other routes will have an F < 1

Question 40

How is total absorption of a drug determined? What does it mean when bioavailability is high?

Answer 40

measuring the area under the concentration-time curve after drug concentrations in the blood are assayed greater F = greater extent of absorption of a drug and anticipated pharmacologic response

Question 41

What is bioavailability used to predict?

Answer 41

DRUG EFFICACY after different routes of administration