Drugs Disposition and Fate of Drugs

Question 1

Drugs MUST have some ability to dissolve in ________ to move around.

Answer 1

WATER (be absorbed, reach sites of action.)

Question 2

In almost all cases, drugs must also have a certain degree of ________ to move around (leave and enter capillaries, enter and leave cells.)

Answer 2

LIPID SOLUBILITY

Question 3

is a preference not an absolute.

Answer 3

SOLUBILITY “water soluble”, “lipid soluble”

Question 4

Drug effects are USUALLY __________________ to drug concentration at the site of action

Answer 4

PROPORTIONAL (though not always linear)

Question 5

Drug concentrations in the ___________________ are USUALLY proportional (and usually linear) to drug concentrations
at the site of action.

Answer 5

BLOOD STREAM (measured in either serum or plasma)

Question 6

TRUE OR FALSE

Drug concentration in the blood stream is ALMOST ALWAYS an excellent predictor of drug action (either efficacy or toxicity) even though they may not
be identical to the concentration in the target tissue.

Answer 6

TRUE

Question 7

are the consequence of physiologic process (that may or
may not be altered by disease.)

Answer 7

pharmacokinetics

Question 8

Drug dissolve in ______________.

Answer 8

Body Fluid (Water)

Question 9

Drugs enter the _____________as __________ enters the circulatory system

Answer 9

circulatory system
fluid

Question 10

Therefore, drugs are not IN the body until they are IN the _____________

Answer 10

bloodstream

Question 11

_____________ must enter the circulatory system before they can distributed to sites of action.

Answer 11

Drugs

Question 12

Advantages in Oral Administration

Answer 12

✓Convenient
✓cheap
✓ no need for sterilization
✓variety of dose forms
(fast release tablets, capsules, enteric coated layered tablets, slow release,
suspensions, mixtures)
✓You can get the dose back of you move fast enough.

Question 13

Disadvantages in Oral Administration

Answer 13

✓ Variability due to physiology, feeding, disease, etc.
✓ Intractable patients
✓ First-pass effect
✓ Efficiently metabolized drugs eliminated by the liver before they reach the
systematic circulation.

Question 14

Patient and Pharmaceutical Factors in Oral Administration

Answer 14

✓ Pill compression, coatings, suspending agents, etc.
✓ GI transit time (too slow or too fast), inflammation, malabsorption, syndromes

Question 15

Regional Differences
in Oral Administration

Answer 15

✓ stomach
✓ mechanical preparation
✓ “flat” absorptive surface
✓ pH extreme
✓ Rumenoreticulum
✓ stratified squamous epithelium
✓ pH varies with diet
✓ metabolism by bacterial flora
✓ significant volume of fluid compared to body water
✓ Small Intestine
✓ large absorptive functions
✓ relatively neutral pH
✓ Colon/Rectum
✓ accessible
✓ large absorptive surface

Question 16

The bolus remains relatively spherical. Mixing and dissolution in tissue fluid occurs from surface of bolus, so entry of drug into
circulatory system limited by rate of drug “dissolution” (Movement from the “bolus” to the tissue fluid).

Answer 16

liquid soluble vehicle

Question 17

Advantages in Subcutaneous Injection

Answer 17

✓ Can be given by the owner (small patients)
✓ Vasoconstrictor can be added to prolong effect at site of interest

Question 18

Disadvantage in Subcutaneous Injection

Answer 18

variability

Question 19

Process in Subcutaneous Injection

Answer 19

Much like intramuscular

Question 20

Patient and Pharmaceutical Factors in Subcutaneous Injection

Answer 20

✓ More autonomic control over blood flow (than muscle)
✓ dehydration
✓ heat
✓ cold
✓ stress

Question 21

Advantages of Topical

Answer 21

✓ IF systemic therapy – easy painless application (e.g. mass medication of
cattle)
✓ IF skin therapy – reduced systemic effects/enhanced skin effects

Question 22

Disadvantages of Topical

Answer 22

✓ Patients groom themselves
✓ Toxic skin reactions
✓ Variable blood flow to skin
COMPLEX relationship between drug, vehicle , skin physiology

Question 23

Process of Topical

Answer 23

✓ Diffusion through stratified epithelium
✓ “Passage” through adnexal structures

Question 24

Patient and Pharmaceutical Factors in Topical

Answer 24

✓ Lipid solubility and molecule size
✓ Skin hydration and abrasion
✓ Area of application
✓ Ambient an patient temperature

Question 25

advantages in intraperitoneal

Answer 25

✓ Larger absorptive surface are than IM / Subcutaneous

Question 26

Disadvantages of intraperitoneal

Answer 26

✓ Drugs or vehicles may cause peritonitis
✓ Damage to organs by needles
Injection into organs

Question 27

Process of intraperitoneal

Answer 27

✓ Similar to subcutaneous
✓ Greater blood flow
✓ Less flow regulation

Question 28

Patient and Pharmaceutical Factors
of intraperitoneal

Answer 28

Generally restricted to laboratory animals

Question 29

advantages in Intrathecal

Answer 29

✓ Direct delivery to site of action

Question 30

disadvantages of intrathecal

Answer 30

✓ Difficult dose calculation
✓ CSF volume is not proportional to body weight
✓ Toxicity likely, and toxicity may be unusual
✓ Introduce infection into a VERY bad location

Question 31

process of intrathecal

Answer 31

✓ Absorption is usually by diffusion and very slow

Question 32

advantages of intra-actular

Answer 32

✓ Direct delivery to site of action
✓ High concentrations can be produces in the joint.

Question 33

Disadvantages of intra-actular

Answer 33

✓ It may be difficult to hit the joint space
✓ Difficult dose calculation
✓ Joint space volume depends on disease

Question 34

Process of intra-actular

Answer 34

Absorption from the site to systemic is variable but often quite fast

Question 35

advantages of Intra-arterial

Answer 35

✓ Produce extremely high concentrations

Question 36

Disadvantages of intra-arterial

Answer 36

✓ Dose calculation is best guess
✓ Intra-arterial lines difficult to insert/maintain.
✓ Dosing is still really systemic.
✓ Limited number of efficacy studies

Question 37

process of intra-arterial

Answer 37

Produce AND SUSTAIN high blood-to-tissue gradient to increase tissue concentrations of drug.

Question 38

advantages of per rectum

Answer 38

✓ Access to GI absorption in unconscious or vomiting patients
✓ Drug can be recovered before absorption is complete

Question 39

disadvantages of per rectum

Answer 39

✓ Animals may not willingly retain the drug

Question 40

process of per rectum

Answer 40

✓ As for oral without mechanical preparation by stomach