General Rules

Question 1

Get a mental picture of what’s going on “inside” (Think about anatomy and histology in terms of “how things work.”)

Question 2

_______ is a preference not an absolute. “Water Soluble”. “Lipid Soluble”

Answer 2

Solubility

Question 3

Drug dissolve in

Answer 3

body fluid (water).

Question 4

Drugs enter the ________ as ____ enters the circulatory system.

Answer 4

circulatory system
fluid

Question 5

Oral Administration

Advantages

Answer 5

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 6

Oral administration
Disadvantages

Answer 6

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 7

Oral administration
Patient and Pharmaceutical Factors

Answer 7

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

Question 8

Oral administration
Regional Differences

Answer 8

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 9

_________ – 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).

Occassionally, vehicle may be absorbed more rapidly than drug. Then the drug “falls” of solution in the tissue and dissolves very slowly.

Produces tissue residues
Reduces effect
Patient and Pharmaceutical Factors
Drug and vehicle solubility
pH extremes
Regional blood flow variability

Answer 9

Liqid soluble vehicle

Question 10

Subscutaneous Administration
Advantages

Answer 10

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

Question 11

Subscutaneous Administration
Disadvantages

Answer 11

Variability

Question 12

Subscutaneous Administration
Process

Answer 12

Much like intramuscular (though the architecture of the tissue is much different)

Question 13

Subscutaneous Administration
Patient and Pharmaceutical Factors

Answer 13

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

Question 14

Topical
Advantages

Answer 14

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

Question 15

Topical
Disadvantages

Answer 15

Patients groom themselves (topically applied, orally absorbed)
Toxic skin reactions
Variable blood flow to skin
COMPLEX relationship between drug, vehicle , skin physiology

Question 16

Topical
Process

Answer 16

Diffusion through stratified epithelium
“Passage” through adnexal structures

Question 17

Topical
Patient and Pharmaceutical Factors

Answer 17

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

Question 18

Topical
Vehicle Effects

Answer 18

“like” vehicles retain drug on skin surface
(e.g, aqueous drug in aqueous vehicle, lipid drug in lipid vehicle)
Drugs in “unlike” vehicles leave the vehicle to move on to skin
(e.g, aqueous drug in lipid suspension, lipid drug in aqueous suspension)

Question 19

Intraperitoneal
Advantages

Answer 19

Larger absorptive surface are than IM / Subcutaneous

Question 20

Intraperitoneal
Disadvantages

Answer 20

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

Question 21

Intraperitoneal
Process

Answer 21

Similar to subcutaneous
Greater blood flow
Less flow regulation

Question 22

Intraperitoneal
Patient and Pharmaceutical Factors

Answer 22

Generally restricted to laboratory animals.

Question 23

Intrathecal
Advantages

Answer 23

Direct delivery to site of action

Question 24

Intra-actular
Disadvantages

Answer 24

It may be difficult to hit the joint space depending on the species (size of joint space).
Difficult dose calculation
Joint space volume depends on disease
Recommended doses tend to be larger than necessary
Irritation of joint surfaces/capsule (chemical effects, biochemical/physiologic effects.)
Introduce infection. (PSGAG - Adequan® - interjections now generally get “antimicrobial chaser”)

Joint “flushes: don’t count.

Question 25

Intra-actular Process

Answer 25

Absorption from the site to systemic is variable but often quite fast. Systemic concentrations of the drug may be produced. Effects in joint may not persist. (Drug and dose form dependent)

Question 26

Intra-arterial Advantages

Answer 26

Produce extremely high concentrations “pointed at” (this is not really targeting) the tissue of interest. Used primarily for anti-tumor therapy and infectious disease therapy when blood supply is questionable.

Question 27

Intra-arterial Disadvantages

Answer 27

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

Question 28

Intra-arterial Process

Answer 28

Produce AND SUSTAIN high blood-to-tissue gradient to increase tissue concentrations of drug. Requires sustained infusion or application of tourniquet following bolus dosing.

Question 29

Per rectum Advantages

Answer 29

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

Question 30

Per rectum Disadvantages

Answer 30

Animals may not willingly retain the drug

Question 31

Per rectum Process

Answer 31

As for oral without mechanical preparation by stomach

Question 32

Drug Distribution

Answer 32

Physiologic spaces Extracellular space Intracellular space Reserved spaces

Question 33

Physiologic “spaces”

Answer 33

Vascular space (plasma / plasma water + RBC’s) There is also “tissue space” Size -7% of body weight Equilibria between water and various plasma / serum proteins between ionized and unionized drug between ionized and unionized drug between plasma and cells Distribution in 10 to 30 minutes (mixing)

Question 34

Extracellular Space (exist in both vascular and tissue spaces)

Answer 34

Size ̴ 15 – 20% of body weight includes extracellular fluid in bloodstream (plasma) Equilibria between water and proteins between ionized and unionized drug Distribution in 30 minutes to 1.5 hours

Question 35

Intracellular space (exist in both vascular and tissue spaces)

Answer 35

Size ̴ 35 – 45% of body weight Equilibria between ionized and unionized drug intracellular pH different (lower) than extracellular Distribution in 30 minutes to 12+hours

Question 36

Reserved spaces

Answer 36

Special barriers between plasma and tissue fluid CSF aqueous humor prostatic fluid Distribution in minutes to never

Question 37

Movement between spaces

Answer 37

Vascular space (extracellular) to tissue (extracellular) space Transcytotic Endothelial junctions wit inflammation Diffusion through endothelial cell membranes Carried in cells or on proteins in very special circumstances Extracellular space (of tissue) to intracellular space (of tissue) Diffusion through lipid bilayer of cells Vascular extracellular space to vascular intracellular space (drugs can mocve into RBC’s and WBC’s) Diffusion through lipid bilayer of cells WBC may actively acquire certain drugs

Question 38

Diffusion Limited Distribution

Answer 38

Diffusion is usually slow (relative to mixing and distribution within vascular system) Tissue distribution of the drug controlled by the ability of the drug to diffuse into the tissue

Question 39

Blood flow limited distribution

Answer 39

Diffusion can be VERY rapid Tissue distribution of the drug controlled by the rate of drug delivery to the tissue (total mg/minute) which is controlled by blood flow / gram of tissue Brain and liver concentration rise faster than muscle or fat

Question 40

Enterohepatic Circulation How does it work?

Answer 40

Drug or it’s Phase II conjugate excreted in bile Drug reabsorbed or Conjugate cleaved by bacteria and drug reabsorbed

Question 41

Enterohepatic Circulation What does it mean?

Answer 41

Elimination rate for drug is lower in spite of efficient hepatic metabolism/secretion Volume of distribution of the drug is higher

Question 42

Enterohepatic Circulation Why do you care?

Answer 42

Interrupt to improve drug elimination Insecticide poisonings, Phenobarbital overdoses, et

Question 43

Mammary Excretion How does it work?

Answer 43

Non – ionic Diffusion (lipid solubility and size dependence) Inflammation reduces barriers to penetration (masititis) Ion trapping normal milk pH = 6.6 (slightly acidic versus blood) Mastitic milk pH is slightly higher

Question 44

Mammary Excretion

Answer 44

Why do you care? May affect treatment of some bacterial infections of the mammary gland Nursing animals may be exposed to toxic concentrations of drug in the milk

Question 45

Salivary Excretion How does it work?

Answer 45

Non – ionic diffusion into salivary secretions Drug in saliva passes into GI tract

Question 46

What does it mean?

Answer 46

Ruminants Recycle certain drugs like enteroheptic circulation (prolonged elimination) Trap certain drugs in the rumen pH dependent (enhanced elimination) Non-ruminants Limit effect on elimination possible

Question 47

Drug Elimination Biotransformation

Answer 47

Conversion of a drug entity to a metabolite Usually inactivates the drug generally reduces drug activity MAY activate the drug Major route of elimination for lipid soluble and protein bound drugs (because other routes are not efficient)

Question 48

Drug Elimination Biotransformation .Chemical Mechanisms

Answer 48

Oxidation, hydroxylation, hydrolysis, reduction, conjugation, (acetylation, glucuronidation, sulfation, etc.)

Question 49

Drug Elimination Biotransformation Efficiency (rate)

Answer 49

Metabolic activity for a specific drug Blood flow to the organ Health of the organ and health of the circulatory system

Question 50

Drug Elimination Biotransformation Organs Involved

Answer 50

Liver (most important for most drugs) Lungs (especially for autocoids) Kidneys

Question 51

Biliary Excretion Active secretion Passive secretion

Answer 51

Drugs with molecular weights > 300 mostly conjugates of original drug Drugs with molecular weights < 300 biliary concentrations similar to plasma water