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Pathology > General Rules > Flashcards

General Rules Flashcards

1
Q

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

A
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2
Q

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

A

Solubility

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3
Q

Drug dissolve in

A

body fluid (water).

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4
Q

Drugs enter the ________ as ____ enters the circulatory system.

A

circulatory system
fluid

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5
Q

Oral Administration

Advantages

A

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.

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6
Q

Oral administration
Disadvantages

A

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.

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7
Q

Oral administration
Patient and Pharmaceutical Factors

A

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

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8
Q

Oral administration
Regional Differences

A

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

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9
Q

_________ – 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

A

Liqid soluble vehicle

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10
Q

Subscutaneous Administration
Advantages

A

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

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11
Q

Subscutaneous Administration
Disadvantages

A

Variability

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12
Q

Subscutaneous Administration
Process

A

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

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13
Q

Subscutaneous Administration
Patient and Pharmaceutical Factors

A

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

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14
Q

Topical
Advantages

A

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

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15
Q

Topical
Disadvantages

A

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

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16
Q

Topical
Process

A

Diffusion through stratified epithelium
“Passage” through adnexal structures

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17
Q

Topical
Patient and Pharmaceutical Factors

A

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

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18
Q

Topical
Vehicle Effects

A

“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)

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19
Q

Intraperitoneal
Advantages

A

Larger absorptive surface are than IM / Subcutaneous

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20
Q

Intraperitoneal
Disadvantages

A

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

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21
Q

Intraperitoneal
Process

A

Similar to subcutaneous
Greater blood flow
Less flow regulation

22
Q

Intraperitoneal
Patient and Pharmaceutical Factors

A

Generally restricted to laboratory animals.

23
Q

Intrathecal
Advantages

A

Direct delivery to site of action

24
Q

Intra-actular
Disadvantages

A

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.

25
Q

Intra-actular
Process

A

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)

26
Q

Intra-arterial

Advantages

A

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.

27
Q

Intra-arterial
Disadvantages

A

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)

28
Q

Intra-arterial
Process

A

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

29
Q

Per rectum

Advantages

A

Access to GI absorption in unconscious or vomiting patients

Drug can be recovered before absorption is complete

30
Q

Per rectum
Disadvantages

A

Animals may not willingly retain the drug

31
Q

Per rectum
Process

A

As for oral without mechanical preparation by stomach

32
Q

Drug Distribution

A

Physiologic spaces
Extracellular space
Intracellular space
Reserved spaces

33
Q

Physiologic “spaces”

A

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)

34
Q

Extracellular Space (exist in both vascular and tissue spaces)

A

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

35
Q

Intracellular space (exist in both vascular and tissue spaces)

A

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

36
Q

Reserved spaces

A

Special barriers between plasma and tissue fluid CSF

aqueous humor

prostatic fluid

Distribution in minutes to never

37
Q

Movement between spaces

A

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

38
Q

Diffusion Limited Distribution

A

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

39
Q

Blood flow limited distribution

A

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

40
Q

Enterohepatic Circulation

How does it work?

A

Drug or it’s Phase II conjugate excreted in bile

Drug reabsorbed or Conjugate cleaved by bacteria and drug reabsorbed

41
Q

Enterohepatic Circulation
What does it mean?

A

Elimination rate for drug is lower in spite of efficient hepatic metabolism/secretion

Volume of distribution of the drug is higher

42
Q

Enterohepatic Circulation

Why do you care?

A

Interrupt to improve drug elimination

Insecticide poisonings, Phenobarbital overdoses, et

43
Q

Mammary Excretion

How does it work?

A

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

44
Q

Mammary Excretion

A

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

45
Q

Salivary Excretion

How does it work?

A

Non – ionic diffusion into salivary secretions

Drug in saliva passes into GI tract

46
Q

What does it mean?

A

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

47
Q

Drug Elimination

Biotransformation

A

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)

48
Q

Drug Elimination
Biotransformation

.Chemical Mechanisms

A

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

49
Q

Drug Elimination

Biotransformation
Efficiency (rate)

A

Metabolic activity for a specific drug

Blood flow to the organ

Health of the organ and health of the circulatory system

50
Q

Drug Elimination

Biotransformation
Organs Involved

A

Liver (most important for most drugs)

Lungs (especially for autocoids)

Kidneys

51
Q

Biliary Excretion
Active secretion
Passive secretion

A

Drugs with molecular weights > 300

mostly conjugates of original drug

Drugs with molecular weights < 300

biliary concentrations similar to plasma water

Pathology (7 decks)

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