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VET - Pharm > Lec5 > Flashcards

Lec5 Flashcards

(66 cards)

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1
Q

Withdrawal Time

A

the period of time after drug administration during which the animal cannot be sent to market for slaughter as food and the eggs or milk must be discarded

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2
Q

Half Life

A

the time required for the amount of drug in the body to be reduced by 50% (usually expressed in hours and abbreviated T 1/2)

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3
Q

Steady State

A

the point at which drug accumulation and elimination are balanced

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4
Q

Pharmacokinetics

A

the study of the physiologic movement of drugs throughout the body; also includes the movement of substances across cell membranes.

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5
Q

The four steps in pharmacokinetics are:

A

Absorption

Distribution

Biotransformation

Excretion

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6
Q

Drug-blood/plasma levels are dependent upon

A

The rate at which the drug is absorbed into the blood stream.

The amount of drug that is absorbed into the blood stream.

The distribution of the drug throughout the body.

The biotransformation of the drug.

The rate and route of drug excretion.

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7
Q

Four basic mechanisms of drug movement across cell membranes include:

A

Passive Diffusion

Facilitated Diffusion

Active Transport

Pinocytosis/Phagocytosis

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8
Q

Passive Diffusion

A

movement of drug molecules from an area of high concentration to an area of low concentration

does not require or expend energy

drug molecules exchange at an even rate so there are equal numbers of molecules both inside and outside the cell

in theory, drug molecules move throughout the body until equilibrium is attained among all body compartments

requires the drug to dissolve in the cell membrane and pass through the cell membrane made primarily of phospholipid with small pores

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9
Q

Lipophilic (+some details of these drugs)

A

dissolves in fat or oil medium

Lipophilic drugs dissolve more readily into the phospholipid cell membranes such as the intestinal mucosa

Lipophilic drugs are well absorbed from the gut by passive diffusion

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10
Q

Hydrophilic (+some details of these drugs)

A

dissolves in water/aqueous medium

Do not pass through lipid rich membranes as easily

Are more readily absorbed in fluid surrounding cells and must diffuse through fluid to reach capillaries

Drugs given IM are ideally hydrophilic for better absorption

IM drugs may be formulated to be lipophilic in form for slower absorption

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11
Q

Ionization (how does this influence drugs/uptake)

A

also affects movement of drugs across cell membranes

Ionized drugs have either a positive or negative charge

Tend to be hydrophilic in form

Non-ionized drugs have no charge and are neutral

Tend to be lipophilic in form

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12
Q

What characteristics of water affinity and ionization lend to effective diffusion?

A

drug molecules that move most effectively across cell membranes are lipophilic/non-ionized

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13
Q

Facilitated Diffusion

A

like passive diffusion but utilizes a special carrier molecule

Carrier molecule helps drugs across the cell membrane

No energy is needed

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14
Q

Active Transport

A

specialized carrier molecules in cell membranes move the drug across the membrane

requires energy

can move against a concentration from areas of lower concentration to higher concentration

allows drugs to accumulate in high concentration within a cell or body compartment

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15
Q

Phagocytosis

A

cell eating that is helpful with large molecules such as proteins that cannot pass through intact membranes

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16
Q

Pinocytosis

A

cell drinking of liquid particles

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17
Q

Absorption

A

the passage of the drug from its site of administration into the bloodstream.

before drugs can reach the site of action, the membranes of the absorptive surfaces must be crossed

drugs that are directly administered into the blood supply do not have an absorptive phase because the drug is placed directly into the plasma compartment!

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18
Q

Bioavailability

A

the degree or percentage of a drug administered that actually enters the systemic circulation

reflects the route of administration and number of barriers the drug must cross and/or delays encountered in reaching therapeutic blood levels (IV>IM>SQ>PO)

drugs that have no barriers (would be considered 100% bioavailable (bioavailability number of 1)

drugs given IV or IA are 100% bioavailable

some drugs are designed to have poor or no bioavailability (topicals, local analgesics, oral dewormers)

the lower the bioavailability, the less drug in the circulation and tissues

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19
Q

factors that affects bioavailability include:

A

blood supply to the area

surface area of absorption

dosage form of the drug

mechanism of drug absorption

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20
Q

Drug factors that affect absorption are:

A

Drug Chemistry (lipophilic vs. hydrophilic)

Drug Size (smaller molecules pass easier)

Ionization of the drug (non-ionized pass phospholipid membranes, ionized diffuse through tissue fluid)

Acid-Base Characteristics (pH of the drug)

Ion Trapping

Drug Form

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21
Q

In an Acid Environment, an Acidic Drug is Predominately (ionization and water affinity)

A

Non-Ionized (Not Charged) and therefore Lipophilic

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22
Q

An Acid Drug in an Alkaline Environment is Predominately (ionization and water affinity)

A

Ionized and Hydrophilic

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23
Q

In an Alkaline environment, an Alkaline drug is (ionization and water affinity)

A

Non-ionized (Not Charged) and therefore Lipophilic

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24
Q

Alkaline Drugs in an Acid Environment are (ionization and water affinity)

A

Ionized (Charged) and therefore Hydrophilic

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25
How does pH (drug/environment) affect ionization
The pH of a drug in the pH of an environment affects the ionization of that drug
26
Ion Trapping
drugs can pass from one compartment to another when the pH changes When a drug changes compartments, it may become ionized and trapped in its new environment, so that it can be absorbed into the bloodstream Ion trapping is especially important in drug excretion, since alterations in urine pH can allow drugs to be trapped in the urine and excreted
27
Drug Form
oral drugs must be lipophilic and small in size to penetrate the GI mucosa Tablets must dissolve into smaller particles Liquids do not have the dissolution step Enteric coating alters dissolution and/or absorption Decreased gastric motility lengthens absorption time Increased gastric motility shortens absorption time (may pass into feces) Presence of food may interfere with dissolution and absorption of certain drugs May be detoxified by the liver due to the first pass effect
28
First Pass Effect
All blood that circulates to the small intestine must travel through the liver on its way to the systemic circulation via the hepatic portal system This system allows the liver to remove potential toxins before they reach the general circulation Some drugs are recognized as foreign substances and may be removed, thus preventing them from reaching the general circulation and tissues Drugs that have an extensive first-pass effect are usually not recommended for PO use!
29
What water affinity must parenteral drugs be in?
hydrophilic form
30
Anything that interferes with drug diffusion from the administration site or alters blood flow to the injection site will delay absorption; what are they?
Limited blood flow at the injection site will slow absorption (fat vs. muscle) Temperature will affect blood flow to the administration site (vasoconstriction vs. vasodilation) Some drugs are formulated for delayed absorption (repository/depot injections) Other drugs may affect blood flow and absorption
31
Patient factors that affect absorption are:
Age Young animals may not have well developed GI tracts and less active enzyme systems General health Fever may increase movement of drug molecules GI disease (vomiting/diarrhea) hinders absorption Metabolic rate Higher metabolic rates may cause more rapid drug metabolism and elimination Genetic factors Individual/species variation in response to drugs Cats have a more rapid GI transit time Sex Males and females have different body fat compositions that may influence the absorption, and distribution of drugs
32
Distribution
the physiologic movement of drugs from the systemic circulation to the target tissues or site of action
33
Factors that affect distribution include
Membrane permeability and tissue perfusion
34
Protein Binding
Some drugs bind to proteins (albumin) in the blood and the large drug-protein complexes become trapped in the circulation Animals with low protein levels will have less protein available for binding and more free drug available for the target tissues
35
Volume of Distribution
Drug concentration in the blood will lower if the drug has a large volume to distribute through Diseases that produce extra body fluid (edema, ascites) will have less drug concentration in the blood and tissues due to a greater volume of distribution
36
Biotransformation or Metabolism
the chemical alteration of the drug molecules into metabolites by the body cells of the animal so that: drugs are changed chemically into a “metabolite” form that can be active, inactive and/or toxic metabolites are generally more ionized, hydrophilic and less chemically active so that they can be eliminated from the body
37
What is the primary organ of biotransformation; list the other places
The primary organ of biotransformation is the liver (cytochrome P450 of the hepatocytes) Other locations include the lungs, skin, intestinal tract, kidney, nervous system
38
What are the four main pathways of biotransformation?
Oxidation, reduction, hydrolysis, conjugation
39
Factors affecting biotransformation include
Plasma protein binding Less plasma protein binding allows excretion Storage in tissue and fat Liver disease Less cytochrome P450 Species/Individual variation Cats have decreased ability to form glucuronic acid Route of administration Some drugs cannot be given orally Body temperature Enzymes are temperature dependant Age of patient Very young or old due to liver status Rumen pH changes with age Nutritional status
40
Excretion or elimination
removal of drug from the body. Most drugs are excreted via the kidney into the urine.
41
Other routes of elimination include
the liver (first pass effect) the lungs (anesthetic gases) sweat/salivary glands (used in forensics) milk (residue concerns for food safety) intestinal tract (via bile and feces) incorporation into hair, nails, hooves
42
Mechanisms of renal excretion include:
- Glomerular filtration (Non-selective,Highly dependant upon blood flow/pressure) - Tubular secretion (Active transport across the convoluted tubule membrane, Moves molecules from blood into urine filtrate) - Tubular reabsorption (Occurs in the loop of Henle, Drugs that are highly lipid soluble/non-ionized will have increased reabsorption)
43
Factors affecting excretion:
renal perfusion clearance rate half life patient age concurrent disease percent of functioning nephrons types of drugs/secondary drugs (concurrent diuretic use) tubular reabsorption
44
Steady state
point at which drug accumulation and elimination are balanced
45
What ways can drugs interact with eachother
- Altered absorption (One drug affects another drug’s absorption) - Competition for plasma proteins (Two drugs may both bind to plasma, One displacing the other) - Altered excretion (drugs that act directly on the kidney may affect excretion) - Altered metabolism (drugs may need the same enzymes for biotransformation and decrease the rate of metabolism) - Microsomal enzyme induction - some drugs cause liver enzymes to be more efficient (The drug’s rate of biotransformation is increased, Must monitor and increase dose periodically to maintain therapeutic blood levels) - Tolerance – decreased response to a drug (
46
What are the two different types of tolerance?
Metabolic – drug metabolized quicker with chronic use Cellular – “down regulation” or decreased cellular receptor response with repeated use
47
Where are the recepters drugs interact with located?
Receptors are three dimensional proteins or glycoproteins located located on: Cell membrane surface Cell cytoplasm Within the nucleus
48
Tissue affinity and receptor sites
cell receptors bind to the drug molecules and then a response occurs through a structural-activity relationship between the drug and receptor
49
Affinity
the strength of binding between a drug and its receptor (measure of affinity is called the dissociation constant or KD)
50
Efficacy
the degree to which a drug has an exact fit to the receptor or produces the desired effect
51
Agonist
a drug that binds to a cell receptor and causes an action (has both affinity and efficacy)
52
Lock and Key comparison
similar to how drugs and receptors interact
53
Partial Agonist/Antagonist
A drug that binds to a cell receptor but has only partial effect (has affinity but only partial efficacy) 
54
Antagonist
a drug that inhibits or blocks the response of the receptor site (has affinity but NO efficacy) 
55
Competative Antagonist
competes for the same receptor
56
Non-competative Antagonist
binds to a different site than the agonist, but changes the shape of the agonist’s receptor, preventing the drug’s action
57
Non-Receptor Mediated Action
there are no cellular receptors with which the drug interacts (Osmotics and Chelators)
58
Osmotics
pull water from tissues and cells due to a molecular size or chemical effect that attracts water 
59
Chelators
types of compounds used as drugs that physically combine with ions (e.g. Ca, Mg, Cl) or other specific compounds to produce their effects 
60
Drug Interaction
an altered pharmacologic response to a drug that caused by the presence of a second (or more) drug
61
Adverse Drug Event
harm to a patient caused by drug administration for therapy or diagnosis
62
What are some causes of Adverse Drug Events?
- Due to medication errors such as wrong drug, wrong dose, wrong patient, etc. - Due to an “adverse drug reaction” from the inherent properties of the drug itself such as poor drug quality or purity, reaction to the drug carrier, etc. - Photosensitivity - Other types of adverse drug reactions include vomiting, diarrhea, impaired hearing, organ damage (liver, kidney, heart), infertility/abortion, cancer, anaphylactic shock and death.
63
Photosensitivity Adverse Drug reaction
drugs that cause changes in the skin
64
Idiosyncratic Adverse Drug reaction
an unusual or unexpected reaction
65
Pharmaceutic Interaction
- physical or chemical reactions that occur as a result of mixing drugs in a syringe or container - may precipitate or be altered when mixed and chemically inactivate the drug(s) or cause an adverse reaction
66
when should adverse drug reactions be reported
ALWAYS All adverse drug reactions should be reported to the drug manufacturer or FDA. the drug company is obligated to report the adverse reaction to the FDA

VET - Pharm (17 decks)

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