Exam 1 Terminology Flashcards Preview

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Flashcards in Exam 1 Terminology Deck (174):
1

Factors Related to the Animal

1. Species
2. Breed
3. Gender
4. Body Condition
5. Age
6. Disease
7. Temperament
8. Idiosyncratic drug reactions
9. Hypersensitivity
10. Tolerance

2

Idiosyncratic drug reactions

Unpredictable abnormal reaction. Not dose-dependent and can occur on first exposure.

3

Tachyphylaxis

An acute form of tolerance, sometimes involves depletion of stored mediator

4

Factors Related to the Drug

1. Route of administration
2. Timing of administration
3. Cumulation
4. Drug-drug interactions
5. Pharmacokinetic effects

5

Summation

Drug A + Drug B = A + B

Two drugs have additive effects

6

Synergism

Drug A + Drug B > A + B

Two drugs have greater efficacy when combined

7

Potentiation

Drug A + Drug B > A + B

One drug increases the availability or efficacy of another

8

Antagonism

Drug A + Drug B

9

Chemical antagonism

The drugs chemically react to each other causing inactivation of one or the other drug (in vivo or vitro)

10

Physiologic antagonism

The drugs work differently and have opposing physiologic effects that cancel each other out

11

Pharmacokinetic antagonism

One drug reduces the concentration of the other drug at its site of action by interfering with its ADME processes

12

Receptor anatagonism

One drug binds to a receptor and prevents the other drug from having its normal activity at that receptor

13

Acidifying the urine ...

... increases excretion of weak bases

14

Alkalinizing the urine ...

... increases the excretion of weak acids

15

Factors related to the environment

1. Ambient temperature
2. Oxygen
3. Humidity
4. Light
5. Contact surfaces

16

Drug disposition

Study of movement of drugs across biological membranes in the body from the time of absorption until elimination

17

Passive Diffusion

Movement with a concentration gradient

18

Paracellular movement

Diffusion through intercellular aqueous channels. Specialized intercellular junctions.

19

Transmembrane movement

Diffusion through lipid membranes and aqueous protein channels in the cell membrane

20

Lipid/water partition coefficient

The relative solubility of a drug in lipid as compared to water. The higher the lipid solubility, the faster it crosses cell membranes

21

Diffusion coefficient

A measure of the diffusional mobility of a particular molecule. Molecular size, molecular conformation, degree of ionization.

22

Ionization

The pKa of a weak acid or base determines in what pH the substance will be ionized (unable to cross lipid membrane or non-ionized (mobile across lipid membrane)

23

pKa = pH

The drug is 50% ionized and 50% non-ionized

24

Acidic drugs are ...

... ionized in basic environments

25

Basic drugs are ...

... ionized in acidic environments

26

Ion trapping

When a drug ionizes and then is unable to cross back over the membrane

27

Facilitated diffusion

Movement with a concentration gradient. No energy required. Movement can be from inside to outside the cell or other way around.

28

Carrier mediated

Facilitated diffusion. Transfer of substances across the membrane involves attachment to a specific macromolecular "carrier". May or may not be specific. The carrier system is saturable.

29

Channel mediated

Facilitated diffusion. Transport across the membrane involves opening of ion channel proteins

30

Active transport

Carrier-mediated transport. Saturable, selective. Movement against concentration gradient. It does require energy.

31

Primary active transport

Energy directly from ATP. Na+/K+ ATPase

32

Secondary active transport

Stored energy in the Na+ electrochemical gradient generated by using ATP

33

Symporter

Secondary active transport, where two substances move together into a cell

34

Antiporter

Secondary active transport, where one substance is exchanged for another

35

P-glycoprotein (P-gp) system

Specific form of active transport in which the transporter is an efflux pump. This protein is an expression of the ABCB-1 gene (formerly called the MDR-1 gene) and will remove substances from specific cells.

36

Pinocytosis

A specific type of endocytosis. Drugs bind to the surface of the membrane that then invaginates and interiorizes the drug. It does require energy (ATP).

37

Weak acids are ...

... absorbed from an acidic environment and sequestered in an alkaline medium

38

Weak bases are ...

... absorbed from an alkaline environment and sequestered in the acid medium

39

Drug Absorption

Movement of the drug from the site of administration into the blood

40

Routes of administation

IV, IM, PO, SC, IP, Inhalation, dermal

41

Factors affecting absorption - related to the drug

1. Molecular size
2. Disintegration and dissolution
3. Lipid solubility
4. Degree of ionization
5. Concentration at the absorptive site
6. Route of administration

42

Factors affecting absorption
- related to the animal

1. Blood flow
2. Absorbing surface area
3. Connective tissue
4. Species
5. Individual variation
6. Fasted vs. fed

43

Enteral (or alimentary)

Routes of administration typically given oral (PO), rectal or sublingual

44

Disintegration

Physical dispersion of a solid dosage from. Affected by exicpients, compaction pressure, enteric coatins, capsules, homegeneity

45

Dissolution

Drug molecules enter the solution. Solubility can be affected by particle size/surface area, binding, local pH, buffers, boundary layers.

DISSOLUTION IS OFTEN THE RATE LIMITING STEP CONTROLLING ABSORPTION!

46

Systemic

Drug is intended to reach the blood stream. If a drug is not given IV then it must undergo absorption to get from the site of administration to the blood stream.

47

Distribution

Transfer of drugs from the bloodstream to tissues around the body

48

Factors Affecting Distribution

1. Physicochemical properties of the drug
2. Concentration gradient between blood and tissue
3. Ratio of blood flow to tissue mass
4. Affinity of the drug for tissue constituents
5. Physiological determinants
6. Tissue barriers
7. Plasma protein binding

49

Physicochemical properties

Of the drug itself will determine how much and how fast it will cross membranes

50

~57%

Of the body is fluid

51

~40%

Intracellular Fluid

52

~17%

Extracellular Fluid

53

~13%

Interstitial Fluid

54

~4%

Blood Plasma

55

When a drug is plasma protein bound it is considered to be ...

INACTIVE

56

Acidic drugs typically bind to ...

Albumin

57

Basic drugs typically bind to ...

B-globulins and glycoproteins.

58

Metabolism

The chemical alteration of the drug by different body tissues. (Also called biotransformation)

59

Bioinactivation

The process of making a drug inactive and easier to excrete

60

Bioactivation

When a prodrug is converted to an active metabolite

61

Prodrug

inactive substance. Drugs needs to be metabolized into an active state before it can have its desired effect.

62

Lethal Synthesis

When an active drug is converted to an active metabolite, or a non-toxic substance can be converted to a toxic metabolite.

63

Cytochrome P450 (CYP450)

Attached to SER, also known as the mixed function oxidase system. A non-specific enzyme that catalyzes Phase 1 reactions in hepatocytes.

64

Phase 1 Reactions (Non-synthetic)

Involve the addition or loss of an electron, often can produce more reactive metabolites that then may have a phase II reaction. Such as oxidation, reduction, and hydrolysis.

65

Phase II (Synthetic)

A molecule (endogenous substance, parent drug, or metabolite) with a reaction group conjugates with a substituent group rendering a final metabolite that is typically inactive and water soluble (polar)

66

Glucuronidation

Is the most common reaction and is microsomal (the others are non-microsomal). Cats are deficient.

67

Factors Affecting Liver Metabolism

1. Species
2. Age
3. Individual variation
4. Route of administration
5. Plasma protein binding
6. Body temperature
7. Liver disease

68

Enzyme Induction

Drugs that increase synthesis, decrease degradation, and/or activate pre-existing compounds. Only microsomal enzymes are induced. Can lead to tolerance or drug-drug interactions.

Ex: Phenobarbital, rifampin, and Kale

69

Enzyme Inhibition

Drugs that inhibit the liver production or certain metabolic enzymes.

Ex: Chloramphenicol, cimetidine, ketoconazole, and Grapefruit Juice.

70

Excretion

Removal of the drug (and metabolites) from the body

71

Renal Excretion

Is comprised of glomerular filtration, active tubular secretion, and tubular reabsorption. The combination of these processes is termed "total renal excretion" of a drug

72

Glomerular filtration

This is a passive process that depends on systemic blood pressure and renal blood flow. Molecular size, charge and protein binding are factors that significantly affect a drugs likelihood of being filtered

73

Active tubular secretion

in the proximal convoluted tubule active secretion occurs. Drugs are moved against a concentration gradient, energy dependent, ionized drugs are moved, insensitive to protein binding, saturability and inhibition.

74

Organic Cation Transporters (OCTs)

Secretion of organic bases.
Endogenous: choline, dopamine
Drugs: Cimetidine, procainamide, nicotine

75

Organic Anion Transporters (OATs)

Secretion of organic acids
Endogenous: Uric acid
Drug: Penicillin, thiazide diuretics, loop diuretics

76

Tubular Reabsorption

Passive diffusion occurs in the proximal and distal convoluted tubules. Lipid soluble, non-ionized drugs have the greatest chance of moving back into ciruclation

77

Acidification of urine

With ammonium chloride or methionine will cause weak basic drugs to be ionized and enhance their excretion

78

Alkalinization of urine

With sodium bicarbonate or potassium citrate will cause weak acids to be ionized and enhance their excretion

79

Factors Affecting Renal Excretion

1. Age of patient (lower in neonates)
2. Heart/Kidney/Liver disease
3. Urine pH
4. Drug factors

80

Hepatic excretion

Typically an active transport of drugs and/or conjugates from the hepatic sinusoids to the bile canaliculi

81

Fecal Excretion

Any drugs excreted in the bile and not reabsorbed will be eliminated in the feces. Drugs that are given orally but not absorbed will be excreted in the feces. Some drugs will move from plasma into the GIT and be excreted in the feces.

82

Excretion in milk/eggs

Concerned about drug residues. Concerned about route of administration (e.g. systemic vs intramammary), ion trapping (some weak basic drugs will be ion trapped in milk), witholding times for drug therapy, maximal allowable residue levels.

83

Pharmacokinetics

Using mathematical models to quantitate the time course of drug absorption and disposition in man and animals

84

The Rate of ADME

How fast the mass (dose) of a drug change per unit time (mg/min)

85

The Extent of ADME

How much the mass (dose) of a drug changes in total.

86

Dosage of Regimen

- Dosage and route of administration
- Frequency of administration
- Duration of administration

87

Dose

Amount of drug given to an individual (mg)

88

Dosage

A "recipe" for how much to give (mg/kg)

89

Compartment model

a collection of tissues that have similar pharmacokinetics

90

One compartment model

Considers the body as consisting of a single homogenous compartment. Volume of compartment is the volume of distribution (Vd)

91

Two-Compartment model

Two compartments. (1) Central compartment into which the drug is added and from which it is cleared. (2) a second compartment to which the drug is distributes.

92

Non-compartmental (stochastic) models

This is the primary method. Involve using statistical analysis of large numbers of actual animal data (time plasma concentration curves).

93

Mean Residue Time

Most useful non-compartmental model. Describes the length of drug persistence in the body.

94

Non-linear Model

When drug follows zero-order kinetics (such as when saturation has occurred - sometimes called dose dependent pharmacokinetics)

95

Population pharmacokinetcs

This system estimates pharmacokinetcs by looking at populations. Mathematical techniques allow studies of large numbers of animals with less individual sampling. This can allow for development of parameters for a drug that would apply to all breeds, ages, gender etc.

96

Allometric scaling

This uses pharmacokinetc data in multiple species to try to predict the behavior of a drug in a species for which this information is unknown (scaling based on size and metabolism)

97

Area under the curve

A measure of drug exposure

98

Bioavailability

The fraction of the given dose which finds it way into the systemic circulation

99

Bioequivalence

Different formations of the same drug are bioequivalent when they are absorbed to a similar extent and similar rate.

When the AUC, Cmax and Tmax are similar.

100

Half Life (t1/2)

The time required for the plasma drug concentration to decrease by one-half (or 50%)

101

Zero-order Elimination

The AMOUNT of drug eliminated per unit time is fixed, regardless of plasma concentration. Half life will be different depending on the starting amount.

102

First-order Elimination

The PROPORTION of drug eliminated per unit time is fixed. The rate of elimination changes at a constant rate.

103

5 half-lives

Commonly used values as for most clinical purposes 97% of the drug being gone means it is essentially eliminated.

104

(Apparent) Volume of Distribution

The volume of a drug would occupy if it was evenly distributed at the same concentration as in plasma (L/kg)

105

Clearance

Volume cleared of the drug per unit time (mL/min/kg)

106

A very low Vd

Suggests that the drug is not being distributed to all of the tissues. Remain mostly in the plasma.

107

A very high Vd (> 1 L/kg)

suggests that the drug is distributing preferentially to tissue and may even be sequestered somewhere. Somewhere outside of the blood stream.

108

Total Body Clearance (CLb)

The volume of distribution of drug in the body cleared of the drug per unit time (mL/min/kg). Takes into account both metabolism and excretion.

109

As Vd increases

t1/2 gets longer

110

As Vd decreases

t1/2 gets shorter

111

As CLb increases

t1/2 gets shorter

112

As CLb decreases

t1/2 gets longer

113

Plasma Concentration at Steady State (Cpss)

the concentration at which the amount of drug going in (repeated dosing or CRI) is equal to the amount going out (clearnace CLb)

114

Pharmacodynamics

the effects of drugs and their mechanisms of action within the body. What the drug does to the animal

115

Therapeutic effects

What we want to see the drug perform

116

Side effects

Which are secondary to the intended effect and may be good or bad

117

Adverse effects

Which are unintended and unwanted, thick includes NOT producing a desired clinical effect. The study of monitoring of adverse effects is called pharmacovigilance.

118

Toxic effects

Responses to a drug that are harmful to the health or life of the animal

119

Targets for drug action

Can be physical interaction or biological interaction

120

Physical interactions

Are considered non-specific effects such as:

1. osmotic diuretics
2. antacids
3. radioactive iodine

121

Osmotic diuretics

these molecules move through the body dragging water with them by osmosis until they are excreted.

122

Antacids

Direct neutralizers; given orally they directly interact with acid in the GIT. A form of physiologic antagonism

123

Radioactive iodine

Iodine is actively concentrated in the thyroid and the radiation will destroy all tissue within 2-3 mm causing focal, controlled destruction.

124

Biological Interaction: Non-receptor - Ion Channels

Blocking of ion channels can occur by the drug molecules physically obstructing the channel to impair ion movement. The drug may also modulate the opening and/or closing of the channel.

125

Biological Interaction: Non-receptor - Enzymes

Drugs can be analogs that compete with the real substrate for binding to the enzyme and thus blocking the enzyme from doing its job.

Drugs can also be false substrates which will interact with the enzyme and lead to the formation of abnormal metabolites.

126

Biological Interaction: Non-receptor - Carrier Proteins

Some small polar molecules cannot cross cell membranes and get carried in and out by carrier proteins. Drugs may alter this movement either preventing re-uptake of a molecule which increases its level in the synapse or preventing output of a molecule to decrease its levels.

127

Biological Interaction: Receptors (signal transductions)

Specific recognition sites for (a ligand) endogenous chemical messengers. Can be:

1. Ligand gated ion channels
2. G-protein coupled
3. Kinase linked receptors
4. Nuclear receptors

128

Ligand-gated ion channels

Ionotropic receptors. Groups of proteins embedded in the cell membrane forming a pore. Something had to bind to the receptor to cause a change in shape or 'opening' of a channel that allows a large influx of ions.

drugs can bind to these to active them (agonist) or prevent them from opening (antagonist)

129

GTP-binding Protein (G-protein) coupled receptors

Also known as 7TM for crossing the membrane back and forth seven times. Transduce an extracellular signal to an intracellular one. These are common receptor types for secretory and smooth muscle functions.

Responses can be either excitatory OR inhibitory, depending on the subtype of the receptor.

130

Gs

G-protein subtype: couples to adenylyl cyclase which increases formation of cAMP, which activates protein kinase A, which phosphorylates cellular constituents.

131

Gi/o

G-protein subtype: couples negatively to adenylyl cyclase, so decreases cAMP formation. It can also close ion channels.

132

Gq

G-protein subtype: couples to phospholipase CB (CBeta) which alters regulation of intracellular calcium and phosphorylation

133

Kinase-linked receptors

Direct activation of enzymes. Extracellular receptor, protein has an intracellular portion with enzymatic activity (kinase domain). Phosphorylation and activation of proteins which then activates effectors.

134

Nuclear receptors

Intracellular; AKA Transcription factor receptors. Receptors are actually located in the cytoplasm but after the ligand binds the receptor they translocate to the nucleus of the cell and bind to a response element within the DNA to initiate specific gene transcription.

135

Receptor subtypes

Endogenous neurotransmitter often bind to more than one type of receptor. Ex: Adrenergic receptors (alpha & beta) - same signaling molecule can then cause different effects or have different affinity in different tissues or species.

136

Receptor Up-regulation

Increase in the number of receptors, resulting in an increase in the effect of the drug

137

Receptor Down Regulation

Decrease in the number of receptors an therefore a reduction in effect

138

Tolerance

Gradual decrease in responsiveness to a drug when given repeatedly over days to months

139

Ligand

Anything that binds to a recognition site

140

Agonist

Mimics the effect of an endogenous ligand

141

Full agonist

Binds to the receptor to elicit a maximal response

142

Partial agonist

Will bind to the receptor but not cause as much effect as a full agonist, it does prevent anything else from binding to the receptor while it is "docked" there. Lower efficacy.

143

Ceiling effect

When the ligand has exerted its maximal effect - that point will generally be at a lower level of efficacy for a partial agonist compared to a full agonist.

144

Reverse (inverse) agonist)

Will bind to the receptor and cause the opposite effect as the endogenous ligand would

145

Antagonist

Or neutral agonist. Binds to the receptor but (in theory) does nothing on its own, however it prevents an agonist from binding and thus blocks effect of the receptor.

146

Competitive antagonism

when the antagonist binds to the same receptor as the ligand, usually a transient bond, and so if both antagonist and agonist are present they will "compete" for the binding.

147

Non-competitive antagonism

adding more agonist cannot reduce the effect of antagonism. Usually from an irreversible bond. Or antagonist is binding somewhere other than the receptor site to alter the binding of normal ligand at the receptor.

148

Mixed agonist-antagonist

Acts as an agonist at one type of receptor and as an antagonist on another type

149

Non-receptor antagonism

1. Chemical antagonism
2. Pharmacokinetic antagonism
3. Physiological antagonism

150

Chemical antagonism

two drugs directly interact and chemically inactivate each other

151

Pharmacokinetic antagonism

A drug alters ADME of another drug and reduces its effect

152

Physiological antagonism

Drugs have opposite effects that cancel each other out, but work through different receptors or pathways

153

Quantification of Drug Response: Efficacy

The maximal effect a drug can have (e=1 is a full effect). A partial agonist may never be able to achieve full efficacy (ceiling effect)

154

Quantification of Drug Response: Potency

A comparison of the concentration of two drugs needed to induce the same magnitude effect. A partial agonist could be more potent.

155

Quantification of Drug Response: Slope

Linear in the ~20-80% range

156

Maximal effect (ceiling)

Point at which increasing concentration does not yield greater response

157

Effective Concentration 50% (EC50)

This is the concentration at which a drug produces 50% of its maximal effect. Only applies in vitro.

158

Effective Dose 50% (ED50)

Dose that produces a result (usually the desired effect) in 50% of animals. Typically in vivo.

159

The therapeutic index is the ratio of LD50 to ED50

A ratio used to evaluate the safety of a drug

160

Narrow Therapeutic Index

(small number, close to 1) means that the dose required to cause death is close to the dose required to have a therapeutic effect

161

Wide Therapeutic Index

(often many time higher) means that the dose required to cause death is much higher than the dose required to have a therapeutic effect

162

Standard Safety Margin

is a more conservative measure. It looks at the dose required to produce a therapeutic effect in ALL animals relative to the dose required to produce a hazardous effect.

163

Quantification of Drug Response: Onset of action

the time required after drug administration for a response to be observed. Also called latent period

164

Quantification of Drug Response: Duration of action

the length of time that a drug is effective (from onset of action until termination of action)

165

Product

A specific formulation of an active substance(s) and has a claim for efficacy and safety at a certain dose

166

Formulation

Includes active ingredients as well as excipients, substances the impact ADME, flavors, etc.

167

Claim

At X dose the produce is effective for Y disease.

168

Why is a veterinary drug different from a list of active ingredients?

A veterinary drug contains active ingredients in a specific formulation as well as excipients that would not be included in a list of active ingredients.

169

Drug Requirements

Must be safe and effective for intended use. Must be manufactured, processed, packaged to maintain drug quality and efficacy. Must be registered with USDA.

170

Drug Safety

Product must be safe for its intended use. Product must be safe for target animal it will be used in. FDA and product registration holder negotiate wording on label and leaflet.

171

Exact Dose

Specific quantity of medication per kg.

172

Dose band

Quantity of medication for a range of body weights.

173

Lowest weight

Max safe dose

174

Highest weight

Min effective dose