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RUSVM Toxicology > Toxicokinetics II > Flashcards

Toxicokinetics II Flashcards

1
Q

Chronicity Factor

A

Acute LD50/Chronic LD50

>2 relatively cumulative toxicant

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2
Q

Risk Ratio

A

Toxicity:Use Level

Ex: urea toxicity = 300 mg/kg, use level = 100 mg/kg
Risk Ratio: 3:1

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3
Q

Henderson Hasselbach Equation

A

PKa of an acid= pH of the medium + log (N/I)
PKa of a base= pH of the medium + log (I/N)

N= nonionized
I= ionized
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4
Q

The ____________ the pKa of a weak acid, the ___________ the N/I; the _________ the pKa of a weak base, the __________ the N/I.

A

Higher, higher

Lower, higher

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5
Q

Absorption of drugs

A

The transfer of the drug from the side of admin to the circulation

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6
Q

What factors do we take into account for drug absorption?

A 
Molecular size
Lipid solubility
Degree of ionization 
Dissolution of drug in water 
Concentration of drug at absorptive site
Route of administration
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7
Q

The smaller the molecule, the ________ the penetration through pores

A

Faster

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8
Q

The greater the lipid solubility, the _____________ the absorption

A

Greater

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9
Q

The higher the ratio between N/I, the ______________ the absorption

A

Greater

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10
Q

Which is faster: oral absorption of lipid drugs or solid drugs?

A

Lipid drugs

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11
Q

What does oral absorption of lipid drugs depend on?

A

Rate of dissolution

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12
Q

What two things does the concentration of a drug at an absorptive site depend on?

A

Dose and concentration

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13
Q

The higher the conc of a drug, the _________ the absorption

A

Faster

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14
Q

List the routes of administration and their absorptive rates in order from fastest to slowest?

A

Sublingual and inhalation- very rapid
IM
SQ
PO

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15
Q

An increase in blood flow causes an increase or decrease in absorption?

A

Increase

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16
Q

What three things can modify blood flow?

A

Drugs
Physiological factors
Dz

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17
Q

What two things can decrease blood flow?

A

Shock

Edema

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18
Q

What is the main site of absorption for drugs given PO?

A

Duodenum (bc of extensive surface area and rich blood supply)

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19
Q

Rate of absorption depends on what?

A

Rate of gastric emptying

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20
Q

What 6 factors affect drug absorption from the GI tract?

A 
PO absorption of solid drugs depends on rate of dissolution
Activity of the gut
Presence of other substances
Blood flow
Species
Individual
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21
Q

Distribution of drugs

A

Transport of drugs from the plasma to the tissues (site of action, site of storage, side of biotransformation)

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22
Q

What 3 things affect the distribution of drugs?

A 
Physiochemical properties 
Concentration gradient
Plasma protein binding
Blood Flow
Tissue barriers
Affinity of drugs to certain tissues
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23
Q

What are two physiochemical properties of the drug?

A

Lipid solubility

Degree of ionization

24
Q

What do acidic drugs bind to?
What do basic drugs bind to?
What do steroids bind to?

A

Albumin
Acid alpha-1 glycoproteins and lipoproteins
Globulin

25
Q

Is plasma protein binding reversible or irreversible?

A

Reversible

26
Q

What is the significance of plasma protein binding?

A

It prolongs the half-life of the drug

27
Q

In plasma protein binding, the bound form is the _________ form, which means it can’t do what 3 things?

A

Inactive
Can’t be distributed, metabolized, or excreted by glomerular filtration
(PP bound drugs tend to be actively excreted)

28
Q

The rate of binding of the drugs depends mainly on what?

A

Amount of drug

29
Q

Drugs compete where in plasma protein binding?

A

On the binding sites

30
Q

True or False. Plasma protein binding depends on the species.

A

True

31
Q

What is something that can modify plasma protein binding?

A

Disease

32
Q

List the 4 highly perfused tissues.

A

Brain
Liver
Kidney
Endocrine glands

33
Q

List the two moderately perfused tissues

A

Muscle

Skin

34
Q

List the two poorly perfused tissues

A

Bone

Adipose tissue

35
Q

What 3 things are causes of alterations of blood flow?

A

Physiological factors
Drugs
Disease

36
Q

What are the 5 tissue barriers?

A 
Brain
Eye
Testicles
Placenta (less effective)
Mammary gland
37
Q

True or False. If the drug can cross the BBB, then it can cross any barrier in the body.

A

True

38
Q

Describe the BBB.

A 
Tight capillary endothelial junctions
Presence of glial cells
Flow of CSF into venous drainage
Active transport mechanisms
High distribution 
Lipophillic
39
Q

What type of transport is used for extrusion of organic acids and bases?

A

Active transport

40
Q

What factors influence the BBB?

A 
Age
Inflammation (meningitis)
Trauma
Allergic rxn
Severe hypotension 
Hypoxia
High doses of organic solvents (alcohol)
High doses of heavy metals (lead, mercury)
41
Q

Tetracycline has an affinity to ______________ in ______________ tissues.

A

Calcium; skeletal

42
Q

Aminoglycosides have an affinity to __________ tissue.

A

Kidney

43
Q

Iodine is trapped by what?

A

Thyroid gland

44
Q

Redistribution of drugs

A

The movement of the drug from the tissues to the blood

45
Q

How do you measure the distribution of drugs?

A

By the volume of distribution (Vd)

46
Q

Biotransformation

A

The chemical alteration of the drug molecule by the cells of the animal

47
Q

What are the two phases of biotransformation?

A

Phase 1- oxidation, reduction, hydrolysis

Phase 2- conjugation

48
Q

If there is a change in physiochemical properties of a drug, the metabolite is more __________, ___________, and __________.

A

Water soluble, polar, and ionized

49
Q

If there is a change in pharmacological activity of a drug what occurs?

A

Bioinactivation or detox of most drugs

Bioactivation or lethal synthesis (few drugs)

50
Q

True or False. Aspirin is an inactive drug.

What is the active metabolite of Aspirin?

A

False

Salicylic acid

51
Q

True or False. Cortisone is an inactive drug.

What is the active metabolite of cortisone?

A

True.

Hydrocortisone (cortisol)

52
Q

True or False. Parathion is an toxic drug.

What is the toxic metabolite of parathion?

A

False. Nontoxic

Paroxon

53
Q

What are some common sites for biotransformation?

A 
Liver- (SER microsomes; hepatocyte cytoplasm, mitochondria, lysosomes, nuclear envelope, plasma membrane)
Nervous tissue
Kidney
GIT
Lungs 
Skin
Plasma
54
Q

What are the 5 components of hepatic metabolism?

A

Enzymes lack specificity
Enzymatic rxns are saturable rxns
Drugs can compete on the same enzyme
Enzymes can be induced or inhibited by drugs
Microsomal enzymes cause oxidation, reduction, hydrolysis, and conjugation to glucuronic acid

55
Q

What are the two types of metabolic rxns?

Which one is synthetic, non synthetic?

A

Phase 1- oxidation, reduction, hydrolysis (non synthetic)

Phase 2- conjugation (synthetic)

RUSVM Toxicology (23 decks)

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