Tox Principles Of Toxicology

Front 1

Why is eating moldy food bad?

Back 1

Tremorgenic Mycotoxins!

Many kinds, most are Penicillium species.

Front 2

What type of toxins do the Penicillium produce, and what are the effects?

Back 2

2 Toxins: Penitrem A and Roquefortine C

Penitrem A - Inhibits Glycine
Verruculogen - inhibits GABA

Front 3

How do you Dx tremorgenic intoxication?

Back 3

Submit sample of the food or stomach contents

Front 4

How do you Tx tremorgenic intoxication?

Back 4

No Antidote - Supportive Care
Mild tremors - Diazepam (Valium) may be okay.

Severe Tremors - Methocarbamol at 55-220 mg/kg slow IV to effect

Severe Seizure - Barbiturate at 3-15 mg/kg slow IV to effect

Front 5

Define:

Toxicant
Toxin

Back 5

Toxicant
aka Poison - any agent (even water) capable of producing a deleterious response in a biological system

Toxin - a poison that originates from biological processses

Front 6

Define:

Toxicity
Toxicosis

Back 6

Toxicity = quantity or amount that causes a toxic effect

Toxicosis = disease state that results from exposure to a poison

Front 7

Define:

Hazard or Risk

Back 7

Hazard or Risk = likelihood that a drug or chemical will cause harm under certain conditions

Front 8

Define:

Dose
Dosage
Route of Exposure

Back 8

Dose = amt of toxicant received
Dosage = amount of toxicant per unit weight
Route - mostly inhalation, oral, dermal

Front 9

Define:

Threshold Dose
LD50
MLD

Back 9

Threshold Dose = Highest Dose of toxicant at which effects are NOT observed
LD50 = dose at which 50% of animals die
MLD = Median LD = LD50

Front 10

Define:

NOEL and NOAEL
LOEL and LOAEL

Back 10

NOEL/NOAEL = No Observed (Adverse) Effect Level

LOEL/LOAEL = Lowest Observed (Adverse) Effect Level

Front 11

Define:

TI
SSM or MoS

Back 11

TI = Therapeutic Index = LD50/ED50
The larger the TI the "safer"

SSM/MoS = Standard Safety Margin / Margin of Safety = LD1/ED99
The larger the SSM/MoS the "safer"

Front 12

Define:

Acute
Subacute
Chronic
Subchronic

Back 12

Acute - 1 or more doses in 24hrs
Subacute - multiple doses for up to 30 days
Chronic - 3 months or longer
Subchronic - 1-3 months

Front 13

What 3 things predispose you to Chronic Toxic Effects?

Back 13

1. Chemical can accumulate
2. Toxic effect is Irreversible
3. Insufficient recovery time bw exposures

Front 14

Interaction of Chemicals:
Give mathematical examples of:

Additive Effect
Synergistic Effect
Potentiation
Antagonism

Back 14

Add --- 2+3=5
Syn --- 2+3=20
Pot --- 0+2=20
Ant --- 4+6=8, 4-4=0, or 4+0=1

Front 15

What are the 3 assumptions of the Dose-Response concept?

Back 15

1. Chemicals interact with a molecule or receptor site to produce a response.
2. The production or degree of response is correlated to the concentration of the chemical at that site.
3. The concentration of the chemical at the site is related to the dose of the chemical received.

Front 16

What is Hormesis?

Back 16

Things (like xenobiotics) that can be great at low doses, but severely damaging at high doses

eg - Selenium, Vitamin A

Front 17

What do heavy metals really hate?

Back 17

Kidneys

Front 18

Where do you usually get hit the hardest by Cadmium if your route of exposure is:

Oral?
Inhalation?
Dermal?

Back 18

Oral - Renal
Inhaled - Lung to Renal
Dermal - no biggy

Front 19

Who basically just gets hosed in terms of toxicity - and why?

Back 19

Cats
Limited ability to glucuronidate
(rely on less efficient metabolic pathway of sulfate and cysteine conjugation)

Front 20

What are the 4 factors of Toxicokinetics? (AMDE?)

Back 20

Absorption
Distribution
Metabolism
Excretion

Front 21

What are the 3 major routes of exposure?

Back 21

Inhalation, Oral, Dermal

Front 22

True or False:

Inhaled Toxins can enter the GI tract

Back 22

TRUE

And can be better/worse depending on degradation or absorption rate in the stomach, intestine, colon...

Front 23

What is the order of effectiveness for exposures? (8 categories - most to least effective)

Back 23

IV, Inhaled, IP, SQ, IM, ID, Oral, Dermal

Front 24

What is filtration?

Back 24

Water flowing in bulk across a porous membrane - and bringing any solutes small enough to fit through the pores with it

Front 25

Is Passive Transport Saturatable?
Is Active Transport Saturatable?

What is the difference bw Active and Facilitated Transport?

Back 25

No
Yes

Active expends E to move AGAINST a [gradient]
Facilitated expends E but does not fight against a [gradient]

Front 26

What is F?

Back 26

Bioavailability

(amt available... so 100% for IV)

Front 27

What are the 4 reasons why some toxicants can not enter the CNS?

Back 27

BBB
1. Capillary Endothelia is Tighter than normal.
2. Endothelial cells have MDR protein that actively kicks drugs out.
3. Capillaries surrounded by Astrocytes
4. Lower ECF [protein] - limiting solute movement

Front 28

In general, drugs with what 2 properties hit the brain?

Back 28

Unbound and High Lipid Solubility

Front 29

What is the Volume of Distribution?

Back 29

Theoretical number - tells you how much leaves the blood.

So if the toxin has a really low Vd - it isn't really leaving the bloodstream, so it probably won't do too much damage besides potentially to the vessels.
A very high Vd goes to many tissues and thus may have effects all over the place.

Front 30

Phase I metabolism in the Liver does what?

Back 30

Convert Apolar compounds to Polar ones

(Hydrolysis, Redox, P450s)

Front 31

Phase II metabolism in the Liver does what?

Back 31

Conjugation of the original substance or the Phase I metabolite to make it more H2O solube

(Glucuronidation - poor cats, Sulfation, Methylation, etc...)

Front 32

Most chemicals are eliminated by _____ kinetics?

Back 32

1st Order

so Rate of Elim ~ Amt of Chemical in Body
(continues to decrease by 30%)

Front 33

How are Zero Order kinetics different?

Back 33

Zero Order use SATURATABLE systems (1st order uses non-sat.)

Therefore, Zero order eliminates by order of the same quantity.
(continues to decrease by 20mgs)

Front 34

How much of a chemical is eliminated at 7 half lives?

Back 34

99.2%

for FIRST ORDER chemicals

Front 35

What is the mg/kg of 14ppm?

Back 35

14 ppm = mg/kg

**ppm also =
0.91 grams/ton
ug/mL

Front 36

What is 10% of ______ actually mean?

(ie -- 10% Dex solution)

Back 36

100 mg Dex / mL

(so add a 0 and you get mg/mL)

Front 37

How much is an ounce of x?

Back 37

~30 *grams OR mLs!

(dry ounce = 28.35 grams)
(fluid ounce = 29.6 mLs)

Front 38

1 tsp = ___mLs?
1 T = ___mLs?
2 T = ___mLs?

Back 38

5mL... or approx 2 mini marshmallows
15mL
30mL aka 1 ounce! ...or approx 1 large marshmallow