Toxicokinetics Distribution & Metabolism

A Vd above 1 will get ____ in the body but a Vd of above 2-3 will ___ In the body?

everywhere

Acumulate somehwere (fat/bone ect...)

How does fat Emulsion work for decontamination of the plasam?

Toxin gets trapped in fat and shuttled to liver to be detox and excreted

(Monitor for lipidemia and drug levels)

What are possible AE of IV fat emulsions?

Hypersensitivity

Pancreatitis

Fat embolism

Nonselective drug sequestration - difficult to admin other drugs for tx

What does phase one metabolism do?

Polarizes molecules (P450 enzyme)

What does activating a P450 molecule do?

Increases metabolism - tolerance/ faster elimination

What does inhibiting P450 molecules do?

Decreases metabolism - drug/ toxin hangs around longer

Which secondary metabolism phases can be depleted?

UGT (Glucoronidation)

GST (Glutathionine) - rare

SULT (Sulur donors)

Why is GST depletion rare?

Used for formation of RBC

Cats are less efficient in ___, ___ , and _____ secondary metabolism pathways?

SULT (sulfur transfer) and UGT (Glucoronidation)

also TPMT (Thyopurine methyltransferase)

What secondary pathway do dogs lack entierly?

NAT (1 and 2)

Cats lack 2

What is a common toxic effect in dogs when given sulfonamide medications?

Renal crystaluria - no acetylation

Explain why acetometophin toxicity in cats tends to be more severe?

Cant use sulfur donors or glucoronidate well

Lack NAT2, so acetaminophen is converted to toxic compound, causing methemoglobinemia,

Cytochrome P450s produce NAPQI, causing hepatotoxicity if glutathione is depleted too quickly

Where is excretion most commonly seen?

Liver and kideys

What are pharmacologic interventions for renal excretions?

Diuretics - furosemide

- give fluids while doing diuretics so no dehydration

What are cathartics?

Osmotic agents used to decrease absorption by decreasing GI transit time

How is zero order elimination different from first order elimination?

The amount of the toxin eliminated is constant until concentration of toxin is low enough it is no longer saturating all of elimination process

What is an ideal antidote?

Same distribution as toxin

Resistant to metabolism but doesn't inhibit it

Forms a non-toxic complex

Rapid excretion

What is a pharmacologic antidote?

Antagonism of the receptor that the poison is binding to

What is a functional antidote?

Physiologic antagonism - binds a different receptor than the poison that midigates/ antagonises its effects

What are chemical antidotes?

Agents that bind poisons directly causing sequestration and excretions?

Identify the type of antidote:

Naloxone/ atipamezole?

Pharmacological

Identify the type of antidote:

Fomepizole, Epinephrine?

Functional

Identify the type of antidote:

antivenoms, protamine

Chemical