Pharmacology Lecture 6_Drug Toxicity

Question 1

Describe a dose dependent pathological ADR

Answer 1

This is an ADR where a toxic metabolite of a drug acumulates and causes damage seperate from the target phyisiology (example acetominophen)

Question 2

What is a TDx

Answer 2

a TDx is the dose at which x percentage of the population will experience a toxic effect from a drug. TD50 would equate to 50% of the population experiencing drug toxicity

Question 3

What are the three considerations for drugs with a low TI

Answer 3

1) Monitor blood levels of drug
2) is the drug necessary (is it having its intended effect)
3) Monitor health of target organs

Question 4

What is a toxic threshold

Answer 4

It is defined as the TD1 (this is essentiall the dose at which side effects first begine to appear in your population.

Question 5

How is a drug margin of safety calculated?

Answer 5

it is the LD1/ED99. Note a larger MOS equates to a safer drug from a dose dependent standpoint (this does not take into account allergic responces)

Question 6

Define a type 2 allergic rxn “Cytolitic rxn”

Answer 6

An antigen binds to a red blood cell. An antibody 9IgM or IgE) then binds to the antigen. This triggers cytotoxic t cell or complement mediated lysing of the red blood cell.

Question 7

Define a type 1 allergic rxn “hypersensitive alergic reaction”

Answer 7

This is an anaphylactic rxn. A protien bound hapten (or just hapten) bind to a Mast cell bound IgE which causes the mast cell to release inflamitory mediators including hitamine, serotonin, and leukotriens

Question 8

What is an “Off target ADR”

Answer 8

these result in an unintended interaction with an unintended receptor

Question 9

What are 5 clinical settings when drug-drug interactions (DDI) are most likely to occure?

Answer 9

1) Drugs with low TI
2) When multipul drugs are being taken (esp>10)
3) When patient has comprimised renal, hepatic, or pulminary function
4) When patient has immunodeficency syndrome
5) When Patient has behavioral of psychiatric disorders (esp drug abuse)

Question 10

Define “Apparent dose”

Answer 10

Apparent dose is the dose that would have resulted in a given blood drug concentration under “normal” conditions (ie the patient does not have an unusaual ADME)

Question 11

What 5 steps can be taken to prevent DDIs?

Answer 11

1) Document all drugs being taken
2) Minimize # of drugs being taken
3) Extreme caution with low TI drugs
4) Look for adverse DIs in differential
5) Use caution with patients that have comprimised organ function

Question 12

How is the therapeutic window defined

Answer 12

it is the range bounded by the ED9 and ED91

Question 13

What are three serum enzyme levels you can check to determine hepatotoxicity?

Answer 13

Alinine aminothransferase (ALT)
Aspartate aminothransferase (AST)
Alkaline phosphatase (ALP)

All three enzymens are hepatocyte celular enzymes. Their presence in serum indicates damage to liver cells

Question 14

Define a type 4 allergic rxn “delayed hyper sensitivity rxn”

Answer 14

An allergen is phagocytosed and travles to a lymph node to be presented to a t cell. The t cell triggers an immune response. Repeated exposures can trigger a cytokine storm.

Question 15

Define a tye 3 allergic rxn “Arthus rxn”

Answer 15

Antigen bound antibodies (IgM or IgG) get depositied on the surface of the endothelium of the vasculature. This attractrs macrophages which release inflamitory cytokines. This can lead to necrosis which is very bad.

Question 16

List 5 factors that effect oral drug absorbtion

Answer 16

Motility (slower motility leads to increased absorbtion), Gastric PH (think ion trapping), blood albumin levels (lower albumin levels lead to increased free drug avaiable), impaired renal function (reduces elimination of drug from the body), impaired hypatocyte function (reduced metabolism of drug)

Question 17

What is a test that can be run to verify nephrotoxicity?

Answer 17

Urine creatinine levels. Low cratinine levels are indicitive of reduced kidney function.

Question 18

What are some of the patient specific factors that effect the quantitiy of drug in the blood

Answer 18

Absorbtion, Distribution, Metabolisium, Elimination (ADME)

Question 19

Describe a dose dependent pharmacological ADR

Answer 19

This is an ADR where the target physiology is pushed to far

Question 20

What is an “On target ADR” list three

Answer 20

An “On Target ADR” is when the adverse drug response results from stimulating the intended receptor. this includes overdose, correct receptor in the wrong tissue, and inhabition/activation from chromic drug exposure