Svensson Lec 8

Question 1

what are the three ways to identify the nature of adverse reactions?

Answer 1

1. side effects
2. augmented response
3. toxic reactions

Question 2

describe side effects

Answer 2

• off target response
• marginal impact on health
• impact patient compliance
• Ex: dry mouth with antidepressants

Question 3

describe augmented responses.

Answer 3

• extension of pharmacologic effect
• usually dose-dependent
• May impair health seriously
• Ex: bradycardia with propranolol

Question 4

describe toxic reactions

Answer 4

• Not predicted pharmacology of drug
• sometimes not dose-dependent
• seriously impact health
• Ex: carbamazepine-induced liver injury

Question 5

Given a cell type that experiences genomic damage, identify clinical outcome.

Answer 5

somatic cells, germ cells, and developing embryos

Question 6

what do somatic cells do?

Answer 6

Cancers
Depends on route of exposure

Question 7

what do germ cells do?

Answer 7

Birth defects
Childhood cancers

Question 8

what do developing embryos do?

Answer 8

Miscarriages
Stillbirths
Birth defects
Occasional childhood cancers

Question 9

Provided specific gestational stages of women, identify whether a teratogen is likely to result in 1) embryo death, 2) major congenital anomalies, 3) functional defects and minor anomalies.

Answer 9

Embryo death
–> 1-2 weeks
Major congenital anomalies
–> 3-8 weeks
Function defects and minor anomalies
–> 9-38 weeks

Question 10

State the criteria for classification of an agent as a teratogen.

Answer 10

1. Exposure results in characteristic set of malformations
2. Effect occurs with exposure at a specific stage of development
3. Effect is dose-dependent

Question 11

what are the mechanisms by drug producing toxic responses?

Answer 11

cellular dysfunction, cellular destruction, and genotoxicity

Question 12

what is cellular dysfunction

Answer 12

1. Disruption of normal cellular function that does not result in embryo death
2. Inc. in oxidative stress → inc in methemoglobin
3. Dec. in G6PD → inc. methemoglobin

Question 13

what is cellular destruction

Answer 13

1. Dysregulation of cellular process provoked by a toxicant resulting in the death of the cell
2. Primary Targets:
   –> ATP depletion
   –> ROS/RNS generation
   –> Ca2+ accumulation

Question 14

what is genotoxicity

Answer 14

• Damage to genetic material caused by an external agent
  –> Could have replication, transcription, cell division, synthesis, etc.

Question 15

what are some determinants of toxic responses

Answer 15

1. Individual susceptibility
   –> Diet, genetics, environment, underlying disease
2. Accessibility of drug to target
   –> ADME
   –> Blood stream
3. Compensatory mechanisms
   –> Acidosis or alkalosis
4. reactivity of drug with target

Question 16

what are the roles of reactive metabolites in drug response and their pathways and actions

Answer 16

• There are 3 pathways
  –> Sulfate
  –> Liver injury
  –> Glucuronide
• Is we deplete or induce one of the pathways it will either cause liver injury or it will not or if we inhibit CYP2E1 then it will reduce injury
  –> Depends