Drug Toxicity

Front 1

3 Biotransformation Rxns that can produce Toxic Metabolites

Back 1

1. Epoxide Hydrolases
2. Monooxgenases (CYP)
3. Enzymes involved with Conjugation Rxns

Front 2

4 Results of Cellular Toxicity

Back 2

Damage Repair

Apoptosis

Necrosis

Fibrosis

Front 3

Which causes inflammation Apoptosis or Necrosis

Back 3

Necrosis

Front 4

3 Results of Apoptosis

Back 4

1. Cyt C from Mitochondria (Reticular -> cytosol)
   
2. Phosphatidyl Serine exposure on surface (instead of inside) which is marker for Macrophages
3. Cell becomes permeable to small molecules

Front 5

T/F Fibrosis leads to non-functional cells

Back 5

T

Front 6

If drug toxicity does not trigger regulator processes, what are 2 other fates

Back 6

1. Receptor-specific effects (On/Off Target effects)
   
2. Detox/Excretion

Front 7

4 Mechanisms of Drug Toxicity

Back 7

1. On-Target effects
2. Off-Target effects
3. Production of Toxic Metabolites
4. Idiosyncratic/Unexpected responses/sensitivity

Front 8

Define "On-Target" effect

Back 8

When drug metabolite acts on intended receptor.

May happen on Intended OR Unintended Tissue

Front 9

Define "Off-Target" effect

Back 9

When drug metabolite acts on unintended receptor.

May happen on Intended OR Unintended Tissue

Front 10

Which anti-histamine was taken off the market and why?

Back 10

Terfenadine due to Cardiotoxicity

(CV effects were "unintended tissues)

Benadryl stayed

Front 11

Explain Anaphylaxis Steps

Back 11

Hapten binds protein stimulates Mast Cell

Front 12

Explain Mismatched Rh Factor Steps

Back 12

1. Incorrect Ag binds RBC
2. Ab binds Ag on RBC
3. RBC is lysed via Complement, CTCell killing, or reticuloendothelial system

Front 13

Explain Lupus Steps

Back 13

1. Ag and Ab bind
2. Ag/Ab complex deposits on tissue
3. Macrophages destroy tissue

Front 14

Explain Poison Ivy Steps

Back 14

1. Hapten (oil) binds Protein
2. Complex phagocytosized by APC
3. APC presents to CTC

Front 15

4 Organ specific manifestations of Toxicity

Back 15

1. Pulmonary Tox
2. Hepatotox
3. Nephrotox
4. Neurotox

Front 16

Other manifestations of Toxicity (3)

Back 16

Immunotox

Tox on genetic material

Reproductive tox

Front 17

What happens in organ tox

Back 17

Cell Death

Disruption of Normal Metabolic Processes

Front 18

Example of Distrupted Metabolic Processes

Back 18

• Inability to maintain intracellular electrolytes
  

Body spends lots of energy putting Na out of cell

If long enough, the cell will not recover

Front 19

6 Results of Pulmonary Tox

Back 19

1. Bronchitis
2. Emphysema
3. Asthma
4. Hypersensitivity Pneumonitis
5. Pneumoconiosis
6. Cancer

Front 20

What is bronchitis

Back 20

Inflammation of Bronchi

Caused by cig smoke and air pollution

Front 21

What is emphysema

Back 21

Air sacs damaged leading to decreased surface area for gas exchange

Front 22

T/F Emphysema occurs rapidly

Back 22

F; years of damage

Front 23

Emphysema Treatment

Back 23

Enriched Oxygen

Front 24

T/F Bronchodilators will work in emphysema

Back 24

F; there is decreased gas exchange no matter how much you dilate the bronchioles

Front 25

5 Major Pulmonary Toxicants: Drugs

Back 25

Amiodarone

Bleomycin

Busulfan

Cyclophosphamide (chemo)

Methotrexate (chemo)

Hint 25

ABBCM

Front 26

6 Major Pulmonary Toxicants: Chemicals

(Damage Lungs)

Back 26

Asbestos

Chlorine Gas

Nitrogen Dioxide

Ozone

Silica (like Asbestos)

Sulfur Dioxide

Hint 26

ACNOSS

Front 27

*What is the cause of nephrotoxicity

Back 27

Compromised RBF

Front 28

Cells of the tubular nephron face 1 exposure to agents in the blood on the 2 side and the filtered urine on the 3 side.

Back 28

1. Double-sided
2. Basolateral
3. Luminal

Front 29

What side of cells are generally the site of nephrotoxicity and why

Back 29

Proximal Tubule Cells

Abundance of CYP 450

Reabsorbs and Concentrates anions/cations from blood

Front 30

4 Drugs that can cause Renal Tox

Back 30

Cephalexin

Cyclosporine A

NSAIDS

ACE I

Front 31

How do ACE I cause Renal Tox

Back 31

When there is decreased RBF, ACE increases Angiotensin to restore RBF

ACE I prevents Angiotensin from restoring RBF

Front 32

3 steps which cause Renal Tox with NSAIDS

Back 32

1. COX --> PG
2. PG --> Renal Protective

NSAIDS inhibit COX

Front 33

2 Chemical which cause Renal Tox

Back 33

Chloroform

Hexachlorobutadiene

Front 34

Where was Melamine used

Back 34

Pet food and Baby formula

Caused Recall

Front 35

Adverse effects of melamine

Back 35

Promotes cystalization in kidney decreasing GFR leading to Kidney Failure

Kidney Stones

Front 36

T/F ACE I is contraindicated in patients with Renal issues

Back 36

T

Front 37

How does a coma occur?

Back 37

No glucose to brain

Front 38

How is the CNS protected from toxicants? What property of these cells is protective

Back 38

Blood Brain Barrier - Tight junctions cause selectivity

Front 39

3 Ways in which CNS is susceptible to toxicants

Back 39

1. Increased Metabolic Rate
2. Increased Lipid Content (lipid soluble drugs)
3. Increased Rate of Blood Flow

Front 40

T/F Neural tissue replicates easily

Back 40

F

Front 41

CNS Toxicants: Drugs (3)

Back 41

1. Cocaine
   
2. Ethambutol
   
3. Quinine
   

Front 42

4 CNS Toxicants: Chemicals

Back 42

1. Lead
   
2. Mercury
   
3. Methanol
   
4. Organochlorine Insecticides
   

Hint 42

LMMO

Front 43

Effects (3) of lead poisoning

Back 43

1. Slow growth in children
   
2. Lower IQ
   
3. Partition into bone
   

Front 44

3 Peripheral Neurotoxicants: Drugs

Back 44

1. Doxorubicin
2. Isoniazid
3. Nitrofurantion

(Anti-cancer and Antibiotics)

Hint 44

DIN

Front 45

4 Peripheral Neurotoxicants: Chemicals

Back 45

Acrylamide

Carbondisulfide

Lead

N-Hexane

Hint 45

ACLN

Front 46

What is the most common single adverse effect causing major drug problems, including withdrawals and refusals to approve

Back 46

Hepatotoxicity

Front 47

5 Hepatotoxicity: Drugs

Back 47

APAP
Ethanol

Estrogen

Isonaizid

Nitrofurantion

Hint 47

AEEIN

Front 48

Hepatotoxicants: Chem

Back 48

Allyl Formate

Be

CaCl4

Vinyldiene Chloride

Hint 48

ABCV

Front 49

Why is the liver susceptible to toxicity

Back 49

1st pass metabolism activates drugs

Front 50

How is the liver proteted

Back 50

1st pass metabolism

Front 51

T/F APAP Can Not be used as anti-infalmmation

Back 51

T

Front 52

What is the max dose of APAP in 24 hours

Back 52

3250 mg in 24 hours

Front 53

What is needed to deactivate APAP

Back 53

Glutathione

Front 54

What enzyme is involved with APAP metabolism

Back 54

CYP2E1

Front 55

What is the toxic intermediate in APAP metabolism

Back 55

N-acetyl-p benzoquinine imine (NAPQI)

Front 56

What are the majority of Phase 2 rxns

Back 56

Conjugation; helps make things polar for excretion

Front 57

Drugs that cause immunotoxicity

Back 57

Azathioprine

Corticosteroids

Cyclophosphamide

Cyclosporine A

Methotrexate

Hint 57

ACCCM

Front 58

Chemicals that cause immunotoxicity

Back 58

Arsenic

Benzene

Lead

Ozone

Hint 58

ABLO

Front 59

Toxic effects on Genetic Material and Cell Replication

Back 59

Mutagenesis

Teratogenesis

Carcinogenesis

Front 60

What is Mutagenesis

Back 60

Change in genetic material

Front 61

What is teratogenesis

Back 61

PRoduction of developmental malformations

Front 62

T/F BRCA1/2 is involved with DNA repair

Back 62

T

Front 63

What are the 3 periouds of development during Gestation

Back 63

Preimplantation - Generally toxic

Organogenesis - susceptibility

Fetal Period - last 6 months of gestation

Front 64

T/F Pregnancy Category A is safe to use as it failed to have affects during 1st trimester

Back 64

T

Front 65

Thalidomide is in what pregnancy category

Back 65

X