Pharm - S2B1 - General Principles 2

Front 1

List 5 fluid compartments that are sites of exclsuion to drugs

Back 1

Cerebral fluid
Ocular fluid
Lymph fluid
Fetal Fluid
Pleural fluid

CLOPF

Front 2

2 major drug binding plasma proteins

Back 2

1. Albumin

2. Orosomucoid = alpha1 acid glycoprotein

Front 3

What is the "negative acute phase plasma protein"?

Back 3

Albumin

Front 4

Name 2 drugs that decrease in the body if albumin is at a lower concentration

Back 4

Phenytoin

Salicylates

Front 5

What is the "Positive acute phase plasma protein"?

Back 5

Orosomucoid

Front 6

When does Orosomucoid increase its concentration?

Back 6

with Inflammation

Front 7

Name two drugs that increase in concentration in the body when Orosomucoid increases

Back 7

Quinidine

Propranolol

Front 8

What 3 things can alter the concentration of free drug in plasma?

Back 8

1. Dose
2. Disease (albuminemia, uremia)
3. Co-administration of other drugs

Front 9

During which semester is the fetus most vulnerable to the teratogenic effects of drugs?

Back 9

1st semester

Front 10

How do drugs enter mammary milk?

Back 10

passive diffusion

Front 11

List 3 general drugs that accumulate in milk and why they do so

Back 11

1. Weak organic bases = milk is more acidic than plasma = "ion trap"

2. Tetracyclines = chelate with calcium

3. Lipid-soluble drugs = milk has high fat content

Front 12

Explain Thiopental Redistribution

Back 12

-Thiopental is IV administered
-initally distributed to areas of highest blood flow: brain, liver, kidneys
-drug is then redistributed to and stored in muscle and adipose tissue = terminated by redistribution

Front 13

The action of what group of drugs are terminated by redistribution?

Back 13

Lipid soluble CNS active drugs

**The duration of action of an initial dose may depend more on the redistribution rate rather than on the half-life
**With repeated doses, fat and other tissue depots become saturated, resulting in longer durations of action than the first dose

Front 14

List 5 things that contribute to the blood brain barrier

Back 14

1. tight jxns
2. glia wrappings
3. low CSF protein = lower than plasma causes drugs to want to stay in plasma
4. Enzymes
5. Transporters

Front 15

List the 5 factors affecting distribution

Back 15

1. blood flow to the organ
2. the solubility of the drug
3. level of binding to substances in the blood versus binding to substances in tissues
4. transporters
5. ion-trapping

Front 16

What do Phase 1 reactions do to drugs?

Back 16

change the functionality of the drug
-metabolite with modified activity
-inactive metabolite

Front 17

What do Phase 2 reactions do to drugs?

Back 17

Synthesis = add something on to the molecule = make drug more hydrophilic

Front 18

What are sometimes referred to as Phase 3 clearance?

Back 18

Tranporters

Front 19

3 important Phase 1 reactions

Back 19

1. Oxidation = loss of electron
2. Reduction = gain of electron
3. Hydrolysis

**HOR

Front 20

6 important Phase 2 reactions

Back 20

1. Glucuronidation
2. Sulfate conjugation
3. Acetylation
4. Glutathione conjugation
5. Methylation
6. Glycine conjugation

*1 and 2 are most important

Front 21

Where are Phase 1 drug-metabolizing enzymes (mixed function oxidases or monooxygenases) located?

Back 21

in lipophilic membranes of SER

Front 22

Phase 1 biotransformation oxidation usually occurs by what?

Back 22

Cytochrome P450 isozyme

Front 23

What are the 4 Oxidation requirements for Phase 1 biotransformation?

Back 23

1. Cytochrome P450
2. Cytochrome P450 reductase
3. NADPH
4. Molecular Oxygen

Front 24

CYP's that encode enzymes for most drug biotransfomations

Back 24

CYP 1, 2, and 3

Front 25

CYP that is extensively express in GI responsible for poor oral bioavailability (first-pass)

Back 25

CYP-3A4

Front 26

Drugs that induce CYP2C9 (3)

Back 26

Phenobarbital
Phenytoin
Rifampin

**To See 9 Fen-Fen Rif's**

Front 27

Drugs that induce CYP2C19 (4)

Back 27

Barbiturates
Carbamazepine
Phenytoin
Rifampin

To See 19 "Barbs, Carbs, Fins, and Rifs"

Front 28

What CYP do the following drugs induce?

Polycyclic aromatic compounds
3-methylcholanthrene
Benzo-a-pyrene

Back 28

1A2

Front 29

Drugs that induce CYP3A4 (2)

Back 29

1. Glucocorticoids

2. Anticonvulsants
-barbs
-phenytoin
-Carbamazepine
-Primidine

Front 30

Drugs that induce CYP2E1 (3)

Back 30

1. Chronic Alcohol
2. Isoniazid
3. Activates carcinogenic nitrosamines

**2 Erick's = Chronic Alcoholic -> Must "ISO"late them
**Erick should not take Acetaminophen

Front 31

CYP that when induced converts Acetominophen to a toxic metabolite

Back 31

CYP-2E1

*induced by Isoniazid and Chronic Alcohol

Front 32

What CYP metabolizes Terfenadine and Astemizole?

Back 32

CYP-3A4

Front 33

List 2 drugs that markedly increase the toxicity of Terfenadine, why, and the physiologic effect

Back 33

-Erythromycin and Ketoconazole

-They inhibit CYP3A4 which causes Terfenadine to accumulate

-QT prolongation -> -> -> Torsade de points

*Terfenadine must be metabolized to be activated (active product is Fexofenadine)

Front 34

List 8 inducers of phase 1 biotransformation (cause other drugs to be metabolized more quickly)

Back 34

1. Phenobarbital
2. Phenytoin
3. Carbamazepine
4. Polycyclic aromatics
5. Glucocorticoids
6. Chronic Alcohol
7. Rifampin
8. St. John's Wort

*1-3 are Anticonvulsants

**St. John, the Chronic Alcoholic, Smokes, eats Carbs, takes Phen-Phen, and gets shots of Cortisol, all while playing Rifs on the guitar

Front 35

List 6 inhibitors of phase 1 biotransformation (decrease the metabolism of drugs)

Back 35

1. Cimetidine
2. Ketoconazole
3. Chloramphenicol
4. Erythromycin
5. Acute Alcohol
6. Grapefruit juice

CAGE-CK

Front 36

2 possible ways a Phase 2 drug conjugate can be formed

Back 36

1. via high energy intermediate and the parent compound

2. Phase 1 metabolite by a transfer enzyme

Front 37

Phase 2 major route of metabolism for both drugs and endogenous compounds

Back 37

Glucuronide conjugation

Front 38

Glucuronide transferase activity is localized to this organelle and organ

Back 38

ER

Liver

Front 39

By what process are glucuronides secreted in the kidney and liver

Back 39

ACTIVE transport = against their concentration gradient with use of ATP

Front 40

2 Phase-2 reactions that especially make compounds more water-soluble and excretable

Back 40

1. Sulfation
2. Glucuronidation

Front 41

2 Phase 2 rxns that often make drugs less water-soluble

Back 41

1. Methylation

2. Acetylation

Front 42

Crystalluria results when __1__(rxn) products of __2__(compound) precipitate in __3__(pH) tubular urine

Back 42

1. acetylated
2. sulfonamides
3. acidic

Front 43

Which Phase reactions are more likely to be preserved in the elderly, Phase 1 or 2?

Back 43

Phase 2 reactions

Front 44

6 liver diseases that can cause decreased drug metabolism

Back 44

1. Fatty liver
2. Hepatitis
3. Cirrhosis
4. Hemochromatosis
5. Liver tumors
6. Drug-induced liver damage

Front 45

2 CYP polymorphisms that can affect biotransformation in different races

Back 45

CYP-2D6

CYP-2C19

Front 46

Do not give this drug if a person has 2 non-functional alleles of Thiopurine S-methytransferase

Back 46

6-mercaptopurine b/c will cause toxicity

Front 47

20% of asians and blacks have a polymorphism of this CYP that has POOR METABOLISM (PM)

Back 47

CYP 2C19

Front 48

If prescribing for Warfarin, you should genetically test for these genes (2)

What would be the ADR?

Back 48

1. CYP 2C9
2. Vitamin K Epoxide Reductase

ADR = bleeding

Front 49

If giving Isoniazid (anti-TB) what gene should be tested for?

What would be the ADR?

Back 49

N-acetyltransferase (Phase II Conjugation)

Hepatoxicity

Front 50

If prescribing 6-Mercaptopurine what gene should be tested for?

ADR?

Therapeutical use of Mercaptopurine?

Back 50

Thiopurine S-methytransferase

Hematological toxicity

Acute Lymphoblastic Leukemia

Front 51

If prescribing Irinotecan, what metabolic gene should be tested for?

ADR?

Irinotecan therapeutical use?

Back 51

1. UDP-Glucuronosyltransferase (UGT1A1)

2. Diarrhea or neutropenia

3. colon cancer

Front 52

If giving Codeine, what gene should be tested for?

ADR?

Codeine therapeutical use?

Back 52

CYP2D6

lack of analgesic effect

Analgesic

Front 53

The reactive metabolite of Acetaminophen may induce this adverse response

Back 53

Hepatotoxicity

Front 54

Reactive metabolites of Aflatoxin may induce this adverse response

Back 54

Tumors

Front 55

Reactive metabolites of Cyclophosphamide may induce this adverse response

Back 55

Cystitis

Front 56

What are 2 Weak Organic Base drugs that can accumulate in Milk and cause harm to babies who are breast-feeding?

Back 56

Amphetamines

Cocaine

Front 57

CYP that when induced activates Carcinogenic Nitrosamines

What induces it? (2)

Back 57

CYP 2E1

Isoniazid & Chronic Alcohol