Medchem Test 3

Front 1

Oral Administration
1. Dosage forms
2. Requirements
3. Advantages
4. Disadvantages

Back 1

1. Tablets, capsules, suspensions, syrups,emulsions
2. a) should be stable in GIT (chemical and metabolic stability)
b) should be absorbable (passive/active transport)

3. simple, inexpensive, convenient, less invasive

4. a) degradation of drug in GIT
b) first pass metabolism
c) slow onset of action

Front 2

Four factors that affect drug absorption

Back 2

1. pharmaceutical (tablet dissolution, excipients)
2. physiochemical (solubility, hydrophilicity/lipophilicity)
3. physiological (GI pH ionization, metabolism enzymes and first pass effect, mucosal thickness-membrane thickness, residence time

Front 3

Amount of drug aborbed = ((conc. extracellular - conc. intracellular)*(area*permeability)) / thickness

Back 3

if c1 (concentration intracellular increases then absorption goes down: high to low)
if c2 extracellular conc.
increases then absorption goes up
if thickness goes up, then absorption goes down

Front 4

5 factors that affect passive absorption/diffusion

Back 4

1. no energy required (most drugs go transcellular(through) rather than paracellular(inbetween)
2. follows concentration gradient (high to low)
3. dependent on ionization states (physiological)
4. dependent on lipophilicity (physiochemical)
5. dependent on duration and area of contact (physiological)

Front 5

4 Examples of drugs that absorb passively

Back 5

acetaminophen(tylenol), ibuprophen, metoprolol, valium

Front 6

6 factors that affect active transport

Back 6

1. requires energy (mostly charged polar molecules are transported actively)
2. movement against concentration gradient
3. saturable kinetics
4. selectivity (in some cases)
5. competitive inhibition
6. drugs may act as substrates, inhibitors, or both

Front 7

3 types of uptake transporters in the GIT

Back 7

1. peptide transporters (PepT1)
2. organic anion transporters (OATs)
3. organic cation transporters (OCTs)

Front 8

3 types of efflux transporters

Back 8

1. (PGP) p-glycoprotein
2. (MDR) multi-drug resistance proteins
3. (BCRP) breast cancer resistance proteins

Front 9

Describe PepT1 uptake transporter

Back 9

1. small intestines= absorption site
2. transports peptide like drugs
3. transports prodrugs of drugs with peptide like characteristics

Front 10

Give a reason for using a prodrug strategy for active transport of drugs

Back 10

Ex: acyclovir has low bioavailability (12-20%), you need to take it 4-5x/day, it is very polar and thus limited absorption, it is not a pept1 substrate
**Valacyclovir has an amino acid valine on it CONH2, it is a pepT1 substrate, increased bioavailability (50%), only dosed 1x/day.

Front 11

What are the two inhibitors of PepT1 transporter

Back 11

1. oral sulfonylureas (starlix, diabeta)
2. coadministration with a high-protein meal (causes saturation of pept1 transporters and low drug substrate absorption

Front 12

1. What are OAT transporters?
2. What are examples of drugs transported?

Back 12

1. transports drugs with negatively charged molecules with high MW (prostaglandins, urates, bicarbonylates)
2. (MCT) monocarboxylic acid transporter- transports COOH
2. Example: Fexofenadine, statins,

Front 13

1. What are OCT transporters?
2. What are examples of drugs transported?

Back 13

1. Organic cation transporters- transport positively charged molecules. Present in SI, kidney, and liver (absorption, metabolism, elimination). Transports natural substrates such as choline and dopamine
2. Examples: metformin, procainamide, choline, dopamine

Front 14

1. What are efflux transporters?
2. What are examples?

Back 14

1. pump molecules back into the lumen to get rid of harmful materials...prevents it from going into the blood stream so it will be excreted, thus decreasing absorption of drug.
2. Example: PGP transporters such as 1)immodium 2) digoxin 3) fexofenadine 4) Taxane.

Front 15

What are PGP substrates, inhibitors, inducers and examples of each

Back 15

1. substrate = imodium, digoxin, fexofenadine
2. PGP inhibitor (decreases the amount of efflux transporters, thus increasing absorption) = Verapamil, quinidine
3. PDP inducer (increases the amount of efflux transporters on the cell, thus decreasing absorption and increasing dose)= Rifampin, St. John's wart
(should not give an inducer and inhibitor together if MTC and MEC is small difference

Front 16

1. What is MDR (multi-drug resistant protein)
2. What are examples of drugs transported

Back 16

1. efflux transporter for anticancer drugs
2. SUBSTRATE= doxorubicin, daunorubicin, taxol, methotrexate
INHIBITOR= verapamil (increases absorption)

Front 17

1. What is BCRP (breast cancer resistance protein)
2. What are examples of drugs transported?

Back 17

efflux transporter of anticancer drugs. Under low oxygen conditions= high BCRP= increase in efflux activity in cancer cells)
2. Examples = topotecan, mitoxantrone, doxorubicin, daunorubicin
INHIBITOR= fumitremorgin C

Front 18

What are the 5 ways in which the oral absorption of one drug can be affected by the concurrent use of another drug (Drug-Drug interaction)

Back 18

1. Have a large surface area upon which the drug can be aDsorbed (ex: small molecule stuck to surface of a large molecule)

2. Bind or chelate the drugs administered and form a complex

3. Alter the gastric pH (ionization state affected, which affets solubility and permeability of other drug)

4. Alter gastrointestinal motility(increasing residence time= increases absorption)

5. Affect transport proteins in the GI tract (efflux, uptake)

Front 19

What are examples of aDsorption drug-drug interactions?

Back 19

the aDsorption of one large molecule with a small molecule= decreases the amount of free (small) drug for absorption.
1. Activated charcoal
2. Bile acid sequestering resins (BAS): cholestyramine
3. Kaolin

Front 20

What are examples of drug-drug interactions due to binding or chelating the drug

Back 20

There is decreased absorption of the drug because instead of the drug dissolving and reacting with water due to hydrogen bonding, it will react with the metal chelate and solubility will decrease.
Ex: NEVER mix Tetracycline antibiotics (doxycycline, vibramycin) and Quinolone antibiotics (cipro) and Thyroid hormones (levothyroxine) WITH dairy or drugs that contain metals (iron, Ca, Mg, Al, Zn)
TETRACYCLINE + Ca = decreased absorption.

Front 21

What are examples of drug-drug interactions that alter gastric pH?

Back 21

If you increase pH (increase base),= decrease ionization of basic drugs (antifungals) = decreased solubility = decreased absorption

DRUGS THAT INCREASE pH (antacids, omeprazole, ranitidine) DO NOT MIX WITH azole antifungals (itraconazole).
LIMITING FACTOR= SOLUBILITY

Front 22

What are examples of drug-drug interactions that alter gastrointestinal motility?

Back 22

Decreasing motility (slowing down peristalsis) = Increasing absorption. Usually a good thing unless drug is toxic.
Ex: Imodium, Lomotil = decrease motility and adding an opiod to that would increase absorption of the codeine.
Ex: Laxatives (dulcolax) = decrease motility = decrease absorption

Front 23

What are examples of drug-drug interactions that affect transport proteins (PGP)

Back 23

Do not mix PGP substrates with PGP inhibitors. Remember that one increases the efflux transporters and one decreases them because there may be some toxicity involved depending on the MTC/MEC.
Ex: Loperamide(imodium) with verapamil (calan)
Do not mix PGP substrates with PGP inducers. This leads to decreased absorption of substrate drug.
Ex: St. John's wart, Rifampin, Phenobarbital WITH Digoxin(lanoxin). The St. John's wart decreases the absorption of Lanoxin.

Front 24

2 Factors affecting Rate of Distribution

Back 24

1. membrane permeability
2. blood perfusion (the most supply of blood is in lung and kidney) (the least supply of blood is in adipose tissue, skin)

Front 25

4 Factors affecting Extent of Distribution

Back 25

1. Lipid solubility (physiochemical property)
2. pH-pKa (ionization states)
3. Plasma protein binding (determined by body)
4. Intracellular binding (determined by body)

Front 26

What is Volume of Distribution Vd?

Back 26

Vd is the fluid volume that would be required to accommodate the total amount of absorbed drug in the body at the plasma steady state concentration.
Vd = Dose/Concentration (of drug in blood)

Drugs with a low Vd = bound to plasma protein = stay present in blood
Drugs with high Vd = well distributed throughout the body or sequestered in tissue reservoirs.

Front 27

What types of drugs are distributed into the 5 compartments:
1. Total body water
2. Extracellular water
3. Blood
4. Fat
5. Bone

Back 27

1. small water soluble drugs (ethanol)
2. larger water soluble drugs (getamycin)
3. very large molecules strongly bound to plasma proteins (heparin)
4. very lipophilic drugs (diazepam)
5. certain ions (lead, fluoride)

Front 28

5 factors that affect Vd

Back 28

1. Lipophilicity (increased Vd= increased lipophilicity= taken up by fat, liver, tissues, lungs= very little found in plasma= long half life)

2. ionization (increased ionization = decreased Vd)

3. stereochemistry (variable)

4. physiological (increased metabolism = decreased Vd)

5. age and gender (as age increases = decrease proportion of muscle to fat = decreased distribution

Front 29

What is the Vd of aspirin and why?

Back 29

low Vd = 11 because weakly acidic drugs are highly bound to plasma proteins so Vd goes down.

Front 30

1.What is sequestration?
2.What are common sequestration sites?

Back 30

1.Accumulation of a drug in certain organs or types of tissues
2. EXAMPLES
a)Plasma Proteins (for acid/base compounds)
b) Adipose tissue (for lipophilic compounds)
c) Bone (for chelating agents & heavy metals)

Front 31

Plasma protein binding: Serum albumin

Back 31

Basic protein that binds to weakly acidic drugs
Ex: NSAIDS, are highly bound to serum albumin

Front 32

Plasma protein binding: alpha1-glycoprotein

Back 32

Acidic protein that binds to weakly basic drugs
Ex: SSRI (fluoxetine) bound to alpha1-glycoprotein

Front 33

What 5 characteristics of drug binding to plasma protein

Back 33

1. usually reversible
2. is non-selective
3. can be affected by disease states
4. limits the ability of the drug to distribute beyond the blood/plasma compartment
5. limits the metabolism of the drug (to metabolize in liver, has to be unbound drug)

Front 34

Name the 2 drugs that are
1. Not bound or weakly bound
2. Moderately bound
3. Strongly bound
to plama proteins

Back 34

1. acetaminohen (tylenol) and atenolol (Vd= inceases)
2. terbutaline and retrovir
3. furosemide, warfarin (Vd = decreases)

Front 35

Why must you never combine a weakly bound plasma protein drug with a strongly bound plasma protein drug?

Back 35

Ex: warfarin (99% bound) + tylenol (0% bound) = makes warfarin become more unbound and go to tissues and stay there longer.

Front 36

Plasma protein binding: Serum albumin

Back 36

Basic protein that binds to weakly acidic drugs
Ex: NSAIDS, are highly bound to serum albumin

Front 37

Plasma protein binding: alpha1-glycoprotein

Back 37

Acidic protein that binds to weakly basic drugs
Ex: SSRI (fluoxetine) bound to alpha1-glycoprotein

Front 38

What 5 characteristics of drug binding to plasma protein

Back 38

1. usually reversible
2. is non-selective
3. can be affected by disease states
4. limits the ability of the drug to distribute beyond the blood/plasma compartment
5. limits the metabolism of the drug (to metabolize in liver, has to be unbound drug)

Front 39

Name the 2 drugs that are
1. Not bound or weakly bound
2. Moderately bound
3. Strongly bound
to plama proteins

Back 39

1. acetaminohen (tylenol) and atenolol (Vd= inceases)
2. terbutaline and retrovir
3. furosemide, warfarin (Vd = decreases)

Front 40

Why must you never combine a weakly bound plasma protein drug with a strongly bound plasma protein drug?

Back 40

Ex: warfarin (99% bound) + tylenol (0% bound) = makes warfarin become more unbound and go to tissues and stay there longer.

Front 41

Sequesteration: Adipose Tissue Binding

Back 41

1. DDT & similar environmental contaminants
2. Patients on lipophilic drugs who are nursing/breastfeeding
3. Obese patients

Front 42

Sequestration: Bone and Teeth

Back 42

1. Divalent-cation chelating agents (tetracyclines)
***Do use Doxycycline as the best choice for children to reduce bone ***

2. Heavy metals (lead, radium)
adsorption onto bone surface

Front 43

Distribution: CNS/BBB

Back 43

Small, lipophilic drugs have good CNS permeation
Ex: opiods, benzos, barbs
***CNS drugs may be removed by efflux pump transporters such as PGPs****

Front 44

Distribution: BBB

Back 44

1. BBB can be beneficial in avoiding unwanted side effects
Ex: Loperimide has a lack of penetration of the CNS and also due to its removal by PGP export pump
2. BBB is a negative factor when it blocks a drug from getting to site of action
Ex: treatment of fungal, viral, bacterial infections of the brain

Front 45

Distribution: Drug-Drug interaction
2 examples

Back 45

1.Displacement of drug from plasma proteins
Ex: Phenytoin (dilantin)= 90% plasma bound, it is a narrow therapeutic index agent
Aspirin, valproic acid, and tricyclic antidepressants can displace phenytoin from its plasma proteins and increase the free blood levels of this agent causing toxicity

2. Sulfonamides antibiotics are known to displace plasma protein bound to bilirubin.
Do not use sulfas while preganant to risk increased bilirubin and jaundice of baby