BPP II

Question 1

Drug transport drugs must cross ______ to reach the _____ in the _______; single membranes include the _____, double includes ______, multiple includes _____

Answer 1

multiple membrane barriers; receptor; target tissue

cell membrane, capillary endothelial cells, various tissues

Question 2

What drugs cannot cross the cell membrane?

Answer 2

Ionized drugs

Question 3

What are the two types of transport processes and their fuel source?

Answer 3

Passive processes (concentration gradient/hydrostatic pressure) and active processes (metabolic energy in form of high energy phosphates like ATP or electrochemical gradients)

Question 4

What is the most common of the passive processes? What are the other two? List properties that would be necessary of the drug to accomplish these processes

Answer 4

Simple diffusion (lipid solubility, size, degree of ionization impact this); facilitated diffusion (uses carrier protein, selective, can inhibit, can saturate) and filtration (hydrostatic pressure using membrane pores or channels b/w cells, limited by drug molecule size)

Question 5

List the two active processes

Answer 5

Active transport (carrier) and micropinocytosis (pinched-off packets of single layer membrane)

Question 6

What can move freely between plasma, interstitial fluid, and intracellular fluid? What cannot and where would they be stopped?

Answer 6

Small molecule and lipid-soluble drugs; lipid-insoluble stuck at cell membrane surface in interstitial fluid, protein bound stuck in plasma

Question 7

What are the pHs of stomach fluid and plasma, respectively? What forms of the drugs can diffuse, the ionized or non-ionized?

Answer 7

1.4 and 7.4; the non-ionized forms can diffuse because of lack of charge

Question 8

Which of the weak electrolyte drugs can be more readily absorbed? What does the ionized/nonionized ratio help predict?

Answer 8

The weak acids because of the H+ in the stomach driving equilibrium towards the plasma and the lack of H+ in the plasma driving intake of HA; the ease of absorption at a particular pH can be predicted

Question 9

What makes up enteral drug administration? What about parenteral?

Answer 9

Enteral: uses portion of GI tract (sublingual, oral, rectal administration); parenteral: doesn’t use portion of GI tract (anything else)

Question 10

What are four things to consider regarding route of administration?

Answer 10

1. Planned use of meds (pts at home or in clinic)?
2. Clinical setting (acute vs chronic): monitor drug effect and titrate dose or daily dose for long term effects?
3. Rapidity of onset of desired action: seizure vs. headache
4. Specific target organ that drug intends to reach

Question 11

Advantages of oral administration? Disadvantages?

Answer 11

Cheap, prolonged absorption for prolonged effects, easy, safe, self-administered;
Absorption too slow, variable and unpredictable, drug too irritating, destroyed by gastric acid/enzymes, could be metabolized on first pass through liver, unavailable for comatose and vomiting patients

Question 12

Advantages of rectal administration? Dis?

Answer 12

Good for infants and comatose, vomiting patient, foul-smelling or distasteful drugs, drugs destroyed in upper GI, avoids first pass effect, and local rectum action;
Nuisance (poor compliance), erratic/incomplete absorption, rectal irritation

Question 13

Sublingual advan, dis?

Answer 13

Bypasses liver when first absorbed, rapid absorption, tablets or sprays;
drug has to be soluble in saliva, not too distasteful, have appropriate pKa for rapid absorption, and tablets must be small

Question 14

IV advan, dis?

Answer 14

Rapid effect, can monitor and titrate dose, all dose enters circulation, for drugs too irritating given as im or sc, drugs given in large volumes of fluid, infusion and continuous monitoring, parenteral admin of hypertonic solutions possible;
Cost, skill in admin, danger of infection, possible anaphylactic reaction, danger of embolus formation due to air, drug precipitation, RBC agglutination, danger of adverse cardiovascular effects if admin too rapid, pain

Question 15

Intraarterial advan, dis?

Answer 15

Admin of radioopaque material for visualization of circulatory tree, high concentration of drug going to local area when desireable;
same as IV

Question 16

IM advan, dis?

Answer 16

Oral route not available, absorption less variable than with oral route, could be less painful with more rapid absorption than sc, possibility of slowing absorption to prolong effect;

pain, sterile technique, possible local necrosis, lag before effect onset, accidental iv injeciton possible, not to be used after anticoagulant administration

Question 17

Sc advan, dis? Intrathecal advan, dis?

Answer 17

Absorption usually slower than after im and effect more prolonged, same as IM otherwise; same with im

When local effect on CNS required and can’t use other route; skill, danger of SCI

Question 18

Topical advan, dis? Inhalation advan, dis?

Answer 18

For local action on or under skin, under membrane, non-invasive; difficulty of skin absorption, danger of excessive absorption through membranes and systemic toxicity

Rapid absorption for systemic action, high concentration attainable for local effect, self admin possible; possible excessive absorption and systemic toxicity, poor regulation of dosage, irritation of pulmonary

Question 19

Of the five routes he lists, which rises the fastest? The highest? Which is prolonged the most?

Answer 19

IV; IV; PO

Question 20

Which route of administration would lead one to think about bioavailability? What could decrease the amount of drug that ends up reaching the circulation?

Answer 20

Oral; variable absorption and first pass effects would affect this value

Question 21

Define bioavailability; what measure could you use to determine it?

Answer 21

(AUCoral/AUCIV) x 100; inject someone with IV drug first to see how long it remains in the plasma, followed by drug given orally

Question 22

How do you predict plasma concentration (equation)? What factor would you need to include if there are limitations in bioavailability? For drugs given orally, what is often the rate-limiting step?

Answer 22

Cp = Dose/Vd; you would need to multiply Dose by “F” since you would want to know the fraction absorbed; dissolution in the GI tract ie stomach

Question 23

What other factors can affect absorption via enteral or parenteral routes?

Answer 23

Enteral: form of drug (solution > suspension > capsule > tablet > timed release), food in the stomach (drug can settle with recently eaten food), illness, blood flow (might not go to the GI tract to promote absorption);
Parenteral: blood flow, heat, cold, illness, form of drug (wafer, rods, injection in oil, transcutaneous patch)