Basic Principles II

Question 1

drug transport

Answer 1

• drugs must cross multiple membrane barriers to reach the receptor in the target tissue
• ability of drug to reach receptor will influence the effectiveness of the drug

Question 2

single membranes

Answer 2

-cell membrane

Question 3

double membranes

Answer 3

• cap endo cells- cross through entire cell or around them

- multiple membranes also in other tissues

Question 4

passive process

Answer 4

• follow a concentration gradient or hydrostatic pressure, don’t require metabolic energy
• simple, facilitated, filtration

Question 5

simple diffusion

Answer 5

• most common
• affected by lipid solubility, size, degree of ionization
• oil/water partition coefficient
• smaller is better
• nonionized is best

Question 6

facilitated diffusion

Answer 6

• uses a carrier protein
• masks drug characteristics that impede simple diffusion
• selective
• can be inhibited or saturated

Question 7

filtration

Answer 7

• driven by hydrostatic pressure and drug dissolved in the moving fluid is transported through pores in a membrane or channels between cells
• drug molecule size will be limiting

Question 8

active processes

Answer 8

• use metabolic energy in the form of high energy phosphates such as ATP or electrochemical gradients
• transport against a concentration gradient
• rapid, selective, can be inhibited, can be saturated

Question 9

active transport

Answer 9

• uses carrier

- accumulates against a concentration gradient

Question 10

micropinocytosis

Answer 10

-drug is transported in pinched off packets of a single layer membrane

Question 11

weak electrolyte drugs

Answer 11

• many drugs
• nonionized drugs diffuse
• lipid soluble
• concentration gradient
• weak acids diffuse in the HA form
• weak bases diffuse in the B+H form

Question 12

pka

Answer 12

• physical characteristic
• determines ratio of ionized to nonionized forms at a particular pH.
• ease of absorption at a particular pH can be estimated

Question 13

absorption of drugs in the stomach

Answer 13

• weak acids are easily absorbed because the stomach pH is low (excess H), so drives to HA, which can diffuse. once inside cell, disassociates again due to higher pH
• weak bases not absorbed because opposite occurs. low pH drives equation to BH, which doesn’t diffuse easily.

Question 14

drug administration

Answer 14

• enteral vs parenteral

- using GI tract vs not using GI tract

Question 15

route of admin considerations

Answer 15

• planned use for the medication- home vs clinical setting
• clinical setting-acute vs chronic- may want to closely monitor the drug effect and titrate the dose vs daily dosing for long term effects
• rapidity of onset of desired action-headache vs seizure
• specific target organ that the drug is intended to reach (BBB)

Question 16

enteral routes

Answer 16

• oral
• rectal
• sublingual

Question 17

oral admin advan

Answer 17

• easy
• safe
• self admin
• cheap
• prolonged absorption and effect

Question 18

oral admin disad

Answer 18

• absorption may be too slow
• absorption often variable and unpredictable
• drug may be too irritating
• drug may be destroyed by gastric acid or enzymes
• drug may be completely metabolized on first pass through liver
• not available for comatose, vomiting patients

Question 19

first pass effect

Answer 19

1. drug admin by mouth
2. enters GI tract
3. active drug is absorbed from stomach and small intestine
4. high blood concentration of free drug is in hepatic portal vein before metabolism
5. low blood concentration of free drug is in systemic arterial or venous circulation after metabolism

Question 20

rectal admin advan

Answer 20

• useful for infants, comatose, vomiting patient
• useful for foul smelling, distasteful drugs
• useful for drugs destroyed in upper GI tract
• for local action in rectum

Question 21

rectal admin disad

Answer 21

• nuisance- poor compliance
• absorption may be erratic or incomplete
• possibility of rectal irritation

Question 22

sublingual advan

Answer 22

• bypasses liver when first absorbed

- rapid absorption

Question 23

sublingual disad

Answer 23

• drugs must be soluble in saliva, not too distasteful, have appropriate pka for rapid absorption
• tablets must be small

Question 24

parenteral routes

Answer 24

• IV
• Intraarterial
• IM
• SC
• Intrathecal
• topical
• inhalation

Question 25

IV advan

Answer 25

• rapid
• can watch and titrate
• all of dose enters circulation
• when oral not available
• for drugs too irritating when given IM or SC
• for drugs given in large volumes of fluid
• for infusion and continuous monitoring
• parenteral admin of hypertonic solutions possible

Question 26

IV disad

Answer 26

• cost
• skill in admin
• danger of infection
• possible anaphylactic reaction
• danger of embolus due to air, drug precipitation, RBC agglutination
• danger of adverse cardiac effects if administered too rapidly
• pain

Question 27

intraarterial

Answer 27

Ad:
-admin of radioopaque material for visualization of circulatory tree
-high concentration of drugs going to local area when desirable
Disad:
-same as IV

Question 28

IM advan

Answer 28

• when oral not available
• absorption less variable than oral
• may be less painful than SC
• absorption more rapid than SC
• possibility of slowing absorption to prolong effect- contraceptives/ anti psychotics

Question 29

IM disad

Answer 29

• pain
• sterile technique
• possible local necrosis
• lag period before effect onset
• accidental IV injection possible
• not to be used after anticoag admin

Question 30

subQ

Answer 30

Ad:
-absorption slower than IM- effect more prolonged
Disad same as IM

Question 31

Intrathecal

Answer 31

• into spinal fluid, gets by BBB
• used when local effect on CNS required and another route isn’t good enough
• skill needed, danger of spinal cord injury

Question 32

topical ad

Answer 32

• for local action on or under skin
• for local action on or under membrane
• non-invasive

Question 33

topical disad

Answer 33

• difficulty of absorption through skin

- danger of excessive absorption through membranes and systemic tox

Question 34

inhalation

Answer 34

AD:
-rapid absorption for systemic action
-high concentration attainable for local effect
-self admin possible
Disad:
-possible excessive absorption and systemic tox
-poor regulation of dosage
-irritation of pulmonary

Question 35

pharmacokinetics of plasma levels depending on route

Answer 35

-IV, inhalation, IM, SC, PO

Question 36

bioavailability

Answer 36

• fraction of a dose available for biologic action
• usually pertains to oral drug administration where variable absorption or first pass effects will decrease the amount of drug which reaches the circulation
• measured by comparing the AUC for the oral dose vs the IV form
• AUC oral/AUC iv times 100

Question 37

to predict plasma concentration

Answer 37

• bioavailabilty of drug impacts size of dose given to achieve plasma level
• Cp=Dose/Vd
• if significant limitations in bioavailability, Cp= (Fxdose)/ vd, F is fraction absorbed
• chemical equivalence does not equal biological equivalence
• dissolution is often limiting step for oral drugs

Question 38

bioavailability is important for

Answer 38

• drugs that are potent in small doses
• drugs given for serious illnesses
• changes in drug manufacturer

Question 39

other factors affecting absorption

Answer 39

• enteral-form of drug, food in stomach, illness, blood flow (gastric blood flow shuts off during stress)
• solution>suspension>capsule>tablet>time release
• parenteral-blood flow, heat, cold, illness
• form of drug- wafer, rods, injection in oil, transcutaneous patch