1
Q
drug transport
A
- 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
2
Q
single membranes
A
-cell membrane
3
Q
double membranes
A
- cap endo cells- cross through entire cell or around them
- multiple membranes also in other tissues
4
Q
passive process
A
- follow a concentration gradient or hydrostatic pressure, don’t require metabolic energy
- simple, facilitated, filtration
5
Q
simple diffusion
A
- most common
- affected by lipid solubility, size, degree of ionization
- oil/water partition coefficient
- smaller is better
- nonionized is best
6
Q
facilitated diffusion
A
- uses a carrier protein
- masks drug characteristics that impede simple diffusion
- selective
- can be inhibited or saturated
7
Q
filtration
A
- 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
8
Q
active processes
A
- 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
9
Q
active transport
A
- uses carrier
- accumulates against a concentration gradient
10
Q
micropinocytosis
A
-drug is transported in pinched off packets of a single layer membrane
11
Q
weak electrolyte drugs
A
- many drugs
- nonionized drugs diffuse
- lipid soluble
- concentration gradient
- weak acids diffuse in the HA form
- weak bases diffuse in the B+H form
12
Q
pka
A
- physical characteristic
- determines ratio of ionized to nonionized forms at a particular pH.
- ease of absorption at a particular pH can be estimated
13
Q
absorption of drugs in the stomach
A
- 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.
14
Q
drug administration
A
- enteral vs parenteral
- using GI tract vs not using GI tract
15
Q
route of admin considerations
A
- 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)
16
Q
enteral routes
A
- oral
- rectal
- sublingual
17
Q
oral admin advan
A
- easy
- safe
- self admin
- cheap
- prolonged absorption and effect
18
Q
oral admin disad
A
- 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
19
Q
first pass effect
A
- drug admin by mouth
- enters GI tract
- active drug is absorbed from stomach and small intestine
- high blood concentration of free drug is in hepatic portal vein before metabolism
- low blood concentration of free drug is in systemic arterial or venous circulation after metabolism
20
Q
rectal admin advan
A
- 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
21
Q
rectal admin disad
A
- nuisance- poor compliance
- absorption may be erratic or incomplete
- possibility of rectal irritation
22
Q
sublingual advan
A
- bypasses liver when first absorbed
- rapid absorption
23
Q
sublingual disad
A
- drugs must be soluble in saliva, not too distasteful, have appropriate pka for rapid absorption
- tablets must be small
24
Q
parenteral routes
A
- IV
- Intraarterial
- IM
- SC
- Intrathecal
- topical
- inhalation
25
IV advan
- 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
26
IV disad
- 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
27
intraarterial
Ad:
-admin of radioopaque material for visualization of circulatory tree
-high concentration of drugs going to local area when desirable
Disad:
-same as IV
28
IM advan
- 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
29
IM disad
- pain
- sterile technique
- possible local necrosis
- lag period before effect onset
- accidental IV injection possible
- not to be used after anticoag admin
30
subQ
Ad:
-absorption slower than IM- effect more prolonged
Disad same as IM
31
Intrathecal
- 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
32
topical ad
- for local action on or under skin
- for local action on or under membrane
- non-invasive
33
topical disad
- difficulty of absorption through skin
| - danger of excessive absorption through membranes and systemic tox
34
inhalation
```
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
```
35
pharmacokinetics of plasma levels depending on route
-IV, inhalation, IM, SC, PO
36
bioavailability
- 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
37
to predict plasma concentration
- 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
38
bioavailability is important for
- drugs that are potent in small doses
- drugs given for serious illnesses
- changes in drug manufacturer
39
other factors affecting absorption
- 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
