Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Medicines design II - solid dosage forms > From Practice Q > Flashcards

From Practice Q Flashcards

0
Q

Pgp increases…

A

As you go down the GI

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
1
Q

Bacteria in the…. May degrade drug

A

Colon

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Colon or small intestine have larger s a?

A

Small intesting

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Stokes einetine equation

A

Diffusivity = Kb T / 6pi viscosity radius

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Contents of the colon or small intest are more viscous?

A

Colon (also has smaller s a)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

5 ways to improve/target absorption

A
  1. Increasing drug lipohilicity – use of prodrugs.
  2. P-glycoprotein inhibitors.
  3. Cytoadhesion – targeting drugs to specific areas or cells in the GI tract.
  4. Mucoadhesive patches.
  5. New delivery systems (e.g. protective coatings, micro- and nanoparticles
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Prodrug example

A

Bacampicillin lipophilic and inactive, easily crosses membrane, cleaved by endogenous esterases to ampicillin (the active)
BA improved from 30-50 up to 80%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Other ways to alter lippohicity to increase absorptions

A

Pro drugs
lipidization (attaching lipids to the drug)
penetration enhancers (essentially partially solubilising the epithelial membrane to increase absorption).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Eg of PGPi

A

topotecan with the P-gp inhibitor elacridar increased oral bioavailabilty in humans from ~40 % to 97 %
(Some also inhibit CYP3A4 to reduce Cl)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Eg mucoadhesives

A

Insulin in mucoadhesive polymer, covered with insoluble coating - protects and directs diffusion to membrane. Improves residence time.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Disadvantages of oral7

A

variable people/pH extremes /motility

Adverse reactions – e.g. gastro-toxicity

High metabolic activity and hepatic first-pass  
Efflux pumps (P-gp)

Impermeability of epithelium(esp large, hydrophobic peptides)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Advantages or oral 4

A

Convenient, accessible, good compliance
Large surface area and rich blood supply
Prolonged retention and potential for zero-order release
Cheap

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Situations where rectal is good

A
  • Unconscious patients
  • Children
  • Patients that are nauseous or vomiting
  • Patients with upper GI tract disease
  • Drugs with an objectionable taste
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Advantages of rectal

A

Sustained release possible
Highly vascularised end
Possibility of avoiding hepatic first-pass (eg lidocaine)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Disadvantage of rectal

A

Metabolism of some drugs by bacteria
people don’t like it
• Complicated by anastomoses

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Absorotion pathways and their prevalence

A

1.Major: transcellular -mainly passive diffusion
(also aqueous pore, endocytosis, facilitated diffusion, active transport)

2.Minor: paracellular

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Para cellular is restricted to …. And is minor except…

A 
minor pathway (except transdermal), 
restricted to small, hydrophilic molecules. < 1000 DA
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Types of barriers to cross paracellularly? And with is rate limiting

A
  1. Tight junctions - rate lim - fused cells
  2. Adherence - actin joins cytoskeleton
  3. Desmosomes - fibrous + common
  4. Gap juntions - hydrophilic pore
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Lipid bilayer is hydrophilic or hydrophobic?

Prevents passage of…?

A

hydrophobic nature

prevents the passage of most polar and charged (i.e. water-soluble) molecules

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Compare facilitated and active diffusion

A

Both selective and carrier medicated
Facilitated- down concentration grad
Active - down or against, requires energy (eg l dopa)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Area ups pores allow passage of

A

Made from aquaporin proteins - allow passage of Some Hydrophilic / neutral solute like urea

21
Q

Endocytosis … Define

A

Internalisation of plasma membrane engulfing extracellular fluid to form lysosome - drug may be degraded or escape

22
Q

Two type of endocytotic

And one example

A

Eg polio vaccine
Pinocytosis - drinking
Phagocytosis - only relevant for advance drug delivery

23
Q

Logs p that are good or bad partitioning

A

Log P < 3 = poor partitioning

Log P > 5-6 = Partitioning too good

24
Oh partition hypothesis
Drugs accumulate on the side where pH favours ionisation | This is because optimal membrane transport is achieved when unionised.
25
Limitations of pH hypothesis7
Type of epithelium •Surface area of the absorption site •Ionized drugs will be absorbed to a small extent •Active transport of drugs •Residence time of drug at delivery site •Mass transfer of fluids •Charged drugs may form ion pairs with oppositely charged species
26
How to count h bond donors and acceptors
Number of hydrogen bond acceptors = N + O | Number of hydrogen bond donors = OH + NH
27
Effect of h bonds on absorption
Hydrogen bonds must be broken before the drug can enter the lipophilic plasma membrane.
28
Eg of h bonds affecting abosorption
Licomycin BA 30% | Clindamycin BA 90% (has Cl instead of oh)
29
What pKas are poorly absorbed
Strong acids (pKa < 3) and strong bases (pKa > 10) are poorly absorbed
30
Consequences of residence time
If movement through the GI tract is too fast, the drug will pass through the system without being absorbed. If movement through the GI tract is too slow, the onset of pharmacological effect will be retarded, the drug may be degraded or the epithelium may be irritated.
31
Meal volume effecting emptying rate
the larger the meal, the quicker the initial emptying rate
32
Content of meal effect emptying rate
fatty acids reduce emptying rate, proportional to concentration and chain length (most influence when carbons = 10 or more). – triglycerides reduce emptying rate; unsaturated more so than saturated – carbohydrates and amino acids
33
Things that reduce emptying rate
Physical state of contents: solutions or suspensions of small particles empty quicker than chunks of material. Chemicals: acids reduce emptying rate (conc.-dependent) while alkalis increase emptying rate at low (1 %) concentrations and decrease it at higher (5 %) concentrations. Drugs: anticholinergics, narcotics and ethanol reduce emptying rate. Body position: lying on the left side reduces emptying rate. Disease: emptying rate reduced by the presence of ulcers and in some diabetics. Exercise: vigorous exercise reduces emptying rate
34
How does retention in the stomach vary with large or small forms
Solution - exists progressively and rapidly | Solid - must wait for housekeeper waves - lag time
35
What might degrade stuff in the stomach
HCL pepsin
36
What might degrade stuff in the duodemum
Carboxylpeptidases a and b Trypsin Elastase Chymotrypsin
37
What might degrade stuff in the small I
CYP mainly 3A4 | Esterases and glucuronosyl transferases
38
What might degrade stuff in the colon
Gut flora
39
Four most common liver metabolises and two results
oxidation, reduction, hydrolysis and conjugation. | More polar and less active
40
Eg of massive first pass effect
Haloperidol 50 % loss | Dose adjust if given by IM
41
Amount of drug reaching circulation depends on three main things
* its release from the dosage form, * stomach, intestinal and hepatic 1st-pass effects * its absorption across the GI membrane
42
Enterohepatic recycling
Drugs eliminated into biliary secretion may be absorbed again into systemic circulation
43
How can food affect absorption
–Delayed gastric emptying – damaging to proteins or acid labile drugs –Stimulation of bile secretion – increased solubilization and absorption of lipophilic drugs e.g. griseofulvin –Increased viscosity of luminal contents –Stimulation of hepatic blood flow – effects on first-pass metabolism –pH changes in the GI tract – decreased pH may aid dissolution of basic drugs –Changes in luminal metabolism –Physical or chemical interaction of the drug with food – a drug may bind to components of a meal and form a non-absorbable complex, e.g. tetracyclines interact with divalent cations. –Competition for uptake transporters, e.g. L-dopa
44
Eg of food effects on a drug
Lapatinib – breast cancer drug. Food ↑ bioavailability by 167 % Fatty meal ↑ bioavailability by 325 %
45
Two examples of food metabolism interactions
Cruciferous vegetables: Induce the CYP1A enzymes, glutathione-S-transferase & quinone oxidoreductase. Grapefruit juice: inhibits CYP3A, increasing bioavailability of estradiol, felodipine and cyclosporin. Statins and muscle toxicity
46
Endogenous purpose of efflux pumps
Protection mechanism - transports substrates out of cells | Affects drug uptake eg cancer chemo
47
Pgp substrates are usually... | Eg...
Substrates are mainly lipophilic or cationic – anthracyclines, cyclosporin, celiprolol. •Taxol, anti-microtubule drug, was not absorbed orally in pre-clinical trials – flux from basolateral side of the membrane back into the lumen was 4-10 times greater than diffusion into the intestinal epithelium
48
Where is pgp found?
170kda found in apical membrane of small intestine - co localised with CYP 3am enhancing metabolism
49
How is mucus a problem
Eg warfarin absorption | Predominately neg charge and a barrier to diffusion
50
Eg of physical state affecting absorption
Leaky epithelia in infants | Men have higher levels of HCL secretion and CYP enzymes

Medicines design II - solid dosage forms (11 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions