Brainscape's Knowledge GenomeTM

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


See full index

Introduction to Cell Physiology and Pharmacology > Lecture 20 + 21: Pharmacokinetics > Flashcards

Lecture 20 + 21: Pharmacokinetics Flashcards

1
Q

What are the main routes of administration?

A 
Oral 
Intravenous 
Intramuscular 
Transdermal 
Intranasal
Subcutaneous 
Sublingual 
Inhalation 
Rectal
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the 4 main processes in drug pharmacokinetics?

A

Absorption
Distribution
Metabolism
Excretion

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

What are the 2 parts of drug in?

A

Absorption and distribution

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

What are the 2 parts of drug out?

A

Metabolism and excretion

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

What is enteral drug administration?

A

Delivery into internal environment of body through the GI tract

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are the 3 examples of enteral drug administration?

A

Oral rectal and sublingual

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

What is parenteral drug administration?

A

Delivery via all other routes that are not the GI

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

What are 3 examples of parenteral drug administration?

A

Intravenous
Subcutaneous
Intramuscular

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

What is the processes of drug absorption if oral route taken?

A

Drug goes into stomach, mixes with chyme, enters small intestine, where it is mostly absorbed

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

What is the typical transit time of drugs in small intestine?

A

3-5h

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

What are the 4 major types of mechanisms in absorption?

A

Passive diffusion
Facilitated diffusion
Active transport
Pinocytosis

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

What is passive diffusion of drugs?

A

Lipophilic drugs (in unionized form) passes down its concentration gradient which is driven by capillary supply carrying drug molecules away from the gut

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are 2 factors that will determine rate of passive diffusion?

A

Blood flow rates - how steep concentration gradient is - faster = higher rate of diffusion
pKa / pKb of drug - determines proportion of drug in unionized form - higher = higher rate of diffusion

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

What is facilitated diffusion of drugs?

A

Using solute carrier transport molecules to allow charged drugs to travel in the direction of the electrochemical gradient

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

What are the 2 types of solute carrier proteins?

A

Organic anion and cation transporter

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

What are 3 locations where solute carriers highly expressed?

A

GI hepatic and renal epithelial

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is secondary active transport of drugs?

A

Using SLC to transport across GI epithelial membrane driven by pre existing electrochemical membrane but not ATP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is endocytosis and exocytosis of drugs?

A

For very large molecules, cell membrane endocytosesmthe drug

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

What are the 3 types of factors that affect drug absorption?

A

Physiochemical factors - relating to drug and the physical properties of GI
Physiology of GI - function of GI
First Pass metabolism by GI and liver

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

What are the 3 physiochemical factors affecting drug absorption?

A
  1. GI length / surface area - higher = higher drug absorption
  2. Drug lipophilicity or pKa - higher = higher drug absorption
  3. Density of SLC expression in GI - higher = higher drug absorption
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What are 3 GI physiology factors affecting drug absorption?

A
  1. Blood flow - after meals may increase = higher drug absorption
  2. GI motility - slows after meals = more time to absorb drug
  3. Food / pH - can increase or decrease drug absorption
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What is first pass metabolism?

A

Enzymes in gut lumen, gut wall and mostly liver metabolize the drugs, reducing drug absorption

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What are the 2 types of enzymes that metabolize drugs?

A
  1. Phase 1 = cytochrome P450s

2. Phase 2 = conjugating

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

How is the surface area in small intestine maximized?

A

Plicae circulares has valves of Kerckring, which have villi which have microvilli

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What is bioavailability?

A

Fraction of a defined dose that reaches its way into a specific body compartment

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

How do you measure oral bioavailability using graphs?

A

2 graphs - [plasma] against time for IV and oral, measure area under curve

F = AUC oral / AUC IV

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Where does drug go when it first enters CVS?

A

Arteries to capillaries via bulk flow

Capillaries to interstitial fluid to cell membranes to targets via diffusion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What are 3 differing levels of capillary permeability that will affect drug diffusion across capillaries?

A

Continuous - tight gap junctions - nth much can pass
Fenestrated - fenestrations - large molecules can pass
Sinusoid - intercellular gaps - cells can pass through

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What are 4 factors that affect distribution of a drug throughout the body?

A

Lipophilicity
Degree to which it binds to plasma proteins = decreases free drugs available for binding
Degree to which it binds to tissue proteins = decreases free drugs in plasma concentration
Mass or volume of tissue and density of binding sites within that tissue

30
Q

What are the 3 main body fluid compartments?

A

Plasma
Extracellular - plasma + interstitial
Total body water - plasma + interstitial + intracellular

31
Q

What is the order of body fluid compartment that the drug penetrates?

A

Plasma
Interstitial
Intracellular

32
Q

What are 2 effects of increased penetration by drug?

A

Decrease plasma concentration

Increase volume of distribution

33
Q

What does volume of distribution represent?

A

Level of penetration of interstitial or intracellular fluid compartment

34
Q

How do you calculate Vd?

A

Drug dose / [plasma drug] at t=0

35
Q

What is elimination of drugs?

A

Set of processes whereby drug is irreversibly removed via metabolic and excretory mechanisms

36
Q

How is drugs eliminated through the body through metabolism?

A

Molecular structure of the drug is changed via phase I and II reactions, ionic charge is increased to enhance renal elimination while lipophilic drugs travel back into plasma

37
Q

What are phase I reactions carried about by?

A

Cytochrome P450 enzymes

38
Q

What do cytochrome P450 enzymes do?

A

Catalyze redox and hydroxylation reactions to increase ionic charge of drugs

39
Q

What kind of molecules do CYP450s metabolize?

A

They are versatile generalists so they metabolize very wide range of molecules

40
Q

How does phase I metabolism activate prodrugs?

A

Some drugs like codeine is metabolized by CYP2D6 to morphine which has higher affinity for its receptor

41
Q

What is phase II metabolism carried out by?

A

Hepatic enzymes

42
Q

What do hepatic enzymes do?

A

Catalyze sulphation, cojugation, methylation reactions to further increase ionic charge and enhance hydrophilicity to enhance renal elimination

43
Q

What are 5 factors that affect drug metabolism?

A
  1. Age
  2. Sex
  3. Disease
  4. Inhibition or induction by other drugs
  5. Genetic factors
44
Q

What are the 3 major categories for factors that affect drug elimination

A

Heart
Renal
Hepatic

All leads to decreased functional reserve

45
Q

What are 3 mechanisms of induction of CYP450 enzymes?

A

Increased transcription
Increased translation
Slower degradation

46
Q

What happens when CYP450 is induced?

A

Rate of elimination of drug increases, plasma level of drug falls, lead to serious therapeutic consequences if levels drop significantly

47
Q

What are 2 mechanisms of inhibition of CYP450 enzymes?

A

Competitive and non competitive

48
Q

What happens when CYP450 is inhibited?

A

Rate of elimination slows down, increasing plasma level of drug, leading to side effects

49
Q

How long is inhibition process?

A

1-2 weeks

50
Q

What is an example of CYP450 induction?

A

Carbamazepine is a anti-epileptic metabolized by CYP3A4 but also induces CYP3A4, lowering its own levels, affecting control of epilepsy

51
Q

How long is the induction process?

A

1 to few days

52
Q

What is an example of CYP450 inhibition?

A

Grapefruit juice inhibits CYP3A4 which metabolizes verapimil used to treat high BP, so if rate of elimination falls, plasma level remains high, BP too low

53
Q

How do genetic factors affect metabolism?

A

Some enzymes are not expressed in different races

54
Q

How does genetic polymorphism affect drug metabolism?

A

CYP2D6 can present in many forms - poor or ultra rapid metabolizers, and it metabolizes codeine to morphine. So if it’s too poor, patient may not experience pain relief and if ultra rapid, leads to morphine intoxication

55
Q

What is the main route of drug elimination?

A

Kidney

56
Q

What are the 3 processes of renal excretion?

A

Glomerular filtration
Active tubular secretion
Passive tubular reabsorption

57
Q

What happens during glomerular filtration?

A

20% of renal blood flow enters here

Unbound drugs enter kidney via Bowman’s capsule

58
Q

What is proximal tubular secretion?

A

Remaining 80% of blood enters via peritubular capillaries
Proximal tubule cells have high expression of OAT and OCT that removes charged molecules from plasma and into proximal tubule

59
Q

What is passive tubular reabsorption?

A

Lipid soluble unionized drugs that goes back down its concentration gradient into plasma bc water has been absorbed so concentration in lumen is higher

Dependent on acidity of urine and pKa of drug

60
Q

What is clearance?

A

Volume or plasma that is completely cleared of the drug per unit time

61
Q

What is drug half life?

A

Amount of time that the concentration a drug in plasma decreases to one half of its initial concentration

62
Q

How to calculate half life?

A

0.693 x Vd / Cl

63
Q

What does it mean when elimination kinetics is linear?

A

Rate of metabolism or excretion is proportional to plasma concentration of drug

64
Q

When can elimination kinetics be linear?

A

Large functional reserve of enzyme sites and transporters

65
Q

When does elimination kinetics become saturated or is zero order?

A

All enzymes and carriers are working, no functional reserve

66
Q

How does the plasma [drug] against time graph look like for linear elimination kinetics?

A

Exponential decrease, log graph will be a straight line

67
Q

How does the plasma [drug] against time look like for zero order kinetics?

A

Straight line

68
Q

How does rate of drug metabolism change as dose of drug increases?

A

At low doses drug metabolism is first order as there is large functional reserve, drug metabolism is proportional to drug dose

At high doses drug metabolism is zero order as there is no functional reserve, drug metabolism is constant and independent of drug dose

69
Q

What is the effect on therapeutic response when drug elimination is first order?

A

Predictable as therapeutic response increases normally w dose

70
Q

What is the effect on therapeutic response when drug elimination is zero order?

A

Therapeutic response can suddenly escalate as elimination mechanisms saturate and small dose increase can produce large increments in plasma [drug] and lead to serious toxicity

Introduction to Cell Physiology and Pharmacology (16 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions