Lecture 1 and 2 (Revised) Flashcards
1
Q
PK?
A
Absorption, Distribution, and Elimination
2
Q
Xenobiotics?
A
Substances that are foreign to the body
3
Q
All drugs at high concentrations are?
A
Toxic
4
Q
Absorption?
A
Process by which drugs enter systemic circulation
5
Q
Only way to bypass absorption?
A
Using an IV
6
Q
Distribution?
A
Phenomenon by which drugs reach its site of action
7
Q
Elimination?
A
Process by which drugs are enzymatically altered (biotransformation) mainly in liver and eventually excreted by the kidneys
8
Q
Elimination mainly occurs in?
A
The liver and eventually excreted by the kidneys
9
Q
Drugs taken by the Hepatic Portal Vein are?
A
NOT absorbed yet because they have not entered systemic circulation
10
Q
If a drug is taken orally and patient has severe diarrhea?
A
It will not enter the systemic system and will not be effective
11
Q
How well a drug can cross cell membrane is correlated with?
A
Physiochemical Characteristics
12
Q
Absorption, Distribution, and Elimination of a Drug all involve?
A
Its passage across cell membranes
13
Q
Factors in Transfer of Drugs Across Membranes?
A
1) Molecular size and shape of drug
2) Solubility of drug (lipid:water partition coefficient)
3) Most drugs are weak acids or weak bases
14
Q
Only highly lipid soluble drugs can?
A
Cross BBB, water soluble does not
15
Q
Only highly lipid soluble drugs can?
A
Cross BBB, water soluble does not
16
Q
Ionized?
A
Charge, cannot pass through membrane
17
Q
Unionized?
A
No Charge, does cross BBB
18
Q
Can readily cross cell membrane?
A
Only non-ionized form of the drugs
19
Q
If there is a charge?
A
It cannot cross membrane
20
Q
Henderson-Hasselbalch Equation?
A
Allows for calculation of degree of ionization for weak acids or weak bases
21
Q
Henderson-Hasselbalch Equation? (Weak Base)
A
22
Q
Henderson-Hasselbalch Equation? (Weak Acid)
A
23
Q
Lower pH?
A
More Acidic
24
Q
pH of Urine?
A
4.0-8.0
25
Weak Acid gets trapped on more?
Basic Side
26
Weak Base gets trapped in more?
Acidic Side
27
Processes of Drug Transfer?
1) Passive Diffusion
2) Active Transport
3) Facilitated Diffusion
4) Bulk Flow
5) Pinocytosis
28
Factors that Influence Drug Absorption?
1) Solubility
2) Concentration
3) Circulation
4) Surface Area
5) Time
29
Passive Diffusion?
-Most common
-Moves only down concentration gradient
-Not saturable
-Not carrier-mediated
30
Higher the lipid:water partition coefficient?
Faster is the passive diffusion
31
Ethanol (Alcohol) is an example of?
Passive Diffusion
32
Which 2 Processes of Drug Transfer are Carrier-Mediated?
-Active Transport
-Facilitated Diffusion
33
Active Transport?
-P-glycoprotein and Multi-drug resistance-associated proteins (MRP) are main transporters of drugs
-Need energy (ATP)
-Drug can move up concentration gradient
-Requires a carrier
-Can be saturated
34
Only process where drugs can go from a lower concentration to a higher concentration?
Active Transport
35
Penicillin in Kidney is an example of?
Active Transport
36
Facilitated Diffusion?
-Drug moves only down concentration gradient
-Involves a carrier (No expenditure of energy)
-Can be saturated
37
Amino Acids transport into Brain are an example of?
Facilitated Diffusion
38
Bulk Flow?
-Movement of molecules through capillary junction
-Only free drugs can move through fenestration between capillaries, but most drugs are bound to plasma protein (Not with BBB)
39
Fenestrations?
Tiny openings, capillaries have fenestrations but Brain does not
40
Pinocytosis?
-Formation and movement of vesicles
-It plays a minor role in drug transport across membrane
41
Solubility?
-Aqueous solution vs. Oily solution
-pH affect solubility
42
Concentration?
High concentration of drug preparations are absorbed more rapidly
43
Circulation?
-Increased Circulation, Increased Absorption (local massage or heat application)
-Decreased Circulation, Decreased Absorption (state of shock or disease state)
44
Surface Area?
-Increase Surface Area, Increase Absorption
45
First-Pass Effect?
-Combined action of bacterial and liver enzyme on drugs BEFORE reaching systemic circulation
-Not 100% of drug will be absorbed
46
Factors that Influence Drug Distribution?
1) Blood Flow
2) Lipid Solubility of Drug
3) Molecular Size
4) Protein Binding
47
Blood Flow?
-Most highly perfused organs receive most of the drug during the first few minutes after absorption
-Delivery of drug to muscle, viscera, skin and fat is slower
48
Lipid Solubility of Drug?
-More lipid solution, better at crossing BBB
-Lipid insoluble drugs, that crosses membrane poorly, are restricted in their distribution and hence in their site of action
49
Molecular Size?
Extremely large drugs are mainly confined to the plasma compartment
50
Protein Binding?
-Distribution may be limited to drug binding to plasma proteins, only unbound drugs cross cell membrane
51
Acidic drugs bind?
Serum Albumin
52
Basic drugs bind?
Alpha-one Glycoprotein
53
Drug Reservoirs?
1) Plasma Proteins
2) Fat
3) Bone
4) Cellular Reservoirs
54
Plasma Proteins?
Many drugs bind to plasma proteins, this binding is predominantly reversible
55
Fat can act as?
Drug Reservoir for highly lipophilic drugs
56
Bone?
Drug may accumulate in bone by absorption onto bone-crystal surface and eventual incorporation into crystal lattice
57
Cellular Reservoirs?
Some drugs may accumulate in muscle or other cells at higher concentrations than in extracellular fluids
58
Blood-Brain Barrier?
-Adaptive
-Barrier is not absolute
-Protects against Xenobiotics
59
Placenta?
-Cellular Barrier
-Not a barrier to drugs
-Fetus is to at least some extent exposed to essentially all drugs taken by mother
60
Elimination is?
-Combination of Biotransformation and Excretion
-Process by which drugs are enzymatically altered mainly in liver and eventually excreted by kidneys
61
Increases water solubility of drugs?
Biotransformation
62
Most important for Biotransformation?
Liver, but can occur in other Organs too
63
Biotransformation can Result in?
1) Inactive Metabolite
2) Metabolite that retain similar activity
3) Metabolite with altered activity
4) Bioactivated metabolites
64
Inactive Metabolite?
Hydrolysis of Procaine to p-aminobenzoic acid results in loss of anesthetic activity
65
Metabolite that retain similar activity?
-Codeine is demethylated to the more active analgesic morphine
-Like a "pro drug" needs to get converted to morphine via P450 enzymes (C2D6) which is polymorphic
66
Metabolite with altered activity?
-Vitamin retinoid acid (Vitamin A) is isomerzied to anti acne agent, isoretinoic acid
67
Bioactivated Metabolites?
-Prodrug, drug administered in inactive form
-Prodrug enalapril is hydrolyzed (by biotransformation enzymes) to enalaprilat, a powerful antihypertensive
68
2 Main Reactions of Biotransformation?
-Phase I (Oxidation, Reduction and Hydrolysis)
-Phase II (Conjugation (via transferases))
69
Phase I (Biotransformation)?
-Mainly degradative resulting in:
1) Inactivation
2) Change in activity, or
3) Conversion of a pharmacologically inactive compound (prodrug) to active drugs
70
Main Phase I reactions?
Oxidation, Reduction and Hydrolysis
71
Enzyme system most responsible for oxidation reactions?
Cytochrome P450 system (CTP)
72
Phase II?
-Mainly involved in coupling of drug or frequently its polar metabolite from Phase I reaction to an endogenous substrate
73
Phase II reaction?
Conjugation (via transferases)
74
Oxidation is the most important?
Phase I reaction
75
Oxidation Enzyme System is found in?
Microsomal Fraction (sER) of cells, mainly in liver and then in lung and kidney
76
Oxidation Enzyme System is found in?
Microsomal Fraction (sER) of cells, mainly in liver and then in lung and kidney
77
Cytochrome P450 system consists of 2 components?
-Cytochrome P450 oxidoreductase
-Cytochrome P450
78
Cytochrome P450 requires?
Molecular oxygen and NADPH
79
Is a family of isoenzymes with overlapping specificities?
Cytochrome P450
80
Key Step in Oxidation?
Insertion of oxygen atom producing a non-stable intermediate which breaks down to yield final product
80
Key Step in Oxidation?
Insertion of oxygen atom producing a non-stable intermediate which breaks down to yield final product
81
Main Reactions Catalyzed by Oxidation?
-Dealkylation
-Hydroxylation
-Sulfoxide formation
-N-Oxidation
-Deamination of primary and secondary amines
82
Non-Microsomal Oxidation System, most important enzymes of this class are?
-Alcohol Dehydrogenase
-Aldehyde Dehydrogenase
(Both located in cytosol)
83
Hydrolysis?
-Carried out by enzymes known as:
-Esterases
-Amidases
-Peptidases
84
