10/22 Pharmacology Flashcards
1
Q
what is pharmacodynamics
A
The drug’s effects on the body or the relationship between drug concentration and effecct! how the amount of drug in the body effects the body.
2
Q
what is pharmacokinetics?
A
The body’s effects on the drug or the changes in drug concentration over time.
3
Q
what is ADME in pharmacology?
A
the Chain of progression for a medicine in the body. This is the processs of pharmacokinetsics: Absorption; Distribution; Metabolism; Excretion.
4
Q
The movement of a drug from its site of administration into the bloodstream
A
Absorption
5
Q
The movement of a drug from the blood stream to the various tissues of the body
A
Distribution
6
Q
The biotransformation of a drug into inactive or active metabolites.
A
Metabolism
7
Q
The removal of a drug from the body.
A
Elimination
8
Q
What does the course of a drug in the body depend on?
A
The body’s affects on drug (Pharmacokinetics) and The drug’s effects on the body (Pharmacodynamics)
9
Q
What are the processes of Pharmacokinetics?
A
Absorption, distribution, metabolism, excretion
10
Q
what are the processes of pharmacodynamics?
A
Mechanisms of action of the drug (biochemical and microbiological)
11
Q
What is the graphical prepresentation of pharmacokinetics?
A
Concentration-time curves
12
Q
what are the graphical representations of the pharmacodynamics?
A
dose-response curves
13
Q
what are the measured parameters of pharmacokinetics
A
bioavailability; Volume of distribution; Half-life; Clearance
14
Q
What are the measured parameters of pharmacodynamics?
A
Efficacy; Potency
15
Q
what does pharmacogenetics have an effect on?
A
both the pharmacokinetics and the pharmacodynamics
16
Q
The fractional extent to which a dose of a drug reaches the systemic circulation.
A
Bioavailability (F)
17
Q
the apparent space in the body available to contain the drug
A
volume of distribution VD
18
Q
a measure of the rate of removal of drug from the body
A
elimination half-life (T1/2)
19
Q
What is the intrinsic activity of a drug?
A
the basic effect that a drug has on a receptor i.e. agonist or antagonist etc.
20
Q
The strength of interaction between a drug and a drug receptor.
A
affinity
21
Q
what must we do if we want to kick gluteus at something?
A
“I’ll keep pushing myself, there’s always some way to do it better…”
22
Q
where would a drug go if it was sublingual (venous)
A
It would bypass the portal system and go right into the caval system of veins by way of the jugular vien ets.
23
Q
where would a drug go if it was rectal
A
It would go to both the portal and the caval drainage, resulting in mixed pharmakinetics.
24
Q
what venous drainage would take place for an oral drug
A
Portal drainage!
25
what are the 9 basic routes of administration of a drug?
oral, sublingual, rectal, transdermal, intradermal, subcutaneous, intramuscular, intravenous, inhalation.
26
what are the routes of administratoin that would bipase the liver?
sublingual, rectal, inhalation would but the lung has some first pass effects as well! and of course the IV would be the "perfect administration. through the skin or muscle would also bypass the portal.
27
how would facilitated vs. plain diffusion differ?
facilitated can be saturated and see a curve that goes to a saturation.
28
what form of a weak acid/base drug is usually more soluble?
the unionized form is mor lipid soluble and able to cross the cell membrane to act!
29
how would the difference in pH from outside of a cell to inside of a cell be important for the action of most drugs
most drugs transit the membrane into the cell in the un-ionized form, but it is the ionized form of the drug that is the active form, so the pH must change in order to activate the drug.
30
How would the surface area and concentration affect the absorption of a drug?
For passive transport, the surface area and concentration gradient is the driving force and is very important.
31
how can the pKa of a drug help to determine when it is in an ionized or non-ionized form?
pH above pKa- deprotinated; pH below pKa- protinated; weak acid - deprotinated=Ionized; Weak base- protinated=ionized
32
when is there an equal amount of protinated/deprotinated weak acid/base
when pH = pKa
33
Equation to relate pH and pKa
pH-pKa = log [protinated] / [unprotinated]
34
The reversible movement of a drug from the bloodstream to the various tissues of the body.
The distribution of the drug
35
what are the various distribution "clouds" or areas of the body to which a drug may go into? (and right back out of!!!)
Blood; extracellular fluid; fat; intracellular fluid; and other (CSF, peritoneum; Fetus etc.)
36
how can we easily estimate the relative size of the different compartments of the body?
2/3 rule! Kg*2/3 = Water; Water*2/3 = intracellular; Water*1/3 = Extracellular; and 2/3* EC = interstitial; 1/3*EC = intravascular. The fat equals the interstitial.
37
The unequal time course of distribution of a drug is characterized by what generala divisions?
an initial rapid phase and a secondary slower phase.
38
Is the distribution to different body compartments characterized by random equal diffusion?
No, different drugs will undergo partitioning into different tissues.
39
wait, wait, drugs binding to protie, what does that mean...
non covalent bonds that are usually reversible, and this binding may impair membrane permeation! this can create tissue reseviors that could be indication for toxicities or adverse effects
40
how can the accumulation of drug in lipid or the binding of drug to protien affect pharmakinetic?
it can either shorten or prolong drug effects.
41
ADME totally dependent of regional blood flow and membrane permeation
distribution
42
these type of drugs tend to bind to alpha-1 acid glycoprotein
weak bases.
43
these type of drugs tend to bind to Albumin or lipoprotien
weak acids
44
what is phase I metabolism?
after absorption drug is made into a metabolite with modified activity. or into a inactive drug metabolite
45
What is phase II metabolism?
it is where a drug gets conjugated...or has extra molecules added to it!
46
organ of drug metabolism
the liver
47
how can a drug become promoted to excretion?
by enhancing water solubility, and/or suitability for renal excretion.
48
what is the result of metabolism?
drug activation or inactivation that can promote excretion or diminsh therapeutic effect, enhance thereapeutic effect, cause toxic or other effects.
49
what would orald drugs be subject to that other drugs delivery don't see?
First pass effect where the drug must go through the liver before it can get to any part of the body?
50
how does the first pass effect change the dossage of a drug?
it means that oral drugs must be taken in higher does than the ones that are taken IV etc.
51
what is the most common enzyme to act on a drug? (the "work horse" of the liver)
CYP3A4/5!! and accounts for 40% of the CYP P450 in the liver!
52
how does the amount of CYP2D6 compare to CYP3A4/5?
2%/40% yet 2D6 still handles the metabolism of about a third of drug metabolism!!
53
what is the second most common enzyme for drug metabolism (about 30%)
CYP2D6
54
why does the reliatievly small amount of CYP2D6 change the way that we give drugs?
It becomes a bottle neck in the pharakinetics of the drug.
55
what is the clinical significance of P450 polymorphisms?
P450 is a major metabolizer of drugs and if you are lacking the P450 then less of the drug would be metabolized!
56
Produces more of the enzyme or ramp up its activity
Induction of an enzyme
57
what characterizes an ultra or poor metabolizer of a drug?
one of the most common indications is a genetic difference in CY2D6 polymorphisms in leading to different P450 rates!
58
decrease in the activity of an enzyme by binding the active site!
Competitive inhibition
59
decrease the activity of an enzyme by binding a site that is not the drug binding site.
non-competitive inhibition
60
what is the P450 Oxidase "workhorse"
3A4
61
what is the P450 Oxidase "bottleneck"
2D6
62
what is the typical phase II drug metabolism reaction and the result fo that reaction?
conjugations (sulfation, methylation, glucuronidation, acelyation) usually make the drug water soluble and inactivate the drug and promote secretion.
63
what is the typical phase I drug metabolism reaction and the result os that reaction?
Transformations (redox, hydrolysis to make OH, NH2, COOH type group for later conjugation.) maybe lead to an active form of the drug.
64
what is the form of most extreted drugs?
As Parent drug matabolites -- most drugs that are excreted have undergone phase I and phase II metabolism
65
What drugs would not be filtered at the glomerulus?
the protein bound drugs.
66
what is the main organ of drug excretion?
the kidney
67
what are the more likely drugs to be excreted and not re-absorbed
the basic drugs since they would be charged in an acid environment.
68
what would the fate of basic or acid drugs be in urine that is pH=5.4?
acid urine means that the drugs will most likely be protinated, so the acid will be non-ionic and the base will be ionic. the ionic drugs will be excreted in the urine since they can't be reabsorbed. the non-ionic drugs will be reabsorbed since they can cross the plasma membrane!
69
how can protien boud drugs be lost in the kidneys?
they can undergo secretion which is an energy dependent transport into the urine! vs. filtration of non-protien bound drugs!
70
what are the two big types of drug transporters?
ATP binding Cassette (ABC); Solute Carrier (SLC)
71
how and where in the kidney would we eliminate the cations and anions
use active transporters in the proximal convoluted tubules.
72
where and how in the kidney would we excrete a weak base?
in the kidney and because the urine is acidic! (The basic drug will be mostly deprotinated in the blood and then mostly protinated in the urine -- making it permeable on the blood side and impermeable on the urine side.
73
what are the important renal excretory mechanisms?
filtration, secretion, and (failed) reabsorption.
74
What are two large classes of drug transporters?
ATP binding Cassette (ABC). Solute Carrier (SLC)
75
diffusion is random and constant kinetics, contrast transporters
selective and saturable.
76
1. the graph
what is the predominate process at the left of the graph? -- Absorption. what couteracts the absorption...distribution away from the blood, and first pass matabolism before it reaches the blood. as you move to the right of the graph what happens the most? -- moving to exretion! The answer: different routes of administratoin -- (look in katsung for the figure) see the time for max concentration is the same for the red and orange curve...so the absorption rate is the same, but the area under the curve is bigger for the red...so the bioavalibility of A is twice that of B! so this must involve a first pass effect on the orange curve. for the blue curve the peak is shifted to the right so the absorption is lower. but for the area under the curve, the blue is the same as the red so the bioavailabilty is the same (both don't have first pass).
77
Case 2.
would the administration of a sodium bicarbonate to alakalinize the urine promote or prevent the clearence of a weak base drug such as methamphetamine? it would be detrimental to the clearence because at a basic level the base will be deprotinated and will be reabsorbed because it will be uncharged.
78
Case 3: what properties confine to the intravascular space?
very large, or very polar, or highly bound to protiens, poor lipid soluble molecules.... it means that it doesn't get out of the intravascular space well...but it still could!
79
Case 4: what cautions?
the half life of the parent drug is short and the metabolite that is toxic has a long half life, so if you build the conc. of the parent drug to get effect then you could build up the metabolite way too high!!!!
80
what phase is N-demethylation?
Phase 1
81
what phase is hydrolysis?
phase 1
82
what phase f metabolism is glucuronidation?
phase 2
83
case 4: what could cause the metabolite to build up even more?
if someone has renal failure then the metabolite could build up even more!!
84
Case 5: grapefuit juice...how would it affect the drug?
grapefruit juice will block the action of the first pass metabolism by CYP3A4. this is bad because normally only a small percent of the drug makes it pass the CYP3A4 and then it can increase the amount of drug that reaches the circulation. then the adverse side-effects can easily come about...myapathy and malagia.
