Pharm Test 1 Flashcards
1
Q
Elimination is dependent on
A
which organ is eliminating the drug
2
Q
The organ that is eliminating a drug is dependent on
A
- Whether or not the drug is a high-extraction drug
- what the blood flow is through that organ
3
Q
If the blood flow through an elimination organ is normal, we call it
A
high
4
Q
If the blood flow through an elimination organ is limited, we call it
A
low
5
Q
Oral morphine doesn’t provide the full effect because
A
After the GI tract morphine goes into the liver and the liver removes a lot of it. It is a high extraction drug
6
Q
What is the range for a high extraction drug?
A
> 0.7
7
Q
What is the range for an intermediate extraction drug?
A
0.3-0.7
8
Q
What is the range for a low extraction drug?
A
<0.3
9
Q
What is Q in the extraction ratio?
A
The blood flow through an elimination organ.
10
Q
What is the Clorgan formula?
A
Clorgan=QE
11
Q
What is E in the extraction ratio?
A
the percentage of drug that comes out of an elimination organ
12
Q
If you have a high E and a low Q, what is your Clorgan?
A
Low
13
Q
If you have a low E and a high Q, what is your Clorgan?
A
Low
14
Q
If you have a high E and a high Q, what is your Clorgan?
A
high
15
Q
If you have a low E and a low Q, what is your Clorgan?
A
low
16
Q
Why is the half life important?
A
It helps us determine how we should dose a patient and how much we should dose them
17
Q
Define half life
A
the time it takes the body to get rid of half of the concentration of a drug in the blood
18
Q
What is the half life formula?
A
T1/2=0.7XVd/CL
19
Q
What is giving a drug in “steady state” mean?
A
Giving the drug at the same rate that the body is eliminating it.
20
Q
What do we do to reach target concentration quickly?
A
Give a bolus of a drug
21
Q
For a drug that has a 4 hour half life, how many half lives would it take for the drug given at steady state to reach target concentration in the blood?
A
16 hours
22
Q
For a drug that has a 4 hour half life, how many half lives would it take for the drug to be completely eliminated from the blood after the infusion is stopped?
A
16 hours
23
Q
What effects half life?
A
Many things, including disease state
24
Q
A true half life will be _____ than the calculated half life
A
greater
25
If you don't wait 4 half lives before taking another dose of the drug, what will happen?
The drug will accumulate in the plasma and can become toxic very quickly
26
How is bioavailability denoted?
F
27
What does bioavailability tell us?
How much of the drug reaches systemic circulation
28
What is the bioavailability of an IV drug?
100%
29
What factors effect bioavailability?
* Physical properties of the drug (hydrophylicity, PKA, solubility)
* Fomulation/route
* GI- diet, gastric emptying, transporters, health
* interactions with other drugs
* disease state
* circadian rhythm
30
What is first pass elimination?
The first system that the drug goes through that changes the concentration of the drug.
31
What are routes that bypass first pass elimination?
* IV
* IM
* SC
* Inhalation
*has it's own first past effect
* sublingual
* transdermal
* rectal
*suppositories might move upward, therefore only 50% bypass hepatic circulation
32
What is target concentration based on?
What we are trying to accomplish in the patient (pain relief, controlling afib)
33
What is the most important factor of the dosing ratess?
Clearance
34
How do you solve for dosing ratess?
CL X Target concentration
35
For bioavailability that is less than 100%, how is the formula changed?
Dosing rateoral=dosing rate (calc.)/Foral
The CL X Target concentration is divided by the bioavailability.
36
If your bioavailability is less, your are going to have to give _____ of the drug
more
37
What is an intermittent dose for oral drugs?
Giving a pill every few hours instead of constantly.
Dosing rate X dosing interval (in hours)
38
If you are given the target concentration, the clearance, and the time interval how do you solve for the intermittent dose?
1. Dosing ratess=CL X Target Concentration
2. Dosing rateoral=dosing cate (calc.)/ForalX dosing interval
39
Describe what is happening in this graph.
The black line is the drug being given in steady state. It is showing that after 4 half lives, the drug reaches 10mg/L and the patient is receiving the targeted effect of the drug.
The red line shows the drug being given every 8 hours. The patient has peaks and troughs that's staying right around the target concentration.
The blue line is the drug being given every 24 hours. You can see that at the peaks the patient is receiving a much higher effect than the target concentration, but the troughs are also much lower. In the case of this siezure drug, you can see how the troughs would leave this patient open to having seizures.
40
How to calculate the loading dose?
LD=Vd X TC
41
The loading dose is assumed that it is given over
5 minutes
42
Why is rate of administrations critical for potentially toxic drugs?
Giving a bolus too fast doesn't allow time for the drug to distribute into compartments and therefore reaches toxic levels in the plasma very quickly
43
How do we monitor for therapeutic dosing?
Peak and trough tests
44
When is the peak test taken?
5-10 minutes after drug administration
45
When is the trough test taken?
30 minutes before the next dose
46
What do the peak and trough tests tell us?
Assessment of individual response to standard population pharmacokinetic variables.
To be able to dose the drug to each individual patient based on their disease state, other drugs they're on etc.
47
If you have a drug that preferentially stays in the fat, which weight do you use?
their actual weight
48
If you have a drug that preferentially stays in the blood stream, which weight do you use?
Their Ideal body weight
49
What test tells us how well the kidneys are functioning, and how does it work?
The creatinine clearance.
The muscles release a steady rate of creatine in the blood as waste which gets down to the kidneys for excretion. If creatinine starts to build up in the body then it is safe to assume that the kidneys are not functioning properly.
50
What is biotransformation?
The changing of a drug to either make it work better, or in most cases to decrease or stop the drug from working altogether.
51
What is the second largest organ in the body?
the liver, after the skin
52
Where does most, but not all, biotransformation happen?
The liver
53
What is in the hepatic portal system?
1. oral
2. gi
3. local veins
4. hepatic portal vein
5. *sinusoids* very leaky
6. hepatocytes
7. hepatic vein
8. vena cava
9. systemic circulation
54
Where is a drug biotransformed?
Hepatocytes
55
What are the 2 different places that biotransformed drugs can go after the hepatocytes?
Back into the blood stream to be delivered to the body
Into the Bile duct to be eliminated through bile
56
What is the circulation for a drug given in a central line?
1. Vena cava
2. r atrium
3. r ventricle
4. l atrium
5. l ventricle
6. systemic cirulation
7. hepatic artery
8. sinusoids
9. hepatic vein
10. vena cava
11. systemic circulation
57
Why are the sinusoids an area with fairly low oxygen concentration?
Because blood from the hepatic portal vein and the hepatic artery both mix here
58
What are the sinusoids in the liver very susceptible to?
Heart failure
59
Do sinusoids regenerate quickly?
yes
60
What are phase 1 reactions?
When we take an enzyme and either add or unmask a functional group (-OH, -NH, -SH et.) very small substances.
61
What are phase 2 reactions?
We're tacking on larger molecules
62
In some way, phase 1 and phase 2 help with the ______ of a drug.
elimination
63
Is there a specific order phase 1 and phase 2 has to happen?
No, and they don't have to go through both reactions.
64
Phase 1 turns the drug into a more _______ metabolite. Making it harder to cross into the cell and therefore easier to eliminate.
polar
65
Phase 2 reactions are ________ reactions.
conjugate
meaning to combine 2 things
66
Phase 1=
oxidation, reduction, hydrolysis
67
After phase 1 most drugs are
inactivated
68
Phase 2 results in drugs with a ________
higher molecular weight, essentially detoxifying the drug by making it harder to cross into the cell.
69
What are the 4 main groups of phase 1?
Oxidation
reduction
dehydrogenation
hydrolysis
70
What is oxidation?
Loss of an electron
71
What is reduction?
Gaining of an electron
72
What is dehydrogenation?
removing an OH group
73
What is hydrolysis?
breaking down of water in a reaction and that breaks a bond
74
Why are we focusing on oxidation reactions?
Because that is how vast majority of drugs are modified in phase 1 reactions.
75
What is used in the primary oxidation pathway?
an enzyme called Cytochrome P450. It's a molecule
76
P450 cycle
1. drug comes in lipophilic
2. binds to CYP450
3. loss of E-
* Flavoprotein oxidizes and becomes oxidized
* then goes through the compound NADPH
* NADPH is reduced turning into NADP+
* NADPH is recycled somewhere in the liver
* Now Favoprotein is recycled and is in it's reduced form
4. P450 molecule is a holder for the drug
5. 2 Oxygen molecules and electrons are added to the drug
6. Oxygen detaches from the drug and attaches to 2 Hydrogen turning into water
7. The other oxygen stays on the drug and becomes a hydroxyl group
8. Drug is then more hydrophilic & is released into either the circulation to be excreted by the kidneys or the bile to be excreted through the intestines
77
What takes electrons from P450?
Flavoprotein
78
What is the most common flavoprotein?
Flavin mononucleotide
FMN
79
By oxidizing P450, Flavoproteins become
oxidized themselves
80
CYP3A4 synthesize what percent of oxidation reduction reactions?
50%
81
CYP2D6 synthesize what percent of oxidation reduction reactions?
20%
82
CYP2B6 synthesize what percent of oxidation reduction reactions?
8%
83
What does CYP short for?
Cytochrome P450
84
What is the most important CYP450?
CYP3A4
85
Where does the oxidation reaction happen inside of the hepatocyte?
Sarcoplasmic reticulum
86
CYP384*1 means
this is a wild type
87
what does the wild type mean?
it is the variant that is most commonly seen in the population.
88
CYP3A4*2
is a mutant of the CYP3A4*1 and may have different activity.
89
What is a polymorphic variant?
A deviation from the wild type that may have a greater, lesser, or same effect as the wild type.
90
What produces variants?
Genetic mutations
91
What is a P450 induction?
a drug(medicine, food, charbroiled) that increases the number of cytochrome P450 enzymes which increases the CYP3A4 enzyme which effects the drug
92
What is a P450 Inhibition?
A drug(medicine, food, charbroiled) that decreases the number of cytochrome P450 enzymes which decreases the CYP3A4 enzyme which effects the drug
93
If a drug is inactivated by CYP3A4, and we take an inducer, what will happen?
The drug will become inactivated at a much faster rate.
Less drug effect
94
What is a prodrug?
something that has to be activated by CYP3A4
95
If a drug is activated by CYP3A4, and we take an inducer, what will happen?
The drug will be become active much more quickly and may reach toxic effects quickly.
more drug effect
96
If a drug is inactivated by CYP3A4, and we take an inhibitor, what will happen?
Less of the drug is being inactivated, meaning more of the drug is being released into the body and you may reach toxic effects faster.
more drug effect
97
If a drug is activated by CYP3A4, and we take an inhibitor, what will happen?
Less of the drug will become activated, meaning that less of the active drug will be available in the plasma.
Less drug effect
98
What is glucuronidation?
attaching a glucose
99
What is the acetylation?
attaching an Acetyl-CoA
100
What is Glutathione conjugation?
attaching a glutathione (GSH)
101
What is Glycine conjugation?
attaching a Glycine
102
What is sulfation?
attaching a Phosphoadenosyl phosphosulfate
103
What is Methylation
attaching a S-Adenosylmethionine
104
What is water conjugation?
attaching a water
105
What is a UGT?
Uridine diphosphate glucuronyltransferases
a type of glucuronidation reaction
They attach a glucuronic acid to molecules
A carrier molecule with the Glucuron transferase (which transfers a glucose molecule from UDP to the drug itself)
106
What do UGT's attach a glucuronic acid to?
Phenols, alcohols, carboxyl, and sufhydryl groups
107
Where are UGT's primarily found?
in the liver
108
What is uridine diphosphate?
the carrier molecule
109
What do the glucuronyltranferases do?
Transfers a glucose molecule from UDP to the drug itself
110
What is the response of a drug undergoing glucuronidation?
It becomes more aqueous soluble, and is excreted via the urine more easily
111
What is a Glutathione-S-transferase? GST
attach a glutathione
112
Glutathione characteristics
ubiquitous
Critically important in detoxification
Increases water solubility to get rid of toxins
113
Where are glutathiones found?
Everywhere. Really high in RBC's because they can build up high amounts of oxidants in them because they carry oxygen.
114
What is a xenobiotic?
something that is foreign in the body
115
What happens to xenobiotics when a glutathione binds to it?
It forms a glutathione conjugate which makes it more likely to be excreted in the urine
116
What does overdosing do?
It overwhelms the normal detox pathways
117
What are extrahepatic metabolism examples?
Brain
Lung
Intestine
Plasma
Kidney
118
What are things that change the way we metabolize drugs?
diet
environment
age and sex
disease state
genetics
DEAD Genetics
