Intro, Pharmacodynamics, Pharmacokinetics Flashcards
1
Q
What is a drug?
A
Any chemical that acts on a living system
2
Q
What is a drug’s generic name?
A
It is understood universally and adopted by the WHO
3
Q
What is a drug’s trade name?
A
t is a registered trademark, when a patent is expired many compagnies can develop products using the same drug and can name it however they like, something catchy for the consumer.
4
Q
Pharmacodynamics is?
A
How a drug acts on the body
5
Q
Pharmacokinetics is?
A
How the body acts on a drug
6
Q
What are the parts of pharmacokinetics?
A
Absorption, distribution, metabolism, excretion
7
Q
Where does the most drug absorption take place?
A
The small intestine
8
Q
Distribution occurs where?
A
in the bloodstream to different organs
9
Q
Where are drugs metabolized?
A
The liver
10
Q
Where are drugs excreted?
A
The kidneys, or the lungs if they are inhaled
11
Q
Oral Administration is?
A
cheap, easy, enteral, Absorption through the small intestine then it passes through the liver (liver inactivation) “first pass” effect, the liver breaks down the part of the drug before it gets into the bloodstream
12
Q
What are modified release tablets?
A
they release the drug over a period of time, slower release
13
Q
Parenteral administration is?
A
injection, fast, accurate, bypasses the liver
14
Q
Types of parenteral administration?
A
intravenous, subcutaneous, intradermal, intramuscular
15
Q
Inhalation administration is?
A
localized, systemic effects, lungs have a large surface area, easily enters the bloodstream, rapid effect (nicotine)
16
Q
Topical administration is?
A
skin, mucosal, skin patch slow absorption
17
Q
Sublingual administration is?
A
rapid, no first pass effect, under tongue
18
Q
The route of administration affects (2 things)?
A
- Time course
- Peak concentrations
- (speed + concentration)
19
Q
Will a drug given orally have lower max concentration in the blood then if given IV?
A
Yes, given orally the drug will be metabolized by the liver through the first pass effect and it takes longer to be absorbed
20
Q
Pharmacodynamics effects what body systems?
A
- Receptors
- Ion channels
- Enzymes
- Immune system
21
Q
What are the different levels of pharmacodynamics?
A
- Organ system
- Tissue
- Cell
- Subcellular target
22
Q
What causes side effects?
A
Side effects are the drug acting on other cells, other than its target
23
Q
AN antiviral drug…?
A
Targets the virus, drug binds to the active site, blocks the virus action
24
Q
what ways does an antihypertensive drug control high blood pressure?
A
- Act on the heart
- Act on the autonomic nervous system
- Act on blood vessels
- Act on the brain
25
What are two types of receptors? (locations)
intracellular receptors, receptors on the cell surface
26
What do antacids do?
controls acids in the stomach, used to help with stomach pain
27
What does an agonist do?
Agonist: binds and stimulates the receptor
28
What does an antagonist do?
Antagonist: blocks agonist/receptor action
29
What do allosteric modulators do?
Allosteric modulators: affect the level of response to an agonist (can modulate the response in a positive or negative direction)
30
what are ion channels?
Ion Channels: transmembrane spanning proteins that open to allow passage, voltage controlled or receptor controlled
31
A GPCR mechanism?
G-protein coupled receptor (GPCR):
- 7 transmembrane domains (cross plasma membrane 7 times)
- Agonist on the outside of cell (binding site)
- Triggers a change in the inside of the cell
- Alpha, beta, and gamma subunits
- Alpha subunit separates, GDP to GTP, activates effector protein
32
What is receptor turnover?
Receptors are constantly being synthesized and placed on the membrane
They are also broken down often
If a drug acts on a receptor, the body can turnover the receptor to get normal function back
33
What function do intracellular receptors have?
They alter gene transcription
34
ED50=?
Effective dose 50, The amount of a drug necessary to see a desired response in 50% of the population
35
why is comparing ED50s for different drugs helpful?
Comparing ED50s for different drugs is useful to see if one drug can have the same effect at a lower dose than another drug. (However, we must always consider the possible side effects of each drug not just compare the effective dose)
36
Threshold dose?
The amount of dose that needs to be given to get a minimal response
37
Ceiling dose?
Ceiling dose: when all people have a response or the maximal effect
38
Can an agonist cause a max effect if not all of the receptors are bound?
Yes, Usually only a small fraction of the receptors needs to be activated to have a max response
39
Do Drugs also differ in affinity for binding sites?
yes
40
A full agonist has a?
large effect, large stimulus to cellular signaling machinery
41
A partial agonist has a?
(small effect) small stimulus to cellular signaling machinery
42
Can a partial agonist have the same response as a full agonist?
No, they don't fully activate the receptor, they can decrease the effect of a full agonist
43
What is the function of an antagonist?
- Block receptor activation
- No response
- Block agonist activity
44
Types of antagonists?
Competitive vs. noncompetitive
Reversible vs. irreversible
45
Competitive antagonist features?
- Will compete with the natural ligand (or agonist) for the binding site
- Can out compete and block the response to stop activity
- Same binding site
46
Noncompetitive antagonist features?
- Different binding site than the natural ligand
- Still lowers the response
cannot block the response fully
47
Which way do competitive antagonists shift the dose response curve?
Shift to the right, need more agonist for the same effect
48
Which way does a noncompetitive antagonist shift the DR curve?
It does not shift the curve, it never allows the full response , the response drops as you add more antagonist
49
Irreversible antagonist features?
- The drug stays bound to the receptor
- The body needs to generate new receptors to the surface of the cell membrane to recover normal function
50
TD50=?
toxic dose 50% of the population
51
LD50=?
THe lethal dose for 50% of the population
52
What is the ideal dose response curve for a drug?
have 99% of people with a desired response and less than 1% of people with adverse effects
Ideal therapeutic window is no toxic effect with 99% of people efficacy (huge therapeutic index)
53
What drug has a huge therapeutic index?
Penicillin
54
Warfarin (anticoagulant) has a smaller therapeutic index, what are some side effects of this?
the adverse effects like bleeding are more common
55
Therapeutic index =?
TI = TD50/ED50 slope may vary so need to know the shape of the curve to see if desired effect does not overlap with toxic effects
56
What is a toxicity Outlier?
Toxicity outliers: no response at all
57
What is a benefit outlier?
Benefit outliers: respond at a small dose
58
Where are weak acids able to be absorbed?
In the stomach
59
Where are weak bases and most drugs absorbed?
In the small intestine
60
Is there a first pass effect with sublingual administration?
No, it goes right into circulation
61
Bioavailability?
Bioavailability: fraction of a drug administered reaching the systemic circulation
62
Which organs will be effected by a drug first?
Heart, brain, liver, organs that have high blood flow
63
What is the drug doing if bound to a protein?
It is not doing anything
64
What can a free drug do?
it is able to act on receptors, cross membranes, be metabolized and excreted
65
How can disease affect drug action?
Lag period, minimum effective concentration (MEC) for effect desired response, peak effect, Duration of action is time from onset of effect
66
Is the placenta an effective barrier to keep drugs out?
no
67
Magnitude of drug effect?
= Pharmacodynamics x pharmacokinetics x individual biological properties
68
Three compartment model?
- High blood flow organs (brain)
- Skeletal muscle
- Body fat (stick in body, effect prolonged, lipid soluble)
69
p-glycoproteins:
transports drugs across the plasma membrane (out of the cell)
70
Volume distribution (VD) = ?
VD = amount of drug in body/concentration in plasma
71
Volume distribution can vary due to :?
- Properties of the drug
- Protein binding
- Tissue binding
72
Protein binding effect on Volume distribution?
Protein binding = high concentration of drug in the blood = low AVD (apparent volume distribution)
73
Tissue binding effect on Volume distribution?
Tissue binding = low concentration of drug in the blood = high AVD
74
If a lot of the drug is in the blood?
There is a low AVD
75
Apparent volume distribution can be used to calculate loading dose because?
Volume distribution varies a lot from one drug to the next
76
What is metabolism?
- convert a drug to a less active or inactive metabolite (more water soluble)
- sometimes (rare) converts an inactive drug to an active one
The concentration of a metabolite increases over time and then goes down as it is excreted
77
Where does the blood from the small intestine go first?
It goes through the liver first, first pass effect
78
The liver?
- second largest organ
- greatest regenerative ability (fix damage to itself/other organs)
- vital for life
- Large functional reserve (can lose a lot before there is loss of function)
79
Why is the first pass effect important?
Sometimes a lot of the drug can be broken down and sometimes none of it will reach circulation
80
Phase 1 of metabolism: oxidation of a drug
- Can inactivate drug function, inactive metabolites
- Can make biologically inactive
Ex. Aspirin, hydrolysis, salicylic acid + acetic acid
Oxidation – inactive metabolite (sometimes still active
81
Phase 2 of metabolism: conjugation
- Put something on drug metabolites to get rid of it
- P450 enzymes, drugs fit into their active sites, drug metabolizing enzymes
82
What are P450 enzymes used for?
P450 enzymes are needed to break down food, steroid hormones, drugs, fatty acids, etc.
83
What are the main cytochrome P450 enzymes for drug metabolism?
CYP1, CYP2, CYP3 are the main ones for drug metabolism
Found in smooth E.R. of Hepatocytes (in liver), in GI tract, lungs, skin, kidneys
(CYP3A4, CYP2E1)
84
Drug metabolizing enzymes can vary from person to person?
Yes, they can also vary within the same person at different points in their lives
85
Does drug metabolism change as you get older?
- Tendency of drug metabolism to be slower in older people
86
Pharmacogenetics?
- Variability from one person to the next
- Look at variation in drug metabolism between people
87
What is polymorphic distribution?
- A trait that has differential expression in less than 1% of population
- Some people break down a drug fast, others very slowly
- Altered drug effect
88
What is an example of individual variation in P450 enzymes?
CYP450 2D6: some people overexpress, some people have none at all
89
What is CYP2D6 involved in?
It breaks down codeine to form morphine in the body
90
Example of a drug that can cause liver damage?
Alcohol
91
Phase 2 metabolites are easily?
easily excreted by the kidneys since they become water soluble
92
How are drugs excreted?
through the urine, some exhaled, some secreted on the skin, hair
93
Renal clearance?
Filtration + secretion – reabsorption
94
What is the half life of a drug?
the time it takes for half of the drug concentration to be eliminated from the body
95
How many half lives to eliminate a drug?
4 half lives
96
First order kinetics?
constant fraction per unit time (straight line)
97
If a drug is given at multiples of the half life how many will it take to have cycling at a steady state?
If give drugs at multiples of the half life in 4 x t1/2, you will reach cycling at a steady state
98
How can you better stay in the therapeutic range when giving a drug?
By giving the drug more times at a lower dose, you will stay in the therapeutic range and be more accurate
99
What is the biggest killer from overdose in the US?
Fentanyl
100
What is tolerance?
No longer respond to a drug and/or need a higher dose to get the same effect
101
what is drug addiction?
Substance dependence
Can have physical and or psychological dependence
102
Human tolerance study 1952?
Addict taking 20 times more per day than several moths before, since he built up a tolerance
103
Types of tolerance?
Acute, chronic, enate, pharmacodynamic, pharmacokinetic, behavioral
104
Pharmacokinetic tolerance?
Pharmacokinetic: lower concentration at the site of action (liver gets rid of the drug faster)
105
Pharmacodynamic tolerance?
Pharmacodynamic: lower effect due to biological adaptation (gets to site of action but doesn’t work as well)
106
Behavioral tolerance?
Behavioral: lower effect due to conditioned response
107
Acute tolerance: cocaine
- Response is much lower on second dose
- Brain adapts very quickly
the effect of the drug goes up fast but also come off fast, can become tolerant with just one dose
108
What is withdrawal?
an effect usually opposite to the drug effect, adverse effect
109
Withdrawal symptoms to a drug that causes inhibition when stop using it?
the body naturally corrected for the inhibition by adding more receptors (causing excitation) when the drug is removed the body there is more excitation and can cause seizures, convulsions
110
Presynaptic functions can adjust?
store, release, reuptake more/less depending on effect of the drug
Factors controlling transmitter synthesis
111
Postsynaptic functions can adjust?
ligand binding, taking into cell, into vesicles or release, degradation in lysosomes all can adapt
112
After chronic agonist, what happens to receptors?
Receptors are down regulated
113
After a chronic antagonist, what happens to receptors?
Receptors are up regulated
114
What is neuroplasticity?
networks can change, individual synapses, brain, spinal chords, many sites in a synapse where neurons can adapt
115
What is surmountable tolerance?
Surmountable tolerance: give enough to get the same effect (postsynaptic down regulation of receptors, if enough drug is given, it can flood the receptors to get the same effect as before)
116
What is insurmountable tolerance?
Insurmountable tolerance: cannot get the same effect (presynaptic decrease in neurotransmitters, decreases the synthesis of transmitters, even if more drug is given will not get the same production of neurotransmitters)
117
What is differential tolerance?
Morphine/fentanyl don’t only relieve pain, they have other effects on the body
We don’t become equally tolerant to the different effects of a drug
We become tolerant to morphine relief of pain over time, but eye constriction does not become tolerant
118
minimal tolerance to death
life systems do not decrease over time
119
Behavioral tolerance?
Initial exposure – compensatory reaction to the drug
Subsequent reactions
Environmental response – compensatory reaction to the drug
120
Behavioral tolerance can involve classical conditioning
- Inject alcohol before daily test
- 1st time decrease performance on test
- After a while performance back to normal
- Other group injection of alcohol after the test
- Other group no given alcohol before the test, did worse than the O.G. group
- No conditioning, cannot do the test well
121
How does the effects of withdrawal change depending on the drug half life?
o If it has a long half life there will be less symptoms because the amount of drug in the system (blood) is going down slowly
o If it has a short half life (cocaine) you come down fast and have more symptoms
122
What is drug rebound?
- Sleeping pill, brain adapts
- After a while you go back to the same effect of not being able to sleep
- Stop taking the pill, rebound in opposite effect, stay awake
- Can take even longer to get back to normal
123
What are 3 ways to treat drug dependance?
- Strongly decrease dose (ethanol)
- Substitute safer drugs, then decrease dose (opioids)
- Prevent relapse with antagonist or partial agonist
124
How do heroin, alcohol, cocaine and nicotine cause addiction?
They activate the reward pathway, release dopamine
125
