Pharmacology Flashcards
(163 cards)
1
Q
Pharmacology
A
study of how a drug interacts with the body
mechanism of a drug with a focus of how it is counteracting the disease
how is the drug interacting with teh body
2
Q
Toxicology
A
studying toxicity and harmful effects
3
Q
Pharmacy
A
focused to the clinical distribution and preparation - need to have clinical license to distribute and work with patients
4
Q
Pharmacokinetics
A
Focussed on processes that affect drug concentration in the body
What is the body doing to the drug
absorp, distribution, metab, elimination
5
Q
Pharmacodynamics
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What is the drug doing to the body - inc or dec HR..
Talking about receptors and signaling pathways that get activated
6
Q
Drug nomenclature - Chemical name
A
nobody really uses this
7
Q
Drug nomenclature - generic name
A
Every chemical has a generic name that never changes - more useful to look at generic name vs trade name
8
Q
Drug nomenclature - trade name
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company holds a patent on it but they expire and change so you can have multiple trade names for the same compound
9
Q
Prescription drugs
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drugs whose sale is restricted and available only with rx from licensed provider
10
Q
All rx drugs in US are controlled by
A
FDA - they decide if a drug requires an rx or not
11
Q
State decides
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who can prescribe the drug
PAs differ at state level
12
Q
Schedule 1 drugs
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High abuse potential, no medical use
Cant get licensed for sched 1
13
Q
Schedule 2 drugs
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High abuse potential, have medical use - potential for physiological and physical dependence (morphine)
14
Q
Schedule 3 drugs
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less abuse potential than 1 or 2, have medical use, low potential for physical dependence but high potential for psychological dependence (annabolic steroids)
15
Q
Schedule 4
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Less abuse potential than 3, have medical use, little potential of dependence
16
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Shcedule 5
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less abuse potential than 4, have medical use, limited dependence
17
Q
Pattern for schedule
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Abuse potential becomes less and there is some medical use for drug as you go down
18
Q
OTC medications - non prescription OTC meds
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Drugs that can be sold without directions for safe use by the public
19
Q
OTC meds - Variation
A
Packaged differently - from drug and therapeutic standpoint they are the same drug but might just have difference in flavor or something
20
Q
Monitoring OTCs
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Nonprescription drugs advisory committee of US FDA
Responsible for making recommendations on the removal of medications from OTC and addition of any to OTC
21
Q
OTCs have to be given significant consideration when treating a patient since:
A
- be a useful therapeutic option for patient
- may exacerbate a medical condition
- interact with another OTC or rx med
- Be used inappropriately
22
Q
Drug development - First
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Identification of a new compound - drug combo, new target, drug modification, mass screening
23
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Drug development - Second
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Experimentation - drug characterization (molecular, cellular) Toxicity (minimal lethal dose animal testing)
24
Q
Drug Development - Third
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Clinical testing
Phases
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Drug development - Phase 1
Limits of safe dosing range
| Subjects are low - goal is about the safety
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Drug development - Phase 2
Does it work?
| More subjects - is it doing what it is supposed to do
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Drug development - phase 3
Well controlled, more patients, see if it is working as expand population and still monitoring safety
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Drug development - phase 4
monitoring while being sold - postmarketing surveillance
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Drug classification - Drug action
Classification based on therapeutic action can result in a broad range of descriptiveness
Ex - antiviral agents
It is very broad and there is no ability to generalize the mechanism of action or side effects with this classification
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Drug classification - Molecular target
Dependent upon an understanding of the molecular target, can include receptors or enzymes
Ex - beta blockers
Need to understand physiology
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Drug classsification - molecular target - what can be predicted
broad distinctions like use, action, side effects
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Drug classification - Drug source
Based on natural source of the drug
| This name gives no indication of how it works or what the physiological target might be
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Drug classification - chemical nature
specific chemical name is rarely used but a broader grouping can provide info on structure, action, or use - grouping like steroid, barbituates..
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Drug classification - generic name
can be derived from chemical name and provides some indication for what class the drug belongs to
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Pharmacokinetics
```
Absorption
Distribution
Metabolism
Elimination
What the body does to a drug
```
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Pharmacodynamics
Drug targets or receptors effects
| What the drug does to the body
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Drug absorption
The movement of an agent from the site of administration into the circulation
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Three types of administration
Enteral
Parenteral
Topical
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Enteral includes
```
Anytime you are using the GI tract to deliver the drug
Oral
Sublingual
Buccal
Rectal
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Enteral - Oral
Taking pill - use stomach or intestine
Easiest and best compliance
First organ after absorbed is liver - could lose up to 8-% of the drug by this time so typically oral dose is higher because you are expecting to lose some with liver metabolism
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Enteral sublingual
under the tongue
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Enteral Buccal
btw cheek and gum
| Goes straight to venous system - not as convenient and compliance is lower
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Enteral Rectal
Good if targeting that tissue
Can also be good if want to use enteral but pt cant swallow
compliance is low and drug is not completely absorbed
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Parenteral
```
You have to pierce the skin
Intravenous
Intramuscular
Subcutaneous
Intrathecal
Epidural
```
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Parenteral - IV
most direct - put drug directly into circulation
| Administer exact amount - mistakes cant be made though
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Parenteral - IM
painful
| can get away with a single dose though and have it diffuse over time
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Parenteral Subcutaneous
insulin is common - cant do orally because stomach would digest
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Parenteral Epidural and Intrathecal
ways to target nervous system - subarachnoid or epidural space - very targeted nerve block
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Topical
```
putting drug on surface that is generally the target tissue - can be internal too though
Topical
Transdermal
Inhalational
Otic/Optic
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Topical - transdermal
applying a drug to the skin but hoping it goes through the skin and into the blood
BC path
Patch behind ear
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Topical - inhalational
breathing in - target might be mucous membrane of lungs but could also be systemci
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Topical - otic/optic
eye drops or ear drops - targeting that site specifically
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How are most drugs transported
passivelt
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Ionized vs non-ionized forms
Non ionized form more readily cross membranes
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Pronated vs unpronated
pronated form of a weak acid is nonionized
| unpronated form of a weak base is nonionized
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Weak acid - absorbed when
pronated (nonionized form)
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Weak base - absorbed when
unpronated (nonionized form)
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Hendersen Hasselbalch equation is used to determine
ration of ionized to non-ionized forms
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HH ratio is dependent upon
the pH (acidity) of the environment and the pKa (pH at which 50% of the drug is ionized and 50% is nonionized)
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HH equation
log (proton/unproton) = pKa - pH
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pKa is defined as
the point at which half is protonated and half is unprtonated
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If pH is less than pKa which form dominates
protonated
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If pH is more then pKa which form dominates
unprotonated
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The more hydrogen ions there are around, (the more acid that is around) the more likely
```
HA is to form
More acidic (lower pH) --> protonated will form
```
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Weak acids are protonated (HA) in
lower pH of the stomach
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Weak bases are nonprotonated in the
higher pH of the intestines
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Weak acids are more readily absorbed from the
stomach (low pH)
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Weak bases are more readily absorbed from the
intestines (high pH)
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GI contents impact absorption - why take some on empty stomach
so that you can get the max absorption and you can reach the therapeutic effect
even presence of just liquids can reduce absorption by 60%
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GI contents impact absorption - why take with a meal
you can slow down the transit time in the GI tract
You can get more absorption if you keep it in the stomach longer - same effect just get higher concentration in the blood if taken with meal
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Drug distribution
the process by which a drug leaves the circulation and enters the tissues perfused by the blood
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Factors that impact distribution
Cardiovascular factors (CO, blood flow, capillary perm, plasma protein binding)
Tissue binding
Drug molecular size
Lipid solubility
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Drug distribution - cardiovascular factors - Cardiac output
The greater the CO the more you are moving blood through the body so the quicker you will distribute it
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Drug distribution - cardiovascular factors - regional blood flow
The more vascularized the tissue, the more the drug has access to the tissue
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Drug distribution - cardiovascular factors - capillary permeability
impacts the acess that the drug has to tissue
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Drug distribution - cardiovascular - binding to plasma proteins
as drugs stick to plasma proteins in the blood some stick more than others and the stickier ones will be less distributed because get trapped in blood
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Drug distribution - tissue binding
once a drug is distributed to the tissue it can get help in that environment
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Drug distribution - drug molecule size
if it is a large drug may have more difficulty accessing the tissue
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Drug distribution - lipid solubility
the more lipid soluble the easier it is to cross membrane and barriers
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Drug metabolism/biotransformation
can be categorized as phase 1 and phase 2 biotransformation
| Reactions can covernt a parent compound into an active or inactive metabolite
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Drug metabolism - biotransformation primarily occurs where? What is the goal
liver
| goal is to take compound and make it hydrophilic (inc water solubility) to make it easier for kidney to excrete
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Phase 1 of biotransformation
Generate a more polar molecule by exposing a functional group on the parent compound
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Phase 2 of biotransformation
rxs yield a more water soluble conjugated product to be excreted
Stick a bulky group on it to make it water soluble
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Biotransformaion - lineality
not a very linear process
some are just eliminated, some start at phase 2 and some go 1 and then 2
Some even require the transformation before being distributed
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First pass effect
drug absorbed by stomach or intestine will first be carried to the liver by the portal vein - drug can be inactivated before even reaching the intended target
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First pass effect - impaired liver function
May have to take a lower dose because they've lost some of the first pass effect so more will get into circulation - danger of reaching toxic level
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Drug elimination - two types
Renal
| Fecal
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Drug elimination - Renal
Primary mechanism of drug elimination
Dependent on several processes - Glomerular filtration rate
- Binding to plasma proteins
- Alkalinization or acidification of urine
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Drug elimination - Fecal
Hepatic secretion into bile
| Enterocyte-mediated secretion
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Drug concentration - bioavailability
the amount of a drug that reaches the systemic circulation
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The bioavailability of a drug adminstered through IV will be
100% - direct administration into the blood
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What impacts the bioavailability of a drug
absorption, metabolism, distribution and elimination
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Most bioavailability to least
```
IV
IM
SC
Oral
Rectal
Inhalation
Transdermal
```
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Drug concentration - half life
The time it takes for the concentration of a drug in the plasma tod ec by 50% (so 50% is gone)
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What half life for most of drug to be gone
4th or 5th half life
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Drug concentration - steady state
the point during a dosing regimen when elimination of a drug is equal to the bioavailability
About 4 or 5 half lives
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When administering multiple doses why does conc plateua instead of continuing to inc
Dosing at every half life - by the 4th or 5th dose, the entire first dose is gone so you arent adding to that first dose anymore
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Drug concentration - the time to reach steady state conc is
NOT dependent on the dose or the frquency of doses - will always be the 4th or 5th half life
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The actual steady state concentration
is determined by dose and dosing frquency
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If you do not have time to wait for the 4 or 5 half lives - what can you do
IV administration or can give a loading dose (high dose on first day)
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Drug receptors
Recognize and bind other molecules (ligands/drug/hormone)
Propgate regulatory signals following ligand binding
Modulate ongoing cellular function
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Drug receptrs - 5 types
Intracellular
Receptors with intrinsic enzymatic activity
Receptors that directly associate with intracellular enzymes
Ligand gated ion channel
7 membrane spanning receptors
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Drug receptors - intracellular receptors
The drug or ligand has to diffuse the membrane to get to the receptor - has to be lipophilic
Drug binds to receptor and intracellular receptor goes into nucleus to change gene expression
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Drug receptor - receptors with intrinsic enzymatic acitvity
Drug binds to these receptors and brings them together (like an on switch) when they come together they act with substrates in the cell that are changed in some way to elicit a function - get some type of cellular change as result
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Drug receptor - receptors that directly associate with intracellular enzymes
drug binds to a receptor and turns on an associated enzyme
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Drug receptor - Ligand gated ion channel
Drug binds to receptor and you change opening or closing of the receptor and the movement of ions across it
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Drug receptor - 7 transmembrane receptors
Weaves in and out of membrane 7 times - G coupled protein receptors
Coupled with G protein that goes on to impact another molecule like cascade of events
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Do all drugs bind to a receptor to elicit response?
no, but most do
| Some we arent targeting receptors though like tums - we are taking it to neutralize and dec aciditiy
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Drug receptors - Receptor numbers
dynamic process - the number of receptors can change
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Drug receptors - Downregulation
Decrease in the number of receptors
| Continued stimulation of the receptor and the receptor will go away
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Drug receptors - Upregulation
Increase in number of receptors
Continued exposure to an inhibitor - you might have to inc dose because now you have more receptors to response and if you are blocking a response you now have more receptors to block
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Dissociation constant (Kd)
There will be one for every drug
| It will tell us a point where there is a mixture of half of your receptors bound to your drug and half are not
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Dissociation constant defines
a drugs affinity
Tells us how sticky the drug is - how tightly that drug is to the receptor
The faster you reach Kd, the more affinity a drug has - so you need less drug to bind half of the receptors
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EC50 =
concentration of drug that produces a half maximal effect/response
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Drug response - go on forever?
No, there is a saturation effect
| A drug response is saturable - there is a max effect
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Potency
A measurement of drug dose used to compare the relative affinity and effectiveness of two or more drugs
Usually done by comparing EC50 of two or more agents
Comparing which drug takes less conc to create a half max response
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Potency is a
comparison
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Efficacy
The max effect a drug can induce (Emax)
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Agonist
A drug or ligand that binds to a receptor and produces a molecular, cellular, or physiological response
Agonists stimulate a response
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Antagoist
A drug or ligand that binds to a receptor and inhibits the response produced by an agonist
Antagonists block a response
Two types
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Two types of antagonists
Competitive and Noncompetitive
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Competitive antagonist
Agonist and antagonist compete for the same binding site - only one can win though
Shift to the right in EC50
Max effect still achievable
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Noncompetitive antagonist
Agonist and antagonist bind to different sites
Dec in max effect because you are knocking out some of the receptors (structurally changed some of the receptors so that the normal hormone doesnt recognize it anymore)
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Partial agonist
A drug that produces a lower maximal response as compared to the agonist
Allows you to reduce responses without blocking them
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ED50
Median effective dose
Dose at which 50% of individuals exhibit a specific quantal effect
Dose where 50% get the effect
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TD50
Median toxic dose
| Dose at which a specific toxic effect occurs in 50% of the individuals tested
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LD50
Median lethal dose
Dose that is lethal for 50% of individuals tested
This is experimentally defined with animals
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TI
Therapeutic Index
Indicator of safey
The ratio of TD50/ED50
The greater the ratio (or the window btw) the safer the drug is because there is more room for error
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Tolerance
Decrease in drug response following repeated administration of the drug
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Causes for tolerance
changes in pharmacokinetic parameters, pharmacodynamic parameters, or behavioral changes
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Sensitization
Reverse tolerance
| Increase in drug response following repeated exposure to a drug
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Senxitization is seen more with
durg drug interactions - maybe one is blocking the metabolism of another so there is more drug available and person has larger response to it - more sensitization
Shift to the left on dose curve
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Additive effect
Occurs when two drugs given in combination produce a response that is consistent with each agents potency
20 + 20 = 40
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Synergistic effect
Response that is magnified beyond the sum of either agents agents potency
20 + 20 = 90
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Advantage to synergistic effect
You can use a lower dose of the synergistic combination to get your desired therapeutic effect and lower dose means less adverse effects
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Varations of drug response - genetic - Polymorphism
Variation in the genetic code present at an allele frequency of grater than or equal to 1% - so it is showing up over and over again
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Types of polymorphism
Single nucleotide polymorphisms (SNP)
| Insertions/Deletions (Indels)
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Single nucleotide polymorphisms
1 SNP every 300 - 1000 base pairs
| There is a change in one base in a DNA coding but it is showing up at a frequency of more than 1%
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Insertions/Deletions
Less frequent than SNPs
| An insertion or deletion of chunk of material that may or may not code for anything but it disrupts the coding
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Pharmacogenetics
The study of the genetic basis for variations in drug response
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Monogenic
Expression of a single gene results in a single phenotype
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Multigenic
Networks of genes acting together to create a single phenotype
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Recessive trait
Phenotype exhibited when a non functional allele occurs on both the maternal and paternal chromosome
Both mom and dad have bad copy and this gives child adverse outcome when processing drug
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Dominant trait
Phenotype exhibited when a non-functional allele occurs n either the maternal or paternal chromosome You only need a bad allele from either mom or dad and it gives you the bad response - outcome is no metabolism of the drug and toxicity can be huge
145
Co-dominant trait
Heterozygotes display an intermediate phenotype as compared to wild type and homozygotes Intermediate type where you have some in between response
Reduction in metabolism by maybe 50%
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Genetic testing can be helpful because
it can tell you if a drug will end up causing someone more harm - it may work well for some but harm others
Better to know that to treat everyone the same
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Monogenic vs. Multigenic
Monogenic (low, intermediate, high)
| Multigenic - not as simple to break down into categories - can be very difficult to manage
148
Codeine
Therapeutic effect of codeine depends on CYP2D6 metabolism to morphine
149
Variations in drug repsponse - Disease - Absorption
Tissue damage or alteration caused by disease can impact how a drug is absorbed
Ex: GI tract - if there is a dec in absorption of nutrients then probably not absorbing drug either
150
Variations in drug response - Disease - Metabolism and Elimination
Disease of tissue involved in metabolism and elimination can impact the pharmacokinetic parameters of a drug
151
Variations in drug response:
1. Genetics
2. Disease
3. Drug interactions
4. Age
5. Sex
6. Environment
152
Variations in drug response - drug interactions - Ciproflocacin and Ca
Some drug interactions can prevent the absorption of both the drug and the nutrient
distribution
153
Variations in drug response - drug interactions - Phenytoin and protein
Some drug interactions will alter the protein free and protein bound fractions of the drug thus increasing the free drug availability or drug
154
Variations in drug response - drug interactions - Ethinyl estradiol
Inc the metabolism and dec the bioavailability - so the drug is less effective
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Variations in drug response - drug interactions - Simvastatin
decrease in metabolism - patient at greater risk of experiencing adverse effects or altered therapeutic effects
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Variations in drug response - drug interactions - Lithium
Competition btw sodium and lithium can result in changes in excretion of the cations
157
Variations in drug response - drug interactions - Monoamine oxidase inhibitors
Drug interactions can increase the action of MAOIs
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Variations in drug response - drug interactions - Warafin
Inhibitory effect of warafarin can be overcome by excessive vit K - vit K can alter the actions of warfarin by reducing its effect
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Variations in drug response - Age
Pharmacokinetic and pharmacodynamic parameters will differ in geriatric and pediatric populations
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Variations in drug response - Age - Peds
Changes occur related to enzyme/protein expression patterns, body composition, and blood flow
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Variations in drug response - Age - Geriatrics
Decline in organ function, more likely to be ill and taking medication, population is more susceptible to variations in a drug response due to drug interactions or disease
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Variations in drug response - sex
Men and women differ with respect to body composition and thus the distribution of drugs may differ
Also there are difference in organ function and enzyme expression that can impact pharmacokinetics
163
Variations in drug response - Environment
Occupational exposure
Diet
Stress
Smoking/alcohol intake
