Dental Pharmacology Exam 1 Flashcards
xenobiotics
chemicals not synthesized in the body
pharmacodynamics =
Pharmacokinetics =
what the drug does to the body
what the body does to the drug
pharmacovigilance =
pharmacogenenics =
the safetly of the drug
variations in response due to genetic differences
examples of drugs that do not follow the receptor method of action
antacids
osmotic diuretics
most drug/receptor bonds are (weak or strong) and are classified as ______ type.
weak
van der waals
name 6 receptor types
transmembrane ion channel transmembrane G protein transmembrane enzymatic cytosolic domains intracellular adhesion extracellular enzyme
explain the nicotinic Ach receptor
- ligand gated ion channel
- the ligand binds to the channel
- allows permeability to Na
G protein activation steps (4)
- Agonist binds
- GTP attaches to Alpha unit, displacing GDP
- alpha-GTP diffuses to the effector
- effector activation
activating adenyl cyclase is (inhibitory or stimulatory)?
stimulatory
major G proteins and their actions (5)
- G(s) = stimulatory = activates adenyl cyclase
- G(I) = inhibitory = inhibits adenyl cyclase
- G(0) = inhibits Ca channes
- G(q) = activates phospholipase C
- G(12/13) = ion transport interactions
Adenyl cyclase reaction
ATP —–[adenyl cylase]——> cAMP——>PKA———> Protein phosphorylation
Phospholipase C reaction
PIP3——-[PLC]——–> DAG + IP3
DAG——–> PKC——–> protein phosphorylation
IP3———-> Ca————> protein phosphorylation
Intracellular receptor example = ______
important characteristics to know about the ligand
steroid hormone, thyroid hormone
- lipohillic
- binds a transcription
- causes changes in genome/protein translation
Ligand A increases cAMP and Ligand B decreases cAMP
Net result?
they cancel each other out
tachyphylaxis
RAPID/REPEATED administration of the SAME DOSE of a drug, resulting in REDUCED effect over time
desensitization
decreased ability of a receptor to respond to stimulation
homologous desensitization vs. heterologous
homo = one receptor has decreased response
hetero = 2 or more receptors have decreased response
inactivation of receptor =
refractory =
down- regulation =
inactivation = loss of ability for a receptor to respond to stimulation by drug or ligand
refractory = a period of time before the next drug/receptor interaction can produce an effect
down-regulation = less receptors available due to persistent drug-receptor interaction
describe down regulation of a receptor
- LESS receptors available due to CHRONIC drug interaction
- the receptor is INTERNALIZED in the cell and SEQUESTERED or DEGRADED
Kd =
K(off)/K(on)
affinity and Kd relationship
inc Kd
dec affinity
Drug A: 3 mg binds 50% of ther receptors
Drug B: 1 mg binds 50% of the receptors
Which has higher affinity? Kd?
Drug B = higher affinity, lower Kd
Kd occurs at ____% binding.
50%
KNOW : graphs on Lecture 1/2 slide 32
:)
On the drug-receptor binding curve:
- 0 LR/R0 =
- 5 LR/R0 =
- 0 = 100% binding
0. 5 = 50% binding
dose-dependent response =
as you increase the dose, you increase the effect
Kd = EC50 means that
at 50% receptor/drug binding, you get 50% of the effect
- does not always occur
ED50
TD50
LD50
- effective (therapeutic) dose = 50% of the pop has a therapeutic response
- toxic dose = same but toxic response
- lethal dose = same but lethal response
which statement is correct?
- The receptor must be bound to the ligand in order for the response can occur
- The receptor may not be bound to the ligand and can till cause a response
2
“some receptors can spontaneously activate with binding of a drug”
CHECK!!!!!
antagonist (2)
- no intrinsic activity
- cause no response
Competitive antagonist binds ____ on the receptor and is (IRREVERSIBLE or REVERSIBLE)?
at the active site
reversible
Non-competitive antagonists bind _____ on the receptor and are (IRREVERSIBLE or REVERSIBLE)?
at the ACTIVE SITE or ALLOSTERICALLY
active site = irreversible
allosteric = both irreversible and reversible
full agonists have an intrinsic activity =
Pure antagonists have an intrinsic activity =
1
0
potency =
efficacy =
potency = response of a drug over a given range of concentrations
- the effective CONCENTRATION (of the agonist) leading to its high maximal effect
efficacy = effect of a drug
define intrinsic activity
maximal effect of a drug or EFFICACY
graph:
y axis: % max response
x axis: [agonist]
in the presence of a COMPETITIVE agonist:
- the curve will shift which way?
- what happens to max response
- curve shifts to the right
- max response remains the same because eventually the the reversible antagonist will pop off.
graph:
y axis: % max response
x axis: [agonist]
in the presence of a NON-COMPETITIVE agonist, what happens to?
- potency
- efficacy
- potency = unchanged
- efficacy = less max activity bc some receptor activity is blocked
In the presence of a non-competitive antagonist, the max activity is (INCREASED or DECREASED)?
- The max activity will be unchanged if, ______ is present?
decreased
spare receptors (and if there is a LOW dose of non-comp antagonist)
Partial agonist =
inverse agonist =
partial = activates receptor but not at max efficacy
inverse = inactivates active receptor
Competitive antagonist:
- effect on potency?
- effect on efficacy?
- action:
- potency = yes
- efficacy = no
binds REVERSIBLY the active site of the receptor, COMPETES with agonist binding.
_____ prevents receptors from going into spontaneous activity
and DEFINE how they achieve this (2)?
inverse antagonist
- have opposite effects of the agonist
- prevents baseline activity of the receptor
spare receptors
- define
- how do they affect EC50 and Kd
50% response before you get 50% binding
EC50 is lower than Kd
Competitive antagonist:
- effect on potency?
- effect on efficacy?
- action:
- potency = no
- efficacy = yes
- binds IRREVERSIBLY to the active site OR allosterically
- prevents conformational change of the receptor
therapeutic index formula =
TI = TD50/ED50
narrow therapeutic window means
- only effective in a narrow range of concentrations
- increased concentrations the drug may become toxic.
What are the four ways in which the body handles the drug
- absorption
- Distribution
- Metabolism
- Excretion
which statement is true?
- When bound to a binding protein, the drug can not be excreted or metabolized.
- In order for the drug to be metabolized or excreted it must be bound to a binding protein.
- When bound to a binding protein, the drug can then bind its receptor
1
Brain capillaries are surrounded by _______ so drugs (can/cannot) pass into the brain
astrocytes
cannot
Blood brain Barrier
Blood brain barrier is permeable to primarily very ______ molecules
lipophilic
Weak acids (e.g. _________ ) are absorbed better in _______ environments (e.g ________).
These weak acids will exist in a ______ form.
aspirin
acidic environments
stomach
HA (uncharged form)
Concentration - TIme curve graph.
Describe
- elevating absorption phase
- rapid declining distribution
- declining excretion phase
Concentration-Time curve graph
Define Cmax, Tmax, half life
Cmax = maximal concentration at full absorption before distribution occurs.
Tmax = the time that Cmax occurs
half life = time to go from Cmax to half max concentrion
PLASMA CONCENTRATION!
Bio availability
the amount of drug administered that actually gets absorbed
first pass metabolism
when drugs get immediately exposed to liver metabolsm
which route of drug administration is more likely to be exposed to first pass metabolism
oral/enteral
Volume distribution (also known as ______) = (FORMULA)
apparent volume
= total amount of drug in the body/drug blood plasma concentration
Weak bases (e.g. _________ ) are absorbed better in _______ environments (e.g ________).
These weak bases will exist in a ______ form.
codeine
basic environments
intestine
A- + H+
High sequestration in the plasma suggests a _____ volume of distibution
LOW
Loading Dose = (FORMULA)
(desired plasma concentration) x (Vd)
Parenteral route of drug administration refers to the administering of drugs ________. Name a view disadvantages
pain
infection
irreversible
skilled personnel
- Highly lipophilic drugs might be distributed to ___ tissue
- Ions might be distributed to ____ tissue
- highly plasma protein-bound molecules
- small water soluble molecules
- large water soluble molecules
- adipose tissue
- bone and teeth
- plasma
- total body water
- extracellular water
high volume of distribution suggests that
the drug is stored in tissue other than blood plasma (e.g. fat)
site or parenteral route drug adminsteration
- subcutaneous (lidocaine)
- intramuscular
- intravenous (morphine)
- intrathecal = Blood brain barrier
Transdermal administration of drugs requires _____ type of drug. Name 2 disadvantages
highly lipophilic
- slow delivery to the site of action
- irritating to skin possibly
IV administration of a drug has an altered concentration-time curve. this is due to_____
very rapid absorption phase because the drug is absorbed immediately.
Describe the concentration-time graph if:
- distribution only (no excretion)
- excretion only (no distribution)
- both distribution and excretion
- distribution will plateau eventually (equilibrium)
- with excretion only, the excretion phase will decline in a linear continuous pattern
- rapid distribution decline and slower excretion decline (both linear)
Polar substances are excreted via _____.
Non-polar substances are excreted via ____.
Which is most common means of excretion?
urine
bile
Urine
elimination includes (2)
metabolism and excretion
Which route of drug administration requires a highly lipophilic drug
- may cause infection?
- few drugs are available in this method?
- susceptible to first pass metabolism
- slow delivery to site of action
- transdermal
- parenteral
- muscous membrane
- oral
- oral and transdermal
Phase 1 metabolism =
Phase 2 metabolism =
- oxidation/reduction phase (Cytochrome P)
- conjugation reactions (glucoronation)
During renal excretion ____% of plasma is filtered.
10%
During renal excretion, some substances are actively secreted (example ___________) and have a ______ half life
penicillin
short
Clearance formula
clearance = (metabolism + excretion)/[drug]
As Vd increases, what happens to the half life?
As Clearance increases, what happens to the half life?
- increases
- decreases
How is half-life effected? (increased or decreased)
- aging
- obesity
- pathologic fluid
- cytochrome P450 induction
- CYP450 inhibition
- cardiac failure
- hepatic failure
- renal failure
- decreases (dec muscle mass dist)
- increases (increased adipose tissue dist.)
- increases
- decreased
- increased
- increased
- increased
- increased
Zero order vs. first order
- Enzyme systems are saturated during
- Constant amount of drug is eliminated per unit time
- Constant fraction of drug is eliminated per unit time
- Most common form of elimination
- elimination is linear
- easier to get into the toxic range
- Zero
- Zero
- First
- First
- Zero
- zero
ethanol is eliminated via ____ order elimination
zero
Concentration steady state define
concentration of blood when the rate of input of the drug equals the rate of output.
Loading dosage define
an increased amount of drug to get the pt into the therapeutic range faster
It takes approximately ____ elimination half lives to reach steady state on any drug regimen
4
Half-life formula =
t1/2 = (Vd x 0.693)/CL
- Continuous infusion of the drug
- Infrequent large doses
- frequent small doses
which can keep the pt within the therapeutic range?
continuous infusion of the drug
freq small doses
Maintenance dose =
concentration steady state x clearance
CYP450s have _____ which aids in the oxidation process
heme groups
True or false.
CYP450 oxidation must occur before Phase II metabolism may occur
false
Conjugation reactions make substances more hydro______ by adding ____ species.
hydrophilic
polar
examples of Drug transport proteins
MDR1
OATP
OCT
Statin is a P450 substrate. St. John’s wart is an inducer. If a pt is taking both, what will happen to:
- metabolism of statin
- effective concentration of statin
- increased metabolism
- lower effective concentration
Most common form of P450.
second most common form of P450.
- most common = 3A4
- second most common = 2D6
