Pharmacodynamics - Mechanism of drug action Flashcards
what two factors determine how quickly a drug initiates an effect and how long the effect lasts
strength and length
penicillin binds to what enzyme on bacterial cell wall to prevent cross linking
transpeptidase
this means if the bacterial load is high a higher dose of penicillin must be given to completely eliminate the bacteria from the body
factors that can affect the pharmacodynamics of a drug include
change in receptor binding
alteration in level of binding protein
decrease receptor sensitivity
genetic mutation
selectivity
malnutrition
aging
effects of other drugs
All drugs only alter the pace of ongoing activity and do not impart new functions on any system or organ
T or F
F
the only exception to this rule is gene based drugs
stimulation and depression is applied to specialized cells while irritation is applied to non specialized cells and is non selective
T or F
T
activated charcoal binds with poisons in stomach is an example of what mechanism of drug action
physical mechanism
in physical mechanism there is no change to cells in the body and the drug effect is strictly physical
other examples include
mannitol as an osmotic diuretic
bulk laxatives e.g ispaghula
example of chemical mechanism of drug action include
antacids e.g NaHCO3
acetylcholineesterase reactivator e.g pralidoxime
cholestyramine for bile and cholesterol sequestration
Chelating agents e.g dimecaprol, penicilamine, desferroxiamine
angiotensin converting enzyme inhibitors use what kind of inhibition
e.g captopril
competitive inhibition
reversible cholinesterase e.g neostigmine
and xanthine oxidase inhibitor e.g allopurinol
are all examples of competitive inhibitors
T or F
T
the action of allopurinol on xanthine oxidase enzyme is what kind of antagonism
competitive inhibition
the effect of aspirin on cyclooxygenase is what kind of inhibition
non competitive inhibition
omeprazole deactivates proton pump in stomach via what mechanism
non competitive inhibition
irreversible anticholinesterase like organophosphate and insecticide act via what mechanism
non competitive inhibition
monamine oxidase inhibitors e.g imipramine act via what mechanism
non competitive inhibition
list 2 examples each of channel blockers of these ions
1. Na
2. K
3. Ca
4. Cl
- Procainamide, quinidine, local anesthetic (
- Amiodarone, sulfonylurea
- nifedipine, verapamil, diltiazem
- benzodiazepens
list 2 uses each of channel blockers of these ions
1. Na
2. K
3. Ca
4. Cl
- Arrhythmia and anesthetic
- Arrhythmia(blockage causes prolonged refractory period)
- Arrhythmia and hypertension
- the slide explanation just dey somehow man
if you see it in incourse skip it
list the inhibitors of these carriers
1.noradrenaline vessicular uptake
2.neuronal reuptake of noradrenaline
3.neuronal reuptake of serotonin
4.weak acid(e.g uric acid) carriers
1.reserpine
2.desipramine
3.fluoxetin
4.probenecid (thus prevents uric acid reabsorption and facilitate excretion)
The specific chemical constituent of the cell with which drugs interact with to produce it’s pharmacological effect is the
Receptor
drug receptors are regulatory micromolecules
T or F
F
macromolecules
list the 4 characteristics of receptors
The 4 S
sensitivity
specificity
selectivity
saturability
list 4 molecules that can serve as a receptor
Enzymes
membrane proteins
nucleic acid
complex polysaccharides
an agent which activates a receptor to produce submaximal effect but antagonizes the agonist is called
a partial agonist
an agent which activates a receptor to produce an effect opposite to that of an agonist is called
inverse agonist
e.g Beta Carboline
the capacity to induce functional changes in the receptor in a way that produces an effect is called
Intrinsic activity / efficacy
irreversible anticholinesterase e.g organophosphates form what kind of bond
covalent bond
most drugs employ what kind of bond to receptors
ionic bond
a receptor would produce a response only when it is occupied by an appropriate ligand with the response directly proportional to the fraction of occupied receptors
This theory is called
Occupancy Theory
this means maximal respones will only occur when all the receptors are occupied
response is proportional to rate of onset and offset of drug binding to receptor
response is proportional to rate of drug-receptor Complex dissociation
The above statement describes what Receptor theory
Rate theory
according to rate theory ______ determines whether a ligand is an agonist, antagonist or partial agonist
the duration of drug-receptor Complex dissociation
response is directly proportional to intrinsic activity and fraction of occupied receptors
the receptor theory above is called
Stephenson Theory
Response is a function of affinity, maximum response can be produced without 100% occupancy
Ariens theory
binding of ligand to receptor is based on plastic modeling with receptor and ligand both undergoing a dynamic process
with agonist inducing conformational change in the receptor
the receptor theory above is the
induced fit theory
when a drug receptor interaction occurs either a specific conformational pertubation(by agonist) which leads to a biological response or a nonspecific conformational pertubation(by antagonist) which leads to no response
This receptor theory is called
Macromolecular conformational theory
List 6 the receptor theory
- Occupancy theory
- Rate theory
- Stephenson theory
- Ariens theory
- Induced fit theory
- Macromolecule Pertubation theory
Receptors have 2 domain which are
Ligand binding domain
Effector domain
it is the effector domain that undergoes conformational change
the basis for designating receptor subtypes is the
relative tissue distribution of receptor
receptor subtypes such as serotonin(5-HT) where delineated from each other based ____
high affinity and displacement by various selective agonist/antagonist
receptors without a known ligand are called
orphan receptors
receptors/site which binds specific drugs without eliciting a pharmacological response are known as
Silent receptors/Drug acceptors/ Site of loss
e.g plasma proteins
the remaining unoccupied receptors in a tissue are called
spare receptors
in upregulation there is increase in number of receptors with subsequent increase in sensitivity
T or F
T
list 2 disease in which there is mutations of genes encoding for G protein coupled receptors
Cancer
Hypoparathyroidism
list the 4 major categories of transducer mechanism
GPCR
receptors with intrinsic ion channels
receptors linked with enzymes
transcription factors(receptors for gene expression)
GPC-receptor have how many transmembrane domain
7
GPCR have ___ alpha helical membrane spanning hydrophobic amino acid segments
7
gpcr have how many loops
3 intracellular and 3 extracellular
6
ligand gated ion channels open very fast and are thus confined to excitable tissue
T or F
T
G proteins have how many sub units
3
Ga GB GY
G proteins are classified into Gi, Gs and Gq based on
their Ga subunit
list the functions of these G proteins
1.Gi
2.Gs
3.Gq
4.Go
1.inhibits adenyl cyclase
2.stimulate adenyl cyclase
3.stimulates phospholipase C
4.inhibits calcium channel
there’s a G12/13 which regulates actin cytoskeletal modeling in migrating cells or cancer cells metastatic
list the 3 second messenger system
CAMP
CGMP
Calcium and phosphoinositol system
in their inactive form G proteins are bound to
GDP
the G protein is bound to the receptor in its active state
T or F
F
in its inactive state
when it the receptor is stimulated it activates the G protein which subsequently detaches from the receptor
this detachment allows the receptor to bind more inactive G proteins and activate them
what are the 3 possible targets for G proteins
adenyl cyclase (for CAMP formation)
phospholipase c (for Ip3 and DAG formation)
ion channels (particularly Ca and K)
the GBY dimer formed (when the G protein is activated and split) function in
modulation of signal
