Pharmarcodymamic Flashcards
Pharmacodynamics describes the effect of _____
the drug on the body
The components of pharmacodynamics includes
*Drug ____(___)
*Drug ____(_____)
Action; invisible
Effect; visible
DRUG ACTION
-Drug action refers to the mechanism by which _______
the drug produces desirable or undesirable effects in the body
TYPES OF DRUG ACTION
-list 5
Stimulation
-Depression
-Irritation
-Replacement
-Cytotoxic
Stimulation
Involves ________
E.g. ___ in Cardiac arrest
the selective enhancement of specific activity done by a specialized cell
Adrenaline
Depression
Involves the ______
E.g. _____ for Hypertension
selective diminution of specific activity done by a specialized cell
Lisinopril
Irritation
Involves producing ______
E.g. ——- for Joint and Muscle pain
non selective noxious effect on non-specialized cells
Methylsalycylate
Replacement
Involves _______
E.g ______ in Diabetes Mellitus
replacement of deficient endogenous substances
Insulin
Cytotoxic action
Involves the _______, usually ———- or _____, without significantly affecting other cells
E.g. ———- for cancer
selective destruction of cells
neoplasm or microbes
Cyclophosphamide
MECHANISM OF THE DRUG ACTION
_____
_____
____
Physical
Chemical
Biochemical
Physical mechanism
-Drug neither produces a _____ or _____
-Effect are purely _____
-E.g.
*______ for Constipation
*______ binds with Poisons
*_____ as an Osmotic diuretic
chemical reaction or change in the cells of the body
Physical
Laxatives
Activated charcoal
Mannitol
Chemical mechanism
-Drugs act by producing ______
-E.g.
*_____ for dyspepsia
*______ as chelating agents.
*_____ as a choline esterase reactivator.
*Cholestyramine for sequestration of bile acids and cholesterol in the gut
a chemical reaction in the body
Antacids
Deferoxamine
Pralidoxime
Biochemical mechanism ( _____ )
List them
RICE
Receptors
Ion channels
Carrier
Enzymes
Receptors
______ for Asthma
Ion channels
______ for Local anesthesia
Carrier
______ for Peptic Ulcer Disease
Enzymes
______ for Hypertension
Albuterol
Lidocaine
Omeprazole
Captopril
RECEPTORS
Ligand gated channel receptors
-Location: ____
-Effectors:____
-Coupling: ____
-Examples: GABA Type __
-Drugs: ——
-Structure: Oligometric assembly of subunits surrounding central pore
Membrane
Ion channel
Direct
A
Benzodiazepines
G-protein coupled receptors
-Location:_____
-Effectors: _____
-Coupling:______
-Examples:_____
-Drugs: _____
-Structure: Monomeric or Dimeric structure comprising seven transmembrane helices.
Membrane
Channel or Enzymes
G-protein
Muscarinic receptors
Atropine
Enzyme linked receptors
-Location: ____
-Effectors: _____
-Coupling: ____
-Examples:______
-Drugs:_____
-Structure: Single Transmembrane Helix linking extracellular receptor domain to intracellular kinase domain.
Membrane
Enzyme
Direct
Insulin receptors
Insulin
Intracellular receptors
-Location:_____
-Effectors:______
-Coupling:_____
-Examples:______
-Drugs:_____
-Structure: Monomeric structure with separate receptor and DNA binding domains.
Intracellular
Gene transcription
via DNA
Steroid receptors
Steroid
DRUG RECEPTOR RELATIONSHIP
____
_____
Affinity
Intrinsic activity
Affinity (A):
________
Propensity of a drug to bind with a given receptor
Intrinsic activity (I.A):
Capacity of a drug to ________
induce functional change in a given receptor in a way that produces a biological response
all drugs have intrinsic activity
T/F
F
Not all
if a drug is using a receptor, there must be ____ and ____
affinity and a bond
DRUG RECEPTOR OUTCOME
List 4
Full agonist
Partial agonist
Inverse agonist
Antagonist
Full agonist
Drug that _______
Full Agonist = A + I.A =___
stimulates a given receptor to produce a maximal biological response
1
Partial agonist
Drug that ________
Partial Agonist = A + I.A = ___
stimulates a given receptor to produce a sub-maximal biological response
> 0 but < 1
Inverse agonist
Drug that _____
Inverse Agonist = A+ I.A = ____
interacts with a given receptor to produce a negative biological response
< 0 but > -1
Antagonist
Drug that _____
Antagonist = A + I.A =__
interacts with a given receptor but does not produce any response
0
DRUG RECEPTOR REGULATION
Up-regulation
Increase in the _____ leads to
Increase _____
Down-regulation
Decrease in the ______ leads to
Decrease ______
number of receptors
sensitivity of the receptor
number of receptors
sensitivity of the receptors
What are:
Spare receptors
Silent receptors
Ise, know it!!!!
A receptor may exist in two interchangeable states, ______ and ______ which are in equilibrium.
active (Ra) & inactive (Ri)
______- any molecule which attaches selectively to particular receptors.
Ligand
Affinity -The ______ of the (reversible or irreversible?) interaction between ______ and ______, as measured by the ______, is defined as the affinity of one for the other.
strength; reversible
a drug and its receptor
dissociation constant
Intrinsic activity – capacity to induce a ______ in the ______.
functional change
receptor
Specificity - A drug that interacts with a single type of receptor that is expressed on only a limited number of differentiated cells will exhibit (Low or high?) specificity.
High
Agonists are ___ that bind to physiological receptors and mimic the ________ of the endogenous signaling compounds
Drugs
regulatory effects
If the drug binds to the same recognition site as the endogenous agonist the drug is said to be a _______
primary agonist.
endogenous agonist’s attachment site is the ______ or ________ site on the receptor
primary or orthosteric
Allosteric agonists bind to a (same or different?) region on the receptor referred to as ________ site.
Different
An allosteric
Antagonists are Drugs that (aid or block?) or (increase or reduce?) the action of an agonist
Block
Reduce
Antagonism most commonly results from competition with an agonist for the same or overlapping site on the receptor (a ______ interaction)
syntopic
Physical antagonist binds to the drug and prevents ________ like _____ binds to ______ and prevents _______.
its absorption
charcoal; alkaloids
Their absorption
Chemical antagonist combines with a substance _____ally like _______ binds with the metals.
chemic
chelating agents
Physiological antagonist produces an action (similar or opposite?) to a substance but by binding to the (same or different?) receptors
e.g. adrenaline is a physiological antagonist of _____ because adrenaline causes broncho_____ by binding to ____ receptors, which is opposite to broncho________ caused by _____ through ____ receptors.
Opposite
Different
histamine
dilatation; β2
constriction; histamine ; H1
Partial agonists -Agents that are ________ regardless of the concentration employed.
only partly as effective as agonists
Inverse agonists -Many receptors exhibit some _______ in the absence of a _____; drugs that _____ such receptors in an ______ conformation are termed inverse agonists (produce effect opposite to that of agonist).
constitutive activity
regulatory ligand
stabilize
inactive
Efficacy of an agonist is A ________ an agonist can produce.
It can be measured with a _________ only.
maximal effect (Emax)
graded dose-response curve
Potency is The _______________
amount of the drug needed to produce a given effect.
potency is not determined by the affinity of the receptor for the drug.
T/F
F
The dose causing 50% potency from the maximal effect (ED50) can be obtained from ________.
graded dose-response curve
In ______________ curve, ED50, TD50 and LD50 are potency variables.
quantal dose response
Repeated administration of a drug results in diminished effect “ _______ ”.
Tolerance
List the types of tolerance
Tachyphylaxis
Desensitization
Tachyphylaxis: is a type of tolerance which ______
occurs very rapidly.
Desensitization: ___eased response to the agonist after its _______ in (small or large?) doses.
Decr ; repeated injection; small
Desensitization
May be due to
1- ______ or ______ of the receptors.
2- Loss of receptors (_____)- due to _____ or ______
3- Exhaustion of _________ (depletion of catecholamine).
Masking or internalization
down regulation
decreased synthesis or increased destruction.
mediators
Answer with competitive or non competitive antagonist
Antagonist binds with the same receptor as agonist
Antagonist chemically resembles the agonist
Competitive
Competitive
Effect of competitive antagonist on agonist Drug response curve?
Parallel rightward shift of agonist DRC
Effect of non competitive antagonist on agonist Drug response curve?
Flattening of agonist DRC
With non competitive antagonism, the antagonist appears to have inactivated a number of receptors
T/F
T
In ______ antagonism, the intensity of response depends on the conc of both agonist and antagonist
Competitive
In ______ antagonism, the intensity of response depends on the conc of only the antagonist
Non competitive
Examples of competitive antagonism
Ach -
Morphin-
Atropine
Naloxone
Examples of non competitive antagonist
Diazepam-
Bicuculline
Drug synergism is When ______________________________ they are said to be synergistic.
the action of one drug is facilitated or increased by the other,
In a synergistic pair, both the drugs can’t have action in the same direction
T/F
F
They can
In a synergistic pair, given alone one may be ____ but still ______ the action of the other when given together.
inactive
enhance
Additive
The effect of the two drugs is in (the same or different?) direction and simply adds up:
The same
In an additive drug pair,
effect of drugs A + B = ______________
effect of drug A + effect of drug B
In a Supraadditive (aka _____ ) drug pair, The effect of combination is (lesser or greater than or equal to?) the individual effects of the components
potentiation
Greater than
In a supradditive drug pair,
effect of drug A+ B __ effect of drug A+ effect of drug B
>
Physiological receptors
List 6
GPCR
Ion channels
Transmembrane enzymes
Transmembrane, non-enzymes
Nuclear receptors
Intracellular enzymes
Physiological receptors have at least two major functions, ______ and ________
ligand binding and message propagation
Two functional domains within the receptor:
-________ domain and
-________ domain.
ligand-binding
effector
The regulatory actions of a receptor may be exerted directly on its ______, on ________, or may be conveyed by intermediary cellular signaling molecules called ______.
cellular target(s)
effector protein(s)
transducers
In Ligand gated ion channels, there is little intervention of G-protein or second messenger.
T/F
F
None
For ligand gated ion channels, Response is (slowest or fastest?) (in _______).
fastest
milliseconds
GPCRs a family of ______ GTP-binding regulatory proteins termed _______
heterotrimeric; G proteins
G proteins are _______ that convey the information that agonist is bound to the receptor from the ______ to one or more ________
signal transducers
receptor
effector proteins.
The G protein heterotrimer is composed of a ____ nucleotide-binding ___ subunit, which confers specific recognition to _____ and _____, and an associated dimer of _____ and _____.
guanine
α
both receptors and effectors
β and ϒ subunits
G–protein-regulated effectors include enzymes such as
-________,
-_______,
-___________ (PDE6),
-membrane ion channels selective for _______
adenylyl cyclase
phospholipase C
cyclic GMP phosphodiesterase
Ca2+ and K+.
GPCRs span the plasma membrane as a bundle of __________.
seven alfa-helices
GPCRs serve as (Intra or Extra?) cellular binding site for ligand and ______ binding site for transducer G-protein.
Extra
Cytosolic
Active alpha-GTP returns to basal state by ____ proteins
RGS
G-proteins :
The subunits fall into four families (_____,_____,____, and _____).
Gs, Gi, Gq, and G12/13
The Gs α-subunit uniformly (activates or inhibits?) _________
the Gi α-subunit can (activate or inhibit?) certain isoforms of _____;
the Gq α-subunit (activates or inhibits?) all forms of ________
the G12/13 α-subunits couple to _________(GEFs), such as p115RhoGEF for the small GTP-binding proteins ___ and _____
Activates ; adenylyl cyclase
Inhibit; adenylyl cyclase
Activates; phospholipase C
guanine nucleotide exchange factors ; Rho and Rac.
RESENSITIZATION AND DOWN-REGULATION OF RECEPTOR
1)
Agonist binding to receptors initiates signaling by promoting receptor interaction with G proteins (Gs) located in the cytoplasm.
Agonist-activated receptors are phosphorylated by a _________, preventing receptor interaction with ___ and promoting binding of a different protein, - ______, to the receptor.
G protein-coupled receptor kinase (GRK)
Gs
β arrestin (β-Arr)
RESENSITIZATION AND DOWN-REGULATION OF RECEPTOR
2)
The receptor- β arrestin complex binds to ____, promoting ______
________________ reduces - β Arr binding affinity, allowing _______ of receptors by ______.
coated pits; receptor internalization.
Dissociation of agonist from internalized receptors
dephosphorylation; phosphatase
RESENSITIZATION AND DOWN-REGULATION OF RECEPTOR
3)
Return of receptors to the ______ result in the efficient resensitization of cellular responsiveness.
Repeated or prolonged exposure of cells to _____ favors the delivery of internalized receptors to _____ , promoting receptor ______ rather than _______
plasma membrane
agonist
lysosomes
down-regulation
resensitization
Enzyme linked receptors
Either
1) With ___________.
or
2)Without _________(but bind a ______ on activation
intrinsic enzymatic activity
intrinsic enzymatic activity ; JAK-STAT kinase
JAKs- STATS PATHWAY
Binding of the cytokine causes _____ of the receptor and recruits the _____ to the cytoplasmic _____ of the receptor.
JAKs __________ and lead to the phosphorylation of the _______.
The phosphorylated STATS translocate to the _____ and __________
dimerization; Janus Kinases (JAKs); tails
trans-phosphorylate; signal transducers and activators of transcription (STATs)
nucleus; regulate transcription
There are proteins termed __________ that inhibit the JAK-STAT pathway
suppressors of cytokine signaling (SOCS)
Therapeutic index = —— Or ——-
——— ————
—— ——
TD50/ED50
LD50/ED50
TD = ________
LD= ________
Toxic dose
Lethal dose
The higher the therapeutic index, the more dangerous a drug is
T/F
F
The safer it is
List 4 common drugs with very low TI
Theophylline
Digoxin
Warfarin
Lithium
Response to steroid receptors
(Slower or faster?) in onset; (shorter or longer ?) in duration
Slower
Longer
All beta receptors use ____ Gprotein
Who uses Gi
Gs
M2,A2,D2
Most 1s and M3 use ____Gprotein
Gq
_____ is a specific TK inhibitor
_______ is a non specific TK inhibitor
Imatinib
Sorafenib
MLCK-
Myosin light chain kinase
stimulation of the nicotinic
receptor by acetylcholine results in _______ and _________
sodium influx and potassium
outflux
agonist stimulation of the
γ-aminobutyric acid (GABA) receptor increases ________
and hyperpolarization of neurons.
chloride influx
Up-regulation of receptors can make the cells more resistant to the effect of
the antagonist.
T/F
T
Which is more clinically useful
Efficacy or drug potency?
Efficacy is a more clinically useful characteristic than is drug potency,
Full agonists have intrinsic activity of ____
Partial agonists have intrinsic activity of ____
inverse agonists have an intrinsic activity of ___
One
greater than zero but less
than one
less than zero
RGS ?
Regulator of G-protein signaling
Lorazepam works on _____ receptors to ____
GABA
Reduce seizures
TYPES OF DRUG EFFECT
_____ Effect
_____ Effect
______ Effect
Desired
Side
Adverse
Desired Effect
Refers to physiological changes that are _____ and _____
expected and desired
Side Effect
Refers to physiological changes that are __________ but ______
expected but undesired
Side effect Occurs at the normal therapeutic dose of the drug
T/F
T
Desired effect Occurs at the normal therapeutic dose of the drug
T/F
T
Side effect of aspirin is ??
Increased bleeding
Adverse Effect
Refers to physiological changes that are _______ and _____
unexpected and undesired
Adverse effects Occurs at a specific dose
T/F
F
At any dose
Adverse effects can be life threatening
T/F
T
About ____ to ____% of the sigmoid curve is a straight line for statistical analysis
20
80
Potency = EC50
T/F
T
Margin of safety is a term used in _______ curve
Dose response Quantal curve
Margin of Safety (M.S)
Refers to the ratio of the _____ dose for __% of the population(___) divided by the effective dose for ___% of the population (____)
lethal
1; LD1
99; ED99
MS= ___/___
LD1
ED99
Examples of potentiation
Levodopa + ______
Amoxicillin + _______
Carbidopa
Clavulanic acid
Example of synergism
Penicillin + _______
Prednisolone + _____
Aminoglycoside
NSAIDs
Example of antagonism
Propranolol + ______
Pilocarpine + ______
Salbutamol
Atropine
Combination of Deferoxamine and _____ metal is an example of a _____ antagonism
Iron
Chemical
List the 3 competitive inhibition in the slide
Ace inhibitor- captopril
Reversibile AchE - neostigmine
Allopurinol- inhibits xanthine oxidase
List the non competitive inhibition in the slide
Irreversible anti ACHE
Aspirin
Monoamine oxidase inhibitor
Proton pump inhibitor
