Biochemicals principles of pharmacology Flashcards
what does ACE inhibitors stand for
angiotensin converting enzyme inhibitors
what are ACE inhibitors
enzyme inhibitors, drugs that target enzymes, protease
targets of enzyme inhibitors include…
enzymes, ion channels, transport proteins, receptors
examples of enzyme inhibitors used as an antibiotic
amoxicillin
examples of enzyme inhibitors used for cardiovascular problems
ACE inhibitors, statins, aspirin
examples of enzyme inhibitors used as an analgesic/pain
paracetamol, ibuprofen, rivaroxaban
examples of enzyme inhibitors used as an anticoagulant/blood thinner
warfarin
what are ACE inhibitors derived from
snake venom
what do ACE inhibitors do
reduced blood pressure
adverse effects of ACE inhibitors
coughs and dizziness
what do the name of ACE inhibitors end in
-pril
captopril, lisinopril, ramipril
what 2 things does ACE inhibitors reduce and what are the effects of it
- reduce formation of angiotensin II- reduces vasoconstriction and salt/water retention
- reduces breakdown of bradykinin (signalling peptides) into inactive peptides- increased bradykinin causes persistent coughing
what causes a persistent cough
increased amount of bradykinin
mechanism of action of a reversible inhibitor
non-covalent
mechanism of action of a irreversible inhibitor
covalent
example of a reversible inhibitor
captopril binding to ACE with hydrogen bonds
example of a irreversible inhibitor
aspirin binding to cox enzymes
what is enzyme kinetics
action of enzyme inhibitors can be determined using experiments that determine the rate of enzymatic reactions in response to changes like changing substrate concentration
name the two types of plot/graphs used in enzyme kinetics
michaelis-menten
lineweaver-burk
what does the michaelis-menten plot show
how rate changes as substrate concentration changes
what is the michaelis-menten constant
Km, concentration of substrate at which the initial velocity of catalysis is half maximal
what does the Km tell us
how well the enzyme binds to the substrate
how to determine Km
doing experiments that vary substrate conc, enzyme conc constant, determine initial velocity (product formation over time)
what is the problem with michaelis-menten plot and what is the solution
the hyperbola is difficult to fit accurately without a computer, solution is to us a double reciprocal plot (1/s and 1/v) which is the lineweaver-burk plot
what is the michaelis-menten equation
v=vmax[s]/Km+[s]
what is the lineweaver-burk equation
1/v=(Km/vmax)(1/[s]
)+1/vmax
how to transform a michaelis-menten graph into lineweaver-burk graph
do double reciprocals of the values in michaelis-menten (put the values 1/x)
why is lineweaver-burk plot better
allows more accurate estimation of Km and vmax
example of a calcium channel blocker
amlodipine
what do calcium ions do
trigger muscle contraction
calcium channel blockers such as amlodipine prevent the uptake of Ca2+ by what two structures
vascular smooth muscle and cardiomyocytes
what are the vascular effects of amlodipine
vasodilation (smooth muscle relaxation)
what are the cardiac effects of amlodipine
decreased contractility and decreased heart rate
what is amlodipine
calcium channel blocker
adverse effects of calcium channel blockers
arterial dilation, veins unaffected, excess fluid goes into surrounding tissue causing tissue to swell
what are ion channels
proteins that facilitate transport of molecules across the cell membrane
two types of ion channels and how they are controlled
- voltage gated- controlled by potential differences
- ligand gated- binding of a ligand will cause it to open
ion channels are multimeric proteins, what does multimeric mean
its a protein composed of several subunits
how does the calcium channel blocker amlodipine work
calcium channel has 4 aspartate residues, amlodipine binds and causes asymmetry in the selectivity filter which prevents calcium ions from passing through
what does potency mean
the amount of drug needed to produce an effect
how is the potency of a drug determined
by comparing the concentration at which 50% inhibition is achieved (IC50)
how is IC50 represented on a graph
10log
IC50 units of low, medium and high potency
low- mM
medium- μM
high- nM
two things that IC50 is used to measure for
ion channels and enzyme inhibitors
what characteristic of a drug is the most desired (potency and IC50)
high potency and low IC50
what are solute transporters
diverse proteins involved in transport of ions and organic compounds
what do thiazide diuretics do
inhibits action of specific transporters
effects of thiazide diuretics
reduce cardiac output, reduce blood volume, lowers blood pressure, increases water and salt excretion
where does energy for active transport come from
hydrolysis of ATP
what inhibits sodium potassium pump
cardiac glycosides
what do cardiac glycosides do
inhibit sodium potassium pump
what are the effects of inhibiting sodium potassium pump
reduces heart rate, increases the force of contraction of the heart muscle
what is used to treat heart failure
cardiac glycosides
example of a cardiac glycoside
digoxin
name 2 inhibitors used to treat hypotension
calcium channel blockers and thiazide diuretics
what are cardiac glycosides used for
treating heart failure
what is used to treat the stomach
proton pump inhibitor
what does the inhibition of sodium potassium ATPase lead to
increased intracellular sodium ion concentration which leads to increase of intracellular calcium ion concentration via the sodium calcium exchange system
name two parts of the nervous system
central and peripheral
name two parts of the peripheral nervous system
somatic and autonomic
difference between somatic and autonomic nervous system
somatic- voluntary control of skeletal muscles, sensory/motor control
autonomic- subconscious, organ function
types of autonomic nervous system
sympathetic and parasympathetic
difference between sympathetic and parasympathetic nervous system
sympathetic- prepares body, flight of fight, increases heart rate, vasoconstriction
parasympathetic- promotes restorative functions, rest or digest, slows heart rate
what is the anatomic difference between somatic and autonomic nervous system
somatic has a single axon extending from neurone in CNS to effector and autonomic is a two neurone system
what are the normal conditions in the heart in terms of signalling from the peripheral nervous system
balanced signals from sympathetic and parasympathetic
what does efferent mean
CNS to organ/muscle
what does afferent mean
organ to CNS
what is ganglion
cluster of peripheral autonomic neurones
anatomy of autonomic nervous system
-preganglionic neurone and post ganglionic neurone
sympathetic- short, long
parasympathetic- long, short
-two neurone chain
-CNS to ganglion to effector tissue
what is a synapse
structure/gap between 2 neurones that allow one neurone to transmit a signal to the second neurone
what does SNAP stand for
sympathetic noradrenaline, acetylcholine parasympathetic
what are beta blockers
competes with binding of noradrenaline/adrenaline to beta 1 adrenergic receptors to block sympathetic signalling to the heart
adverse effects of beta blockers
affinity for beta 2 adrenergic receptors so it can exacerbate asthma
short definition of beta blockers
antagonist of beta 1 adrenergic receptors
what are beta blockers used to treat
angina- chest pain from narrowing arteries supplying the heart
heart failure- not enough blood pumped to body
atrial fibrillation- irregular heartbeat
heart attack- blocked blood supply to heart
4 types of receptors
-ligand gated ion channels
-GPCR
-kinase linked receptors
-nuclear receptors
example of GPCR
adrenergic and cholinergic
example of ligand gated ion channel receptors
nicotinic acetylcholine
what does GPCR stand for
G protein coupled receptors
what do drugs do to receptors
drugs can stimulate or inhibit receptors, stimulators are agonists and drugs that inhibit are called antagonists
what are agonists
drugs that stimulate receptors
example of an agonist
adrenaline
what are antagonist
drugs that inhibit/block receptors
example of an antagonist
beta blockers
at effector organs what is the receptor for acetylcholine
muscarinic receptors
name the receptor adrenaline and noradrenaline binds to
adrenergic receptors
name of receptor acetylcholine binds to
cholinergic receptors
what is a ligand
chemical that can form a complex with a receptor
what is a receptor
protein that recognises a specific chemical signal from outside the cell
principles of signalling
specificity, amplification, modularity, desensitisation/adaptation, integration of signalling
what is specificity
receptor recognises a specific signal leading to a response
what is amplification
signal of a single ligand gives rise to many second messengers and modified molecules in the cell
describe the process of amplification
-ligand L binds to receptor R
-receptor R binds to intracellular G protein
-G protei activates enzyme (AC=adenylyl cyclase) that produces a second messenger cAMP
-signalling cascade
membrane proteins involved in gpcr signalling
integral, lipid modified, accessory
what is modularity
receptor signalling uses interchangeable parts
-both receptors use the same chemical to stimulate but different outcomes
what is desensitisation/adaptation
activation of a receptor triggers a feedback loop that inactivates the receptor
what is integration of signalling
activation of two or more receptors lead to a receptor that integrates both signals
describe scatchard analysis
what is B max in the scatchard analysis
total number of binding sites
what is the dissociation constnat in the scatchard analysis
1/2Bmax
autonomic nervous system anatomy
sympathetic- short, long
autonomic- long, short
what is potency
measure of drug activity expressed in terms of amount required to produce an effect
what is EC50
effective concentration at 50% of max response
what is receptor occypancy
fraction of receptors bound by ligand/drug
what is efficacy
ability of a drug to produce an effect
equation for response of drug
R=Rmax x conc of drug/(conc of drug+EC50)
what is a partial agonist
agonist that is unable to produce a full response even when all receptors are occupied
what is an agonist
stimulator
what is an antagonist
inhibitor
what does affinity of a ligand mean
ability of ligand to bind to a receptor
what is potency
concentration of an agonist required to reach half maximum effect
reversible antagonist and an example
non covalent ligand receptor interaction, competitive and uncompetitive
eg. propanolol to beta1 adrenergic receptors
irreversible antagonist and an example
covalent ligand and receptor interaction
eg. phenoxybenzamine binding to a1 and a2 adrenergic receptors
what is a pure antagonist
no effect on receptor activity
what is an inverse angonsist
inhibits constitutive activity
what are spare receptors
fraction of receptors not occupied at max response
what does unsurmountable mean
non competitive, irreversible, no amount of concentration can increase the response
what does parasympatholytic mean and example
substance that reduces the activity of the parasympathetic nervous system like atropine (antagonist)
what does sympathomimetic mean and example
substance increases sympathetic signals like adrenaline (agonist)
what is -mimetic and -olytic
sympathomimetic/parasympathomimetic= increases signals/activity
sympatholytic/parasympatholytic= reduces activity
what is therapeutic index and its equation
ratio of dose of drug that causes adverse effects to the dose that leads to desired pharmacological effect
Ti=TD50/ED50
TD50=toxic dose for 50% population
ED50=effective dose
