Intro to Pharmacology Flashcards
what is pharmacology
the study of the action of drugs on the function of living systems
what are the different elements of pharmacology
pharmacokinetics and pharmacodynamics
what is a drug
a chemical substance or natural product that affects the function of cells, organs, systems or the whole body
how can drugs be described as
bioactive
when did pharmacology first emerge as a scientific discipline
in the mid 19th century
what was used as medicine before drugs were discovered
herbal and other remedies
what did the 1692 collection of choice remedies list
concoctions of worms, dung, urin and moss from a dead mans skull
what makes drugs poisonous
their dosage
what are some different sources of the drugs
natural products
serendipity
changing the structure of an existing molecule
using an existing drug in a new disease
computer aided design
studying disease processes
what are examples of natural products of drugs
plants and animals
what does serendipity mean
discovered by accident
what are structure activity relationships
changing the structure of an existing molecule
describe the discovery of pencillium
1928 - alexnader fleming first noted the antibacterial properties of it
1938 - howard florey and ernst chain isolated penicllin from the mould and tested it in human volunteers
what drug is produced from willow trees and give the function
aspirin - painkiller
what drug is produced from cocoa plants and give the function
cocaine - local anaesthetic
what drug is produced from the cinchona tree and give the function
quinine - anti malarial
what drug is produced from poppies and give the function
morphine - painkiller
what drug is produced from foxgloves and give the function
digoxin- heart failure
what drug is produced from guggul trees and give the function
statins - cholesterol lowering
what drug is produced from leeches and what does it do
hirudin, an anticoagulent
what drug is produced from cone snails and what does it do
ziconotide, powerful painkiller
what drug is produced from bothrops jararaca
a peptide which lowers blood pressure, which is a forerunner for ACE inhibitors
what is sildenafil
viagra
when was viagra invested
1989 through accidental repurposing
what are the three types of drug names
chemical
generic
proprietary
what are chemical names for drugs
IUPAC name that describes the chemical structure of the drug
what are general names for drugs
international non proprietary name given to a molecule
what are proprietary names for drugs
trade names given to an approved drug by the manufacturer
when are drugs given code names
during their development as a way to disguise their identity
what is pharmacokinetics
looking at what the body does to the drug, ie the fate of the drug molecule following administration to a living organism or how a drug molecule is affected by exposure to living cells
what is pharmacodynamics
what the drug does to the body, the mechanism of drug action or what happens to cell, organs, systems as a result of drug exposure
what is nitrous oxide
an inhaled gas with an analgesic effect which can help with the pain of labour or tooth extraction
what does amyl nitrate do
reduce anginal symptoms through inhalation
why canaspirin not be used in children
causes reyes syndrome, which leads to liver or brain damage
what are the drug effects on the level of the cell
effects on receptors, ion channels, enzymes, transporters and DNA
what are the impacts of drugs at the level of the organ and organ system
effects on heart, liver, kidney, CV, central nervous system etc
what is the impact of drugs at the level of the organism
therapeutic effects on disease state or process, as well as adverse effects or side effects
what is the impact of drugs on the level of society
cost, misuse and drug resistance (antimicrobial stewardship)
how many different cell types in the body
200
what are the primary tissues
- muscles
- nerves
- epithelium
- bone
- connective
how do many drugs work
by mimicing the action of endogenous molecules like neurotransmitters and hormones. can also block this activity
which sites do drugs commonly work at
receptors
ion channels
enzymes
transporters
how do drugs act
they are small chemical molecules that interact chemically with cellular constituents. they must bind to their targets in order to produce an effect
will a drug work if it is not bound
no
what can drugs target aside from receptors and ion channels
circulating proteins
DNA
bacterial cell wall
what is the primary use of receptors
cell to cell communication
what is cell cell comunication important in the context of
neurotransmission
effects of chemical mediators in the bloodstream
hormone and growth factor signalling
what is a receptor
recognition molecule for a chemical mediator through which a response is transduced
what is the common structure of receptors
protein or complex of proteins that is expressed on the surface of cells, although there are some exceptions to this
how do many drugs act in order to do
minimise effects or mimic them
what is the lock and key concept
receptor is the lock, drug is the key
this concept depends on the drug structure
most locks have a master key called an endogenous ligand
what is the basic receptor structure (diagram included in answer)
1 - extracellular domain
2 - transmembrane domain
3 - intracellular domain
what is the extracellular domain of the basic receptor
this is where there are basic ligand binding sites that are comprised of hydrophilic amino acids
what is the transmembrane domain
anchors the protein in the membrane
comprised of hydrophobic amino acids
alpha helical structure
what is the intracellular domain of the basic receptor
interacts with effector mechanisms and is comprised of hydrophilic amino acids
what is the series of events of basic signal transduction
signal
reception
transduction
response
what is the signal step of signal transduction
this is when the ligand arrives at the receptor
what is the reception
this is when the ligand binds to the receptor
what is transduction
ligand bound receptor changes conformation
what is an example of a fast signal transduction
nictotinic acetylcholine receptor
describe type A receptors
very fast signal transduction
describe type B receptors
fast signal transduction
describe type C receptors
short signal transduction
describe type D receptors
very slow signal transduction
give an example of a type B receptor
muscarinic acetylcholine receptor
give an example of a type C receptor
cytokine receptors
give an example of type D receptors
oestrogen receptors
what is an agonist
a drug that binds to a specific site on a receptor and mimics the effect of the endogenous ligand for that site
what is an antagonist
a drug that binds to a specific site on a receptor, and blocks the effect of the endogenous ligand
how do agonists work in lock and key
agonist fits into the lock, mimics the action of the key, and can be used to pick the lock and activate the receptor
describe how antagonists work in the lock and key concept
antagonist fits into the lock, gets stuck and prevents opening of the lock by either the endogenous ligand or the agonist
describe the affinity and efficacy of agonists
they have both
describe the affinity and efficacy of antagonists
they have affinity only
what is affinity
measure of the strength of association between the ligand and the receptor
what is efficacy
a measure of the ability of an agonist to evoke a cellular response
what is pharmacology
study of substances that mostly mimic or block the physiological actions of endogenous chemicals
what are the core concepts of pharmacology
pharmacokinetics
pharmacodynamics
what is pharmacokinetics
what the body does to the drug
what is pharmacodynamics
what the drug does to the body
how do drugs act
by binding to specific sites on target proteins, receptors, ion channels, enzymes and transporters
what are receptors
membrane bound recognition molecules that transduce chemical signals into cellular responses
what are the main causes of pharmacological variability
age
genetics
disease state
drug interactions
environment
describe general anaesthetic
- done through inhalation or injection
- dampens neural activity by blocking neurons in the brain
- reduces transmission by hyperpolarising the nerves
describe local anaesthetic
blocks sodium channels to block nerve transduction so when teeth are being extracted, the nerves are blocked and the person is unaware of the pain
what does general anaesthetic sedate
the entire body
describe the synaptic blocking pathway of general anaesthetic
descreases presynaptic calcium ion entry and this reduces the release of transmitter.
increases the post synaptic hyperpolarisation to increase chlorine ion influx
describe the conduction blocking pathway of local anaesthetic
decreases axonal sodium entry to decrease action potential propagation
why are the local anaesthetic structures all sort of similar
they all need to act by blocking sodium channels
what is the pKa of most local anaesthetics
8-9 - weak bases
describe neuronal cell membranes at rest
mostly impermeable to sodium ions
resting negative membrane potential
what are the three states of sodium channels
resting
open
inactivated
describe the mechanism of action of local anaesthetics
- LA binds to target site on the intracellular side of the sodium channel
- LA prevents sodium ion influx, preventing depolarisation
- prevents action potential propagation to pervent perception of pain
- prevents sodium influx in two ways - blocks channel and stabilises it
is the block of nerve conduction by local anaesthetics irreversible
no
what must local anaesthetics do in order to be effective
- diffuse from the site of administration, across the nerve cell membrane to the intracellular side
- bind to the local anaesthetic target site
what is the half life of ester linked anaesthetics
less than three minutes
what is the half life of amide linked anaesthetics
1-3 hours
why is the half life of ester linked anaesthetics relatively short
it is taken up from the plasma quickly, so does not need as high of a half life
why are the half lives of amide linked anaesthetics relatively long
they have to travel in the blood to the liver to be metabolised, and so must live longer
describe the chemical structure of local anaesthetics
weak bases
has an amine group, which is ionised or unionised
pKa ranges from 7.6 - 9
at pH 7.4, both ionised and neutral forms of the local anaesthetic exists, although there is more of the ionised form
describe cocaine
medium onset
medium duration
half life of an hour
good tissue penetration
side effects on the CNS and the CV
describe procaine
medium onset
short duration
half life of less than an hour
poor tissue penetration
CV and CNS effects
describe lidocaine
rapid onset
medium duration
half life less around 2 hours
good tissue penetration
CV effects
describe tetracaine
very slow onset
long duration
half life of an hour
moderate tissue penetration
CV effects
describe bupivacaine
slow onset
long duration
half life of two hours
moderate tissue penetration
CV effects
describe prilocaine
medium onset
medium duration
half life of two hours
moderate tissue penetration
few side effects
describe articaine
rapid onset
short duration
half life of 30 minutes
good tissue penetration
CV effects
what are local anaesthetics often administered alongside
a vasoconstrictor
what causes side effects of local anaesthetics
escapism into systemic circulation
how can the side effects of local anaesthetics be managed
by being careful with dosage
describe the uses of topical anaesthesia
mucous membranes only, not effective on skin
examples of topical anaesthetics
lidocaine
tetracaine
benzocaine
describe subcutaneous anaesthetics
infiltration into tissue, combined with vasoconstrictor
examples of subcutaneous anaesthetics
most local anaesthetics
describe intravenous anaesthetics
used with pressure cuff to limit the spread
example of intravenous regional anaesthesia
lidocaine
prilocaine
describe nerve block anaesthesia
injected close to nerve plexus, for minor surgery and dentistry
example of nerve block anaesthesia
most local anaesthetics
describe spinal anaesthesia
surgery to the abdomen and pelvis when the general anaesthetic is not suitable
example of spinal anaesthesia
lidocaine
describe epidural anaesthesia
form of spinal anaesthesia, given mostly in childbirth
example of epidural anaesthesia
lidocaine
bupivacaine
what are the three most important things to know about drugs
what it does
its potency
its selectivity
describe potency
this is a measure of the dose or concentration of a drug at which it is effective
describe what a potent drug is
one that is effective at low doses
what does it mean if a drug is selective
if it works on one receptor but not on others
does a high potency mean a drug is good or bad
neither
