(pharm) intro to pharmacology Flashcards
what is pharmacology?
the study of drug action - how a drug interacts with living organisms and influences physiological function
what is therapeutics?
concerned with drug prescribing and treatment of disease
differentiate between pharmacology and therapeutics
pharmacology is to do with the drugs whereas therapeutics is to do with the patient
what is pharmacodynamics?
study of what the drug does to the body
what is pharmacokinetics?
study of what the body does to the drug
differentiate between pharmacodynamics and pharmacokinetics
pharmacodynamics studies ‘what the drug does to the body’ and pharmacokinetics studies ‘what the body does to the drug’
if you want to work out how a drug exerts its effects on the body, what questions need to be asked?
1 - what effect? (drugs have multiple effects)
2 - where is this effect produced?
3 - what is the target for the drug?
4 - what is the response that is produced after the interaction with this target?
what must happen for a drug to produce a measurable effect?
it must bind to a specific target in the body
what are the four drug target proteins?
transport proteins
enzymes
receptors
ion channels
what are the two possible effects when drugs act on targets?
stimulatory - enhance activation of the target
inhibitory - prevent activation of the target
what happens when drug selectivity is low?
can bind to many structurally similar targets and bring about other effects you don’t want (side effects)
why is dose an important consideration when administering drugs?
the lower the dose, the more specific the effects of the drug (will interact with only one, desired target)
dose increases, effect becomes less specific (will interact with more targets) = unwanted effects
what are the four types of chemical interaction through which drugs interact with their receptors?
hydrophobic interactions (important for lipid-soluble drugs)
electrostatic interactions (van der Waals, hydrogen bonds)
covalent bonds (irreversible)
stereospecific interactions
what is an agonist?
a drug that bind to a receptor inducing activation
what is an antagonist?
a drug that bind to a receptor preventing activation
define affinity
extent to which a drug binds to receptors at any given drug concentration
define efficacy
the ability of an individual drug molecule to produce an effect once bound to a receptor
what does affinity determine?
the strength of the drug-receptor complex
higher affinity = stronger drug-receptor complex
explain what an full agonist is in terms of affinity and efficacy
drug that has affinity for the receptor and maximal efficacy
= maximal response
explain what an receptor antagonist is in terms of affinity and efficacy
drug has affinity for receptor BUT no efficacy
= prevents activation by preventing agonist binding
explain what an partial agonist is in terms of affinity and efficacy
drug has affinity for the receptor but sub-maximal efficacy
= partial response but cannot induce maximal response
define potency
concentration or dose of a drug required to produce a defined effect
differentiate between potency and efficacy
potency is the concentration or dose of a drug that is required to produce a desired response HOWEVER
efficacy is the ability of the drug to produce the effect once bound to the receptor
what are the categories of efficacy?
full agonists, partial agonists, antagonists
what is the standard measure of potency?
EC50 (half maximal effective concentration) = concentration of drug required to produce a 50% tissue response
what is EC50?
half maximal effective concentration = concentration of drug that is required to produce a 50% tissue response
what is ED50?
half maximal effective dose = dose of drug required to produce desired effect (in 50% of individuals)
differentiate between EC50 and ED50
EC50 = hald maximal effective CONCENTRATION but ED50 = half maximal effective DOSE
while EC50 is the concentration of the drug that will produce a 50% tissue response, ED50 is the dose of drug required to produce desired effect (in 50% of individuals tested)
what does it mean if a drug is very potent?
very potent = very small amounts of the drug are required to to produce the desired response
what is more potent: a full agonist or a partial agonist?
cannot compare potency as full/partial agonist are measures of efficacy
potency is related to dose of drug required to produce response WHEREAS efficacy determines the ability of the drug to produce a desired effect and has nothing to do with concentration/dose
what does it mean if a drug is highly potent?
very small amounts of the drug are required to produce a large response
what does it mean if a drug is highly efficacious?
the drug can produce a maximal response
what is more important potency or efficacy?
efficacy - as the priority is to produce the maximal response
even if potency is low, the dose can be adjusted to a higher one as long as the maximal response is achieved
define absorption
the passage of the drug from the site of administration into the plasma
define bioavailability
the fraction of the initial dose that gains access to the systemic circulation
differentiate between absorption and bioavailability
absorption deals with the process of drug transfer into the systemic circulation however bioavailability refers to the outcome of the drug transfer into the systemic circulation (i.e. how much)
what determines absorption and bioavailability?
site of administration
what are the forms of drug administration?
oral dermal (percutaneous) inhalation intranasal intravenous intramuscular
what are the specific absorption and bioavailability in terms of intravenous drug administration?
absorption - process is injecting full dose straight into bloodstream
bioavailability - outcome is as drug injected straight into the systemic circulation = 100% bioavailability
what are the two methods that drugs use to move around the body?
bulk flow transfer (i.e. in the bloodstream)
diffusional transfer (i.e. molecule by molecule across short distances)
what is bulk flow transfer?
movement in the bloodstream
what is diffusional transfer?
molecule by molecule over short distances
in terms of the intravenous route, what method of drug transfer is used?
bulk flow transfer delivers the drug to the site of action
what is the more common method of drug transfer?
diffusional transfer
what are the four mechanisms by which chemicals can diffuse across plasma membranes?
1 - pinocytosis
2 - simple diffusion across membranes (lipid-soluble substances only)
3 - diffusion across aqueous pores
4 - carrier-mediated transport (using transmembrane protein)
explain the process of pinocytosis
a small part of the cell membrane envelops the chemical molecule and forms a vesicle containing the drug which can be released on the other side
explain the process of simple diffusion of drugs
lipid-soluble molecules will diffuse across lipid membranes down a concentration gradient
what feature must molecules exhibit to take part in simple diffusion?
lipid solubility
explain the process of drug diffusion using carrier-mediated transport
transmembrane proteins will bind drugs on one side and will undergo a configurational shape change that causes movement of the drug to the other side
explain the process of drug diffusion across pores
uncommon as the are gaps between endothelia/epithelial cells that are usually less than 0.5nm in diameter so won’r fiit drug molecules
what are the two main structural types for drugs?
weak acid or weak base (so they exist either in the ionised or unionised form)
what do weak acids do in their ionised form?
donate protons (H+)
what do weak bases do in their ionised form?
accept protons (H+)
which form of the drug is likely to take part in simple diffusion: ionised or unionised? (and why)
unionised - as they are more lipid soluble
what two factors determine the ionisation status of a drug?
the pKa (dissociation constant)
the pH in that particular part of the body
what happens when the pKa of the drug and the pH of the tissue is equal?
the drug will be equally dissociated between the two forms: 50% ionised, 50% unionised
what happens to the ionisation status as the pH changes for weak acids?
if pH decreases for weak acids (i.e. become more acidic) = more unionised
if pH increases for weak acids (i.e. become more alkaline) = more ionised
what happens to the ionisation status as the pH changes for weak bases?
if pH decreases for weak bases (i.e. become more acidic) = more ionised
if pH increases for weak bases (i.e. become more alkaline) = more unionised
why is bioavailability likely to be under 100% for most of the routes of drug administration?
as most drug transfer occurs via diffusional transfer first rather than bulk flow transfer directly (only intravenous)
what determines drug distribution to tissues?
regional blood flow, plasma protein binding, capillary permeability, tissue localisation
how does regional blood flow determine drug distribution?
at rest, different tissues receive different amounts of the cardiac output and therefore different concentrations of the drug
when can regional blood flow change?
during exercise (more blood diverted to muscles)
after a meal (more blood diverted to GI tract)
once in the systemic circulation, what do drugs bind to?
plasma proteins (e.g. albumin)
what three factors determine how much drug is bound to plasma proteins?
concentration of free drug
affinity of drug for plasma protein
concentration of plasma protein
what are the four types of capillary structures?
continuous (w H2O filled gap junctions)
discontinuous
blood brain barrier (w tight junctions)
fenestrated
what is the most common capillary structure?
continuous
how are lipid-soluble drugs delivered to tissues?
simple diffusion across the endothelial cells (i.e. continuous capillaries)
how are non-lipid-soluble drugs delivered to tissues?
carrier proteins (i.e. blood brain barrier)
where can discontinuous capillary structure be found?
liver
where can fenestrated capillary structure be found?
glomerulus of the kidney
why does the liver have discontinuous capillaries?
to enable the majority of the drugs in the bloodstream to diffuse into the liver tissue and be metabolised
why does the glomerulus of the kidney have fenestrated capillaries?
to enable small drugs to be excreted more efficiently from the bloodstream
explain tissue localisation in terms of drug distribution
a lipid soluble drug is more likely to remain in a region with a high fat content (high retention in the brain)
a water soluble drug is more likely to remain in a region with a high water content (i.e. high retention in plasma)
in order for a drug to be excreted, what property must it exhibit and why?
high levels of water solubility so they remain in the bloodstream and are easier to excrete and elimainate
in order for a drug to be excreted, what property must it exhibit and why?
high levels of water solubility so they remain in the bloodstream and are easier to excrete and eliminate in urine/bile
why is it important to excrete/eliminate drugs from the body?
to prevent them from have a continuous, unwanted effect
what are the two steps to drug metabolism in the liver?
phase 1 metabolism - add a reactive group to the drug
phase 2 metabolism - add a conjugate to the reactive group
which enzymes are responsible for phase 1 drug metabolism in the liver?
cytochrome p450 enzymes
which enzymes are responsible for phase 2 drug metabolism in the liver?
transferases
what can phase 1 metabolism in the liver sometimes also form?
pharmacologically active drug metabolites that can have negative unwanted effects
what is first pass (pre-systemic) metabolism?
when orally administered drugs are metabolised in the liver prior to enter the systemic circulation = little active drug reaches circulation
how can the problem posed by first pass (pre-systemic) metabolism be tackled?
administer a larger dose of orally administered drug to ensure sufficient levels of active drug reach the systemic circulation
why does pre-systemic metabolism occur?
orally administered drugs are absorbed form the small intestine and then travel to the liver via the hepatic portal system
= so can be metabolised before reaching the systemic circulation (little active drug ends up here)
what are the main ways drugs can be excreted by the body?
via lungs (e.g. alcohol breath test)
via breast milk (in females - careful not to take drugs that can affect baby)
via kidney (in urine)
via liver (in bile)
what are the three routes for excretion via the kidney?
glomerular filtration (depends on size of drug)
active secretion (acidic and basic drugs secreted using transporters)
passive reabsorption (based on urine pH and extent of drug metabolism - only lipid soluble drugs)
explain how glomerular filtration is a method od drug excretion
drugs w a molecule weight less than 20,000 can diffuse into the glomerular filtrate
= additional method of excretion so quicker rate of excretion
explain how glomerular filtration is a method of drug excretion
drugs w a molecule weight less than 20,000 can diffuse into the glomerular filtrate
= additional method of excretion so quicker rate of excretion
explain how active tubular secretion is a method of drug excretion
drug can be excreted via active transport carrier systems
explain how passive diffusion is a method of drug excretion
if drugs are particularly lipid soluble, will be reabsorbed from tubule back into the systemic circulation
what two factors determine the extent of drug reabsorption via passive reabsorption in the kidney?
drug metabolism (water soluble phase 2 metabolism less well reabsorbed)
urine pH (acidic drugs better reabsorbed at lower pH, basic drugs better reabsorbed at higher pH)
you are taking Drug A as an analgesic – it is a weak acid
the urine pH suddenly increases from 6.5 to 8
will the drug effect be prolonged or reduced over the next few hours?
weak acid + pH increase = more ionised
if more ionised = less lipid soluble so less drug passively reabsorbed in the kidney tubule so more efficient excretion SO drug effect reduced over next few hours
describe how biliary excretion is a method of drug excretion
drugs transported from plasma into bile via liver cells, excreted into intestines and eliminated in faeces
how does enterohepatic recycling prolong drug effect?
metabolite is transported into the bile
metabolite is excreted into the small intestine, where it is hydrolysed by gut bacteria releasing the conjugate
loss of the conjugate increases the lipid solubility of the molecule
increased lipid solubility allows for greater reabsorption from small intestine back into the hepatic portal blood system for return to the liver
the molecule returns to the liver where a proportion will be re-metabolised (conjugate re-added), but a proportion may escape into the systemic circulation to continue to have effects on the body
