general principles of pharamacology lec 1 Flashcards
what are diagnostic drugs used for
to interpret particular clinical measures
what are the 2 types of pharmaceutical agents used by optometrists
- topical
- systemic
name the 2 different pharmacological principles
- pharmacodynamics
- pharmacokinetics
what does the pharmacodynamics of a drug describe
what a drug does to the body
what are the 3 main principles/stages of pharmacodynamics
- drug: receptor interaction
- biochemical and physiological effects
- relationship between the drug and therapeutic response
e.g. what the drug binds to, then what the result of that binding is and the relationship of that drug and therapeutic response is.
what does the pharmacokinetics of a drug describe
what the body does to the drug
what are the 4 main principles/stages of pharmacokinetics
- absorption e.g. as tablets, oral, injection, inhaled or topical
- distribution e.g. within the vascular system if its a systemic drug
- biotransformation e.g. how the body reacts to drugs via biochemical reactions/transformations i.e. how the drug is metabolized and modified chemically
- excretion e.g. to get rid of the drug
what is an agonist
something that mimics the naturally occurring chemical and binds to that receptor
what is an antagonist
something that blocks the agonist
how do drugs alter the physiological function of cells
exerting their effects by binding to specific target protein molecules
list the 4 specific target protein molecules that drugs bind to in order to alter the function of cells
- classic receptors
- enzymes
- transmembrane transport proteins
- ion channels
give 3 examples of classic receptors that drugs bind to
- beta adrenergic
- alpha adrenergic
- histamine
give 2 examples of ion channels that drugs bind to
- sodium channels
- calcium channels
give 2 examples of enzymes that dugs bind to
- carbonic anhydrase
- cyclooxygenase
give 2 examples of transporters that drugs bind to
- Na+ K+ ATPase
- Na+ K+ Cl- co-transporter
name and explain 3 sources of drug
- natural e.g. alkaloids which are extracted from plants, such as atropine
- semi-synthetic e.g. prepared by chemical modification of natural drugs, such as cyclopentolate
- synthetic e.g. prepared by chemical synthesis in pharmaceutical laboratories
what is an agonist drug
a drug that stimulates receptors
what is an antagonist drug
a drug that binds to receptors without stimulating them or preventing binding of the natural agonist
name the two forms of antagonists
competitive or non-competitive
how does a non-competitive antagonist work
the drug sits on the active site and inhibits the receptor
what is the ideal theory about drug specificity and what is the drawback to this theory
ideally a drug should show a high degree of specificity in terms of its binding site, however specify is rarely absolute as increasing the dose of the drug can cause it to affect targets other than the principal one (bind to other things from an overdose), which can lead to side effects
the lower the potency of the drug, the….
higher the dose needed and the greater likelihood of unwanted side effects
what does the ‘dose response curve’ represent
a characteristic relationship between the dose of the drug and its pharmacological effect
what type of effect does a low concentration drug have as shown in the ‘dose response curve’
a no effect range = an initial latency period where the concentration of the drug is too low to have any therapeutic response
what type of effect does an increasing dose of a drug have as shown in the ‘dose response curve’
a range of increasing effect = the therapeutic response increases rapidly as the concentration of the drug increases
what type of effect does an even more increasing drug dose have as shown in the ‘dose response curve’
a maximum effect range = when all the receptor sites are occupied
(the curve is flat as there is no more effect of the drug on the body)
what are the 2 other words for drug toxicity
- adverse drug reaction - ADR
or - adverse drug event - ADE
what is drug toxicity defined as
manifestations of the adverse effects of drugs administered therapeutically or in the course of diagnostic techniques
e.g. during pregnancy, the affect of a drug on the mother could impact the foetus
what is the ratio between the toxic dose and the therapeutic dose of a drug used for
it us used as a measure of the relative safety of the drug for a particular treatment
if the toxic dose of a drug is 1000mg, then what should the therapeutic dose of the drug be, to consider it a safe drug
he therapeutic dose should have a large difference to the toxic dose, so ideally i should be e.g. 1mg
when do you need to take caution when taking a drug
if the toxic dose and therapeutic dose is similar
what may inter-individual responses arise due to
pharmacokinetic and pharmacodynamic variation
as well as pharmacokinetic and pharmacodynamic variation, what also appears to be a significant source of variability observed in the response to drugs
genetic heterogeneity (pharmacogenetics)
give an example of a drug where different individuals respond differently
tropicamide - dark and light irides respond differently = inter-individual variability or differ from genetics
what 4 things is pharmacokinetics the study of with a drug
- absorption
- distribution
- metabolism
- excretion
what is understanding the drugs pharmacokinetics important for
when choosing an appropriate route of administration (to see how the body will handle that particular drug)
what can pharmacokinetic factors of a drug cause
inter-individual variability on therapeutic response
what is the most preferred route for a drug to be administered in most cases
oral route - enteral
other than oral route, what 2 other alternative routes can a drug be administered
- parenteral (non-oral) e.g. injection
- local administration e.g. ophthalmic drugs or inhaled drugs to treat asthma
when will a parenteral (non-oral) e.g. injection route of administration be chosen
if a drug is poorly absorbed from the gut or causes gastrointestinal irritation
is an alternative route to oral (enteral)
where do all drugs end up within the body in order to interact with their target
in the blood plasma and into the blood stream
why can drugs be excreted within breast milk
because there is a small barrier between breast milk and the plasma
which form of drug readily penetrate cell membranes
non-polar unionised forms of drug as they go across lipid membranes easily
what can most drugs which are weak acids or weak bases exist in
ionised or unionised forms
what is the ratio between ionised and unionised forms of drug determined by
the surrounding pH and the dissociation contact (pK), of the drug which represents the pH at which the drug is 50% ionised
which form of drug doesn’t cross the lipid membrane easily
ionised drugs
what does the degree of ionisation determine
how the drug crosses the plasma membrane
for a weak acid, what equation is the ionisation reaction represented by
Ka
HA > A- + H+
what equation is the degree of ionisation of a weak acid calculated from
the Henderson-Hasselbalch equation:
pH = pKa + log [A-]
[HA]
pKa = association constant (this determines the position of that equation) A- = ionised form of acid HA = unionised form of acid
in an ACID environment (where the pH is low), where will this equation:
Ka HA > A- + H+
the left = the unionised form
the (unionised) drug will get absorbed more readily in the plasma membrane and the acid will be absorbed a lot in the stomach where the pH is low
in an ALKALINE environment (where the pH is high), where will this equation:
Ka HA > A- + H+
the right = the ionised form
the (ionised) drug won’t get absorbed through the intestine
what form will a weak acid in an acid solution mainly be in
its unionised form
what form will a weak acid in an alkaline solution mainly be in?
and what will this result in?
the weak acid will be trapped in its ionised form
the result is that an acidic drug will be concentrated in a compartment with a high pH e.g. an alkaline environment
for a weak base, what equation is the ionisation REACTION represented by
Kb
BH+ > B + H+
what equation is the DEGREE of ionisation of a weak base represented by
pH= pKb + log [B]
[BH+]
in an ACID environment (where the pH is low), where will this equation:
Kb BH+ > B + H+
the left = the ionised form
the (ionised) drug WON’T be absorbed across the stomach
in an ALKALINE environment (where the pH is high), where will this equation:
Kb BH+ > B + H+
the right = the un-ionised form
the (un-ionised) drug WILL be absorbed across the stomach
what form will a basic drug in an alkaline solution be in and what will this mean for the drug
the drug will be in its non-ionised form
it will have greater ability to cross lipid membranes
what form will a basic drug in an acid environment be in and what will this mean for an alkaline drug
the drug will be trapped as it is ionised
the result is that an alkaline drug will be concentrated in a compartment with a low pH
give an example of a drug along with its pKa value, which is most likely to be absorbed from the STOMACH
a weak acid such as Aspirin
pKa = 3.5
give an example of a drug along with its pKa value, which is most likely to be absorbed from the SMALL INTESTINE
a weak base such as Pethidine (like morphine)
pKa = 8.6
what 2 things is drug absorption in the intestine determined by
ionisation
and
lipid solubility
what two types of drugs are poorly absorbed by the intestine and why
strong bases pK >10
and
strong acids pK
how much % of an orally administered drug is typically absorbed and within how many hours
75% in 1-3 hours
name 5 factors which affect drug absorption
- gut motility
- splanchnic blood flow
- physiochemical factors
- a drug taken after a meal
- drugs specifically formulated to delay absorption e.g. capsules, tablets with resistant coatings
what affect does a drug taken after a meal have on absorption
it is more slowly absorbed since progress to the small intestine is delayed
(done if want to increase absorption time)
how does the drug tetracyclines prevent their absorption
by binding strongly to calcium and calcium rich foods (especially milk or antacids)
what is tetracyclines contraindicated in and why
pregnancy and lactation since they both affect tooth and bone formation
what other drugs to tetracyclines reduce the absorption of
as with other antibiotics, tetracyclines reduce the formation of oral contraceptives
(so px is advised to use alternative forms of contraception during treatment)
when the drug is absorbed, at what two times can it either be metabolised
- either before it gets to the blood stream
or - either in the liver
it then goes to the wider circulation
what does the term bioavailability refer to
and what is bioavailability dependent on
the fraction of the dose that proceeds unaltered from the site of administration and becomes available at the site of action
this is dependent on the rate of absorption
what is bioavailability dependent on
the rate of absorption
in the case of orally administered drugs, other than rate of absorption, what other factors affect the bioavailability
first pass metabolism
what does first pass metabolism represent
the breakdown of a drug by biotransformation by enzymes within the gut wall or liver before it reaches the plasma compartment
(even before the drug has got into the blood stream, it has already undergone biotransformation)
what does first pass metabolism explain about the drug glyceryl trinitrate (GTN) used for angina
that it is effective sublingually, but not when swallowed
if GTN is given orally, it will not work because glyceryl will be deactivated during first pass metabolism
what may first pass metabolism show between individuals
inter-individual variation
what next thing happens with the drug following absorption
distribution
list 5 things may cause the distribution of a drug to not be uniform
- physiochemical properties of the drug
- differences in blood flow between tissues
- degree of leakiness of the blood vessels in a particular tissue (e.g. bv’s in retina are very tight and don’t leak much)
- a drug may have an affinity for a particular tissue component e.g. melanin or fat
- plasma protein binding
in what 2 forms can drugs travel in the plasma
- partly in solution (unbound drug)
or - bound to plasma proteins (bound drug)
name the 2 main types of plasma protein which both bids specific drugs
- albumin
- b-globin and a-acid glycoprotein
what types of drug does albumin mainly bind
acidic drugs
e.g. warfarin and non-steroidal anti-inflammatory drugs (NSAID)
what types of drug does b-globin and a-acid glycoprotein mainly bind
basic drugs
e.g. propanolol
what does protein binding potentially reduce
the availability of the active form of the drug
protein-bound drugs show a restricted tissue distribution and slow elimination i.e. it is a variable that affects the amount of drug that reaches the target
in what 2 processes does the elimination of drugs from the body occur by
- metabolism (biotransformation)
and - excretion
what does the metabolism of a drug involve
the enzymatic conversation of the drug into another chemical entity
what does excretion of a drug involve
the elimination of the unchanged drug (or its metabolites)
where does drug metabolism predominantly occur
in the liver
what two types of chemical transformation does drug metabolism involve
phase I
and
phase II reactions
what is the purpose of drug metabolism
to make the drug more hydrophilic, to hasten its excretion by the kidneys
what do phase I reactions of metabolism involve
adding or unmasking a functional group to the uncharged hydrophobic ionised form of the drug to make it charged e.g. -OH, -NH2, -SH. oxidations are the most common reactions and are usually carried out by a family of microsomal enzymes (in the liver) known as cytochrome P450 (CYP)
in other words…
the drug is made more hydrophilic by unmasking the iconic groups within the molecule by introducing a +ve or -ve charge, this is done by oxidation which makes the molecule more +ve or -ve charged or done by adding functional groups
what is another term for phase II processes of metabolism
conjugation
what do phase II processes of metabolism involve
the attachment of a substituent group e.g. glucuronyl, acetyl, methyl or sulphate. these reactions make the drug more polar (adds more charge) making it more hydrophilic so that it can be excreted by the kidneys
how are most drugs excreted from the body
and in what two forms can they be
in the urine
either unchanged or as polar metabolites
other than in the urine, how are other drugs excreted
they are first secreted into bile via the liver, followed by loss of the drug via the faeces
how is the rate of renal clearance variable
some drugs are lost in an single transit whilst others are cleared more slowly
which type of drug action can only be terminated by renal elimination and what implications does this have
the drugs that are excreted without biotransformation
therefore these types of drugs (which are secreted via the kidney) need to be prescribed with special care in the elderly and in those with altered renal function
list 4 types of variables affecting drug metabolism
- some drugs increase the activity of drug metabolising enzymes e.g. barbiturates
- other drugs inhibit drug metabolising enzymes e.g. erythromycin, ethanol (drugs that interact with other drugs)
- genetic polymorphisms lead to inter-individual variation in drug metabolism
- age
explain how neonates are a variable that affects drug metabolism
neonates may have an immature drug metabolising mechanism
explain how the elderly are a variable that affects drug metabolism
the elderly may have impaired hepatic metabolism of drugs and also show impaired glomerular filtration rate reducing renal clearance
list 4 types of topical drugs used by all optometrists
- diagnostic drugs e.g. mydriatics, cycloplegics, topical anaesthetics
- lubricants e.g. hypromellose, sodium hyaluronate
- anti-infectives e.g. fusidic acid, chloramphenicol
- anti-allergy e.g. anti histamine, mast cell stabilisers
list 2 types of topical drugs used by specialist therapeutic prescribers
- corticosteroids
- anti-glaucoma
list 2 types of systemic drugs used by all optometrists
- antihistamines e.g. cetirizine, loratadine
- NSAIDs e.g. ibuprofen, aspirin
- eye-nutrients e.g. anti-oxidant vitamins/essential fatty acids
list 2 types of systemic drugs used by specialist therapeutic prescribers
- oral antibiotics e.g. tetracyclines
- carbonic anhydrase inhibitors e.g. acetazolamide
