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Flashcards in general principles of pharamacology lec 1 Deck (103):

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
- 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

HA > A- + H+


what equation is the degree of ionisation of a weak acid calculated from

the Henderson-Hasselbalch equation:

pH = pKa + log _[A-]_

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:

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:

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

BH+ > B + H+


what equation is the DEGREE of ionisation of a weak base represented by

pH= pKb + log _[B]_


in an ACID environment (where the pH is low), where will this equation:

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:

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

lipid solubility


what two types of drugs are poorly absorbed by the intestine and why

strong bases pK >10
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
- 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



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)
- 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)
- 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
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



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