What does pKa mean and why can it influence drug ......solution is low then the pKa will be a larger...
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To understand what pKa is and how it works there are a few concepts to get under our belt first: pH: Most everyone has a basic idea of what pH is and how it works. However, here’s a little explanation for those of you who may need a little refresher: Hydrogen ions can gain or lose protons based on what type of solution they are in. Acidic solutions, as we know, are full of H+ ions (protons). If an acid is put into a basic solution (one with less protons) it will give away its protons to that solution. In giving away protons it will become negatively charged. If we flipped this around and dropped some basic solution into an acidic one then the bases will gain protons and thus becoming positively charged. Think of it like this: H+ ions don’t like being lonely; they want to hang out with more H+ ions so they are nice and share their friends. They will either give away some friends if they have lots or take some if they have few. What does pKa mean and why can it influence drug absorption and excretion? We know that some things are acidic and some are basic (or alkali), but what does that really mean? When looking at the pH of a solution we are looking at its hydrogen concentration: § An acidic solution is a solution that has a high concentration of hydrogen ions (H+) § A basic solution on the other hand is one with a low concentration of hydrogen ions (see our little friends below) pH Scale Ionisation/charge: Lets say I was to drop a strong acid such as Hydrochloric Acid (HCL) into a glass of water (neutral pH). The HCL molecule will dissociate (break up) into a H+ ion and Cl- ion. This can also be termed as the HCL molecule becomes completely ionised in water. This also means that the molecules acquire a charge either negatively or positively through gaining or losing electrons. A weak acid on the other hand such as Aspirin doesn’t dissociate very well in water, it has less H+ ions to give away to the water so it will dissociate only partially or become partially ionised (RSC 2017).
Transcript of What does pKa mean and why can it influence drug ......solution is low then the pKa will be a larger...
TounderstandwhatpKaisandhowitworksthereareafewconceptstogetunderourbeltfirst:pH: MosteveryonehasabasicideaofwhatpHisandhowitworks.However,here’salittleexplanationforthoseofyouwhomayneedalittlerefresher:
Hydrogenionscangainorloseprotonsbasedonwhattypeofsolutiontheyarein.Acidicsolutions,asweknow,arefullofH+ions(protons).Ifanacidisputintoabasicsolution(onewithlessprotons)itwillgiveawayits
protonstothatsolution.Ingivingawayprotonsitwillbecomenegativelycharged.Ifweflippedthisaroundanddroppedsomebasicsolutionintoanacidiconethenthebaseswillgainprotonsandthusbecomingpositivelycharged.Thinkofitlikethis:H+ionsdon’tlikebeinglonely;theywanttohangoutwithmoreH+ionssotheyareniceandsharetheirfriends.Theywilleithergiveawaysomefriendsiftheyhavelotsortakesomeiftheyhavefew.
What does pKa mean and why can it influence drug absorption and excretion?
Weknowthatsomethingsareacidicandsomearebasic(oralkali),butwhatdoesthatreallymean?WhenlookingatthepHofasolutionwearelookingatitshydrogenconcentration:§ Anacidicsolutionisasolutionthathasahighconcentrationof
hydrogenions(H+)§ Abasicsolutionontheotherhandisonewithalowconcentrationof
hydrogenions(seeourlittlefriendsbelow)
pHScale
Ionisation/charge: LetssayIwastodropastrongacidsuchasHydrochloricAcid(HCL)intoaglassofwater(neutralpH).TheHCLmoleculewilldissociate(breakup)intoaH+ionandCl-ion.ThiscanalsobetermedastheHCLmoleculebecomescompletelyionisedinwater.Thisalsomeansthatthemoleculesacquireachargeeithernegativelyorpositivelythroughgainingorlosingelectrons.AweakacidontheotherhandsuchasAspirindoesn’tdissociateverywellinwater,ithaslessH+ionstogiveawaytothewatersoitwilldissociateonlypartiallyorbecomepartiallyionised(RSC2017).
pKa: ThisbringsustotheideaofpKa;AfrequentmisconceptionisthatpHandpKaarethesamething,justopposites.pHandpKaarerelated,however
theyarenotthesamething.ThepKavalueisthepHatwhichadrugisfoundtobe50%ionisedand50%notionised.ItisabletotellushowamoleculewillbehavewhenitisputintosomethingwithacertainpHvalue.TheconceptofpKaisderivedfromsomethingcalledtheaciddissociationconstant(Ka).Thisisanumberthatdescribesthedegreethatanacidwilldissociateinwater(liketheabovereactionwithHCL).TheKaisusuallyaveryhighnumberandcanbeinthe10,000,000,000’s,thismakesitprettyinconvenientforustotryandwrapourheadsaroundsoweusepKainstead.ThepKaisthenegativelogarithm*oftheKavalueandsubsequentlyisamuchsmallernumber(ChemGuide2002).TIP:AgeneralruleofthumbisifthepHofasolutionishigh(acidic)thenthepKawillbeasmallernumber,ifthepHofasolutionislowthenthepKawillbealargernumber.Drugs & pKa: TherelevanceofallthispHandpKatalkessentiallycancomedowntodrugsandhowtheyworkinourbody.
Drugsareweakacidsorbases,sowhereadrugendsupandhowitisabsorbedorexcretedisrelatedto3things:1. ThepHofthesolutionthatthedrugisin2. ThepKaofthedrug3. TheconcentrationofthedrugThecellsofourbodyhavemembranessurroundingthemthataremadeoutoflipids.Ioniseddrugs(drugswithcharge)cannotpassthroughthemembranethereforetheyaresolubleinwaterandwillbeexcretedoutthroughtheurine.Non-ioniseddrugscanpassthroughthelipidmembranethusgettingabsorbedintothebodytocreateanaffect(Peterson,M.2013).OurbodiesaremadeupofmanydifferentareasthatallhaveadifferentpH.WeknowthatthestomachhasaverylowpH(around1-3),ourplasmahasasemi-neutralpH(around7.4)andurineanalkalinepH(around8).WealsoknowthepKavaluesofdifferentdrugsandthereforecangainanideaofwhereinthebodyadrugwouldmostlikelybedistributed.Forexample:Letsthinkintermsofsomeoneoverdosingonamedication,forexampleAspirin.WeknowthatAspirinisaweakacidwithapKaof3.5(Roche2007),thereforewecandeducethattheionizationofthedrugwillbegreatestatanalkalinepH.Soifyouthinkaboutit,weneedtogetasmuchdrugaspossibleintotheionisedformsothatitcanbeexcretedfromthebody.WecanreversetheaffectsofoverdosebyalkalizingbodypHsomoreofthetoxicAspirincanbepartitionedintotheurineandexcreted.
“Alogarithmisthepowertowhichanumbermustberaisedinordertogetsomeothernumber”(UOM2004)
References
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