Different Routes of Administration with its Advantages & Disadvantages Route of Administration

Advantages
'afe (onvenient Does not require assistance )ften painless *edicament need not be sterile, hence, cheaper

Disadvantages
'low onset of action +ot for emergencies +ot for uncooperative, unconscious or vomiting patient Absorption of drug may be variable and erratic where certain drugs are not absorbed ,as first pass effect +ot %&&- bioavailability of drugs Irritation to gastric mucosa- nausea and vomiting

Oral

Route of Administration Sublingual / Buccal

Advantages
Absorption -rapid (fast onset of action) Avoids first pass effect in liver Drugs with high first pass metabolism can be absorbed directly into systemic circulation

Disadvantages
Inconvenient Unpleasant taste of some drugs Drugs are usually available in small doses that requires repetitive administration

Route of Administration

Advantages
Used for systemic effect and also for patient that is vomiting, unconscious or children Avoids first pass effect as drug enter the systemic circulation without passing liver ood for drugs affecting the bowel such as la!atives

Disadvantages
Inconvenient Drug absorption is often irregular and difficult to predict

Rectal

Route of Administration Respiratory/ Inhalation

Advantages "arge surface area provided by lungs for absorption Action of onset is very rapid #astest method ( $- %& seconds for drug to reach brain)

Disadvantages Inflammation of respiratory tract may be caused by irritant vapours Drugs do not stay long in blood stream, so repetitive dose needed

Route of Administration
arenteral

Advantages
.referred when rapid absorption is essential Used in cases of emergency or when patients are unconscious or unable to accept oral medication astric irritation and vomiting are not provo/ed Avoids first pass effect %&&- bioavailability Used for longer period of drug administration "arge volumes can be infused Usually for supplement or cell or tissue activation purpose

Disadvantages
.reparation is sterilised *ore e!pensive Invasive and painful ,ave are chances of local tissue in0ury Assistance of another person might be needed (e1g1 insulin by diabetic patients) 2ital organs li/e heart and brain get e!posed to high concentration of the drug +ot for treatment purpose

Intravenou s infusions

Intravenou s injection

%&&- bioavailability of drug as whole drug enters blood stream Accurate dose is delivered quic/ly (an be used for irritating solutions (if given by subcutaneous or intramuscular in0ection they cause pain and tissue damage)

Difficult to administer than a subcutaneous or intramuscular in0ection because inserting a needle into a vein may be difficult, especially if people are obese

Route of Administration !opical

Advantages
Avoid the I tract and hepatic first pass metabolism 3educes systematic side effects Improves patient compliance #ast action onset Allows higher concentration of action at side of application ,ave low to!icity level that gives a wide therapeutic inde!

Disadvantages
(annot deliver drugs with high dose efficacy )nly a small amount of drug can be applied at one time (auses rash as common side effect 3ate of absorption may vary Dosing deliver may require ad0ustment

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Route of Administration "iscellaneous Ocular Otic #aginal $rethra

Advantages Application of the drug on site of action directly ensures a higher concentration of the drug that will be absorbed into the body1 "ower chances of side effects as its treated locally 4asy administration of drug into eye or ear upon repeated training

Disadvantages 3etention of drug at site of action is poor due to low tear volume 5he application of ointment formulations to the eye may result in a temporary blurring of vision1 )cular formulations are sterile and hence require detailed preparation

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&igure '8 2ascular pathway of drugs absorb from various systemic routes of administration and sites of first pass metabolism.

Distribution of Ions Across %ell "embrane

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(ells have a phospholipid bilayer membrane that serves as the cell membrane that differentiates the cell into its intracellular and also e!tracellular region1 *ost cells consist of charged ions and hence, they have an electrical potential gradient across the plasma membrane where there is a difference in the distribution of ions in the intracellular and e!tracellular fluid1 5he intracellular fluid and e!tracellular fluid is found in the intracellular and e!tracellular region respectively1there are several different charged ions that are unevenly distributed in the intracellular and e!tracellular fluid1 Among the ions that are distributed in the cell across its semipermeable membrane along with its concentration is as shown below8 5able %8 Distribution of ions across the cell membrane 697
%omponent )mmol/*+ <> +a> (a9> total (a9> free (l,()=p, Amino acids, proteins ?1@ %?& = % %%& 9? $1=@ %& %?&( varies among cells) %& % &1% = %& $ %9& Outside Inside

&igure (8 A patch of membrane of an e!citable cell at rest with part of the surrounding intracellular and e!tracellular media1 At the sides of the figure, the si:es of the symbols reflect the proportions of the corresponding ion concentration1 5he intracellular anion (A -) is important to the achievement of electroneutrality; however, A- is derived from large immobile and impermeable molecules (<A), and thus A- does not contribute to ionic flow1 At rest, the membrane behaves as if it were permeable only to potassium1 6=7

+a>, (l- and bicarbonate (,()=-) are the main solutes in the e!tracellular fluid and < >,*g9>, phosphate and proteins are the dominant solutes in the cell1 6%7 5he distribution of ions are influenced by8 5he 'emipermable *embrane (oncept 4lectrochemical radient .umps

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!he Semipermeable "embrane %oncept .olar molecules cannot diffuse through the lipid bilayer and the presence of proteins embeeded in the membrane is relied on to allow permeability to these ions1 5he proteins tend to form channels that may be selective in nature1 #or instance, some channels (<> channels) allow only potassium ions to pass, while others are specific for sodium (+a> channels)1

#or this reason, two membranes that have the same permeability to potassium because they have the same number of <> channels may have quite different permeability to sodium if they contain different number of +a> channels1 6?7 ,lectrochemical gradient 5he membrane potential acts li/e a battery, an energy source that affects the traffic of all charged substances across the membrane1 5he two forces that drive the diffusion of ions across a membrane are8 chemical force ( following the ionAs concentration gradient) electrical force ( effect of the membrane potential on the ionAs movement) 5hese both combinations of forces acting on an ion is called the electrochemical gradient whereby it moves from areas of high concentration to low concentration down its gradient1 'odium ions in the e!tracellular fluid are attracted by the e!cess of negative charges on the inner surface of the cell membrane, so both chemical and electrical forces drive +a > into the cell1

5he chemical gradient for potassium ions tends to drive them out of the cell, but the movement is opposed by (%) the attraction between <> and the negative charges on the inside of the cell membrane and (9) the repulsion between < > and the positive charges on the outside of the membrane1 6@7

umps - !he Sodium. otassium ump

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&igure 08 5he 'odium- .otassium .ump !he Sodium/ otassium ump %ycle 5his pump is an active transport mechanism that is driven by the brea/down of A5. and wor/s through a series of conformational changes in a transmembrane protein 5hree sodium ions bind to the cytoplasmic side of the protein, causing the protein to change its conformation protein In its new conformation, the molecule becomes phosphorylated at the e!pense of a molecule of A5. 5he phosphorylation induces a second conformational change that translocates the = sodium ions across the membrane In this new conformation, the protein has a low affinity for sodium ions and the = bound sodium ions dissociate from the protein and diffuse into the e!tracellular fluid 5he new conformation has a high affinity for potassium ions, two of which bind to the e!tracellular side of the protein

[6]

5he bound phosphate now dissociates and the protein reverts to its original conformation, e!posing the two potassium ions to the cytoplasm on the inside of the cell 5his conformation has a low affinity for potassium ions, so the 9 bound potassium ions dissociate from the protein and diffuse into the interior of the cell1
6$7 6$7

5his pump accomplishes several vital functions8

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It helps establish a net charge across the plasma membrane with the interior of the cell being negatively charged with respect to the e!terior1 5his resting potential prepares nerve and muscle cells for the propagation of action potentials leading to nerve impulses and muscle contraction1 5he accumulation of sodium ions outside of the cell draws water out of the cell and thus enables it to maintain osmotic balance 5he gradient of sodium ions is harnessed to provide the energy to run several types of indirect pumps such as symport pumps and antiport pumps1 6B7

!he Resting "embrane otential It is the membrane potential of a neuron that is not transmitting signals Is the result from the diffusion of <> and +a> through ion channels that are always open and ungated 1 5he +a> and <> gradients are maintained by the sodium-potassium pump At the resting potential, most gated channels are closed1 5he opening of gated channels alters the rate of ion movement across the cell membrane and thus changes the transmembrane potential1 In neurons, the membrane potential is between -C& and -B& m2 when the cell is not transmitting signals1 5he 4m is dependant and proportional to the concentration of <> on each side of the membrane1 *embrane potential is highly sensitive to the concentration of < > and the membrane contains many channels that allow only < > to diffuse across the membrane and this prevent (l - ions to pass causing cytosol region to be negatively charged1 5he action of sodium-potassium pump only results in slight difference in 4 m while indirect action of the pump and movement of < > and +a> down its already established concentration gradient contributes to ma0ority of membrane potential1

Action otential If a cell has gated ion channels, its membrane potential may change in response to stimuli that open or close those channels1 5he distribution of membrane channels can vary from one region of the cell membrane to another; this variation can affect how and where a cell responds to specific stimuli1 1yperpolari2ation 8 an increase in the magnitude of the membrane potential ( the inside becomes more negatively charged) is triggered1 5his may be caused by the opening of <> channels, which increases the membraneAs permeability to < >1 Depolari2ation 8 a reduction in the magnitude of the membrane potential ( the inside of the membrane becomes less negative)1 5his may be due to the opening of gated +a> channels, which increases the membraneAs permeability to +a >1 3raded potential 8 are the changes in membrane potential because the magnitude of the hyperpolari:ation or depolari:ation varies with the strength of the stimulus where

11

a larger stimulus causes a larger change in permeability and thus a larger change in the membrane potential1 !hreshold 8 is when depolari:ations are graded only up to a certain membrane potential in most neurons1 6%&7

&igure 4 8 2ariation on how a cell responds to a specific stimuli1

roduction of Action otential )A + Action .otential 8 response when a stimulus strong enough to produce a depolari:ation that reaches threshold1 are signals that carry information

A. production involves both voltage-gated +a > and voltage-gated <> channels1 Doth type of channels are opened by depolari:ing the membrane but they respond independently and sequentially where +a> channels open before <> channels1 4ach voltage-gated +a> channel has two gates, an activation and an inactivation gate, and both must be open for +a> to diffuse through the channel1 4ach voltage-gated <> channel has 0ust one gate, an activation gate1 5he initiation of an A. in a!ons depends on +a> influ! and in some cells (a9> influ!1

11

&igure 53ole of voltagegated ion channels in generation of Action .otential

%8

At the resting potential, the activation gate on +a > and <> channels are closed and an inactivation gate on +a> channel is open1 5he membraneAs resting potential is maintained1 Ehen a stimulus depolari:es the membrane, the activation gates on some +a > channels open, allowing more +a> to diffuse into the cell1 5he +a > influ! causes further depolari:ation, which opens the activation gates on still more +a > channels, allowing even more +a > to diffuse into the cell1 If the depolari:ation reaches the threshold, it triggers an action potential1 )nce the threshold is crossed, depolari:ation opens the activation gates on most +a > channels, while the <> channelsA activation gates remain closed1 +a > influ! ma/es the inside of the membrane positive with respect to the outside1 5he inactivation gates on most +a > channels close, bloc/ing +a > influ!1 5he activation gates on most <> channels open, permitting < > rapid efflu! which again ma/es the inside of the cell negative1 It is the final phase of an action potential where both gates of the +a > channels are closed, but the activation gates on some <> channels are still open1 As these gates close on most < > channels, and the inactivation gates open on +a > channels, the membrane returns to its resting state1 5he A.-induced depolari:ation of cell membrane spreads a small distance in either direction inside the a!on1 6F7

98

=8

?8

@8

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References 6%7 697 4eshils, *aurice,et. al.,Modern Nutrition in health and disease,%&th ed,9&&C
*anson,Gones and *orris, Crash Course Cell Biology & Genetics, =rd ed1,Dan ,orton-':ar, *osby .ublication,9&&9, p1=C %1&9am,%$th 'eptember 9&%% H http8IIwww1bem1fiIboo/I&=I&=1htmJ

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6?7 6@7

*ader,Biology,Fth ed, *c raw ,ill International 4ducation, +ew Kor/,9&&B, p1 BBLBF %1=&am, %$th 'eptember 9&%% Hhttp8IIcw!1prenhall1comIboo/bindIpubboo/sImartinidemoIchapter%9ImedialibI(,%9IhtmlIc h%9M@M%1htmlJ

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91%@am, %$th 'eptember 9&%% Hhttp8IIbcs1whfreeman1comIthelifewireBeIpagesIbcs-mainMbody1aspN sO&@&&&LnO&&&%&LiO&@&%&1&%LvOchapterLoOPFF&&&PLnsO&LuidO&LrauO&J

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91=&pm, %$th 'eptember 9&%% Hhttp8IIhighered1mcgraw-hill1comIolcwebIcgiIpluginpop1cgiN itOswf88@=@88@=@88IsitesIdlIfreeI&&$9?=$=%CI%9&&CBIbio&=1swf88'odium-.otassium -9&4!change-9&.umpJ

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=1?&pm, %$th 'eptember 9&%% Hhttp8IIusers1rcn1comI0/imball1ma1ultranetIDiology.agesIDIDiffusion1htmlJ

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(ampbell 3eece, Biology,$th ed, Den0amin (ummings .ublication ,'an #rancisco, 9&&@, p1%&%$-%&9& Dy .1 *ichael (onn, Neuroscience in medicine, p1C&,=1@&pm, %$th 'eptember 9&%% Hhttp8IIboo/s1google1com1myIboo/sN idOsorMro<lus/(LpgO.A@BLdqOdistribution>of>ions>across>cell>membraneLhlOenLeiO vg!&5u-GKr5rQe9gu0AAwLsaORLoiOboo/MresultLctOresultLresnumO=LvedO&(D/QCA4wAgSv OonepageLqOdistribution-9&of-9&ions-9&across-9&cell-9&membraneLfOfalseJ <D 5ripathi, Essentials of Medical Pharmacology,Cth ed, Gaypee Drothers *edical .ublishers (.) "td , +ew Delhi,9&&C, p1C-%&

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