1 basic principles- intro ppt

Pharmacology and TherapeuticsPharmacology and TherapeuticsPharmacology and TherapeuticsPharmacology and Therapeutics

A.Q. Sangalang, MD, FPOGSA.Q. Sangalang, MD, FPOGSFACULTY OF PHARMACYFACULTY OF PHARMACY

UNIVERSITY OF SANTO TOMASUNIVERSITY OF SANTO TOMAS

A.Q. Sangalang, MD, FPOGSA.Q. Sangalang, MD, FPOGSFACULTY OF PHARMACYFACULTY OF PHARMACY

UNIVERSITY OF SANTO TOMASUNIVERSITY OF SANTO TOMAS

General Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of PharmacologyGeneral Principles of Pharmacology

PHARMACOLOGYPHARMACOLOGY

Body of knowledge concerned with the action Body of knowledge concerned with the action of chemicals on biologic systems, especially by of chemicals on biologic systems, especially by binding to regulatory molecules (binding to regulatory molecules (receptorsreceptors) and ) and activating or inhibiting normal body processesactivating or inhibiting normal body processes


MEDICAL PHARMACOLOGYMEDICAL PHARMACOLOGY

Area of pharmacology concerned with the use of chemicals in the prevention, diagnosis,

and treatment of disease, especially in humans


TOXICOLOGYTOXICOLOGY

Area of pharmacology concerned with theArea of pharmacology concerned with the undesirable effects of chemicals on undesirable effects of chemicals on

biologic systemsbiologic systems


MOLECULAR BIOLOGYMOLECULAR BIOLOGY

Identifies the exact mechanism of action Identifies the exact mechanism of action of one particular drug of one particular drug

Identifies the receptorsIdentifies the receptors


DRUGDRUG

Any substance that brings about a change Any substance that brings about a change in biologic function through chemical actionsin biologic function through chemical actions


RECEPTORRECEPTOR

Specific molecule in the biologic system that Specific molecule in the biologic system that plays a regulatory roleplays a regulatory role


THE NATURE OF DRUGSTHE NATURE OF DRUGS

Inorganic ions, nonpeptide organic molecules, Inorganic ions, nonpeptide organic molecules, small peptides and proteins, nucleic acids, small peptides and proteins, nucleic acids, lipids, and carbohydrateslipids, and carbohydrates

Found in plants or animals, many are partially or Found in plants or animals, many are partially or completely syntheticcompletely synthetic


PHYSICAL NATURE OF DRUGSPHYSICAL NATURE OF DRUGS SolidSolid LiquidLiquid GasGas

Drugs are given at a site distant from the Drugs are given at a site distant from the

intended site of actionintended site of action


DRUG SIZE AND MOLECULAR WEIGHTDRUG SIZE AND MOLECULAR WEIGHT (MW)(MW)

Vary in size Vary in size MW 7MW 7 (lithium) (lithium) MW 50,000MW 50,000 (thrombolytic agents) (thrombolytic agents)

Majority have Majority have MWMW between between 100 100 and and 10001000


DRUG SIZE AND MOLECULAR WEIGHTDRUG SIZE AND MOLECULAR WEIGHT (MW)(MW)

100 MW100 MW For selective bindingFor selective binding

1000 MW1000 MW For traversing to different barriers of the bodyFor traversing to different barriers of the body

>1000 MW>1000 MW Cannot move within the bodyCannot move within the body Given directly at the site of actionGiven directly at the site of action


DRUG RECEPTOR BONDSDRUG RECEPTOR BONDS

Chemical forces or bonds through Chemical forces or bonds through which the drug interacts with the which the drug interacts with the receptorsreceptors

Weaker bonds are more selective Weaker bonds are more selective bondsbonds



COVALENT BONDSCOVALENT BONDS StrongestStrongest IrreversibleIrreversible



ELECTROSTATIC BONDSELECTROSTATIC BONDS More commonMore common Weaker Weaker Eg, between cation and an anionEg, between cation and an anion



HYDROPHOBIC BONDSHYDROPHOBIC BONDS WeakestWeakest Highly lipid soluble drugsHighly lipid soluble drugs


THE MOVEMENT OF DRUGS IN THE THE MOVEMENT OF DRUGS IN THE

BODYBODY To reach its receptors and bring about biologic To reach its receptors and bring about biologic

effecteffect A drug molecule (eg, sedative) must A drug molecule (eg, sedative) must

travel from the site of administration travel from the site of administration

(eg, gastrointestinal tract) to the site (eg, gastrointestinal tract) to the site

of action (eg, brain)of action (eg, brain)


A.A. PERMEATIONPERMEATION

Movement of drug molecules into and withinMovement of drug molecules into and within the biologic environmentthe biologic environment


A.A. PERMEATIONPERMEATION1.1. AQUEOUS DIFFUSIONAQUEOUS DIFFUSION Movement of molecules through the watery Movement of molecules through the watery

extracellular and intracellular spacesextracellular and intracellular spaces Membranes of capillaries with small water- Membranes of capillaries with small water-

filled poresfilled pores Passive processPassive process Governed by Fick’s law Governed by Fick’s law


A.A. PERMEATIONPERMEATION2.2. LIPID DIFFUSIONLIPID DIFFUSION Movement of molecules through membranesMovement of molecules through membranes

and other lipid structuresand other lipid structures Most important factor for drug permeationMost important factor for drug permeation

Large lipid barriers that separate theLarge lipid barriers that separate thecompartments of the bodycompartments of the body

Passive process Passive process Governed by Fick’s lawGoverned by Fick’s law


A.A. PERMEATIONPERMEATION3.3. TRANSPORT BY SPECIAL CARRIERSTRANSPORT BY SPECIAL CARRIERS Drugs transported across barriers by Drugs transported across barriers by

mechanisms that carry similar endogenousmechanisms that carry similar endogenous

substances substances Amino acid carriers, weak acid carriersAmino acid carriers, weak acid carriers

Capacity limitedCapacity limited Not governed by Fick’s lawNot governed by Fick’s law


A.A. PERMEATIONPERMEATION

3.3. TRANSPORT BY SPECIAL CARRIERSTRANSPORT BY SPECIAL CARRIERS

ACTIVE TRANSPORTACTIVE TRANSPORT Needs energyNeeds energy Against a concentrationAgainst a concentration gradientgradient

FACILITATED DIFFUSIONFACILITATED DIFFUSION No energy requiredNo energy required DownhillDownhill


A.A. PERMEATIONPERMEATION4.4. ENDOCYTOSISENDOCYTOSIS Binding to specialized components Binding to specialized components

(receptors) on cell membranes(receptors) on cell membranes Internalization by infolding of the area of Internalization by infolding of the area of

the membrane and contents of the vesicle the membrane and contents of the vesicle

are subsequently released into the cytoplasmare subsequently released into the cytoplasm


A.A. PERMEATIONPERMEATION4.4. ENDOCYTOSISENDOCYTOSIS Permits very large or very lipid-insolublePermits very large or very lipid-insoluble

chemicals to enter the cellchemicals to enter the cell Eg, BEg, B1212 with intrinsic factor and iron with with intrinsic factor and iron with

transferrintransferrin


A.A. PERMEATIONPERMEATION5.5. EXOCYTOSISEXOCYTOSIS Reverse processReverse process Expulsion of membrane-encapsulated Expulsion of membrane-encapsulated

material from the cellmaterial from the cell


B.B. FICK’S LAW OF DIFFUSIONFICK’S LAW OF DIFFUSION Predicts the movement of molecules across Predicts the movement of molecules across

a barriera barrier Drug absorption is faster in organs with Drug absorption is faster in organs with

larger surface areas (eg, small intestine) larger surface areas (eg, small intestine)

than from organs with smaller absorbing than from organs with smaller absorbing

areas (eg, stomach)areas (eg, stomach)


B.B. FICK’S LAW OF DIFFUSIONFICK’S LAW OF DIFFUSION

Drug absorption is faster from organs with Drug absorption is faster from organs with

thin membrane barriers (eg, lungs) than thin membrane barriers (eg, lungs) than

those with thick barriers (eg, skin)those with thick barriers (eg, skin)


FICK’S LAW OF DIFFUSIONFICK’S LAW OF DIFFUSION

Area x Permeability coefficientArea x Permeability coefficient

((CC11––CC22) ) X X ______________________________ ______________________________

ThicknessThickness

CC11-higher conc-higher conc

CC22-lower conc-lower conc

Permeability coefficientPermeability coefficient-measure of the mobility -measure of the mobility of the drug in medium of the diffusion pathof the drug in medium of the diffusion pathThicknessThickness-thickness (length of the diffusion path)-thickness (length of the diffusion path)


C.C. WATER AND LIPID SOLUBILITY OF WATER AND LIPID SOLUBILITY OF DRUGSDRUGS

1.1. AQUEOUS DIFFUSIONAQUEOUS DIFFUSION Aqueous solubility of a drug is a function of Aqueous solubility of a drug is a function of

the electrostatic charge (degree of ionization,the electrostatic charge (degree of ionization,polarity) of the moleculepolarity) of the molecule

Water molecules are attracted to chargedWater molecules are attracted to charged drug molecules forming an aqueous shell drug molecules forming an aqueous shell

around themaround them Lipid solubility of a molecule is inversely Lipid solubility of a molecule is inversely

proportional to its charge proportional to its charge



2.2. LIPID DIFFUSIONLIPID DIFFUSION Many drugs are weak bases or weak acidsMany drugs are weak bases or weak acids pH of the medium determines the fraction of pH of the medium determines the fraction of

molecules charged (ionized) versus unchargedmolecules charged (ionized) versus uncharged(nonionized)(nonionized)

Fraction of molecules in the ionized state canFraction of molecules in the ionized state canbe predicted by means of the H-H equation be predicted by means of the H-H equation


THE HENDERSON-HASSELBACH EQUATIONTHE HENDERSON-HASSELBACH EQUATION

(protonated)(protonated)

log ___________ = pka - pHlog ___________ = pka - pH

(unprotonated)(unprotonated)

Protonated means associated with a proton Protonated means associated with a proton (a hydrogen ion)(a hydrogen ion)


C.C. WATER AND LIPID SOLUBILITY OF WATER AND LIPID SOLUBILITY OF

DRUGS DRUGS 3.3. Ionization of Weak Acids and Weak BasesIonization of Weak Acids and Weak Bases

WEAK BASEWEAK BASE Neutral molecule that can form a cation Neutral molecule that can form a cation

(+ charged) by combining with a proton (+ charged) by combining with a proton (hydrogen ion)(hydrogen ion)

Ionized, more polar, more water soluble Ionized, more polar, more water soluble when they are protonatedwhen they are protonated



3.3. Ionization of Weak Acids and Weak Bases Ionization of Weak Acids and Weak Bases WEAK ACIDWEAK ACID

Neutral molecule that can reversibly Neutral molecule that can reversibly dissociate into an anion (- charged) and dissociate into an anion (- charged) and

a proton ( hydrogen ion)a proton ( hydrogen ion) Not ionized, less polar, less water solubleNot ionized, less polar, less water soluble when they are protonatedwhen they are protonated


RNHRNH33++ RNHRNH22 ++ HH++

protonated weakprotonated weak unprotonated weakunprotonated weak protonproton

base (charged,base (charged, base (uncharged, morebase (uncharged, more

more water-soluble)more water-soluble) lipid-soluble)lipid-soluble)

RCOOHRCOOH RCOORCOO__ ++ H H++

protonated weakprotonated weak unprotonated weakunprotonated weak protonproton

acid (uncharged,acid (uncharged, acid (charged, moreacid (charged, more

more lipid-soluble)more lipid-soluble) water-soluble)water-soluble)


The Henderson-Hasselbach EquationThe Henderson-Hasselbach Equation

Clinically important when it is necessaryClinically important when it is necessary

to estimate or alter the partition of drugsto estimate or alter the partition of drugs

between compartments of different pHbetween compartments of different pH


The Henderson-Hasselbach EquationThe Henderson-Hasselbach Equation When a patient takes an overdose of a weak When a patient takes an overdose of a weak

acid drug, excretion maybe accelerated by acid drug, excretion maybe accelerated by alkalinizing the urine alkalinizing the urine

Weak acids dissociate to its charged, polar form Weak acids dissociate to its charged, polar form in alkaline urine and cannot readily diffuse back in alkaline urine and cannot readily diffuse back from the renal tubule back to the bloodfrom the renal tubule back to the blood


Large number of drugs are weak bases with Large number of drugs are weak bases with amine containing moleculesamine containing molecules

Nitrogen of a neutral amine has 3 atoms Nitrogen of a neutral amine has 3 atoms associated with it plus a pair of unshared associated with it plus a pair of unshared electronselectrons

PrimaryPrimary SecondarySecondary TertiaryTertiary QuaternaryQuaternary

HH R R R R RR

. .. . . . . . . . . . . .. .

R : N : R : NR : N : R : N : R : N :: R : N : R : N : RR : N : R

. .. . . . . . . . . . . .. .

HH H H R R RR


ABSORPTION OF DRUGSABSORPTION OF DRUGSA. ROUTES OF ADMINISTRATIONA. ROUTES OF ADMINISTRATION Drugs usually enter the body remote from the Drugs usually enter the body remote from the

target tissue or organ and require transport by target tissue or organ and require transport by the circulation to the intended site of actionthe circulation to the intended site of action

BIOAVAILABILITYBIOAVAILABILITY

amount absorbed into the systemic circulationamount absorbed into the systemic circulation amount of drug administeredamount of drug administered


ABSORPTION OF DRUGSABSORPTION OF DRUGSA.A. ROUTES OF ADMINISTRATIONROUTES OF ADMINISTRATION

1.1. ORALORAL (swallowed) (swallowed) Maximum convenienceMaximum convenience Absorption maybe slower, and less completeAbsorption maybe slower, and less complete Some drugs have low bioavailability when Some drugs have low bioavailability when

given orallygiven orally



1.1. ORALORAL (swallowed) (swallowed) Subject to Subject to first-pass effectfirst-pass effect (significant amount (significant amount

of the agent is metabolized in the gut wall, of the agent is metabolized in the gut wall, portal circulation, and liver before it reaches portal circulation, and liver before it reaches the systemic circulation)the systemic circulation)



2.2. INTRAVENOUS (IV)/PARENTERALINTRAVENOUS (IV)/PARENTERAL Instantaneous and complete absorptionInstantaneous and complete absorption Bioavailability by definition is 100%Bioavailability by definition is 100% Potentially more dangerous, high blood Potentially more dangerous, high blood

levels reached if administration is too rapidlevels reached if administration is too rapid



3.3. INTRAMUSCULAR (IM)INTRAMUSCULAR (IM) Absorption is often faster and more complete Absorption is often faster and more complete

(higher bioavailability) than oral(higher bioavailability) than oral Large volumes (>5 ml into each buttock) if the Large volumes (>5 ml into each buttock) if the

drug is not irritatingdrug is not irritating



3.3. INTRAMUSCULAR (IM)INTRAMUSCULAR (IM) First-pass effect is avoidedFirst-pass effect is avoided Heparin cannot be given by this route, Heparin cannot be given by this route,

causes bleeding in the musclecauses bleeding in the muscle



4.4. SUBCUTANEOUSSUBCUTANEOUS Slower absorption than IM route Slower absorption than IM route First-pass effect is avoidedFirst-pass effect is avoided Heparin can be given by this route, does Heparin can be given by this route, does

not cause hematomanot cause hematoma



5.5. BUCCAL AND SUBLINGUALBUCCAL AND SUBLINGUAL Buccal routeBuccal route (in the pouch between gums (in the pouch between gums

and cheeks) and cheeks) Permits absorption direct into the systemic Permits absorption direct into the systemic

circulation, bypassing hepatic portal circuit circulation, bypassing hepatic portal circuit and first-pass metabolismand first-pass metabolism



5.5. BUCCAL AND SUBLINGUALBUCCAL AND SUBLINGUAL Slow or fast depending on formulation of Slow or fast depending on formulation of

the productthe product Sublingual routeSublingual route (under the tongue) offers (under the tongue) offers

the same featuresthe same features



6.6. RECTALRECTAL (suppository) (suppository) Partial avoidance of first-pass effect Partial avoidance of first-pass effect

(not completely as the sublingual route)(not completely as the sublingual route) Suppositories tend to migrate upward inSuppositories tend to migrate upward in

the rectum where absorption is partiallythe rectum where absorption is partially

into the portal circulationinto the portal circulation



6.6. RECTAL RECTAL (suppository)(suppository) Larger amounts of unpleasant drugs Larger amounts of unpleasant drugs

are better administered rectallyare better administered rectally May cause significant irritationMay cause significant irritation



7.7. INHALATIONINHALATION For respiratory diseasesFor respiratory diseases Delivery closest to the target tissueDelivery closest to the target tissue Results into rapid absorption because of Results into rapid absorption because of

the rapid and thin alveolar surface areathe rapid and thin alveolar surface area



7.7. INHALATION INHALATION Drugs that are gases at room temperature Drugs that are gases at room temperature

(eg, nitrous oxide), or easily volatilized (eg, nitrous oxide), or easily volatilized (anesthetics) (anesthetics)



8.8. TOPICAL TOPICAL Application to the skin or mucous membraneApplication to the skin or mucous membrane

of the eye, nose, throat, airway, or vagina of the eye, nose, throat, airway, or vagina

for local effectfor local effect



8.8. TOPICAL TOPICAL Rate of absorption varies with the areaRate of absorption varies with the area

of application and drug’s formulationof application and drug’s formulation Absorption is slower compared to other Absorption is slower compared to other

routesroutes



9.9. TRANSDERMAL TRANSDERMAL Application to the skin for systemic effect Application to the skin for systemic effect Rate of absorption occurs very slowlyRate of absorption occurs very slowly First-pass effect is avoidedFirst-pass effect is avoided


ABSORPTION OF DRUGSABSORPTION OF DRUGSB.B. BLOOD FLOWBLOOD FLOW Influences absorption from IM, subcutaneous, Influences absorption from IM, subcutaneous,

and in shock and in shock High blood flow maintains a high drug depot-High blood flow maintains a high drug depot-

to-blood concentration gradientto-blood concentration gradient Maximizes absorptionMaximizes absorption


ABSORPTION OF DRUGSABSORPTION OF DRUGSC.C. CONCENTRATIONCONCENTRATION Concentration gradient Concentration gradient Major determinant of the rate of absorption Major determinant of the rate of absorption

(Fick’s law)(Fick’s law)


DISTRIBUTION OF DRUGSDISTRIBUTION OF DRUGSA.A. DETERMINANTS OF DISTRIBUTIONDETERMINANTS OF DISTRIBUTION

1.1. Size of the organSize of the organ Size of the organ determines the concentrationSize of the organ determines the concentration

gradient between blood and the organ gradient between blood and the organ Eg, skeletal muscle and brainEg, skeletal muscle and brain



2.2. Blood flowBlood flow Important determinant of the rate of uptakeImportant determinant of the rate of uptake Well-perfused organs Well-perfused organs

BrainBrain Heart, kidneys Heart, kidneys Splanchnic organsSplanchnic organs



3.3. SolubilitySolubility If the drug is very soluble in cells, the If the drug is very soluble in cells, the

concentration in the perivascular space concentration in the perivascular space

will be lower and diffusion from the vessel will be lower and diffusion from the vessel

into the extravascular tissue will be facilitatedinto the extravascular tissue will be facilitated



4.4. BindingBinding Binding of drugs to macromolecules in Binding of drugs to macromolecules in

the blood or tissue compartment will tend the blood or tissue compartment will tend

to increase the drug’s concentration in thatto increase the drug’s concentration in that

compartmentcompartment


DISTRIBUTION OF DRUGSDISTRIBUTION OF DRUGSB.B. APPARENT VOLUME OF DISTRIBUTIONAPPARENT VOLUME OF DISTRIBUTION

VVdd

Amount of drug in the body to the Amount of drug in the body to the concentration in the plasmaconcentration in the plasma


METABOLISM OF DRUGSMETABOLISM OF DRUGSA.A. AS MECHANISM OF TERMINATION OF AS MECHANISM OF TERMINATION OF

DRUG ACTIONDRUG ACTION Action of many drugs is terminated before theyAction of many drugs is terminated before they

are excretedare excreted Metabolized to biologically inactive derivativesMetabolized to biologically inactive derivatives Conversion to a metabolite is a form of Conversion to a metabolite is a form of

eliminationelimination


METABOLISM OF DRUGSMETABOLISM OF DRUGSB.B. AS MECHANISM OF DRUG ACTIVATIONAS MECHANISM OF DRUG ACTIVATION

PRODRUGSPRODRUGS Inactive as administered and must beInactive as administered and must be

metabolized in the body to become active metabolized in the body to become active Eg, levodopa, minoxidilEg, levodopa, minoxidil

Many drugs are active as administeredMany drugs are active as administered

and have active metabolites as well and have active metabolites as well Some benzodiazepinesSome benzodiazepines


METABOLISM OF DRUGSMETABOLISM OF DRUGSC.C. DRUG ELIMINATION WITHOUT DRUG ELIMINATION WITHOUT

METABOLISMMETABOLISM Drugs not modified by the bodyDrugs not modified by the body Continue to act until they are excretedContinue to act until they are excreted Eg, lithiumEg, lithium


ELIMINATION OF DRUGSELIMINATION OF DRUGSDeterminants of the duration of action for most Determinants of the duration of action for most

drugsdrugs DosageDosage Rate of elimination following the last dose Rate of elimination following the last dose

Disappearance of the active molecules Disappearance of the active molecules

from from the bloodstreamthe bloodstream


ELIMINATION OF DRUGSELIMINATION OF DRUGS Drug elimination is not the same as drug Drug elimination is not the same as drug

excretionexcretion A drug maybe eliminated by metabolism A drug maybe eliminated by metabolism

long before the modified molecules are long before the modified molecules are

excreted from the bodyexcreted from the body


ELIMINATION OF DRUGSELIMINATION OF DRUGS For most drugsFor most drugs, excretion is by way of the , excretion is by way of the

kidneys (except anesthetic gases-lungs)kidneys (except anesthetic gases-lungs) For drugs with active metabolitesFor drugs with active metabolites

(eg, diazepam), elimination of the parent (eg, diazepam), elimination of the parent

molecule by metabolism is not synonymousmolecule by metabolism is not synonymous

with termination of actionwith termination of action For drugs that are not metabolizedFor drugs that are not metabolized, excretion, excretion

is the mode of eliminationis the mode of elimination


ELIMINATION OF DRUGSELIMINATION OF DRUGS A small number of drugsA small number of drugs combine irreversibly combine irreversibly

with their receptors, disappearance from thewith their receptors, disappearance from thebloodstream is not equivalent to cessation of bloodstream is not equivalent to cessation of drug actiondrug action

Very prolonged actionVery prolonged action Eg, phenoxybenzamine, irreversible inhibitor Eg, phenoxybenzamine, irreversible inhibitor

of alpha receptors is eliminated from the of alpha receptors is eliminated from the bloodstream in 1 h or less after administration,bloodstream in 1 h or less after administration,drug’s action lasts for 48 h drug’s action lasts for 48 h


ELIMINATION OF DRUGSELIMINATION OF DRUGSA.A. FIRST ORDER ELIMINATIONFIRST ORDER ELIMINATION Rate of elimination is proportionate to the Rate of elimination is proportionate to the

concentration (ie, the higher the concentration, concentration (ie, the higher the concentration, the greater the amount eliminated per unit the greater the amount eliminated per unit time)time)

Drug’s concentration in plasma decreases Drug’s concentration in plasma decreases exponentially with timeexponentially with time


ELIMINATION OF DRUGSELIMINATION OF DRUGSA.A. FIRST ORDER ELIMINATIONFIRST ORDER ELIMINATION Half-life of elimination is constant regardlessHalf-life of elimination is constant regardless

of amount of drug in the bodyof amount of drug in the body Concentration of such drug in the blood will Concentration of such drug in the blood will

decrease by 50% for every half-lifedecrease by 50% for every half-life Most common processMost common process Followed by most drugs Followed by most drugs



FIRST ORDER KINETICSFIRST ORDER KINETICS

Plasma conc.(Cp)

Time (h)

2.5 units/h

1.25 units/h

5 units/h5 units/h

ELIMINATION OF DRUGSELIMINATION OF DRUGSB.B. ZERO ORDER ELIMINATIONZERO ORDER ELIMINATION Rate of elimination is constant regardless Rate of elimination is constant regardless

of concentrationof concentration Occurs with drugs that saturate theirOccurs with drugs that saturate their

elimination of mechanism at concentrations elimination of mechanism at concentrations

of clinical interestof clinical interest


ELIMINATION OF DRUGSELIMINATION OF DRUGSB.B. ZERO ORDER ELIMINATIONZERO ORDER ELIMINATION Concentration of such drugs in plasma Concentration of such drugs in plasma

decrease in linear fashion over timedecrease in linear fashion over time With higher doses, there will be bigger With higher doses, there will be bigger

chances of toxic effect because the patientchances of toxic effect because the patient

may not be able to eliminate itmay not be able to eliminate it Eg, alcohol, phenytoin, aspirinEg, alcohol, phenytoin, aspirin



ZERO-ORDER KINETICSZERO-ORDER KINETICS

2.5 units/h

Plasma conc.(Cp)

Time (h)

2.5 units/h

2.5 units/h

1 basic principles- intro ppt

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