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 PINES CITY COLLEGES COLLEGE OF PHARMACY COMPREHENSIVE PHARMACY REVIEW November 28 and Dec. 5, 2012

Compre Review Bioparm

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PINES CITY COLLEGES

COLLEGE OF PHARMACY

COMPREHENSIVE PHARMACY 

REVIEW 

November 28 and

Dec. 5, 2012

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BIOPHARMACEUTICS Deals with the study of the relationship of a

drug product’s physical and chemical

properties to its bioavailability 

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DRUG-RECEPTOR 

INTERACTION RECEPTOR 

Site in the biophase to which drug molecules

can be bound BIOPHASE

 Actual site of action of drugs in the body 

Maybe surface of the cell or within thecell ( organelles)

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DRUG-RECEPTOR INTERACTION

STRUCTURAL

NONSPECIFIC

DRUGS

STRUCTURAL

SPECIFIC DRUGS

a. Pharmacologicalaction

-not directly dependent onchemical structure

-dependent directly on the chemicalstructure

b. Thermodynamic

activity 

-Directly dependent

( large doses needed)

-solely dependent

( low doses needed)

c. Modification inChemical structure

- No change - Change ( fromincreased activity toantagonism)

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DRUG-RECEPTOR THEORIES

CLARK’S HYPOTHESIS 

HYPOTHESIS OF ARIENS AND STEPHENSON

RATE THEORY AKA HYPOTHESIS OF PATON LOCK AND KEY THEORY 

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TYPES OF ANTAGONISM

1. CHEMICAL ANTAGONISM

2. COMPETITIVE ANTAGONISM 3. PARTIAL ANTAGONISM

4. NON-EQUILIBRIUM ANTAGONISM

5. NONCOMPETITIVE ANTAGONISM

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PHARMACOKINETICS>Liberation

> Absorption

> Distribution> Metabolism

> Excretion

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LIBERATION 1st step which determines the onset of action, rate

of absorption and bioavailability 

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 ABSORPTION Entry of a drug into the systemic circulation from

the site of its administration

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PERMEATION

Disposition of drug across the cellular membrane barriers

Dependent on the ffg:

 A. SOLUBILITY 

B. CONCENTRATION GRADIENT

C. SURFACE AREA 

D. VASCULARITY 

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MODES OF DRUG TRANSPORT

 ACROSS A MEMBRANE

MECHANISM ENERGY REQUIRED

CARRIER DIRECTION SATURABLE

PASSIVEDIFFUSION

No No Down

gradient

No

FACILITATEDDIFFUSION

No Yes Downgradient

 Yes

 ACTIVETRANSPORT  Yes Yes Against

gradient Yes

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MODES OF DRUG

TRANSPORT ACROSS A 

MEMBRANE

CONVECTIVE TRANSPORT

 AKA PORE TRANSPORT

ENDOCYTOSIS

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FACTORS AFFECTING DRUG

 ABSORPTION 1. Food intake

2. Disease state

3. Age 4. Site of Absorption

5. Type of Dosage Form

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GASTRIC EMPTYING TIME Example:

1. Meal Content

2. Emotional factors 3. Anticholinergic drugs

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FACTORS AFFECTING DRUG

 ABSORPTION 1. DISSOLUTION

2. PARTICLE SIZE AND SURFACE AREA 

3. PARTITION COEFFICIENT AND EXTENT OFIONIZATION

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IONIZATIONIonized= Water soluble ( HYDROPHILIC)

Nonionized= Lipid soluble ( LIPOPHILIC)

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IONIZATION WA & WB exist in either Nonionized or Ionized

forms in an equilibrium depending on the pH of theenvironment and their pKa (the pH at which themolecule is 50% ionized and 50% nonionized)

Nonionized (uncharged) form of a drug crosses biomembranes

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IONIZATION

% of ionization is determined by theHENDERSON-HASSELBACH EQUATION

[ionized]

 WA: pH-pKa = log -------------------[ nonionized]

[ nonionized]

 WB: pH-pKa = log -------------------

[ionized]

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4. SALT FORMATION 5. POLYMORPHISM

6. HYDRATES

7. SURFACTANTS

8. COMPLEX FORMATION

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RATE-LIMITING STEP

Disintegration of the drug product andsubsequent release of the drug

Dissolution of the drug in an aqueous

environment Absorption across cell membranes into the

systemic circulation

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Tablets/Capsules

Granulesor

aggregates

Fineparticles

Drug insol’n 

Non-ionic

Ionic

 ABSORP-

TION

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BIOAVAILABILITY (f)

Measure of the fraction of a dose that reachesthe systemic circulation

BIOEQUIVALENCE

Same bioavailability, same rate of absorption Cmax and tmax are rate dependent

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PLASMA CONC’N VS. TIME CURVE 

DURATION

MTC

MEC

T I M E

Cmax

tmax

   P   L   A   S   M

   A 

   C   O   N   C   ’   N

 THERAPEUTIC

WINDOW

ONSET OF TIME

LAG TIME 

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METHODS OF MEASURING

BIOAVAILABILITY  1. PLASMA DRUG CONCENTRATION VS. TIME

CURVE A. Tmax

B. Cmax

C. AUC

2. URINARY DRUG CONCENTRATION

 A. Cumulative amount of the active drug excreted

B. Rate of drug excretion in the urine

C. Time for the drug to be completely excreted

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BIOAVAILABILITY  RELATIVE BIOAVAILABILITY 

AUC ( dP)

R. B = ---------------

 AUC ( Ref.std)

 ABSOLUTE BIOAVAILABILITY 

AUC po

F= ------------- AUC iv 

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PHARMACEUTIC ALTERNATIVES

PHARMACEUTIC EQUIVALENTS

PHARMACEUTIC SUBSTITUTION THERAPEUTIC ALTERNATIVE

THERAPEUTIC EQUIVALENT

THERAPEUTIC SUBSTITUTION

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DISTRIBUTION Process when drug molecules that have entered

the vascular system pass from the bloodstreaminto the interstissue to various cells of the tissuesand organs such as mucsles and heart

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DISTRIBUTION Depends on the ffg:

BLOOD FLOW/ CAPILLARITY 

BLOOD VOLUME PARTITIONING LOAD

DEGREE OF BINDING

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DISTRIBUTION Vd

Kinetic parameter that correlates dose with

plasma level at zero timeDose

 Vd = --- - -----

Conc’n 

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METABOLISM BIOTRANSFORMATION

Metabolic conversion of drugs, generally to

less active compounds but sometimes toisoactive or more active forms

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METABOLISM PHASE 1

Oxidation

Reduction Deamination

hydrolysis

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METABOLISM PHASE 11

Glucoronidation

 Acetylation Conjugation

Methylation

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METABOLISM LIVER 

Most important organ in metabolism

Others:Kidney 

Tissues

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METABOLISM

DETERMINANTS OF BIOTRANSFORMATIONRATE

1. Genetic factors

Hydrolysis of esters

 Acetylation of amines

Oxidation

2. Other drugs- Enzyme induction

- Enzyme inhibition

- Inhibitors of intestinal P-glycoprotein

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EXCRETION Irreversible removal of drug from the body by all

routes of elimination

Divided into 2 major components: RENAL EXCRETION

BIOTRANSFORMATION

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1. RENAL EXCRETION

Process in which the drug passes through the

kidney to the bladder and ultimately into theurine

Other pathways include:

Bile, sweat, saliva, milk ( via lactation),

lungs

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2. BIOTRANSFORMATION OR DRUGMETABOLISM

Process by which the drug is chemically converted in the body to a metabolite

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EXCRETION CLEARANCE

Removal of drug from the plasma

3 KINETICS:

1. GLOMERULAR FILTRATION

2. TUBULAR REABSORPTION 3. ACTIVE SECRETION

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IONIZATION INCREASES RENAL

CLEARANCE OF DRUGSOnly free, unbound is filtered

Both ionized and unionized forms of drug are

filteredOnly nonionized forms of the drug undergo

active secretion and active or passivereabsorption

Ionized forms of drugs are trapped in the filtrate

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IONIZATION INCREASES RENAL

CLEARANCE OF DRUGS ACIDIFICATION OF URINE= increases

ionization of weak base- increases renalelimination

 ALKALINIZATION OF URINE= increasesionization of weak acids- increases renalelimination

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PHARMACOKINETIC

CALCULATION LOADING DOSE ( LD)

LD= Vd x Css Where: Vd= Volume of drug distribution

Css= plasma at steady state

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PHARMACOKINETIC

CALCULATION CLEARANCE

Cl= k x Vd Where: k= elimination rate constant

INFUSION RATE= Cl x Css

MAINTENANCE DOSE= Infusion rate xdosing interval = Cl x Css x time

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STEADY STATE

Reached if either rate in = rate out

Time to reach steady state is dependent only inthe elimination t1/2 of a drug and is dependenton the dose size and frequency of administration

RATE AND ORDER OF

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RATE AND ORDER OF

REACTION  Zero –order reaction

C= -kot + Co

Half-life (t1/2)

½ C0

t1/2 = -------ko

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RATE AND ORDER OF

REACTION First Order Reaction

In C= -kt + In Co

-kt

OR log C = ------- + log Co

2.303

Half-life

0.693t1/2 = --------

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 THANK YOU

and

GODBLESS