Compre Review Bioparm
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Transcript of Compre Review Bioparm
8/3/2019 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 = --------
k