phrmacokinetics bds
TRANSCRIPT
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Dr.U.P.RathnakarDr.U.P.Rathnakar
MD.DIH.PGDHMMD.DIH.PGDHM
a1
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PK is the quantitative studyof drug movement in,
through and out of thebody
During these processes the
drug has to cross variousbiological membranes
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PK-Membrane Transport
Mechanism by which drugs cross biological membrane
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Membrane Transport..
Passive diffusion and Filtration
Specialized transport
Carrier transport
Facilitated diffusion Active transport
Pinocytosis
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PaPassive diffusionssive diffusion Bidirectional process, Movement of molecules from
higher to lower conc [Down the gradient]
Lipid soluble drugs- Passive diffusion, afterdissolving in the lipid of cell membrane
Acidic drugs are unionized in acidic medium
Alkaline drugs are unionized in alkaline Medium
Unionized drugs are readily absorbed More lipid soluble Diffuses quickly
Greater the difference in concn gradient
Quicker diffusion
Ion trappingUrine alkalanizedin poisoning withacidic drugs
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Filtration
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FILTRATION
Capillaries (Except in brain-Tightjunction) have large pores & most
drugs filter through these.Lipid insoluble drugs cross
biological membranes byfiltration through these pores
Diffusion of drugs is dependent onRate of Blood Flow
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Specialized transport: Carrier mediated Drug + CARRIER in the membrane complex is
transported from one side of the membrane to other.
Eg. Calcium & iron absorption Carrier transport
1. Specific,
2. Saturable,3. Competitively inhibited by - which utilize the same
carrier.
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Specialized transport: Carrier mediated
Facilitated diffusion
No energy required Drug + carrier[SLC Transporter] in the
membrane, diffusion across the cell
membrane.
Movement ONLY higher to lower conc[ALONG]
Eg. Vit. B12 absorption
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Specialized transport: Active transport
Movements of molecules Low
conc. To high conc.Against the conc.gradient
Require energy.
P-glycoprotein
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Specialized transport Active transport:Primary
Primary Active Transport
ATP Binding Cassette-
Transporter
Only out of the cytoplasm
Energy derived from ATP
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Specialized transport Active transport
:Secondary:
Energy derived from movement of anothersubstance
In the same direction-Symport
In opp.direction -Antiport
Pinocytosis; By formation of vesicles
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Membrane Transport..Facilitated diffusion
Primary active
Secondary active- Symport
Secondary active-Antiport
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Absorption
[Movement from site of administration tocirculation]
ORAL:
S.c, i.m: Absorbed by capillaries or lymphatics
Topical: Lipid solubility-Hyoscine, Fentanyl, GTN,
Nicotine, Testosterone, Estradiol
Cornea
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BA=30/150
First pass metabolism
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Absorption: Bio-Availability The fraction [F] of administered dose of a drug that
reaches systemic circulation in the unchanged form
I.V. 100% Bio-availablity
Oral-Not 100%. WHY?1. Incompletely absorbed
2. First pass metabolism
i.m or s.c. also may be lessthan 100% -Local binding
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Absorption:Factors
Aqueous solubility
Concentration
Area of absorbing surface Vascularity
pH and ionization
Food Other drugs
Diseases
Route
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DISTRIBUTION
Reversible transfer of drugsbetween body fluid compartments
After absorption drug entersvarious body fluid compartments.
Plasma Interstitial fluid compartment
Cellular fluid compartment.
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Drug enters body
Plasma compartment:Large mol.wt.Bound to plasma proteinsCannot cross capillariesRemains trapped in vascularcompartment [4L]
Extracellular fluid:Low mol.wt.HydrophilicCan cross capillaries(Slit junc)Can not enter cells(Crossplasma membrane-Not lipidsoluble)Remains inPlasma+InterstitiaL fluid[14L]
Total body water:Low mol.wt.HydrophobicCan cross capillariesCan enter cells(Cross plasma membrane)Distrbutes in vol. of 60% ofbody wt.[42L]
Other sites:In pregnancy-FetusFat-Thiopental
Usually drugs not confined
One compt.
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Drug in beaker Drug + Charcoal in beaker
Drug=10mgConcn=20mg/LaVD=10/20mg/L
=500ml=Vol.of
beaker
Drug=10mgConcn=2mg/LaVD=10/2mg/L
=5000ml=Muchmore thanVol.ofBeakerand charcoal
Apparent Volume of Distribution
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Apparent volume of distribution aVD: The volume that would accommodate all thedrug in the body, if the concn.throughout was thesame as in plasma
Lipid insoluble: Small aVD-Eg.Gentamicin-.25L/kg
Highly protein bound-Eg.Diclofenac-0.15L/kg.
Highly tissue bound-Eg.Morphine-3.5L/kg
High vol. of distribution-poisoning-difficult toremove by dialysis
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Redistribution
Highly lipid solubleThiopentone-i.v
Distributed toorgans with high
blood flow.
Eg.Brainsite ofaction
Unconcious
Less vascularareasEg.Fat,muscle
Plasmaconcn.falls
Concious[Drug
withdrawnfrom
brain]
Redistribution
10Sec
10Mts
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Blood Brain Barrier
BBB ONLY Lipid soluble and unionized drugs cross
Anesthetics, Barbiturates
Meningitis increase permeability- Impermiablesubstances Cross!
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Placental barrier Bet.mother and fetus Lipid soluble and unionized cross-anesthetics, alcohol
High mol.wt.do not-insulin Teratogenicity ( Teratos = Monster) Tetracyclines, Thalidomide Anti-cancer drugs, Sex
hormones
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l b
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Plasma protein binding
Drug
ABSORPTION
Enters circulation
Binds to plasma proteins
[acidic to albumin, basic to a-acidglycoprotein]
Bound- inactiveTemp. storage site,Long duration,Hemodialysis noteffective
Freeform-
Active
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Plasma protein binding: Clinical Imp.
Favors drug absorption
Affects Vd
Delays metabolism, excretion,
Not available for actionStorage site
Displacement reactions-
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