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Lecture 2

Pharmacokinetics I

QuestionAnswer
Pharmacokinetic principles once a drug is administered: Absorbed into bloodstream Distributed to site of action Permeate through each compartment Metabolized (liver) Eliminated (kidney)
Prodrug inactive precursor chemical that is absorbed and then converted to active drug (clopidogrel for ex.)
Drug routes for enteral PO, SL, buccal
Drug routes for parenteral IV, IM, SC, ID
Advantages for parenteral rapid onset of action; dosing control
Disadvantages for parenteral local tissue damage/infections
IV rapid effect and max control; bolus; infusion
IM aqueous solutions; specialized depot preps; sustained dose over an extended interval
SC simple diffusion; minimizes risks seen with IV injection; not recommended for drugs that cause tissue irritation
Oral toxicities/overdoses treated with antidotes; disadvantages include pathways involved with drug absorption; enteric-coated preparations; extended-release preparations ER, XR, XL, SR
ID used for diagnostic purposes, desensitization
Inhalation/nasal preps effects almost as rapid as with IV bolus
Intrathecal/IV directly into CSF; local rapid effects
Topical used for local effect
Transdermal systemic effects; rate of absorption varies, characteristics of skin at application site and lipid solubility of medication
Rectal bypasses 50% of portal circulation, minimizing biotransformation of drugs by liver; bypasses GI, absorption erratic and incomplete
Absorption administration site into bloodstream; administration routes (not IV) cause partial absorption/lower bioavailability
Absorption factors where drug is absorbed; characteristics of drug; route of administration
Bioavailability percent of medication that reaches circulation
Passive Diffusion high to low concentration; no carrier; not saturable; lipid-soluble go through liid bilayer; water soluble - channel pore
Special Carriers ** active transport and facilitated diffusion; ABC (ATP-binding cassette) family: p-glycoprotein, multi drug resistance, type 1 transporter
Special Carriers selective, saturable, inhibitable
Facilitated Diffusion transmembrane carrier proteins undergo conformational changes; large molecules; faster than passive diffusion; does not require energy; saturable; competition for carrier protein
Active Transport carrier proteins span the membrane; energy dependent; across a concentration gradient; can be saturated; selective
Endo/Exocytosis large size drugs; in/out of cell
Factors Influencing Absorption expression of p-glycoprotein; contact time; total surface area; blood flow; pH
Weak Acids/Bases acidic drugs release protons forming a charged anion; weak bases release a proton; uncharged drugs pass through; lower pKa of a drug --> more acidic
Weak Acids/Bases uncharged form more lipid soluble; weak acids excreted faster in alkaline urine; weak bases excreted faster in acidic urine
P-glycoprotein efflux; expression decreases absorption; associated with drug resistance
Bioavailability IV drugs = 100%; converted to oral 50%; PO drugs = first pass metabolism
Bioavailability factors influencing solubility of drug = hydrophilic drugs poorly absorbed --> not soluble in aqueous body fluids, cannot reach cells chemical instability = in stomach pH; GI tract enzymes Nature of drug formulation --> effects dissolution and rate of absorption
Capillary Permeability slit junctions --> large protein bound; NOT BRAIN (undergo active transport) tight junctions prevents protein bound and hydrophilic --> form BBB lipid soluble drugs readily penetrate CNS
Protein Binding ** plasma proteins: albumin = major drug binding protein --> keeps drug in blood
Protein Binding tissue proteins: drugs in tissues and tissue reservoirs = source of drug
Volume of Distribution fluid volume required to contain the entire drug in body at same concentration measured in plasma
"Apparent" volume of distribution ratio of total amount in body vs. drug plasma concentration
High Vd lots of drug in tissue; extravascular and lipophilic
Low Vd lots of drug in blood; size MW, plasma, hydrophilic
Factors affecting Vd ** 1) size (MW): high MW drugs remain in plasma, low VD 2) plasma protein; binding/extravascular --> plasma (same water) = low VD; extravascular = high vd 3) hydrophilic = low vd; lipophilic = high vd 4) capillary permeability
Created by: bluedolphin7
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