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Pharmacodynamics action of the drug on the body: The relationship of the dose of drug given a patient to the concentration of drug achieved in the blood stream
What are the four process of pharmacodynamics? 1. absorption 2.distrubtion 3.metabolism 4.excretion
Describe the time course of drug concentration in the plasma after IV administration When we give a bolus directly into the bloodstream, we get an immediately high concentration or peak effect that declines over time to lower concentration;Allows tightest control;Most rapid effect Lower variability & increased predictability
Describe the time course of drug concentration in the body after a non-parenteral route of administration. No direct access to blood stream; start with 0 drug in bloodstream and gradually increase over slow time
Absorption Transfer of drug from site of administration to systemic circulation
Distribution Transfer of drug from systemic circulation to tissues
Metabolism Enzymatic alteration of a drug
Excretion Removal of drug from the body
Potential 3 step process in drug absorption – Disintegration or Release – Dissolution – Absorption
What are the three Transport process? • Passive diffusion (high to low) • Facilitated diffusion (high to low w/transport proteins) • Active transport (high to low w/energy)
What are the three PhysiologicFactors of the Membrane • phospholipidbilayer • hydrophilic surfaces with lipophilic centers • Surface area
What are the two Physical/chemical Properties of the Drugs? –  Oil/water partition coefficient • lipophilic vs hydrophilic –  Ionization at pH of absorption site vs blood stream • unionized form absorbed
Passive Diffusion Increased by what four things? • Lipophilicity (Favorable oil/water partition coefficient) • Larger surface area • High concentration gradient • Thinner membrane
Describe how rate and extent of absorption affect the concentration versus time curve. Absorption only affected when drug administration is via a non-parenteral route. slower the rate & lower the extent of absorption will increase the time it takes for a drug to reach therapeutic & peak plasma concentrations.
Which form diffuses across membrane? Non-ionized
Amount of nonionized drug available is determined by drug pKa and pH gradient across membrane
What does pKA mean? • A characteristic of a drug • The pH at which half of the molecules are in the ionized form and one half are in the unionized form
What is theHenderson-Hasselbalch equation for acids? pH= pKA + I/U
What is theHenderson-Hasselbalch equation for bases? pH=pKA + U/I
Acid drug in more acidic environment becomes ionized or non-ionzied? non-ionized
Acid drug in more basic environment becomes ionized or non-ionzied? ionized
Basic drugs in more acidic environment becomes ionized or non-ionzied? ionized
Basic drug in a more basic environment becomes ionized or non-ionzied? non-ionizied
Uniporters ATP energy source
antiporters 2ndary; transporter that carries the drug your interested in; another compound being transported the opposite direction that supplies the energy
symporters 2ndary;same direction w/transport energy
the processes of liberation & how those processes can affect the absorption process Liberation is the extra step before absorption for any medication that is not given in solution; Disintegration & release Dissolution Absorption -not a factor for IV drugs
ABC (ATP binding cassette) P-glycoprotein MDR1 ATP dependent export of drugs from cells Transport drugs – out of the body and into the gut
OATP (Organic Anion Transporter Polypeptides) OATP1A2 Influx transporter – Gut to blood
Stomach related to drug absorption Acidic ,Limited surface area ,Primary site for oral drug disintegration and dissolution (dissolved here)
Duodenum related to drug absorption Less acidic to neutral pH,Large surface area, Rich blood supply to maintain concentration gradient – Primary site of oral drug absorption
Drug absorption is affected by what main thing? 1st pass effect- Extent of biotransformation prior to reaching systemic circulation; delivery system and solubility
What are the physiologic factors that effect distribution? Blood flow (CO) Body Composition ( lean vs fat) Protein Binding
What are the two types of protein binding? alpha1 acid glycoprotein -binds basic drugs albumin-binds acidic drugs
What are the Physical/Chemical Factors that effect distribution? O/W partition coefficient Degree of ionization
What is Ion Trapping? Drugs move from basic body part to more acidic body part as it is going to get more ionized and trapped there; Weak acids will accumulate on the side with the higher pH (basic) ;Weak bases will accumulate on the side with the lower pH (acidic)
With protein binding..drug gets stuck in the bloodstream and only (bound/unbound) drug can move around? unbound/ free drug
what is Bioavailability? The proportion of a drug or other substance that enters the circulation when introduced into the body and so is able to have an active effect (how much of a given dose is “available to systemic circulation”) F
what is Volume of Distribution? Does not necessarily refer to an identifiable physiological volume, but the fluid volume required to contain all the drug in the body at the same concentration measured in the blood Relates dose administered to concentration achieved in the blood stream
What is clearance? Efficiency of extraction of a drug from bloodstream (remains constant unlike elimination)
what is Half life? Length of time required for concentration of drug in blood stream to be reduced to ½ the original concentration
Drugs need to be lipophilic or hydrophilic to be transported in to CNS? lipophilic
Define Pharmacokinetics Fate of the drug in the body (how the body affects the drug). The relationship of the dose of drug given to the concentration of the drug achieved in bloodstream Involves: liberation, ADM(biotransformation)E
Describe Metabolism/ Biotransformation Usually enzymatic Purpose to inactivate and eventually eliminate drug not easily cleared through the kidney Increase polarity Changes drug from lipophilic to hydrophilic for excretion by the kidneys Liver is most common site
Describe Excretion Removal of intact drug Non-volatile Water soluble Low molecular weight (<1000) No or slow biotransformation Primarily accomplished by kidney
What are Major Consequences of Xenobiotic Biotransformation • Increase water solubility • Increase rate o felimination • Terminate biologicactivity (not always) • Bioactivation–desired (pro drug)or undesired
Describe Phase I –  Usually occur first and introduce or expose a functional group;increasing polarity –  Include oxidation (loss of electron), reduction (gain electron), hydrolysis –  Cytochrome P-450 (primarily enzymes) -effected by aging=O2 dependent
Describe Phase II Conjugating reactions *covalent attachment of small polar endogenous molecule such as glucaronic acid, sulfate or glycine to water soluble compounds – Glucuronide • entero-hepatic recycling
Describe the nomenclature of the cyctochrome P 450 system Family(#) Subfamily (letter) Gene product (amino acid similarity) #
What is Glucuronidation ? -more water soluble -Glucuron conjugate -mostly excreted in the bile -active drug can be reabsorbed -enterhepatic recycling= reintroduction of drug( prolonged drug t1/2) Produces large, polar metabolite phase 2 reaction
What is done with passive diffusion and limited by protein binding and is also driven by hydrostatic pressure? Glomerular Filtration
What is done by an active process that Increases excretion and requires energy and carrier ? Tubular Secretion
What does Tubular Reabsorption require and what does it do? Reduces excretion*moves back into bloodstream Unionized form & Lipophilic
What are the Characteristics of acidic drugs? -Bound to Albumin - Small Vd (<.7L/kg) – Often hydrophilic – Often renally excreted • Less extensively metabolized
What are the Characteristics of basic drugs? -Bound to 1 acid glycoprotein – Often lipophilic – Usually metabolized • first-pass
What pharmacokinetic parameters are used to determine loading dose Volume of Distribution(Vd): – LD=Vd X Cp desired ; • Relates dose administered to concentration achieved in the blood stream
What pharmacokinetic parameters are used to determine maintenance dose Clearance: Maintenance Dose = Cl X Concentration ;
What pharmacokinetic parameters are used to determine dosing interval half-life; Length of time required for concentration of drug in the blood stream to be reduced to half of the original concentration • T1/2= (0.693 Vd)/Cl
Half life is________ related to volume of distribution which also reflects drug distribution directly
Half life is________ related to clearance inversely
The (longer/shorter) the half life is when you need a loading dose? longer
rate constant is________ related to half-time inversely
Takes about ___half lifes to get for the doses to start repeating themselves (Steady State) five
What do you need in order to reach a steady state? constant dosing interval & constant dose ; if your dosing interval is equal to your half life then you will reach a steady state and steady state peak will be doubled the 1st peak
Created by: tmay