Basic Principles of Pharm (2) Flashcards
What does Pharmacokinetics determine?
The concentration of a drug in the plasma or at the site of the drug effect (Pharmacokinetics is defined as what the body does to the drug)
Receptor Theory The maximal effect a drug can produce and the ability of a drug to activate the receptor once bound is called _________
Efficacy
Receptor Theory The amount of drug needed for a given effect is called __________
Potency
Drug potency depends on what 3 things?
Affinity to receptor Amount of drug that reaches the receptor site **Drugs with low ED50 are more potent than drugs with a high ED50
Drug Absorption What are some factors that affect absorption? ________ transport requires no energy ________ transport requires energy
Pain, Stress, Stomach Contents, drug formulation drug interaction Passive Active
Drug Absorption Drug absorption is affected by the __________ of ____________
Method of administration (IV- very fast, sublingual, inhalation)
What are the 4 principles are pharmacokinetics?
Absorption Metabolism Distribution Elimination
First Pass Effect
When drugs are circulated to the liver first, immediately after enteric absorption, before the drug enters circulation (Only part of the drug is circulated systemically)
What is distribution? What is a central compartment relative to distribution? What are the elements of the central compartment?
Once the drug enters the systemic circulation, it must be distributed. The drug suddenly becomes more dilute due to distribution in the plasma or tissues. The central compartment is the site where the drug becomes dilute within the first minute of administration. The venous blood volume of the arm, the volume of the great vessels, the heart, the lung **highly fat soluble drugs may be avidly taken up in the first passage through the lung
Drug Distribution Drugs distribute to which organs first?
To organs with a large blood supply: Heart, Liver, Kidneys, then to other organs
Drug Distribution Drugs can be ______ soluble or _______ soluble Lipid soluble drugs can cross the ______________
Water, Lipid Blood-brain barrier
Lipid Solubility The more lipid soluble an anesthetic is, the more ________ it is Lipid solubility parallels ________ _________ Agents with higher lipid solubility may last _______ because they are less likely to be cleared by blood flow
Potent Protein Binding Longer
Protein Bound VS Unbound The more highly protein bound an agent is, the more difficulty is has dissociating from the _______ ________, leading to a longer _________ of _________ Name two drugs that have no protein binding?
Sodium Channel Duration of Action Procaine and Chloroprocaine
Drug metabolism occurs in which 4 places?
Liver, Plasma, Kidneys, and Membranes of Intestines
Drug Metabolism What happens to inactive metabolites? What happens to active metabolites? What are Prodrugs?
They are excreted They exert a pharmacological action Drugs that are inactive until metabolized
Drug Metabolism Drug metabolism is affected by what 4 things?
Disease state Genetics Environment Developmental changes
Drug Elimination Drugs are eliminated mainly through the ________, but also through what other 4 outlets? The time it takes for half (50%) of the drug to be eliminated is called the drug’s ______ ______
Kidneys; Lungs, exocrine glands, skin, and intestinal tract Half Life
Drug Elimination Steady state is defined by the rate of distribution _________ the rate of excretion Drug elimination is affected by what 3 factors?
Equaling Rate of absorption Metabolism Method of excretion
Onset of Action Time interval from ___________ to __________ effect
Administration, Therapeutic
Peak Concentration __________ rate equals __________ rate
Absorption, Elimination
Duration Length of time that a drug produces a __________ effect
Therapeutic
Drug Distribution (After Systemic Absorption) _________ determines degree of diffusion Non Ionized drugs are _______ ________ Ionized drugs are ________ _________
Ionization Lipid soluble (can absorb) Lipid insoluble (cannot absorb)
Drug Distribution (After Systemic Absorption) Does pH affect systemic absorption? Weak bases end up trapped in an ________ environment (stomach) Local anesthetic become trapped in the acidic environment of the ________
Acidic Fetus
Drug Distribution (After Systemic Absorption) Does protein binding affect systemic absorption? Renal failure leads to ________ free fraction, leading to greater chance of _______ _______
Yes, more binding to plasma proteins (albumin), less Vd (Volume Distribution) Increased Drug Toxicity
Fetal Ion Trapping Local anesthetics cross the ________ and become more _________ ionized in the acidic fetus The anesthetic becomes “trapped” in fetal tissues, leading to systemic ________ in the fetus
Placenta, Ionized Toxicity
Fetal Ion Trapping This is less likely to occur with highly ________ bound local anesthetics which diffuse ________ across the placenta This is also less likely to occur with _______ local anesthetics, where rapid hydrolysis is responsible for a small quantity of drug being able to cross the placenta
Protein, Slowly Ester
Fetal Ion Trapping Which two anesthetic agents cause this to happen? What factor causes this occurrence? The non ionized form of the local anesthetic crosses the ________ ________. Once in the fetus, the drug converts to an ________ form. The ionized form cannot cross the placental barrier, thus becomes trapped.
Mepivacaine and Prilocaine (amide locals that are not highly protein bound) Fetal pH is lower (7.2) than the mother’s pH (7.4) More acidic environment = Ion Trapping Placental Barrier Ionized
Volume of Distribution (Vd) The volume of _______ body fluid into which a drug “appears” to distribute Known dose is administered IV, then ________ concentration is measured In a 70 kg adult, plasma = ____, interstitial fluid = ____, and intracellular fluid = ____
Total Plasma 3L 11L 28L
Volume of Distribution (Vd) Formula
(Vd)= amount of drug administered (mg) ——————————— Plasma drug concentration (mg/L)
Volume of Distribution (Vd) What factors affect Vd?
Lipid solubility, binding to plasma proteins, molecular size Very young or very old age (increased Vd) Liver/Kidney disease (increased Vd secondary to decreased plasma protein) Burn injury/Trauma (increased Vd)
Volume of Distribution (Vd) Non-depolarizing NMB’s bind to plasma proteins and are poorly lipid soluble They have high plasma concentration and ______ (Vd) ___________ and ____________ are highly lipid soluble (will be concentrated in tissue) and have a _____ plasma concentration and high (Vd)
Low Thiopental, Diazepam Low
Pharmacodynamics “What the drug does to the body” Study of drug _________ interaction and __________ effect
Receptor, Biological
Phase I pathway of metabolism include what actions? Which patient population loses phase I pathways first?
Reduction, oxidation, and hydrolysis Geriatric population