Everything that happens to the chemical (drug) outside of the receptor. Its how the body handles the drug. PK = absorption, distribution, elimination
What is Pharmacodynamics?
The drug-receptor interactions; what the drug does to the body as a result of the D-R; Lock and Key phenomenon
What is stereochemistry?
The study of molecular 3-D shape. 3-D shape and size are essential for proper receptor drug interaction.
What is chirality?
Describes the center of an uneven 3-D shape.
What is an enantiomer?
The exact opposite configuration of the same chemical structure (left and right hand. May exhibit different reactions at receptors based upon the form of the molecule. Essentially, the receptor is selective for how the drug looks and fits its 3D configuration.
What is racemic mixture?
An equal number of enantiomers in a solution.
What compartment model explains IV drugs?
The 2-compartment model adequately predicts IV drugs.
What is elimination?
Gradual decline in drug concentration gradients due to drug metabolism and excretion. Over time concentration gradients change and drug leaves the receptors and begins the elimination phase.
Differentiate between elimination ? time from elimination ? life? Can you use these terms interchangeably?
Elimination ? time is the amount of time it takes for a drug to decrease by 50% in the plasma. Elimination ? life is the amount of time is takes for a drug to decrease by 50% in the body or time it takes for a drug to be eliminated by ? after injection.
Describe the relationship between elimination ? time (drug distribution) and clearance?
Elimination ? time is directly proportional to its Vd and inverse to the clearance. Drug distribution and clearance is a function of the volume of distribution of the drug.
What is context sensitive half time (CSHT)?
Context-sensitive half-time is time necessary for plasma concentration of a drug to fall to 50% aftera continuous infusion of a specific duration.
What is the bioavailability of drugs given intravenously?
100% bioavailability or absorbed
The administration and effect of drug is dependent on what factors?
1. Bioavailability: GREATEST IMPACT 2. The amount of drug that actually gets into the circulation: first pass effects (liver, lungs) and protein binding (bound drugs are essentially inactive) 3. The Vd how much dose the target (brain) sees of the drug and how much goes to fat
What mostly affects drug absorption with lipid soluble agents?
For lipid soluble agents TYPICALLY absorption is blood flow related.
The volume of distribution of a drug is based on what 3 drug characteristics?
Lipid solubility (degree of ionization), Protein binding, Molecular size
Do lipid soluble drugs tend to be nonionized?
The degree of ionization of a drug depends on what?
True or False: The more lipid soluble the more it binds to proteins.
True or False: Only free, unbound drugs can cross membranes.
True, they are the only active drug.
What is the final stage of pharmacokinetics and is a principle factor in drug dosing?
Drug clearance and elimination
What order of kinetics explains when the clearance rate increases with concentration?
1st Order kinetics
What order of kinetics is not dependent on drug concentration and clearance is said to be rate limited?
Zero order - drug clearance is constant over time.
What is the most important factor of drug clearance when a drug has a high hepatic clearance? What ratio is considered a high hepatic clearance?
Blood flow; hepatic extraction ratio) > 0.7
What is the most important factor of drug clearance when a drug has a low hepatic clearance? What ratio is considered a low hepatic clearance?
A decrease in protein binding or an increase in enzyme activity, as associated with enzyme induction, will greatly increase hepatic clearance of a drug with low hepatic extraction ration. Low extraction clearance (HER < 0.3) liver
What metabolism pathway makes the molecule more polar?
What metabolism pathway includes oxidation, reduction, and hydrolysis reactions in the CYP450 enzymes?
Are CYP450 enzymes are low or high in neonates?
Are plasma cholinesterase enzymes a member of the CYP450 super family of enzymes?
What describes the amount of the drug needed to produce a response?
Potency, the smaller amount of the drug needed to produce the response, the more potent.
Define the Median Effective Dose(ED50)?
The amount of the drug that produces half of the maximum effect.
What describes the maximum intensity the drug can produce?
Efficacy, increasing the dose will not produce better results
What three factors facilitate the transfer of the inhaled agent from the machine to the alveoli?
The transfer from the alveoli to the blood is related to what three factors?
The alveolar and venous partial pressure difference, the lipid solubility of the agent(BGC) and CO
Transfer of the gas from the arterial blood to the brain is a function of what two factors?
The arterial venous partial pressure difference and CBF.
What describes the ability of an agent to cross membranes?
Partition coefficient, higher solubility equates with higher potency.
Will a R to L shunt prolong or hasten the rise of VA for low soluble agents?
What are the factors that INCREASE MAC?
Alcoholism [BH1:p50](* Different from SH4), Hyperthermia, Increased pheomelanin concentration(i.e. natural red hair womendue to mutation of melanocortin-1 receptor gene), Cyclosporine, Hypernatremia, Drug-induced increase in CNS catecholamine level, Increased catecholamine stores
What are the factors that DECREASE MAC?
Increasing age(Decrease in MAC of 6% per decade after 30 y/o, also decreased in <6-8 months old), Hypothermia, Preoperative medication (e.g. Opioids), Acute alcohol ingestion, Alpha-2 agonists (e.g. clonidine), Pregnancy(due to progesterone), Postpartum(Returns to normal in 24-72 hours), Lithium, Lidocaine, Cardiopulmonary bypass, Hyponatremia, Drug-induced decrease in CNS catecholamine level, PaO2 < 38mmHg, BP <40 mmHg, Decreased catecholamine stores
What is the amount of agent required to inhibit movement under surgical stimulation in 50% of the population (aka the ED50)?