Morgan & Mikhail Chap 7(Pharmacological Principles) Flashcards
Key Concept 1: Drug Molecules obey the laws of mass action…
Drug molecules obey the law of mass action. When the plasma concentration
exceeds the tissue concentration, the drug moves from the plasma into tissue. When the plasma concentration is less than the tissue concentration, the drug moves from the tissue back to plasma.
The rate of rise in drug concentration in an organ is determined by that organ’s
perfusion and the relative drug solubility in the organ compared with blood. The
equilibrium concentration in an organ relative to blood depends only on the relative
solubility of the drug in the organ relative to blood unless the organ is capable of metabolizing the drug.
Key Concept 2: Most drugs that readily cross the…
Most drugs that readily cross the blood–brain barrier (eg, lipophilic drugs like hypnotics and opioids) are avidly taken up in body fat.
Lipophilic molecules can readily transfer between the blood and organs. Charged molecules are able to pass in small quantities into most organs. However, the
blood–brain barrier is a special case. Permeation of the central nervous system by ionized drugs is limited by pericapillary glial cells and endothelial cell tight junctions. Most drugs that readily cross the blood–brain barrier (eg, lipophilic drugs like hypnotics and opioids) are avidly taken up in body fat.
Key Concept 3: Biotransformation is the chemical…
Biotransformation is the chemical process by which the drug molecule is altered
in the body. The liver is the primary organ of metabolism for drugs.
An exception is the esters, which undergo hydrolysis in the plasma or tissues. The end products of biotransformation are often (but not always) inactive and water soluble. Water solubility allows excretion by the kidneys.
Key Concept 4: Small, unbound molecules…
Small, unbound molecules freely pass from plasma into the glomerular filtrate. The nonionized (uncharged) fraction of drug is reabsorbed in the renal tubules, whereas the ionized (charged) portion is excreted in urine.
Key Concept 5: Elimination half-life is the time…
Elimination half-life is the time required for the drug concentration to fall by
50%. For drugs described by multicompartment pharmacokinetics (eg, all drugs used in anesthesia), there are multiple elimination half-lives.
Key Concept 6: The offset of a drug’s effect…
The offset of a drug’s effect cannot be predicted from half-lives. The context-sensitive half-time is a clinically useful concept to describe the rate of decrease in drug concentration and should be used instead of half-lives to compare the pharmacokinetic properties of intravenous drugs used in anesthesia.
Pharmacokinetics
Pharmacokinetics defines the relationships among drug dosing, drug concentration in body fluids and tissues, and time. It consists of four linked processes: absorption,
distribution, biotransformation, and excretion.
Pharmacokinetics: Absorption
Absorption defines the processes by which a drug moves from the site of administration to the bloodstream. There are many possible routes of drug administration: inhalational, oral, sublingual, transtracheal, rectal, transdermal, transmucosal, subcutaneous, intramuscular, intravenous, perineural, peridural, and intrathecal. Absorption is
influenced by the physical characteristics of the drug (solubility, pKa, diluents, binders, formulation), dose, the site of absorption (eg, gut, lung, skin, muscle), and in some cases (eg, perineural or subcutaneous administration of local anesthetics) by additives such as epinephrine.
Pharmacokinetics: Distribution
Once absorbed, a drug is distributed by the bloodstream throughout the body. Highly perfused organs (the so-called vessel-rich group) receive a disproportionate fraction of
the cardiac output (Table 7–1). Therefore, these tissues receive a disproportionate
amount of drug in the first minutes following drug administration.
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Half Lives and Emergence Time
The complex process of drug distribution into and out of tissues is one reason that
half-lives provide almost no guidance for predicting emergence times.
Pharmacokinetics: Biotransformation
Metabolic biotransformation is frequently divided into phase I and phase II reactions. Phase I reactions convert a parent compound into more polar metabolites
through oxidation, reduction, or hydrolysis. Phase II reactions couple (conjugate) a parent drug or a phase I metabolite with an endogenous substrate (eg, glucuronic acid)
to form water-soluble metabolites that can be eliminated in the urine or stool.
Although this is usually a sequential process, phase I metabolites may be excreted without undergoing phase II biotransformation, and a phase II reaction can precede or occur without a phase I reaction.
Pharmacokinetics: Excretion
Some drugs and many drug metabolites are excreted by the kidneys. Renal
clearance is the rate of elimination of a drug from the body by kidney excretion. This concept is analogous to hepatic clearance, and similarly, renal clearance can be
expressed as the renal blood flow times the renal extraction ratio.
Small, unbound drugs
freely pass from plasma into the glomerular filtrate. The nonionized (uncharged)
fraction of drug is reabsorbed in the renal tubules, whereas the ionized (charged) portion remains and is excreted in urine. The fraction of drug ionized depends on the pH; thus, renal elimination of drugs that exist in ionized and nonionized forms depends
in part on urinary pH. The kidney actively secretes some drugs into the renal tubules.
Many drugs and drug metabolites pass from the liver into the intestine via the biliary system. Some drugs excreted into the bile are then reabsorbed in the intestine, a process
called enterohepatic recirculation. Occasionally metabolites excreted in bile are subsequently converted back to the parent drug. For example, lorazepam is converted by the liver to lorazepam glucuronide. In the intestine, β-glucuronidase breaks the ester linkage, converting lorazepam glucuronide back to lorazepam.
Compartment Models
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