CH 1-10 Lehne's Pharmacotherapeutics

Six consequences of drug Metabolism

1) accelerated renal excretion of drugs 2) drug inactivation 3) increased therapeutic action 4) activation of "prodrugs" 5) increased toxicity 6) decreased toxicity

Bioavailability

1. A measure of the extent of drug absorption for a given drug and route (from 0% to 100%). 2. Drugs are equal in bioavailability if they absorb at the same rate and to same extent 3. Absorption/bioavailability impacted by ROUTE

Drug metabolism in elderly

1. Aging liver produces fewer microsomal enzymes, affecting drug metabolism Reduced blood flow to the liver 2. Decrease dosage to avoid toxicity

Three factors determining Distribution of a drug

1. Blood flow (or lack thereof) to tissues (abscess/solid tumors) 2. Ability for the drug to exit vascular system (BBB/Placental) 3. Protein binding- bound/unbound; affinity, binding site competition 4. Ability of drug to enter cells- lipd-solubility or transport system

Drug metabolism in infants

1. Enzymes in the liver to metabolize drugs are immature, so drugs cannot be broken down until 1 year. 2. Decrease dosage to avoid toxicity

Three processes of renal drug secretion

1. Glomerular filtration (fluids & small molecules pushed through capillary pores to tubular urine) 2. Passive tubular reabsorption (lipid-soluble drugs reabsorbed and ions and polar compounds remain for excretion 3. Active tubular secretion (transport system pumps drugs from blood to tubules)

What meds can NOT penetrate cell membranes

1. Polar molecules- water-soluble drugs 2. Ions- except for the VERY small (like dissolves like) 3. Ion trapping/pH partitioning (drug accumulates on a side that encourages ionization (undissolved)

What impacts the rate of absorption

1. Rate of dissolution (immediate release, enteric coating, etc.) 2. Surface area (blood flow, lipid solubility, & pH partitioning)

Prescriptive authority- 2 components

1. Right to prescribe independently 2. Right to prescribe without limitation

Decline from plateau- drug elimination after d/c

94% of the drug is eliminated over 4 half-lives

Absorption via

Cell membranes (lipid-based) 1. Channels & Pores (small molecules) 2. Transport system (selective) 3. DIRECT PENETRATION (LIPID SOLUBLE)

Consequence of slow drug Metabolism

Drug accumulation--> TOXICITY

Inhibitors

Drug that slows, blocks, or interferes with a chemical action (i.e. competitive binding at receptor sites); decreased rates of metabolism

Substrate

Drugs or other substances metabolized by enzymes

Inducers

Drugs that act on the liver to increase rates of drug metabolism

Drug metabolism in the malnurished

Hepatic drug-metabolizing enzymes require co-factors which may be altered

Peak drug level

Highest plasma concentration of drug at a specific time. Indicates rate of absorption.

P450

Liver enzymes that break down drugs to a form to be excreted or to be taken to and enter tissue cells to perform desired effect

Trough drug level

Lowest plasma concentration of a drug. Measures the rate at which the drug is eliminated.

PGP (p-glycoprotein)

Multi-drug transport protein (transport system) that moves drugs OUT of cells

Therapeutic range

Plasma drug concentration between the minimum effective concentration and the toxic concentration 1. Med dosing goal 2. The larger the range the safer the drug

Glucuronidation

Process in which a hydrophilic glucose derivative is attached to a highly lipophilic drug in the liver to make it more hydrophilic; converting lipid-soluble to water-soluble

Steady state or plateau

Repeated doses produce drug concentrations where the accumulated amount of drug coming in is balanced with the more rapid elimination of drug and the peaks and troughs become more consistent. 1. Typically occurs in 4-5 half lives 2. 5 X T 1/2 3. Drugs with rapid elimination and short half-lives reach steady state quickly 4. Slow elimination and long half-lives may require days or weeks; may require loading dose

Metabolism (biotransformation)

The biochemical alteration of a drug into an inactive metabolite, a more soluble compound, a more potent active metabolite, or a less active metabolite

First Pass Effect (Metabolism)

The initial metabolism in the liver of a drug is absorbed from the gastrointestinal tract before the drug reaches systemic circulation through the bloodstream resulting in NO therapeutic effect

Pharmacokinetics- (Tics--> TIME)

The movement of the drug in the body over time through absorption, distribution, metabolism, and excretion

Minimum effective concentration

The smallest amount of drug necessary in the blood or target tissue to see therapeutic effect

Half-life

Time required for the drug in the body to decrease by half Determines dosing INTERVAL

Pharmodynamics

What the drug does to the body--> biological response

Drug excretion

the process of eliminating medications, usually through the kidneys in urine, but also through sweat, feces, saliva, or breast milk