Ch 4-8 Flashcards
Factors Affecting Drug Absorption
- The rate of drug dissolution
- The absorptive surface area
- Blood flow at the site of absorption
- Lipid solubility of the drug
- pH partitioning between the site of absorption and plasma
enteral drugs
Drugs administered by the oral route (per os, or PO)
parenteral
drugs administered outside the GI route
Capsule:
Drugs given by mouth pass through the stomach and are metabolized in the liver before reaching systemic circulation
Syringe:
Drugs administered by syringe immediately enter the circulatory system
Patch
Parenteral routes such as a transdermal patch release drugs directly into systemic circulation.
PO
oral or enteral
Bioavaliability
The percentage of a drug dose that actually reaches the systemic circulation chemically unchanged
IP
Intraparitoneal - up the ass
causes of low oral bioavalability
- The drug does not dissolve readily.
- Enzymes in the intestine may metabolize some of the drug before it is absorbed.
- The liver, metabolizes some of the drug on its first pass through the liver on the way to the systemic circulation.
advantages to IV route
- Has no membrane barriers; absorption is instantaneous and complete (100% bioavailability)
- Allows precise control of drug dose and duration
- Permits administration of poorly soluble drugs that must be dissolved in a large volume of fluid
- Allows irritating drugs to dilute rapidly in blood (e.g., cancer chemotherapeutic drugs would damage muscle if administered IM)
can enteric coated drugs be crushed and given through feeding tubes?
never because the protective coating will be lost. The crushed drug (now without the enteric coating) may be inactivated by the gastric acid or the drug may irritate the gastric mucosa.
can Sustained-release (XL, ER) medications be crushed and administered via feeding tubes?
Never. because crushing such formulations will cause a problem called dose dumping. Rather than a continuous delivery of medication to the site of absorption in the intestine, with dose dumping the entire dose is absorbed at once, and drug concentrations in the blood could reach toxic levels.
Can meds be desolved in hot water before being put in a feeding tube?
Never. Hot water may inactivate some drugs and precipitate others. The precipitate may accumulate on the side of the container or on the feeding tube itself and not be absorbed.
Disadvantages of IV administration of drugs
expensive, invasive, inconvenient
•Cannot remove the drug once it has been administered
•Risk for too high a drug concentration if injected too rapidly
•Risk for fluid volume overload
•Risk for infection
•Risk for embolism (from a clot, cellular debris, undissolved drug, or air)
•Risk for using wrong formulation (e.g., a concentrated solution designed for IM injection)
What if your IV solution looks dark?
Do not administer it! •IV solutions are dilute; IM solutions are concentrated and can be fatal if administered by IV.
Rate of absoorption after subcutaneous or IM injection is affected by…
- The ability of the drug to move through the fenestrations (gaps) in the capillary wall
- The solubility of the drug in water (plasma)
- Blood flow at the site of injection
disadvantages of IM and subcutaneous administration
- Bioavailability may be less than 100%.
- Non–water-soluble drugs may precipitate at the injection site.
- IM injections can cause local tissue injury and nerve damage if not administered properly.
- If a serious adverse reaction occurs (e.g., allergy), further absorption cannot be stopped.
Advantages of Transdermal adminstration
They provide for zero-order delivery, which means there is a constant plasma drug concentration with no peaks and troughs.
Peaks and Trophs
The highest and lowest drug levels in the plasma as measured over time
Characteristics needed in a drug for successful transdermal delivery
•A small molecular size
•Both hydrophilic and lipophilic properties
◦Lipophilicity is needed to penetrate the stratum corneum barrier.
◦Hydrophilicity is needed to diffuse into the extracellular fluid
The amount of drug delivered to the blood from transdermal patches
- The concentration of the drug in the patch or ointment
- The size of the application area
- The thinness of the stratum corneum and number of hair follicles (drug absorption from the chest > legs > arms > scalp > axillary > posterior ear > shin > palm)
when are Fluctuating drug levels in the blood (peaks and troughs) desirable?
antiinfectives, cancer chemotherapy
T or F: Drugs that can be absorbed through the skin are both lipid and water soluble.
True!
Are most PO drugs weak bases or weak acids, and where are they absorbed?
weak bases absorbed from the duodenum through the portal vein to the liver.
What is the range of rate at which the stomach can empty its contents (gastric emptying)
from a few minutes to 12 hours
Factors that decrease the rate of gastric emptying
- High-fat meal
- Heavy exercise after eating
- Lying on the left side after eating
- Drugs that inhibit the vagus nerve (e.g., anticholinergic drugs such as certain antihistamines, opioid pain relievers, antidepressants, and antipsychotics)
Factors that increase the rate of gastric emptying
•Taking PO medications with cold water on an empty stomach
•Lying on the right side (see figure)
Patients who receive tube feedings may have very rapid gastric emptying because of high osmolality. Some medications called prokinetic agents (e.g., metoclopramide [Reglan]) increase gastric emptying, so the drug may not completely dissolve in the stomach.
The oral bioavailability varies with the:
- type of formulation (e.g., syrup, tablet, time-release capsule)
- degree of first-pass metabolism in the small intestine and liver
these are called enteric-coated formulations.
Some formulations are manufactured with a special outer coating; Enteric-coated formulations are designed to avoid dissolution in the stomach and dissolve readily in the duodenum
Advantages of enteric-coated drugs
- Coatings protect the stomach from irritating drugs (e.g., erythromycin, bisacodyl [Dulcolax]).
- Coatings prevent gastric acid and pepsin from destroying the drug (e.g., pancreatic enzyme replacements).
Disadvantates of enteric-coated drugs
- Absorption varies with gastric emptying time (from minutes up to 12 hours).
- Coatings may not dissolve, in which case medication is not absorbed at all.
- Patients must avoid taking calcium supplements or antacids within 2 hours of taking enteric-coated drugs to avoid premature dissolution of coating
sustained release preparations
also called extended-release [ER] or XL) are designed to provide a constant (zero-order) rate of drug absorption over an extended period (12 to 24 hours).
Disadvantages of sustained release preparations
- Bioavailability varies more than with solid tablet counterparts.
- If a sustained-release formulation is crushed (and then, for instance, put down a feeding tube), the patient will absorb the entire dose at once, causing toxic drug levels in the blood. This is called dose dumping
Give examples of Some PO drugs undergo a degree of first-pass metabolism in the intestine
- Bacteria (called gut microflora) metabolize digoxin to a degree. Antiinfective therapy can kill these bacteria, causing a sudden increase in digoxin bioavailability (Figure A).
- Intestinal CYP3A4 enzymes metabolize a portion of certain antihypertensives (calcium channel blockers) and cholesterol-lowering agents (statins) before absorption
Why are some drugs not to be taken with grapefruit?
◦Grapefruit, limes, and citron (but not oranges) inhibit intestinal CYP3A4 causing more drug to be absorbed.
The treatment for poisoning can be influenced through manipulation of urine pH. The nurse correlates this with what?
Ion trapping: With manipulation of urinary pH, ion trapping draws toxic substances from the blood into the urine, thereby accelerating their removal from the body
The nurse correlates the faster absorption of highly lipid-soluble drugs with what
Rate of crossing cell membrane
In administering an intravenous medication by way of the antecubital vein over 1 minute, the nurse anticipates that the drug will reach the CNS in how many seconds?
Performing IV injections slowly has the advantage of reducing the risk of toxicity to the central nervous system (CNS). When a drug is injected into the antecubital vein of the arm, it takes about 15 seconds for it to reach the brain.
What laboratory results (which organ is depressed)would the nurse recognize as most significant when considering excretion of drugs?
Depressed renal function
What is the “First Pass” effect?
refers to the rapid inactivation of certain oral drugs as they pass through the liver. Drugs absorbed from the gastrointestinal tract are carried directly to the liver by way of the hepatic portal vein. Drugs that have a too-rapid first-pass effect may be completely inactivated and require administration by way of a different route.
Enteric-coated medis are designed to desolve where?
in the small intsetine
The most important protein for the binding of drugs
Albunin
The objective of drug dosing is to maintain ____ drug levels within the therapeutic range.
plasma
A drug that has only moderate intrinsic activiy
Partial Antagonist
A drug that activates receptors
Agonist
A drug that prevents receptor activation by endogenous regulatory molecules
Antagonist
Simple occupancy theory
the intensity of the response to a drug is proportional to the number of receptors occupied by that drug and that a maximal resonse will occur when all available receptors have been occupied.
Maximal efficacy
the largest effec a drug can produce; not always desirable to give it.
How do transcription factors differ from other receptors?
- found within the cell, not on the cell membrane; responses that activate these receptors are delayed
The distribution of a drug in the body is determined by:
- Blood flow to the tissues
- Capacity of the drug to move out of the blood
- Capacity of the drug to move into cells
Bioavalability
percentage of the dose that passes through the liver to the systemic circulation unchanged
Your patient is suffering from digoxin toxicity. He is seeing halos around lights and has cramps in his legs. He reports that he started taking an antibiotic 4 days ago for “walking pneumonia.” You suspect that
the antibiotic killed the intestinal bacteria that metabolize digoxin
The body’s compartments involved in drug distribution include:
- Interstitium (extracellular fluid) (e.g., low-molecular-weight, hydrophilic drugs)
- Total body water (extracellular and intracellular fluid) (e.g., low-molecular-weight, hydrophilic drugs)
- Plasma (e.g., drugs strongly bound to plasma proteins and drugs with a very high molecular weight)
- Adipose (fat) tissue (e.g., lipophilic drugs)
- Muscle tissue (e.g., drugs such as digoxin)
- Bone (e.g., drugs that bind to calcium)
The distribution of a drug in the body is determined by:
- Blood flow to the tissues
- Capacity of the drug to move out of the blood
- Capacity of the drug to move into cells
•Drugs that are distributed into breast milk or fetal tissues are those that are
◦Lipophilic
◦Nonionized
◦Small in molecular size
•Drugs that are not distributed into breast milk or fetal tissues are those that are:
◦Polar
◦Ionized
◦Large in molecular size
◦Protein bound
The volume of distribution (Vd)
the ratio of the total amount of drug in the body (D) to the plasma concentration of the drug (C): Vd = D/C
large Vd means that:
- Most of the drug is distributed in some body compartment (e.g., muscle, bone, fat)
- A smaller fraction of the drug is in the plasma
A small Vd means that:
- The drug is highly bound to plasma proteins
* The drug does not distribution widely into other compartments
There are two principal plasma proteins that bind drugs:
- Albumin (binds acidic drugs)
* Alpha-1-acidic glycoprotein (AAG) (binds alkaline drugs)
which conditions decrease plasma albumin and increase free drug levels
- Malnutrition (especially in the elderly)
- Liver disease
- Kidney disease
- Aging
- Trauma (especially burns)
Some conditions increase liver synthesis/release of AAG and decrease free drug levels
Aging
Trauma
and inflamed liver (HepA)
Sites of biotransformation
- Stomach (alcohol dehydrogenase)
- Intestine (CYP3A4 enzyme in the brush border and bacteria metabolize some drugs before absorption;)
- Liver (over 12 different enzyme families exist in the smooth endoplasmic reticulum and cytosol)
- Kidney (per gram, more metabolically active than liver, but only a few drugs are metabolized)
Endogenous Substrates
Made by the body: •Vitamin D hormone
•Cholesterol
•Steroid hormones
•Bilirubin
Exogenous Substrates
Foreign compounds: •Compounds in charcoal-broiled food
•Compounds in cigarette and marijuana smoke
•Caffeine
•Alcohol
•Toxic compounds in plants
•Drugs
site of first-pass mechanism for alcohol
Stomach
•Alcohol dehydrogenase
converts some alcohol to acetaldehyde, which is then further metabolized in the liver.
- Low-ER drugs have high oral bioavailability. (Less than 20% of a PO dose undergoes first-pass metabolism.)
- PO doses of low-ER drugs are similar to IV doses.
- Small changes in hepatic enzyme activity have little effect on the bioavailability of low-ER drugs.
Low-ER drugs
- High-ER drugs have low oral bioavailability (80%-97% of an oral dose is metabolized by the liver before reaching the systemic circulation).
- PO doses of high-ER drugs must be higher than IV doses to compensate for the extensive first-pass metabolism.
- Small changes in hepatic enzyme activity produce large changes in the bioavailability of high-ER drugs.
High-ER drugs
cytochrome P-450 enzymes (CYPs
complex system of enzyme families housed by smooth endoplasmic reticulum