Chapter One - TextBook (Lippincott.) Flashcards
(117 cards)
1
Q
Pharmacokinetics
A
Refers to what the body does to a drug, whereas pharmacodynamics describes what the drug does to the body
2
Q
There are four pharmacokinetic properties that determine the onset, intensity, and the duration of drug action
A
Absorption
Distribution
Metabolism
Elimination
3
Q
Absorption
A
First, absorption from the site of administration permits entry of the drug (either directly or indirectly) into plasma
4
Q
Distribution
A
Second, the drug may then reversibly leave the bloodstream and distribute into the interstitial and intracellular fluids.
5
Q
Metabolism
A
Third, the drug may be bio-transformed by metabolism by the liver or other tissues
6
Q
Elimination
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Finally, the drug and its metabolites are eliminated from the body in urine, bile, or feces
7
Q
Routes of Drug Administration
A
Many include enteral, parenteral, and topical, among others
8
Q
Enteral Administration
A
The safest and most common, convenient, and economical method of drug administration.
9
Q
Different methods of Enteral Administration
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The drug may be swallowed, allowing oral delivery, or it may be placed under the tongue (sublingual), or between the gums and check (buccal), facilitating direct absorption into the blood stream.
10
Q
Oral administration provides many advantages
A
Self Administered, and toxicities and/or overdose of oral drugs may be overcome with antidotes. Example: Activated Charcoal
11
Q
Enteric Coated Preparations
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Chemical envelope that protects the drug from stomach acid, delivering it instead to the less acidic intestine, where the coating dissolves and releases the drug
12
Q
Enteric coating is useful for certain drugs that are
A
- acid unstable such as omeprazole
- irritating to the stomach, such as aspirin
13
Q
Extended release preparations
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- Special coatings or ingredients that control the drug release, thereby allowing for slower absorption and a prolonged duration of action
- Can be dosed less frequently and may improve patient compliance
14
Q
Extended release preparations may maintain concentrations within
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The therapeutic range over a longer period of time, as opposed to immediate-relate dosage forms, which may result in larger peaks and troughs in plasma concentration
15
Q
ER formulations are advantageous for drugs with
A
Short half-lives…For example oral morphine is 2-4 hours, and it must be administered six times daily to provide continuous pain relief. However, only two doses are needed when extended-release tables are used.
16
Q
Sublingual/Buccal allows a drug to?
A
Diffuse into the capillary network and enter the systemic circulation directly
17
Q
Buccal is similar to the
A
sublingual route
18
Q
Sublingual administration has several advantages
A
- Ease of administration
- Rapid absorption
- Bypass of the harsh GI environment
- Avoidance of first pass metabolism
19
Q
Parenteral
A
This route introduces drugs directly into the system circulation
20
Q
Parenteral administration is used for drugs that are?
A
- Patient is unconscious and in circumstances that require a rapid onset of action
- Poorly absorbed form the GI tract (ex. Heparin) or Unstable in the GI tract (ex. Insulin)
21
Q
Which route has the highest bioavailability and are not subject to first-pass metabolism or the harsh GI environment?
A
Parenteral Administration which provides the most control over the actual dose of drug delivered to the body
22
Q
Which Administration is irreversible?
A
Parenteral which may cause pain, fear, and local tissue damage, and infections
23
Q
What are the three major parenteral routes?
A
Intravascular (Intravenous or intra-arterial)
Intramuscular
Subcutaneous
24
Q
Most common parenteral route
A
Intravenous
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When would a Intravenous administration be useful?
For drugs that are not absorbed orally such as the neuromuscular blocker rocuronium.
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When IV is injected as a bolus what is the amount delivered?
The full amount of drug is delivered to the systemic circulation almost immediately
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When IV is administrated as an infusion?
The drug is infused over a longer period of time, resulting in lower peak plasma concentrations and an increased duration of circulating drug levels.
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IV administration is advantageous for drugs that cause?
Irritation when administered via other routes, because the substance is rapidly diluted by the blood.
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Adverse Reactions of IV administration?
- Higher risk of infection to the site
- Induce hemolysis
- If delivered too quickly, higher concentrations
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Intramuscular Route
Drugs administered this route can be administered in aqueous solutions, which are absorbed rapidly, or in specialized depot preparations which are absorbed slowly.
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Depot preparations often onsite of?
Suspension of the drug in a non aqueous vehicle such as polyethylene glycol
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What is the MOA for Depot Preparations?
- As the vehicle diffuses out of the muscle, the drug precipitates at the site of injection
- The drug then dissolves slowly, providing a sustained-release drugs are haloperidol and depot medroxoyprogesterone
33
Subcutaneous (SC) is similar to which kind of injection?
IM injection, This route provides absorption via simple diffusion and is slower than IV route.
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SC injection minimizes the risks of?
Hemolysis or thrombosis associated with IV injection and may provide constant, slow, and sustained effects.
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SC should not be used with which drugs?
Drugs that cause tissue irritation , because severe pain and necrosis may occur.
36
Drugs commonly administered via SC route include?
Insulin and Heparin
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Oral Inhalation both oral and nasal provide what kind of delivery?
Rapid delivery of a drug across the large surface area of the mucous membranes of the respiratory tract and pulmonary epithelium
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Oral inhalation drug effects are almost as rapid as those with?
IV bolus
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Drugs that are gases and those that can be dispersed in an aerosol administered?
Inhalation
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Oral Inhalation is effective and convenient for patients with?
Patients with repository disorders such as asthma or chronic obstructive pulmonary disease, because the drug is delivered directly to the site of action, thereby minimizing systemic side effects.
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Examples of drugs administered via inhalation include?
Bronchodilators such as albuterol, corticosteroids such as fluticasone.
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Nasal Inhalation
Directly into the nose.
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Examples of nasal agents include?
Nasal decongestants, such as oxymetazolin, and corticosteroids such as mometasone furoate.
Desmopressin (for diabetes insipidus)
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Intrathecal/intraventricular is mainly used because?
The BBB typically delays or prevents the absorption of drugs into the CNS
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Intrathecal are used for local, rapid effects, it is necessary to introduce drugs directly into the?
CSF
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Topical Application is used when?
A local effect of the drug is desired.
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Transdermal route of administration achieves?
Systemic effects by application of drugs to the skin, usually via a transdermal patch.
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The rate of absorption of a transdermal patch can be marked depending on?
Physical characteristics of the skin at the site of application, as well as the lipid solubility of drug.
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Transdermal is often used for?
Sustained delivery of drugs, such as antianginal drug nitroglycerin, the antiemetic scolpamine, and nicotine patch, for smoking cessation.
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Rectal Route
50% of the drainage of rectal region bypasses the portal circulation, the biotransformation of drugs by liver is minimized with this administration.
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Which route is often used to administer antiemetic agents?
Rectal
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The rectal administration is usually?
Erratic and incomplete, and many drugs irritate the rectal mucosa.
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Oral Route Absorption Pattern
Variable; affected by many factors
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Oral Route Advantages
Safest and most common, convent, and economical route of administration
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Oral Route Disadvantages
Limited absorption of some drugs, Food may affect absorption, Patient compliance is necessary, Drugs may be metabolized before systemic absorption
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Intravenous Route Absorption Pattern
Absorption not required
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Intravenous Route Advantages
Can have immediate effects, ideal if dosed in large volumes, suitable for irritating substances and complex mixtures, valuable in emergency situations, dosage titration permissible, ideal for high molecular weight proteins and peptide drugs
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Intravenous Route Disadvantages
Unsuitable for oily substances, bolus injection may result in adverse effects, most substances must be slowly injected, strict aseptic techniques needed
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Subcutaneous Route Absorption Pattern:
Depends on drug diluents; aqueous solution: prompt, Depot preparations: slow and sustained
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Subcutaneous Route Advantages:
Suitable for slow-release drugs, ideal for some poorly soluble suspensions
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Subcutaneous Route
| Disadvantages:
Pain or necrosis if drug is irritating, unsuitable for drugs administered in large volumes
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Intramuscular Route Absorption Pattern:
Depends on drug diluents; aqueous solution: prompt, Depot preparations: slow and sustained
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Intramuscular Route Advantages:
Suitable if drug volume is moderate, suitable for oily vehicles and certain irritating substances, preferable to intravenous if patient must self-administer
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Intramuscular Route Disadvantages:
Affects certain lab tests (creatine kinase), can be painful, can cause intramuscular hemorrhage (precluded during anticoagulation therapy)
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Transdermal Patch Route Absorption Pattern:
Slow and sustained
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Transdermal Patch Route Advantages:
Bypasses the first pass effect, convenient and painless, ideal for drugs that are lipophilic and have poor oral bioavailability, ideal for drugs that are quickly eliminated from the body
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Transdermal Patch Route Disadvantages:
Some patients are allergic to patches, which can cause irritation, drug must be highly lipophilic, may cause delayed delivery of drug to pharmacological site of action, limited to drugs that can be taken in small doses
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Rectal Route Absorption Pattern:
Erratic and variable
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Rectal Route Advantages:
Partially bypasses first-pass effect, bypasses destruction by stomach acid, ideal if drug causes vomiting, ideal in patients who are vomiting, or comatose
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Rectal Route Disadvantages:
Drugs may irritate the rectal mucosa, not a well-accepted route
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Inhalation Route Absorption Pattern:
Systemic, absorption may occur, this is not always desirable
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Inhalation Route Advantages:
Absorption is rapid; can have immediate effects, ideal for gases, effective for patients with respiratory problems, dose can be pirated, localized effect to target lungs: lower doses used compared to that with oral or parenteral administration, Fewer systems side effects
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Inhalation Route Disadvantages:
Most addictive route (drug can enter the brain quickly), patient may have difficulty regulating dose, some patients may have difficulty using inhalers
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Sublingual Route Absorption Pattern:
Depends on the drug: Few drugs (for example, nitroglycerin) have rapid, direct systemic absorption, Most drugs erratically or incompletely absorbed
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Sublingual Route Advantages:
Bypasses first-pass effect, bypasses destruction by stomach acid, drug stability tainted because the pH of saliva relatively neutral, May cause immediate pharmacological effects
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Sublingual Route Disadvantages:
Limited to certain types of drugs, limited to drugs that can be taken in small doses, may lose part of the drug dose if swallowed
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Depending on their chemical properties, drugs may be absorbed from the GI tract by?
Passive diffusion, facilitated diffusion, active transport or endocytosis.
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Passive Diffusion
Drug moves from a region of high concentration to one of lower concentration. Does not involve a carrier, is not saturable and shows a low structural specificity.
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The vast majority of drugs are absorbed by which mechanism?
Passive Diffusion
Water-Soluble drugs penetrate the cell membrane through aqueous channels or pores
Lipid-Soluble drugs readily move across most biologic membranes due to their solubiliity in the membrane lipid bilayers
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Other agents can enter the cell through specialized tranasmemebrane carrier proteins that facilitate the passage of?
Large Molecules
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Carrier proteins undergo conformational changes, allowing the passage of drugs or
Endogenous molecules into the interior of cells and moving them from an area of high cocnetration to an anrea of low concentration.
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Facilitated diffusion does not require?
Energy, can be satruated, and may be inhibited by compounds that compete for the carrier.
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Active Transport
A few drugs that closely resembe the strucutre of natrually occuring metabolites are actively transported across cell membranes using specific carrier proteins.
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Energy-Dependent active transport is driven by?
The hydrolysis of adenosine triphosphate. It is capable of moving drugs against a cocnetration gradient, from a region of low drug cocnetration to one of higher drug concentraiton.
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Active transport is saturable and are selective and may be?
Competivively inhbited by other cotransported substances.
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Endocytosis and Exocytosis
This type of absorption is used to transport drugs of exceptionally large size across the cell membrane.
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Endocytosis
Invovles engulfment of a drug by the cell membrane and transport into the cell by pinching off the drug filled vesicle.
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Exocytosis
Secrete subsntances out of the cell through a similar process of vesicle formation.
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Vitamin B12 is transported across the gut wall by?
Endocytosis
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Norepinephrine are stored in?
Intracellular vesicles in the nerve terminal and released by exocytosis.
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Drugs pass through membranes more readily if it is?
Uncharged!
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BH^(+)...B + H^(+) which form readily passes through the membrane?
B, when there is a loss of proton.
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HA...H^(+) + A^(-) which form readily pass through the membrane?
HA, the protanated form.
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The lower the pKa?
The more acidic the drug is.
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The higher the pKa?
The more basic the drug is.
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Distribution equilibrium?
Acheived when the permeable form of a drug acheives an equal concentration in all body water spaces.
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The intestines recieve much more blood flow than the?
Stomach. That's why the Intestines are favored more for blood flow absorption.
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With a surface rich in brush borders containing microvilli, the intestine has a surface area about 1000-fold that of the ?
Stomach. Making total surface area available for absorption of the drug across the intestine more efficient.
99
When pH is less than pKa, which form predominates?
HA and BH+
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When pH is more than pKa, which form predominates?
A- and B
101
When pH equals pKa, which form(s) predominates?
HA=A- and BH+=B
102
If a drug moves through the GI tract very quickly, as can happen with severe diarrhea, it is?
Not well absorbed.
103
Anything that delays the transport of the drug form the stomach to the intestine delays the?
Rate of absorption of the drug.
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P-glycoprotein is a transmembrane transpoter protein responsible for transproting various?
Molecules, including drugs, across cell membranes. It is expressed in tissues throughout the body, including the liver, kidneys, placenta, intestines, and brain capillaries, and is invoved in transportation of drugs from tissues to blood.
105
P-glycoprotin "pumps" drugs?
Out of the cell, thus in areas of high expression, this pump reduces drug absorption. It is also associated with multidrug resistance.
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Bioavailability is determined by comparing?
Plasma levels of a drug after a particular route of adminstraiton with levels acheived by IV adminstration.
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By plotting plasma concentrations of drug versus time, what can be measured?
AUC, area under the curve.
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The total AUC reflects the?
Extent of absorption of the drug.
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Bioavailabity equation?
AUC following oral adminstration to AUC following IV adminstration times 100.
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What are factors that influence bioavaialabiltiy other than first-pass metabolism?
The chemical and physical characteristics of the drug, determines the rate and extent to which the agent reaches the systemic circulation.
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Definition of First-Pass Metabolism?
When a drug is absorbed from the GI tract, it enters the portal circulation before entering the systemic circulation. If the drug is rapidly metabolized in the liver or gut wall during this intial passage, the mount of unchanged drug entering the systemic circulation is decreased.
112
For a drug to be readily absorbed, it must be largely?
Lipophillic, yet have some solubility in aqueous solutions, this is one reason why many drugs are either weak acids or weak bases.
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Chemical Instability: Some drugs such as penicillin G, are _____ gastric contents?
unstable in the pH
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Chemical Instability: Insulin, is destroyed in the?
GI tract by degradative enzymes.
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Nature of the drug formulation: Drug absorption may be altered by factors unrealated to the chemistry of the drug. For example?
Particle size, salt form, crystal polymorphism, enteric coatings, and the presence of excipients (such as binders and dispersing agents) can influence the ease of dissolution and therfore, alter the rate of absorption.
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Definition of Bioequivalence?
Two drug formulations are bioequivalent if they show comparable bioavailability and similar times to achieve peak blood concentrations.
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Definition of Therapeutic equivalance?
Two drug formulations having the same dosage form, contain the same active ingredient and use the same route of adminstration.
