Pharmacokinetics/dynamics

What are the two types of administration for drugs?

Enteral and parenteral

Enteral

through the alimentary canal

Parenteral

through alternate routes

What are the advantages of oral administration?

Safe, easyW

What are disadvantages of oral administration?

Some drugs can be difficult to absorb or broken down too quickly, can cause stomach irritation, subject to first-pass effect, less predictable rate or absorption

First-pass effect

drug is absorbed from small intestine, transported to liver and metabolized before entering systemic circulation

Special case for oral administration

extended release formula

What is the saying for by mouth?

per orum or PO

What is sublingual or buccal administration?

drug placed under the tongue (sublingual) or between the cheek and gums (buccal) to be absorbed through the oral mucosa into venous system

What are the advantages of sublingual and buccal administration?

No first-pass effect, fast, easier than oral or rectal

What is a disadvantage of sublingual and buccal administration?

Limited amounts can be absorbed this way

What are advantages of rectal administration?

Useful if patient is unconscious or has profuse vomiting or for local conditions

What are disadvantages of rectal administration?

Some drugs are not absorbed well through rectum, rectal mucosa

What are the three types of enteral administration?

Oral, sublingual/buccal, and rectal

What are advantages of administration of drugs via inhalation?

Useful for drugs that are gases or in aerosol form, large surface area for absorption, fast entry into bloodstream

What are disadvantages of pulmonary administration?

Some drugs can irritate the respiratory tract or become trapped, difficult to predict how much drug will reach the target tissue, can be difficult to self-administer for some patients,

What are the four types of injection administration?

Intravenous (IV), intra-arterial, subcutaneous (SC or subQ), intramuscular (IM)

What are disadvantages of administration via injection?

Must maintain sterility, not all can be self-administered

Bolus

accurate quantity of drug, delivered in a short time

What are advantages of IV administration?

Reaches target site quickly with accurate concentration of drug

What is disadvantage of IV bolus administration?

Can result in more adverse reactions

What are advantages of IV drip administration?

Prolonged, steady infusion via IV cannula, maintains specific level without fluctuations

Why is intra-arterial administration considered dangerous and difficult?

High pressure

Risk of thrombosis, gangrene, ischemia, limb loss

Direct toxicity

Deep and painful access

Subcutaneous administration

Injection of medication directly beneath the skin used for local response or slow systemic release

What is an advantage of subQ administration?

Self-administration often feasibleWha

What is a disadvantage of subQ administration?

Amount of drugs is low

What are intramuscular administration useful for?

Local treatment or prolonged release

What is a disadvantage of intramuscular administration?

Can cause pain and muscle soreness

Intrathecal administration

delivery of medication within a sheath

What are examples of location for intrathecal administration?

Subarachnoid or epidural space

What does intrathecal administration allow for>

Local delivery to spinal cord, bypass of blood-brain barrier to treat CNS

What are advantages of topical or mucous membrane topical use?

Well-absorbed, useful for local conditions on skin

What are disadvantages of topical administration?

Often poorly absorbed through skin, can cause adverse systemic effects if large amount of drug is absorbed

Transdermal administration

applying drugs directly to surface of skin with intent of absorption through dermal layers and into subcutaneous tissues or peripheral circulation

What are methods of transdermal administration?

Patch, iontophoresis, phonophoresis

Iontophoresis

via electric current

Phonophoresis

via ultrasound

What is a disadvantage of transdermal administration?

Drug must penetrate skin and not degrade in dermis

Absorption

entry of drug into body

Bioavailability

extent to which the drug reaches the systemic circulation or percent of administered drug that reaches bloodstream

What are two variables that bioavailability depends on?

Route of administration and drug’s membrane permeability

Distribution

movement of drug to target site

What are factors affecting distribution?

Membrane/tissue permeability, blood flow, binding to plasma proteins, binding to subcellular compartments

Describe the equation for the volume of distribution

amount of drug administered over the concentration of drug in plasma

If the volume of distribution is equivalent to the body fluid volume, what would the concentration of drug in plasma be?

Uniform distribution

If the volume of distribution is less than the body fluid volume, what would the concentration of drug in plasma be?

retained in plasma

If the volume of distribution is greater than the body fluid volume, what would the concentration of drug in plasma be?

Sequestered in tissues

What are possible adverse consequences of drug storage?

Toxicity leading to local damage, reservoir effects, may not reach target or possible drug redistribution much later

Biotransformation

chemical changes that take place in the drug after administration

What is the altered version of the drug following biotransformation called?

Metabolite

Where does biotransformation primarily occur?

Liver

What are the three types of reactions that can occur in phase I of biotransformation?

Oxidation, reduction, hydrolysis

Oxidation

addition of oxygen or removal of hydrogen

Reduction

removal of oxygen or addition of hydrogen

Hydrolysis

water molecule reacts to breakdown chemical bonds

What reaction occurs in phase II of biotransformation?

Conjugation

Conjugation

coupling of drug or phase I metabolite to another substance

Enzyme induction

prolonged drug use enables enzymes to more easily break down the drug

What can enzyme induction result in?

Tolerance and need to take higher dose of drug to produce same effect

Elimination

needed to terminate drug’s effects and remove it from body

Excretion

removal of drug from body primarily by kidneys

How does biotransformation help excretion occur?

Creates polar, water-soluble metabolite

Clearance

systemic or organ-specific ability to eliminate a drug

Describe the systemic clearance equation

Rate of drug elimination divided by the concentration of the drug in plasma

Describe organ-specific clearance

The difference between the concentration of drug entering an organ and concentration leaving organ is multiplied by the blood flow to the organ and the product is divided by the concentration entering the organ

Half-life

amount of time necessary for 50% of drug remaining to be eliminated

What are factors that affect half-life?

Clearance and volume of distribution, can all be affected by disease states

When would there be 25% of the drug left?

4 hours

Loading dose

a large initial dose to rapidly achieve a therapeutic level

What factors affecting drug response and elimination?

Genetics, disease, drug interactions, age, diet, sex, environmental

How may age affect drug response and elimination?

Elders have slower metabolism

Receptor

the component of a cell that interacts with a drug and initiates the chain of biochemical events leading to drug’s observed effects

Surface receptors linked directly to ion channels

Change membrane permeability and, when bound to drug, receptor activates and opens pore

Surface receptors linked directly to enzymes

extracellular receptor site and intracellular enzymatic component with a binding and catalytic domain

Surface receptors linked to regulatory (G) proteins

Receptor links to G protein to activate it and activated G protein alters activity of an intracellular effector

Intracellular receptors

Endogenous hormone or hormone-like drug binds to receptor in cytoplasm or nucleus, then the complex moves to nucleus to affect gene expression

What affect do intracellular receptors generally have?

On gene expression

Affinity

amount of attraction of drug for the receptor

How is affinity measured?

by amount of drug needed to bind to unoccupied receptors

Allosteric modulators

local regulators that can bind to receptor at a different site and change the affinity of a drug for the receptor

What factors do the drug’s ability to bind to a receptor depend on?

drug’s size and shape relative to receptor’s binding site

Describe the affect of a selective drug on cells/tissues and its response

Affects only one type of cell or tissue and produces a specific physiological response

Describe the affect a nonselective drug has on cells/tissues and its response

Affects multiple cells or tissue types and has beneficial effects and non-beneficial effects on

What is the dose-response curve shape related to?

Number of receptors bound by the drug

Agonist

drug that binds receptor and causes a change in the cell’s function

Differentiate between a full versus a partial agonist

Full agonist cause maximal response while partial agonist do not cause maximal response

Describe why the difference in efficacy between full agonists and partial agonists may be important

Since full agonists can achieve the maximum possible biological effect, they may be used for conditions requiring a significant physiological effect. Partial agonists only produce a submaximal response and are used to minimize side effects and maximize therapeutic benefits.

Antagonist

drug that binds receptor but does not cause a functional response

Competitive antagonist

competes with agonist to occupy same receptor

Noncompetitive antagonist

forms strong, permanent bond to receptor

Mixed agonist-antagonist

drug that acts as an agonist on some receptor subtypes and an antagonist on others (double agent)

Inverse agonist

drug that binds to the same receptor as agonist but has opposite effect on cellular function

Desensitization

brief, transient decrease in receptor responsiveness

What is an example of why desensitization may occur?

Receptor modification such as phosphorylation

What receptor regulation is the opposite of desensitization that allows for a brief transient increase in receptor responsiveness?

Super-sensitivity

Down-regulation

slower, more prolonged process that decreases number of available receptors

What are examples of why down-regulation may occur?

Increased removal of drug/receptor or decreased synthesis

What is the opposite of the process that decreases number of available receptors?

up-regulation

What are ways drugs may cause a response without binding to a receptor?

Alter synthesis of cell components, direct chemical reactions, direct alteration of enzyme function, chelation of harmful agents