Exam 1 - Pharmacokinectics

Question 1

A medicine or other substance which has a physiological effect when ingested or otherwise introduced into the body

Answer 1

Drug

Question 2

The study of how a drug enters the body, circulates within the body, is changed by the body, and leaves the body

Answer 2

Pharmacokinetics

Question 3

What are the 4 major pharmacokinetic steps of drug movement in the body

Answer 3

1. Absorption
2. Distribution
3. Metabolism
4. Excretion

Question 4

The study of the biochemical and physiologic actions of drugs, and their mechanisms of drug action at the cell level and sub-cell level (what the drug does to the body)

Answer 4

Pharmacodynamics

Question 5

What 4 characteristics of drug molecules influence whether a drug can cross a lipid membrane?

Answer 5

1. Lipid solubility
2. Degree of ionization (charge cannot cross)
3. Molecular Size
4. Shape

Question 6

Weak acid in an acidic environment = ____
Weak acid in a basic environment =____
Weak base in acidic environment = ____
Weak base in a basic environment = ____

Answer 6

Lipid soluble
Water soluble (dissociates)
Water soluble (dissociates)
Lipid soluble

Question 7

(lipid/water) soluble = non ionized (no charge)

lipid/water) soluble = ionized (polar

Answer 7

Lipid

Water

Question 8

____ = drugs given by this route are placed directly into GI tract - ORAL/RECTAL

Answer 8

Enteral

Question 9

____= administration bypasses the GI tract and includes various injection routes, inhalation, and topical drug administration

Answer 9

Parenteral

Question 10

9 parenteral drug routes

Answer 10

1. Inhalation
2. Intravenous *** MOST RAPID/PREDICTABLE
3. Intramuscular - slow
4. Topical - local or systemic
5. Subcutaneous
6. Sublingual
7. Transdermal - patch. more concentrated
8. Intrathecal - epidural
9. Intraperiotoneal - dialysis

Question 11

T/F rectal (enteral) drug administration is poorly/irregularly absorbed from rectum

Answer 11

True

Question 12

Describe rate of onset for:

1. IV
2. IM
3. Patch
4. Sublingual
5. Subcutanerous
6. Inhalation:
7. Ointment/spray
8. Oral

Answer 12

1. Controlled rate/continuous/rapid/predictable
2. delivers large quantity, slow sustained due to high blood flow through skeletal muscles
3. continuous delivery, slow release
4. rapid delivery
5. slow onset
6. rapid
7. dose controlled
8. usually enteral, cheapest/easiest

Question 13

4 ways molecules cross membranes

Answer 13

1. Diffusion - lipid soluble drugs/passive/high to low
2. Filtration - small molecules -> membrane pores
   Specialized transport for large/ionized/water soluble molecules
3. Facilitated diffusion - carrier
4. Active transport - ATP

Question 14

3 factors that influence rate of drug movement

Answer 14

1. Physiochemical factors
2. Solubility
3. Route of administration

Question 15

T/F the closer the site of administration is to a blood vessel, the faster a drug can be absorbed

Answer 15

True

Question 16

Drugs that are administered orally pass from the stomach to the intestine to the portal veins to liver

Answer 16

“first pass effect” of drug metabolism after oral absorption (metabolize drugs to inactive forms before they have the change to enter the systemic circulation

Question 17

What type of drugs bypass the first pass effect?

Answer 17

drugs given parenterally - direct to bloodstream

Question 18

____= the fraction of the administered drug that becomes available in the plasma. FREQUENTLY influenced by the “vehicle” of the drug (difference between generic/brand name drugs)

Answer 18

Bioavailability - only IV administration gives 100%

Question 19

FDA mandates that generics must have ___% of the availability of the parent compound

Answer 19

90

Question 20

2 forms in which drugs are in the blood

Answer 20

1. Bound to plasma proteins - no effect

2. Free - can pass cell membranes and exert desired effect

Question 21

____= most drugs cross easily; lipid-soluble drugs cross most easily

Answer 21

Placenta

Question 22

____= drugs that can cross this barrier are lipid-soluble, very small molecular weight/size, and exert effects on the CNS

Answer 22

Blood Brain Barrier

Question 23

Drug Redistribution - movement of the drug from the site of ____ to nonspecific sites of ____. Duration of action can be affected by redistribution from one ____ to another. If redistribution occurs between specific sites and nonspecific sites, the drugs action will be ____. Example: An “____” agent is administered to induce sleep before anesthesia for surgery. After a few minutes, the action is terminated, bc the drug has been redistributed from the CNS via the plasma to skeletal muscle to finally ___ ___ in the body.

Answer 23

Action
Action
Organ
Terminated
Induction
Fat Deposits

Question 24

_____= converts lipid soluble drugs to water soluble metabolites (so kidneys can easily excrete and metabolites are less likely to bind to plasma proteins or store in fat)

Answer 24

Biotransformation aka drug metabolism

Question 25

Where does biotransformation mostly occur?

Answer 25

Liver - also in kidneys, lungs, nerves, plasma, intestines

Question 26

What 4 things can alter liver drug metabolism and often require a does modification?

Answer 26

1. Increased age 2. Cirrhosis 3. Hepatitis 4. Damage from drugs

Question 27

In the liver, where does most drug transformation take place?

Answer 27

Microsomes in hepatocytes

Question 28

Active to inactive =_____ Inactive to active =_____ Active to active =______

Answer 28

Active to inactive = most common- formed from active parent drug Inactive to active = converted to active after metabolism Active to active = metabolite is active

Question 29

What happens in the 2 phases of drug biotransformation?

Answer 29

Phase I - drug is modified through oxidation, reduction or hydrolysis Phase II - drug molecule is modified by conjugation to a large polar endogenous molecule (adds bulky group) INACTIVE, prepares for excretion

Question 30

When is microsomal oxidation enzyme system used?

Answer 30

Endoplasmic like intracellular organelles which possess the enzymes required for biotransformation of most drugs in liver hepatocytes

Question 31

_____= known value describing excretion rates

Answer 31

clearance rates - all drugs in the blood are filtered by the kidneys

Question 32

Salivary drug concentration mimics _____ concentration

Answer 32

plasma

Question 33

Name 5 ways drugs are excreted from the body

Answer 33

1. urine 2. feces 3. sweat 4. saliva 5. lungs 6. breast milk

Question 34

The amount of time needed for the plasma concentration of a drug to fall to 1/2 its blood level per unit of time is known as? What is the time that most drugs are cleared by?

Answer 34

"Half life" | 4-5 half lives (conversely, it takes approximately 4-5 half lives for a drug to build up to a steady state level)

Question 35

What concept is described as the amount of drug eliminated is dependent upon the amount of drug in the plasma at any given time?

Answer 35

First order drug elimination - a constant fraction of the drug is eliminated per unit time = clearance rate

Question 36

What is being described; following administration of multiple therapeutic dosages of a drug at regular time intervals, a plateau level of drug accumulates?

Answer 36

Plasma steady state concentration

Question 37

What does the plateau level indicate during the plasma steady state concentration?

Answer 37

A rate of drug administration that is equal to the rate of drug elimination

Question 38

How is the steady state concentration achieved?

Answer 38

At a regular dosing frequency, the drug does not accumulate and a steady state or equilibrium is eventually reached

Question 39

What are the 2 most common ways drugs bind with receptors?

Answer 39

Hydrogen and iconic (other less common ways include covalent, ionic, or hydrophobic)

Question 40

The affinity of a drug for a particular receptor and the type of binding is intimately related to the drug's what?

Answer 40

``` Chemical structure (Higher binding affinity to plasma proteins = remains in blood longer) ```

Question 41

Drug binding occurs at _____ sites ( amino acid residues) on protein structure. Binding to one or more AA residue causes _____ ____ in the protein molecule (aka receptor) This results in a modification of the tertiary structure to bring other AA residues _____ to the drug, called "_____ ___". Drugs also bind to receptor proteins within the ____ structure. The receptor protein does not exist as an _____ substance external to the cell. Receptor protein may be a _____ or ____ component of the cell membrane (aka part of the cell membrane)

Answer 41

``` Multiple Conformational change CLOSER Induced fit Cell Isolated Structural Enzymatic ```

Question 42

In drug-receptor interaction, the receptor proteins recognize selected molecules at the ____ surface and transmit information ____ the cell. These receptor proteins exist naturally as receptors for _____, _______, and ____ ____.

Answer 42

``` External Inside Hormones Neurotransmitters Growth Factors ```

Question 43

What type of protein receptor communicates with both sides of the cell membrane?

Answer 43

Membrane spanning

Question 44

Molecule that binds to the receptor protein or receptor glycoprotein is called a?

Answer 44

Ligand - may be hormones, neurotransmitters, growth factors, or drug molecules

Question 45

Name for when a ligand binds to a specific area of the receptor protein on the outer surface of the cell, or within the cell membrane, a CONFORMATIONAL CHANGE occurs in the receptor-protein molecule which is transmitted to the inner surface of the cell membrane.

Answer 45

Cell signaling - initiates the cells response to the binding for the ligand

Question 46

What are 4 examples of cellular responses that occur following cell signaling.

Answer 46

1. Ion channel opening or closing 2. Formation of intracellular second messenger 3. Alteration in gene expression of the cell 4. Initiation or alterations in cell growth and differentiation

Question 47

Ligand binding occurs directly to receptor at ____ site. Receptors are located on ___-___ channels and ___-___ channels. Bidning causes the channel to open, allowing for the ___ of ions. *Binding ____ cell membrane permeability to ___ and ___ which determines depolarization or _____ of nerve (aka the nerve firing)

Answer 47

``` Channel ligand-gated voltage-gated influx INCREASES Sodium Potassium Hyperpolarization ```

Question 48

What are the first messengers vs second messengers?

Answer 48

First messenger = ligand (receptors are located in cell membrane and transmit info from outside to inside cell. Second messenger = pass the message from the inside of the cell to the effector organ (target site of action)

Question 49

What are G-proteins and where are they located?

Answer 49

They are coupled with receptors which regulate the generation second messengers Located at the internal portion of cell membranes

Question 50

What are 3 results of effector activation?

Answer 50

1. Generate cAMP 2. Phospholipase C - phosphorylation of proteins 3. Change in membrane channel - change in ionic conductance

Question 51

Term that is described as the amount of drug necessary to produce the effect

Answer 51

Drug potency | - Related to affinity of drug to its receptor

Question 52

Term that is described as the degree of maximum intensity of the drug.

Answer 52

Efficacy - max response produced by a drug - related to receptor occupancy by drug molecules - additional does produce no additional benefit "ceiling dose"

Question 53

____ is dose, ____ is effect

Answer 53

Potency | Efficacy

Question 54

____ drug produces SIMILAR EFFECTS as endogenous chemicals, it is able to bind to a receptor and produce an effect (think ligand)

Answer 54

Agonist

Question 55

____ drug produces NO EFFECT. It binds to receptor but is unable to active it therefore it reduces/inhibits an effect. "blocker" drug

Answer 55

Antagonist

Question 56

Who binds first, an agonist or an antagonist?

Answer 56

ALWAYS THE ANTAGONIST

Question 57

A competitive antagonist competes with agonist for the same ____ ____, and blocks the receptor. But it is ______. Administering additional agonist will ____ the antagonist from the receptor, allowing the ____ to produce its effect.

Answer 57

Receptor site REVERSIBLE Displace agonist

Question 58

Noncompetitive antagonist binds _____ and cannot be displaced. Can bind to either the same receptor site as the agonist or a different site but both actions ___ the effect of the agonist. (think poisons)

Answer 58

IRREVERSIBLY | Inhibit

Question 59

____ ____: activates pathways that oppose the action of the agonist. Agonist and antagonist act independently on 2 different receptors. Less desirable in medicine than receptor-specific antagonists.

Answer 59

Physiologic Antagonists

Question 60

____ ____: Both agonist and antagonist compete for the same receptor site. Antagonist binds first. Prevents agonist from producing effect. Either competitive or non-competitive

Answer 60

Pharmacologic Antagonism

Question 61

The RANGE of the doses (concentrations) of a drug that elicits a therapeutic response, without unacceptable side effects (toxicity) in a population of people is know as?

Answer 61

Therapeutic Window - Blood plasma levels of a drug with a small therapeutic window must be monitored closely!