Pharmacology Test 1 2011

Front 1

What are the first 4 steps in the decision making map that have been discussed in class thus far?

Back 1

1. Alteration in the patient
2. Therapeutic Goal
3. Drug Option
4. Mechanism of action

Front 2

What is pharmacodynamics?

Back 2

How a drug works

* Action of drug due to interaction with receptors

Front 3

Types of drug interactions-how do most drugs act?

Back 3

Via an interaction with certain proteins (p.76)

**Exceptions are drugs which the activity is based on physical properties

Front 4

What are the four types of proteins targeted by drugs?

Back 4

1. Enzymes
2. Carriers
3. Ion channels
4. Receptors
(P.77)

Front 5

What is a receptor?

Back 5

A molecule or polymeric structure in the surface or inside of a cell that specifically recognizes and binds an endogenous compound (p.78)

Front 6

How do receptors and acceptors differ?

Back 6

Receptors possess an effector system (singal-transduction pathways) and acceptors do not have an effector system (p.78)

Front 7

What makes a drug an agonist?

Back 7

When it produces a measurable physiological or pharmacological response characteristic of the receptor (contraction, relaxation, secretion, enzyme activation,etc) (p.78)

Front 8

What is a full agonist?

Back 8

A drug that produces a maximal effect under a given set of conditions (p.78)

Front 9

What is a partial agonist?

Back 9

A drug that produces a submaximal effect regardless of the amount of drug applied (p.78)

Front 10

What is an antagonist?

Back 10

A drug that binds to a receptor site and prevent the action of natural agonists (neurotransmitters, hormones,etc...) )p.78)

Front 11

What are the 2 forms of antagonism?

Back 11

1. Competitive antagonism
2. Non-competitive antagonism
(p.78)

Front 12

What is competitive antagonism?

Back 12

Antagonists act on the same receptors as agonists

**This is said to reversable when it can be surmounted by increasing the concentration of the agonist (p.78)

Front 13

What is non-competitive antagonism?

Back 13

When a drug blocks the cascade of events normally leading to an agonist response, at some downstream point (p.78)

Front 14

What does the concept of physiological antagonism refer to?

Back 14

The interaction of two drugs whose opposing actions on a physiological system tend to cancel each other out (p.78)

Front 15

What is an inverse agonist?

Back 15

A drug that acts at the same receptor as that of on agonist, yet produces an opposite effect (p.78-she said don't stress over this concept)

Front 16

The concentration-effect relationship is determined by what 2 features?

Back 16

1. Drug affinity
2. Drug efficacy
(p.80)

Front 17

What is meant by the affinity of a drug?

Back 17

Its ability to bind to a receptor

** Affinity determines the concentration of drug required to form a significant number of drug-receptor complexes that in turn are responsible for drug action (p.80)

Front 18

How is drug affinity determined?

Back 18

By the chemical structure of the drug, and minimal modification of the drug structure may result in a major change in affinity (p.80)

Front 19

What is drug efficacy?

Back 19

The drug's ability, once bound, to initiate changes that lead to production of responses.

It is a property of the lignand/receptor pair (p.81)

Front 20

What is drug potency?

Back 20

Corresponds to the concentration of drug required to achieve a given effect (p.81)

Front 21

What is EC50?

Back 21

*Effective concentration-how potency of a drug is expressed

The concentration of a drug that produces 50% of the max possible response (p.81)

Front 22

What are the two functions of transmembrane receptors?

Back 22

1. Ligand Binding
2. Message transduction
(p.83)

Front 23

What are the 4 superfamilies of receptor proteins?

Back 23

1. Ligand-gated ion channels (membrane-bound receptors,directly linked to an ion channel)
2. G-protein coupled receptors (membrane-bound receptors coupled to G-proteins)
3. Tyrosine kinase-linked receptors (membrane-bound receptors containing an intrinsic enzymatic function)
4.Transcription factor receptors (intracellular receptors regulatinf gene transcription)
(p.83)

Front 24

What is the difference between activation of a metabotropic receptor and an ionotropc receptor?

Back 24

*The activation of metabotropic receptors leads to a series of intracellular events (metabolic changes within the cell) that may result in ion channel opening
* Activation of an ionotropic receptor opens a channel that immediately allows ions suchas Na,K, or Cl to follow (p.83)

Front 25

How do G-protein-coupled receptors (seven transmembrane receptors) function?

Back 25

*They transduce an extracellular signal (ligand binding) into an intracellular signal (G-activation).

*GP may act directly on an ionic channel or activate an enzymatic system to release a range of second messengers, which ultimately permits certain ions to enter or leave the cell (p.83)

Front 26

What are tyrosine-kinase receptors and what do they consist of?

Back 26

* They are metabotropic cell surface receptors, which exert their regulatory effect by phosphorylating different effector proteins

* They consist of an extracellular binding site and an intracellular portion with enzymatic activity (p.83)

Front 27

What do ionotropic receptors activate and what is special that they contain?

Back 27

*Activate transmembrane ion channels

*Contain a central pore that functions as a ligand gated ion channel (p.83)

Front 28

What are transcription factor receptor and how do they function?

Back 28

* They are intracellular proteins serving as transcription factors

*After binding of the ligand, the activated receptors translocate to the nucleus and bind to a DNA sequence called the response element and initare the transcription of specific genes (p.83)

Front 29

What are ion channel receptors and how do they function?

Back 29

*Ion channel inhibitors or lignand gated receptors are protein forming on aqueous pores in the plasma membrane.

1. Lignand binds at a specific site on the the receptor which leads to conformational changes

2. These changes open the channel and allow ions to flow into the cell

3. The change in ion concentration within the cell triggers cellular response (p.84)

Front 30

Why are G-proteins called seven transmembrane receptors?

Back 30

G-protein receptors are single polypeptide chains forming seven transmembrane domains within the membrane with a segment able to interact with G proteins (p.84)

Front 31

What are the two states of G protein-coupled receptors?

Back 31

B-1 (inactive state)

B-2 (active state)
(p.84 letters correspond to fig 4.8)

Front 32

How does the B-1 (inactive state) of G protein-coupled receptors function?

Back 32

G protein is attached to the cytoplasmic side of the membrane and is inactive as long as a ligand binds to a G protein-coupled receptors

(p.84 letters correspond to fig 4.8)

Front 33

How does the B-2 (active state) of G protein-coupled receptors function?

Back 33

1. Binding of ligand changes shape of G protein-coupled receptor that interacts with G protein

2. Interaction causes activation of G protein with guanosine diphosphate (GDP) being exchanged with guanosine triphosphate (GTP)

3. The activated G protein moves either toward an enzyme, or directly modulates the conductance of an ionic channel

4. When an enzyme is activated a second messenger is generated and can mediate an action. Then G protein hydrolyses GTP back to GDP
(p.84 letters correspond to fig 4.8)

Front 34

What are the two states of tyrosine kinase receptors?

Back 34

C-1 (inactive state)

C-2 (active state)

(p.84 letters correspond to fig 4.8)

Front 35

What is a C-1 (inactive state) tyrosine kinase receptor?

Back 35

Tyrosine kinase receptors are transmembrabe receptors consisting of individual polypeptides each with a large extracellular binding site and an intracellular tail with an enzyme
(p.84 letters correspond to fig 4.8)

Front 36

What happens when tyrosine kinase receptors are in their active state (C-2)?

Back 36

1. When a ligand binds to both receptors, the 2 receptor polypeptides aggregate to form a dimmer

2. This activates the tyrosine kinase part of the dimmer-each uses ATP to phosphorylate the tyrosines in the tail of the other polypeptide as well as other down stream signaling proteins

3. The receptor proteins are now recognized by relay proteins inside the cell. Relay proteins bind to the phosphorylated tyrosines and may activate different transduction signals
(p.84 letters correspond to fig 4.8)

Front 37

What are nuclear receptors and how do they function?

Back 37

They are intracellular receptors located in the cytoplasm or nucleus.

* The ligand binds to a nuclear receptor and migrate to the nucleus after binding. This activation pathway leads to a long lasting effect usually over several hours (p.84)

Front 38

What is the term used to describe a gradual decrease in responsiveness to chronic drug administration?

Back 38

Tolerance (p.87)

Front 39

What is the term for acute tolerance?

Back 39

tachyphylaxis (p.87)

Front 40

What is down-regulation and up-regulation?

Back 40

*Down-regulation: Chronic stimulation of receptors with a drug which resulted in a state of long term desensitization. Often due to a decrease in the number of receptors

*Up-regulation: Understimulation of receptors which leads to an increase in the number of receptors and functional supersensitivity (p.87)

Front 41

What are the 4 key physiological processes that govern the time course of drug fate in the body?

Back 41

1. Absorption
2. Distribution
3. metabolism
4. Elimination
ADME process (p.11)

Front 42

What is pharmacokinetics?

Back 42

The study of the time course of drug concentrations in the body (p.11)

Front 43

What is the primary pathway for drugs to cross lipid membranes?

Back 43

By passive diffusion through the lipid environment (p.13)

Front 44

What is the primary mechanism by which a chemical can be excreted from the body?

Back 44

By becoming less lipophilic and more hydrophilic

*This is required for excretion in the aqueous fluids of the urinary or biliary systems (p.14)

Front 45

How does ionization effect movment across membranes?

Back 45

* Membranes are more permeable to the nonionized than the ionized form of weak organic acids and bases (p.14)

Front 46

The amount of drug in the ionized or nonionized form is dependent on what 2 things?

Back 46

1. pKa of the drug

2. pH of the medium on either side of the membrane (p.14)

Front 47

Are protonated weak acids and bases ionized or nonionized?

Back 47

*Protonated weak acids: nonionized

*Protonated weak bases: ionized
(p.14)

Front 48

Under what conditions does 50% of the drug exits in the ionized state and 50% in the nonionized,lipid soluble state?

Back 48

When the pH of the medium and the pKa of the dissolved drug are equal (p.14-15)

Front 49

What is the difference between a protonated form of an acid and base?

Back 49

protonated form of an acid is neutral

* Protonated form of a base is ionized (p.15)

Front 50

When is the ratio on ionized to nonionized 10?

Back 50

When the pH is one unit less or one unit more than the pKa for weak bases or acids

** Thus each unit of pH away from the pKa results in a tenfold change in this ratio (p.15)

Front 51

Based of the definition of "drug" from the Federal Food, Drug, and Cosmetic act-what articles are recognized as drugs?

Back 51

1. Articles recognized in the offical US Pharmacopoeia, offical Homeopathic Pharmacopoeia of the US, or official National Formulary, or any supplement to any of them

2. Articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals

3. Articles (other than food) intended to affect the structure or any function of the body of man ot other animals

4. Articles intended for use as a component of any article specified in above clauses
(class handout)

Front 52

How do you calculate the terapeutic index?

Back 52

Divide the lethal dose (LD50) by effective dose (ED50)
(class slide set 3)

Front 53

What are the 3 main labeling components?

Back 53

1. Package Insert

2. Client Info Sheet

3. Bottle/Vial/ Outer Box labeling
(Monday exercise #2)

Front 54

What 9 things should be included on a package insert?

Back 54

1. Indications
2. Dosage and administration
3. Contraindications
4. Warnings
5. Precautions
6. Adverse reactions
7. Clinical pharmacology
8. Effectiveness
9. Animal safety
(Monday exercise #2)

Front 55

What is the study of how drugs move within the body?

Back 55

* Pharmacokinetics

* The fate of drugs in the animal

Front 56

What is the study of the actions of drugs due to interaction with receptors?

Back 56

* Pharmacodynamics

*

Front 57

What is biophase?

Back 57

* The site of action (where receptors are located)

* Drug action is related to achieved drug concentration at biophase

Front 58

What is meant by an alteration in the patient?

Back 58

* Not the disease, but what is going on within that disease process

* i.e. Diabetes mellitus is a disease; hyperglycemia is an alteration; insulin is a drug option

Front 59

What 5 things are included in a drug regimen?

Back 59

1. Drug choice
2. Dosage
3. Route
4. Frequency
5. Duration

Front 60

What are some factors that explain differences of drug effect in separate, unique patients?

Back 60

• Difference between prescribed and administered dose: patient compliance, medication errors

•Difference between administered dose and biophase conc.: rate/extent of absorption, body size and composition, body fluid distribution, plasma binding, rate of elimination

•Difference between achieved biophase conc. and the intensity of action: drug-receptor interaction, functional state of receptor, placebo effects

•Differences in patients: physiological, pathological, and genetic factors; interaction with other drugs; development of tolerance

Front 61

What are factors that influence the choice of drug?

Back 61

* Therapeutic index
* Efficacy
* Side effects
* Patient history
* Therapeutic goal

Front 62

What are regulatory proteins involved in intercellular communication?

Back 62

Receptors

* molecule or polymeric structure on surface or inside cell that specifically recognizes and binds an endogenous compound or ligand

Front 63

What are molecules of complementary shape to protein-binding site?

Back 63

Ligands

Front 64

How do acceptors work since they do not have signal-transduction pathway?

Back 64

* Acceptors have a binding process that is not followed by a physiological response

(i.e. an ion channel is not a receptor—it opens without causing signal transduction)

Front 65

What is the difference between a full and partial agonist?

Back 65

• Full agonist: produces max effect under given set of conditions; fully activates the receptors

* Partial agonist = produces a submax effort, regardless of drug quantity administered; interaction response is less than (or slightly different than) with the endogenous compound

Front 66

What is a drug that acts on same receptor as agonist to block or reverse agonistic effects?

Back 66

Competitve antagonist

Front 67

What is a drug that prevents agonist from producing its effect at given receptor site?

Back 67

Noncompetitve antagonist

Front 68

What type of drugs are known as "silent drugs"?

Back 68

* Antagonists = “silent drugs”

* Ligand that binds to and interacts with receptor site, but blocks the normal response (or action of other agonists); does not cause physiological response itself

Front 69

What is the difference between selectivity and specificity?

Back 69

* Specificity = ability of drug to produce a single particular effect by acting on a single target; concerns the drug-receptor interaction and macromolecular structure

* Selectivity = when all effects produced by a drug are due to a single mechanism of action; drug acts at only one type of receptor but may produce multiple pharmacologic effects because of many different locations of receptors

Front 70

What 2 things determinf the drug concentration and effect relationship?

Back 70

Drug affinity and efficacy

Front 71

What term describes a drugs ability or tendency to bind/combine with particular receptor type?

Back 71

Affinity

Front 72

What term describes a drug’s ability, once bound, to initiate changes that lead to production of responses?

Back 72

Efficacy

Front 73

What is the term for the concentration of drug required to achieve a given effect with particular intensity?

Back 73

Potency

Front 74

What influences potency?

Back 74

• Influenced by affinity of drug for receptor site and by processes that determine drug concentration in biophase (absorption, distribution, elimination)

Front 75

What activates/opens transmembrane ion channels to allow flow of ions?

Back 75

Ionotropic receptor

Front 76

What is a metabotropic receptor?

Back 76

A receptor that causes changes in metabolic processes in the cell

Front 77

What is down-regulation?

Back 77

State of long-term desensitization caused by chronic stimulation of receptors with a drug agonist

Front 78

What is up-regulation?

Back 78

* Caused by understimulation of receptors

* Leads to increase in number of receptors and a functional supersensitivity

Front 79

What is the process of drug movement (ADME)?

Back 79

* Absorption = process of moving from site of administration to bloodstream

*Distribution = occurs via movement into and out of central compartment (vasculature)

* Metabolism = occurs only on free drug; affects drug-time curve movement across membranes

* Excretion = all drug leaves the body

* Elimination = parent drug is completely excreted, but drug metabolites may still remain

Front 80

What is the difference between excretion and elimination?

Back 80

* Excretion = all drug leaves the body

* Elimination = parent drug is completely excreted, but drug metabolites may still remain

Front 81

Where is the only place from where drugs can be metabolized or excreted?

Back 81

The Central Compartment: vasculature + highly vascular organs; where a drug is absorbed into

Front 82

Within the central compartment a drug can be free or protein-bound---which type is available for biotransformation/metabolism?

Back 82

* Free drug is available for biotransformation/metabolism, whose product metabolites travel in bloodstream

* Metabolites or free drug can be excreted from CC

Front 83

What 4 things determine the rate of diffusion of a compound across a biological membrane?

Back 83

1. Lipophilicity
2. Protein-binding
3. Fick’s Law: conc. gradient, lipid:water partition coefficient, diffusion distance, diffusion coefficient
4. Ionization

Front 84

Do ionized or non-ionzed forms of drugs have lower lipid solubility?

Back 84

Ionized form of drugs has lower lipid solubility than non-ionized form

Front 85

Are membranes more permeable to the ionized or non-ionized form of a weak acid/base?

Back 85

* Membranes are more permeable to non-ionized form of weak acid/base

Front 86

What determines the amount of drug ionization?

Back 86

* Amount of drug ionized is dependent on pH and its pKa

(when pH = pKA, half of drug is ionized)

Front 87

Is the protonated form of an acid neutrol orionized? What about a protonated base?

Back 87

* Acid: protonated form (HA) is neutral

* Base: protonated form (HB+) is ionized

Front 88

Under what condition do neutral forms of acids and ionized forms of bases predominate?

Back 88

At low pH values

Front 89

What is "ion-trapping"

Back 89

Side of membrane favoring ionized drug will have higher total drug concentration

Front 90

Is a weak base or acid readily absorbed from an acidic environment into an alkaline medium?

Back 90

Weak acids are readily absorbed from an acidic environment into an alkaline medium

Front 91

Is a weak base or acis absorbed from an alkaline environment and trapped in an acidic environment?

Back 91

* Weak bases are absorbed from an alkaline environment and trapped in an acidic environment

Front 92

What is the P-glycoprotein system?

Back 92

* A class of drug transporters involved in removing drugs after absorption into specific cells or tissue sites

* Acts to pump toxic chemicals out into environment via central channel/pore in transporter

Front 93

Wjay is bioavailability?

Back 93

* The proportion of drug administered that is absorbed into bloodstream

(fraction of administered dose of unchanged drug that reaches systemic circulation)

Front 94

How do you calculate bioavailability?

Back 94

(AUC of Route)/(AUC IV)

AUC= Area under curve of concentration-time model graph

AUC (IV) = 150 and AUC (IM) = 50, F = 33%

Front 95

Where is the primary absorption site for oral drugs?

Back 95

Small intestine

Front 96

What is disintegration?

Back 96

* Process where a solid dosage form physically disperses and its constituent particles are exposed to GI fluid

Front 97

What is the pharmaceutical phase; when drug molecules enter solution?

Back 97

* Dissolution

Front 98

What is meant by prolonged-release?

Back 98

Deliberately slowing the dissolution process via dispersion into differently-dissoluted particles or multilamination of dosages

Front 99

What is enterohepatic recycling?

Back 99

When a drug (or its metabolite) from systemic circulation is excreted into bile and reabsorbed from SI back into bloodstream

Front 100

What is first-pass metabolism?

Back 100

Drug absorbed across gut wall between oral cavity and rectum enters portal circulation, where it is subject to biotransformation in liver before it reaches plasma (and is measured)

Front 101

What is absorption?

Back 101

The movement of the drug from the site of administration to the blood

Front 102

What are the 3 primary routes of drug absorption from environmental exposure in mammals?

Back 102

1. GI
2. Dermal
3. Respiratory

Front 103

What is the common factor in all forms of oral drug administration?

Back 103

A method to deliver a drug such that it gets into solution in the GI fluids from which it can then be absorbed across the mucosa and ultimately reach the submucosal capillaries and the systemic circulation

Front 104

Why is the small intestine an ideal environment for absorption of drugs?

Back 104

1. pH is more basic than the stomach
2. Epithelial lining is conductive to drug absorption
3. Higher blood flow to SI
4. Presence of villi and microvilli increase surface area