Pharmacology basics

Question 1

How do drugs interact with receptors

Answer 1

Drug interact as a ligand with a receptor (large protein macromolecule responsible for cellular signaling). This results in activation of cellular biochemical processes by way of a transduction pathway that ultimately brings about the pharacological effect

Question 2

What is a sucide substrated

Answer 2

A competitive inhibitor that is converted to an irreversible inhibitor at the active ste of the enzyme.

Question 3

What are the general mechanisms by which drugs work

Answer 3

Vanderwal’s interaction: like repel each other, weak interaction;
Hydrogen bonding- weak;
Ionic- share more than one hydrogen;
Covalent- irreversible bound (aspirin)

Question 4

Principle of induced fit

Answer 4

Also called lock and key; drug acts as a key, receptor as a lock, combination yeilds a response; Dynamic and flexible interaction

Question 5

Tachyphylaxis

Answer 5

Rapidly decreasing response to a drug after administration of only a few doses; repeated same doses are less effective over time. Morphine addiction. Adding ketamine to fentanyl delays tachyphylaxis

Question 6

Desensitized (tolerance)

Answer 6

Decreased response to the same dose with repeated (constant) exposure; or more drug needed to achieve same effect. Receptors don’t respond to it

Question 7

Inactivation

Answer 7

Recptors normally results in a depression of maximal response of agonist dose-response curves; complete response

Question 8

Refractory period

Answer 8

A total inability to respond in an effective time

Question 9

Down-Regulation

Answer 9

tolerance/sensitivity at the cellular level may be due to a change in the number of receptors (without the appropriate subunit) due to change in stimulation. Less receptors there to respond. Example hormones

Question 10

Pharmacodynamics

Answer 10

What happened in the process of the drug, binding one receptor; then multiple binding to a lot of receptors, which then going stimulate a local response prior to a body response

Question 11

Graded dose response relationship

Answer 11

Constructed for responses measured on a continuous scale (hear rate). They relate the intensity of reponse to the size of the tose and hence are useful to characterize the actions of the drugs.

Question 12

Quantal dose response

Answer 12

Constructed for drugs that elicit an all or none response (prescence or abscense of convulsions) for most drugs the doses required to produce specific quantal effect in a population are log normally distributed so that the frequence of distribution of teh responses plotted agains log dose is a guassian normal distribution curve. The percentage of the population requiring a paticular dose to exhibit the effect can be determined from these curve.

Question 13

Dose response curves

Answer 13

Percent effect (y), drug dose (x); depicts the relationship between drug dose and magnitude of drug effect

Question 14

Define Potency

Answer 14

The measure of the drug concentration required to elicit a particular effect; The concentration or dose (ED 50) of a drug required to produce 50% of the drug’s maximal effect as depicted by a graded dose response curve; concentration in which you get 1/2 of efficacy

Question 15

Define Efficacy

Answer 15

The maximum effect a drug can have (full response)

Question 16

Agonist

Answer 16

Receptor interaction with a drug that results in some level of activation

Question 17

Full agonist

Answer 17

Results in maximal effect

Question 18

Partial agonists

Answer 18

Results that are not maximal

Question 19

Inverse agonist

Answer 19

an agent that binds to the same receptor as an agonist but induces a pharmacological response to that agonist; inactive a receptor that is normally on. Bind to the agonist site or elsewhere to induce a response

Question 20

Antagonist

Answer 20

interacts selectively with receptors but it lacks intrinsic efficacy and this is able to block or reduce the action of an agonist at the receptor; Has no effect if nothing has been given that it needs to reverse

Question 21

Competitive antagonist

Answer 21

Competitive occurs at the same recptor site- reversible (easily dissociate from the receptor) or irreversible (form a stable chemical bond with receptor (alkylation); Torb is a competitive antagonist- may have to give enough fentanyl to overcome

Question 22

Non-competitive active site antagonist

Answer 22

binds to the active site and is irreversible or very close

Question 23

Non-competitive allosteric antagonist

Answer 23

binds to a distinctly separate binding site from the agonist exerting their action to the receptor via the other binding site. Do not compete at the active binding site. The bound antagonists may prevent conformational changes in the receptor required for receptro activation after the agonists bindts- will decrease efficacy

Question 24

What are spare receptors

Answer 24

Explains a maximum response beign achieved when only a fraction of the total number of receptors is occupied. Amplification of signal through G protein amplification. Binds to receptors, when it falls off it can then activate another receptor and the first receptor stays active

Question 25

Therapeutic Window

Answer 25

The range of a drug or its concntration in a bodily system that proves safe effective therapy

Question 26

Therapeutic Index

Answer 26

is a measure of a drug’s safety LDF50/ED 50; The higher the value the safer the drug

Question 27

ADME

Answer 27

Absorption, distribution, metabolism, elimination/excretion; Four dynamic drug movements; plasma drug concentrations at any point in time after administration of a dose reflect the combined effects of four dynamic drug movements

Question 28

Absorption- define

Answer 28

From the site of administration (orally, parentally) to systemic circulation; Bioavailabillity, oral absorption play a role

Question 29

Distribution- define

Answer 29

From systemic circulation to tissues (target/nontarget) and back again. Protein binds- systems blood and lymph

Question 30

Metabolism- define

Answer 30

breaks it down, activates, or deactivates the drug

Question 31

Excretion- define

Answer 31

elimination of the drug from the body

Question 32

What is pH trapping (ion trapping)

Answer 32

The build up of a higher concentration of a chemical across a cell membrane due to the pKa value of the chemical and difference of pH across the cell membrane. Move to one compartment to another then hydrogen is stuck or gives it. Weakly acidic likely to give up hydrogen ion

Question 33

What drug properties favor drug entry into the CNS

Answer 33

Lipid Soluble, small size- low mocular weight, can use exisiting, BB protiens, deliver intratheical, non protein bound

Question 34

Define bioavailability

Answer 34

The percentage of an administered dose of drug that reaches systemic circulation and is thus able to induce a response. Used to predict drug efficacy after different routes of administration or administration of different formulations

Question 35

Explain the process of first pass metabolism

Answer 35

The concentration of a drug is greatly reduced before it reaches systemic circulation due to the liver (only)

Question 36

Factors affecting drug absorption from oral administration

Answer 36

Reach systemic circulation from absorption from the small intestine; pH- favors absorption of weak acids; surface area favors SI vs. Stomach; motility;concentration of diffusible drug at the site of movement; permeability and thickness of the mucosal epithelium; and intestinal blood flow which maintains the concentration gradient across the mucosal epithelium

Question 37

Explain volume of distribution

Answer 37

Is a constant that relates the amount of drug in the body to the plasma drug concentration, but does not necessarily correspond to any actual anatomic volume or compartment

Question 38

What organs/tissues are responsivel for metabolism of drugs

Answer 38

Is the enzymatic conversion of one chemical compound into another. Most drug metabolism occurs in the liver, although some will occur in the gut wall, lungs, skin, or blood plasma.

Question 39

What factors influence renal excretion

Answer 39

Host factors determine renal excretion include renal blood flow (including glomerular filtration rate), active tubular secretion, and tubular (generally passive) reabsorption. The kidney is also capable of metabolizing some drugs, although only occasionally clinical important. Glomerular filtration is a passive process

Question 40

What factors influence biliary excretion

Answer 40

Slow; more contact with intestines leading to adverse GI reactions; chemic struction, polarity, and molecular weight, with MW being the major determinant.

Question 41

How are drugs concentrated in the urinary system

Answer 41

Drugs excreted in the urine that do not undergo passive reabsorption will be progressively concentrated in the renal tubule. Tubular cells

Question 42

Describe the process of enterohepatic recirculation

Answer 42

Conjugated (phase II) drugs excreted by this route may undergo enterohepatic circulation if intestinal bacteria or due to pH change unconjugate the drug or metabolite. Allowing intestinal absorption to occur. Prolongs elimination half life and further exposes gastrointestinal tract to the drug

Question 43

Define Drug Clearance

Answer 43

Parameter used to assess the excretory capacity and thus physical well being of an organ relative to plasma concentration. Differs from elimination because it is a volume per unit of time, not a rate constatnt

Question 44

Define First-order Kinetics

Answer 44

Decrease exponentially with time, rate of elimination is proportional to concentration, plot of log [drug] or ln [drug] versus time are linear; t1/2 is constant regardless of the [drug]; cant saturate the eliminating step

Question 45

Define Zero-order kinetics

Answer 45

[drug] decreases linearly with time, rate of elimination is constant, rate of elimination is independent of [drug], no true t1/2; no point of CRI with zero order kinetics, as can staturate, ex. Buprenorphine

Question 46

Define halflife

Answer 46

disappearance of drug from plasma

Question 47

Define elimination half life

Answer 47

the time necessary for plasma or blood concentrations to decline by 50%; Should be the basis for an appropriate dosing interval

Question 48

How does age affect the volume of distribution of a drug

Answer 48

Body composition changes as people; physiologic functions generally decline steadily with increasing ages. Energy requirements of dogs decrease as they age. Organ mass reduces in size and function by approximatly 25%

Question 49

How does obesity affect the volume of distribution of a drug

Answer 49

Increased porportion of body fat is accompanied by a decrease in total body water and cell mass; as distribution of water solubel drugs decreased with total body water, PDCs tend to increase. The distrubution of lipid soluble drugs increase as the proportion of body increases, however which tends to decrease PDCs unless the patient is dose on mg/kg bases

Question 50

How does pathologic fluid accumulations affect the volume of distribution of a drug

Answer 50

Edema formation and intravenous fluid administration contribute to a vast increase in total body water substantially increasing Vd of hydrophilic antimicrobials

Question 51

How does cholestasis induce or inhibit cytochrome p450 enzymes

Answer 51

Cholestasis decrease the content or activity of cytochrome p450 drug metabolizing enzymes and thus can affect the elimination of drugs that are not secreted in bile

Question 52

How does liver failure affect the volume of distribution of a drug

Answer 52

Decreased protein binding of drugs that may accompany liver disease. Increase hepatic clearance and thus compenasate for reduced hepatic metabolism. Further complicated by the effects of fluid, electrolyte, and acid-base imbalances, which are also likely to occur.

Question 53

How does kidney failure affect the volume of distribution of a drug

Answer 53

Uremia induced alterations in tissue receptors or from decreased or increased PDCs caused by disease induced changes in pharmacokinetic; decreased renal blood flow which tends to parallel glomerular filtration and tubular secretion.

Question 54

How does heart failure (decreased cardiac output) affect the volume of distribution

Answer 54

Primary or compensatory disturbances that lead to altared drug disposition include renal sodium and water retention, increased pulmonary and systemic venous pressures, and increased sympathetic nervous systme output