Exam #1

Question 1

Pharmacology

Answer 1

“study of properties and effects of drugs on living systems”

Question 2

Nomenclature (naming)

Answer 2

Chemical: acetyl salicylic acid

Generic: aspirin

Trade: Bayer

Question 3

Drug

Agonist vs Antagonist

Answer 3

“chemical that interacts with specific molecule and exerts biological effect”

Agonist: stimulates response

Antagonist: inhibit response

Question 4

Drug receptor

Answer 4

“functional macromoelcule to which drug binds and produces measureable effect”

Question 5

Ligand-gated ion channel receptors

Answer 5

bind and open gate (ms)

Ex. ACH open Na channel (nicotinic receptors)

Question 6

G-protein-coupled receptors

Answer 6

G protein load GTP and release alpha/beta second messengers (also gamma subunit)

Ex. AcH muscarinic receptors

Question 7

Kinase linked receptors

Answer 7

Mebrane bind, conformational change activates a kinase which phosphorlyates 2nd messengers-

amino acids tyrosine, serine, threonine (cascade amplification)

Ex. Cytokine, insulin

Question 8

**Nuclear receptors **

Answer 8

DNA coupled intracellular receptors–> stimulate gene transcriptio–> protein/enzyme synthesis

Ligand lipiphilic to cross membrane

Ex. Steroid hormones (estrogen, progesterone, cortisol, thyroid hormone)

Question 9

Mechanism of Action

Answer 9

“specific cellular change mediated by a drug that cause clinically evident response”

Ex. Aspirin–>decrease CoX enzyme->decrease prostaglandin synthesis->decrease inflammation, edema, pain

Question 10

Receptor occupancy

Answer 10

=number of receptors bound to drug

depends on concentration of drug and its affinity for a given receptor

(specificity and selectivity)

Question 11

**Intrinsic activity **

Answer 11

how much effect does drug have on receptor action

Question 12

**Sensitivity **

Answer 12

Up-regulation= more sensitive to drug due to increase # of receptors

Down-regulation= less sensitive due to less # of receptors or more tolerant to drug

Question 13

Agonist

Antagonist

Answer 13

bind to receptor to trigger response

Can be competitive and bind depending on afinity and concentration

block receptor and access of drug to block flow of ions into and out of cell

Question 14

Efficacy

Emax

Answer 14

“magnitude of drug response”

How well it does what its supposed to?

Emax= maximal drug response

Question 15

**Potency **

ED₅₀

Answer 15

“concentration of drug necessary for an effect”

ED₅₀- effective dose to get 50% max response

desired response in 50% individuals

Question 16

Competitive antagonist

Noncompetitive antagonist

Answer 16

=decrease ED₅₀ but not Emax

=decrease Emax but not ED₅₀

(agonist no longer induce same effect, not competing for same site so decrease overall magnitude of drug response)

Question 17

Grade dose response curves

Quantal dose curves

Answer 17

% response over drug concentration

yes or no of individual responses

(# responding vs log₁₀ dose)

Exampine descrete outcomes versus gradation of responses

Question 18

Toxicology

side-effect

adverse effect

toxic effect

Answer 18

“undesired effect of drugs and chemicals”

• minor, uncomfortable
• compromising or potentially harmful
• major or life threatening at high dose

Question 19

TD₅₀ or LD₅₀

Answer 19

toxic or lethal dose

toxicity or death in 50% of animals tested

Question 20

**Therapeutic Index **

Answer 20

margin of safety

=TD₅₀/ED₅₀

Acetominophen=30 (30xs recommended dose get toxic)

Cancer drugs= 1

Question 21

Safety Margin

Answer 21

LD₁/ED₉₉

distance betweeb quantal dose-response curves for desired effect undesired effect

More concervative measure (how safe, risk vs benefit)

Question 22

_Biological variability _

Hyper-reactivity

Hypo-reactivity

Tolerance

Tachyphylaxis

Idiosyncrasy

Number-needed-to-treat (NNT)

Answer 22

=people respond differently to different medications

• response at low dose
• no response until high dose
• hyporeactivity results from repeate administration
• rapid onset of tolerance
• unexpected deviation from normal

unexpected drug response

:# patients who must be expose to drug for 1 patient the deisred effect (takes into consideration individual variations among patients wieght, age, genetics)

Question 23

_Pharmodynamics _

Pharmokinetics

Answer 23

=biological, chemcial, physiological effects of drug

=dealing with absorption, distribution, metabolism, exretion of a drug

“rate at which drug concentration accumulates in and are broken down and eliminated from organs of body”

Question 24

**Bioavailability **

Answer 24

fraction of unchanged drug reaching systemic circulation

degrees to which drug reaches site of action

intravenously versus orally

Question 25

_**Absorption** _

Answer 25

=drug entry into systemic circulation from site of administration rate influenced by route of administration oral, sublingual, subcutaneous, topical, intravenously, intramuscular, inhalation

Question 26

**_Biological membranes_** **Simple diffusion** **Facilitated diffusion** **Active transport**

Answer 26

=lipid soluble, water-filled channels, carrier proteins - small/nonpolar- with electrochemical gradient - big/charged- with electrochemical gradient - need ATP- against electrochemical gradient

Question 27

**_Absorption_** **Compatibility and blood flow** **Ionization **

Answer 27

depends on size, charge, ionization Oral-\>GI lumen-\>GI epithemlium-\>mesenteric vessels-\> blood flow weak acids non-ionized (no charge) in acid solutions weak based non-ionized basic solutions = better diffusable/absorbed in like solutions

Question 28

**Iontophoresis**

Answer 28

-transcutaneous drug diffusion occurs via electrical repulsion push drug across membrane (electicity may vasoconstrict holding drug in area- most drug passive diffusion)

Question 29

**_Absorption_** **Disease effects **

Answer 29

GI disease decrease absorption (digoxin blood levels decrease, malabsorption) Inflammation decrease absorption change ionization state of drug HA\<-\>H+ + A- Stomach pH 1-3 Small intestine pH 5-7

Question 30

**_Absorption_** **Drug/Food effects**

Answer 30

Iron sulfate- form complex with many agents and decrease absorption (thyroxine, methyldopa, penicill) Calcium can inhibit iron absorption Neomycin and phenytoin cause malabsorption as side effect Food/liquid can slow transit time (pop pH\<3)

Question 31

**_Absorption_** **PT effects** **Age effects**

Answer 31

Exercise-\>decrease GI blood flow-\>decrease GI absorption Intense exercise--\>change GI pH-\>change drug solubility Heat, massage, exercise--\>increase local drug absorption administered transdermally Secondary to cutaneous ateriodilation -impaired GI (active) transport and decrease bioavailibility

Question 32

**_Distribution_**

Answer 32

"transfer drug from blood to extracellular fluids and tissues" Interstitial=12 L Intracellular= 24 L Vascular= 5 L

Question 33

**Volume of distribution **

Answer 33

V_D= dose/Co (plasma concentration at time 0) Small= most drug stay in blood Large= not concentrated in blood compartment (dilute)

Question 34

**_Factors of distribution_** **Tissue permeability** **Blood flow** **Drug bind plasma proteins** **Bind subcellular components**

Answer 34

Albumin: drug bind, not as bioavailable Drug storage: Adipose- fat soluble drugs Bone- heavy metals Muscle- mefloquine-antimalarial drug Organ- streptomycin in renal proximal tubule

Question 35

**1st pass effect**

Answer 35

drugs given orally are absorbed by small intestine through portal system to liver (limits bioavailibility)

Question 36

**_Distribution_** **Disease effects** **Drug effects**

Answer 36

Hypoalbuminemia- renal/hepatic disease decrease bind drup typically bind to albumin--\> increasing availability free drug (increase toxicity) Chronic renal failure- uremia decrease drug bound to protein--\> unbound phenytoin levels--\> increase toxic levels even when total blood levels normal -protein bound drugs can be displaced at binding sites by other drugs Ex. Warfarin displaced from binding protein by metronidazole= may result in hemorrhage

Question 37

**_Distribution_** **PT effects** **Age-related**

Answer 37

Redistribution by exercise, massage, heat, ultrasound 2ndary to increase blood flow Exercise change blood pH and may change drug's ability to cross tissue membrane Increase body fat--\>retention lipid soluble drugs Decrease water content-\> water soluble drugs more concetrated Decrease serum albumin-\>increase biolavailbility albumin bound drugs

Question 38

**_Metabolism_** **Make drug hydrophilic** **Make drug less active** *Prodrugs*

Answer 38

-Necessary for excretion in renal tubes Enzyme increase regulatioin occur with repeated admin -metabolite not as effective as parent drug Exception: prodrugs Metabolites more active- converted into more active Ex. L-dopa-\>dopamine Codeine-\> morphine

Question 39

**_Metabolism_** **Inactivation, detoxification, or bioactivation** ***Phase 1*** ***Phase 2***

Answer 39

1. Transform drug into more polar molecule- oxidations (cytochrome P-450s) , reduction, hydrolysis 2. Nonpolar drug--\>polar via _conjugation_ with _transferase_ Ex. Glucaronide, glutathione Morphine (prodrug)--\> morphine glutathione

Question 40

**_Metabolism_** **Disease effects** **Drug effects**

Answer 40

Hepatic disease- impaired metabolism Chronic heart failure alter hepatic perfusion (alter metabolism lidocaine, propanol) Induction/Inhibition of metabolizing enzymes can increase or decrease 1/2 life of drug Barbiturate/rifampin=increase metab oral anitcoagulants Lovastatin/simvastatin+ketconozole/grapfruit=decr Disulfirom (antabuse)= inhibit aldehyde dehydrogenase (alcoholism- alde dehydr help detox/digest ethanol)

Question 41

**_Metabolism _** **PT effects** **Age-effects**