pharm principles wk 2 ch 2

Question 1

drugs must be _____ soluble to penetrate the cell

And must be ____ soluble to get out of body

Answer 1

drugs must be lipid soluble to penetrate the cell

And must be water soluble to get out of body

Question 2

when a drug moves from the drug moves from a region of high concentration to one of lower concentration what kind of drug transport is this

Answer 2

passive diffusion

Question 3

what is facilitated diffusion

does it require energy

Answer 3

drug moves from high conc to low conc by entering the cell through specialized transmembrane carrier proteins that facilitate the passage of large molecules. These carrier proteins undergo conformational changes, allowing the passage of drugs or endogenous molecules into the interior of cells

eg glucose

doesnt require energy

Question 4

what kind of movement across the membrane requires ATP and carrier proteins

can it move against a conc gradient

Answer 4

active transport

yes can go from low conc to high conc

Question 5

what kind of drugs rely on endocytosis and what does this process involve

Answer 5

These types of drug delivery systems transport drugs of exceptionally large size across the cell membrane. Endocytosis involves engulfment of a drug molecule by the cell membrane and transport into the cell by pinching off the drug-filled vesicle eg vit B12 across the gut wall

Question 6

what is pharmacokinetics

Answer 6

What the human body does to drug molecules

also is the study of drug movement in, through, and out of the body.

Question 7

what is pharmacodynamics

Answer 7

What a drug does to the human body

Question 8

pharmaco___ includes

 Absorption
 Distrib
 Metb
 Excretion

Answer 8

pharmacokinetics

Question 9

what are some issues faced w pharmacokinetics

Answer 9

Compliance
Dosing & medication errors
Absorption
Tissue and body fluid mass 
	and volume
Drug interactions
Elimination
Drug metabolism

Question 10

what are some issues faced w pharmacodynamics

Answer 10

Drug receptor status
Genetic factors
Drug interactions
Tolerance

Question 11

what does absorption entail

Answer 11

The process that occurs from the time a drug enters the body to the time it enters the bloodstream to be circulated

Question 12

does oral absorption vary?

what about IV?

Answer 12

yes oral varies and can be incomplete

IV is 100% bioavailable and absorbs immed

Question 13

what are the enteral route of admin

Answer 13

Enteral: oral, sub-lingual (buccal), rectal

Question 14

what route is intrathecal

Answer 14

parenteral

Question 15

which of the following routes might have a systemic effect (depending on the drug)

inhalation
topical application to skin
topical application to lungs

Answer 15

all might be intended for systemic depending on drug

Question 16

what drug factors affect drug absorption

Answer 16

Formulation eg depot, enteric coating,
Ionization
Solubility-lipids allow it to move across membrane of cell
Drug molecular weight

FISD

Question 17

drug molecular wt as a factor of absorption

is smaller absorbed more easily across membranes egs of this

eg of bigger size and why this is advantageous

Answer 17

small molecules cross membranes easier, alcohol crosses BBB/placenta/etc, ASA has molecular size 180 da., biologics like monoclonal antibodies used in cancer are large protein molecules (can be 150,000 da) which do not enter normal cells but bind to cancer cell receptors (thus safer than other treatments).

Question 18

are highly ionized molecules easier to absorb than weakly ionized?

where is it easier to absorb an acidic drug?
basic?

Answer 18

strongly ionized molecules not readily absorbed so need to be metabolized

Stomach with pH of 1 (highly acidic) so weak acid drugs more readily absorbed, (ASA)

Intestines have pH of 7 (highly basic) so weak base drugs are more readily absorbed

Question 19

eg of meds that are basic and so get ionized in stomach and unionized in intestines

Answer 19

(Quinidine and pyrimethamine are antimalarials and basic, so are ionized in stomach and unionized in intestines, from where they are absorbed.)

Question 20

what is a prodrug

Answer 20

medication that is administered as inactive and becomes active when metabolized in liver: certain kinds of chemotherapy and immunotherapy are like this, also L-dopa gets converted to dopamine

from book o Prodrug- is a parent drug that isn’t pharmacologically active. This gets metb to pharmacologically active metabolites. Freq the prodrug is more easily absorbed than the metabolites.

Question 21

what are some pt factors that can affect absorption

Answer 21

Route of administration

Gastric pH: acid compounds more readily absorbed in stomach

Contents of GI tract: some drugs need empty stomach, some must be taken with food

placenta

blood brain barrier

Question 22

some drugs must be taken w food does this generally speed absorption

do mny drugs bind to food

Answer 22

– food generally delays absorption, one example antibiotic nitrofurantoin (macrobid) often used for UTIs must be taken with food for proper bioavailability

yes

Question 23

in order to cross the glial membrane what qualities must drugs have

Answer 23

Must be lipophilic, small, and evade active extrusion

Question 24

t or f most drugs enter the placenta to some degree

one example of a teratogen (something teens miht be on)

Answer 24

t

accutane

Question 25

does transdermal have first pass effect? when is this used

is absorption slow or fast

action short or long

Answer 25

usually very slow absorption; used for lack of first-pass effect; prolonged duration of action

Question 26

is the first pass of rectally admind drug more or less than PO
how is its bioavailability in comparison

Answer 26

PO. 5-100 bioavail. most convenient; first-pass effect may be significant

rectal. 30-100bioavail. less first-pass effect than oral

Question 27

when is the peak of a drug given IV vs one given PO

Answer 27

IV peak is immediate and amount in system dec linearly

PO rises, peaks early then slwoly falls

Question 28

what proteins do drugs bind to

what kind of drugs bind to which proteins

what part of pharmacokinetics does this relate to

Answer 28

The proteins commonly involved in binding with drugs arealbumin, lipoproteins, and a1-acid-glycoprotein(AGP).

Acidic and neutral compounds will tend to bond with albumin, which is basic, while basic substances will primarily bind to the acidic AGP molecule.

distribution

Question 29

can the bound portion of a drug act on receptors

Answer 29

no the bound portion isnt active. only the “free” part is

Question 30

what cn happen when pt is taking 2 drugs that bind to proteins

eg heparin and dilantin

Answer 30

Using 2 drugs at the same time may affect each other’s fraction unbound

Eg take drug A and then adding drug B (which is more binding) then it displaces drug A making lots of free drug A.
Eg pt takes coumadin and dilantin (both highly protein binding) and stops coumadin but this makes less dilantin availabe becaue theyre no longer filling binding sites with coumadin so the dilantin will have to bind to more sites and less is availseizure

Question 31

Normal albumin level = ?
0.5-2.0 g/L
10-25 g/L
35-50 g/L
45-100 g/L

Answer 31

35-50 g/L

Question 32

What causes hypoalbuminemia?

assessmnet data

Answer 32

Nephrotic syndrome/Liver cirrhosis/Heart failure
Burns/trauma/surgery/sepsis
Chronic Malnutrition/Stress response/inflammation (most common cause)
Look at elderly for malnutrition…

Assessment: edema, dry skin, bradycardia, hypotension, muscle wasting,

Question 33

what qualities does ETOH have in terms of size, is it able to enter BBB and placenta

Answer 33

alcohol is absorbed in the GI tract, small lipophilic molecule non-ionized easily crosses cell membranes and blood-brain barrier and placenta

Question 34

what is distribution

Answer 34

The movement of drug from the blood to and from the tissues

Question 35

what is metabolism and where does it occur

Answer 35

The method by which drugs are inactivated or bio-transformed by the body
Metabolism occurs wherever appropriate enzymes occur: mainly in liver also
Plasma, kidney, lung, gut wall

Question 36

what does liver do to fat soluble drugs

why is this important

Answer 36

Liver also converts molecules from fat soluble to water soluble so they can be excreted

(Important to make drug more water-soluble for excretion)

Question 37

what is the main liver enzyme system

what factor affects this

Answer 37

CYP (cytochrome P450) enzyme system

genetics/ethnicity affects this

Question 38

what are phase 1 and phase II of biotransformation

during whih phase is the drug converted to an active metabolite

Answer 38

phase 1: modification

Phase I converts drug to active metabolites

phase II: conjugation

Question 39

what occurs in phase 1 modification of biotransformation

Answer 39

Oxidation via cytochrome p450 enzymes mostly
Reduction
Hydrolysis
Phase I converts drug to active metabolites
Elderly have phase I metabolism

Question 40

MAO and alcohol dehydrogenase are examples of what type of phase 1 and what is the risk with this in r/t MAO

Answer 40

neural transmitters and alcohol respectively, inhibiting MAO leads to increased dopamine and serotonin, but many foods need MAO to be broken down too -> food restrictions with MAO-Is)

Question 41

phase II conjugation what occurs

Answer 41

An ionized active metabolite is conjugated with other ionized molecules to create a water soluble molecule excretion

Question 42

what factors affect metabolism

Answer 42

Variability in Cytochrome p450 enzymes according to race/ethnicity
Gender differences (Propranolol oxidation M>F)
Age differences
Disease processes (liver, kidney disease, GI tract)
Drug dose (Acetaminophen has complex dose response curve)
Environmental factors
Drug-Drug interaction through enzyme induction or inhibition or other processes (alcohol induces CYP2E1 which metabolizes acetaminophen to toxic metabolite)
Drug-Herbal interaction (St. John’s Wort induces CYP3A4 which inactivates cyclosporin which leads to transplant rejection)
Diet (empty stomach vs with food, more later)

Question 43

what are some of the major carcinogens from cig smoke

how does this relate to environmental factors

Answer 43

PAH = Polycyclic aromatic hydrocarbons (PAHs) – products of incomplete combustion – are some of the major lung carcinogens found in tobacco smoke

(cigarette smoke PAHs induces CYP1A2 which metabolizes PAH to carcinogens)

Question 44

where does cimetidine affect absorption

tagamet inhibits or prolongs action of other drugs?

Answer 44

Certain drugs affect the absorption of GI tract (eg Cimetidine) an H2receptor antagonist aka Tagamet, prolongs the action of other drugs

Question 45

what is max daily dose of acetaminophen what dose leads to liver damage

Answer 45

(maximum dose 4000mg/day, taking over 7000mg/day leads to liver damage

Question 46

what organs does acetaminophen damage and what causses the damage

Answer 46

kidney and liver injury caused by reactive metabolites of acetaminophen biotransformation.

Question 47

are all metabolites of acetaminophen toxic? is any amount of this metabolite toxic?
when does it become toxic

Answer 47

when a therapeutic dose it is metabolised primarily via conjugation to sulfate and glucoronide (easily cleared by kidneys and nontoxic), and to a much lesser extent via a P450 pathway. But at higher doses these pathways get saturated and body starts using P450-mediated metabolism which leads to formation of a toxic metabolite, N-aceteyl-p-benzoquinoneimine (NAPQI) that is very reactive and causes cellular injury Under normal conditions, NAPQI is naturally conjugated to glutathione in the body and effectively neutralized but once at a ertain level body is overwhelmed

Question 48

in review
toxic metabolite of acetaminophen is
this metabolite normally conjugated to
other two Enzymes for metabolism of acetaminophen

Answer 48

toxic metabolite of acetaminophen is: N-aceteyl-p-benzoquinoneimine (NAPQI)

this metabolite normally conjugated to: GLUTATHIONE

other two Enzymes for metabolism of acetaminophenN-aceteyl-p-benzoquinoneimine (NAPQI): gluconide and sulfate

Question 49

if your pt has decreased kidney function how much would they generally reduce te dose?
what other factor is considered (among many im sure)

Answer 49

dec by 50%

depends on liver fx

Question 50

what is excretion and what are the two most common routes

other routes of excretion

Answer 50

The process by which drugs or metabolites are irreversibly transferred from internal to external environment through renal or non renal route.

most common is renal
biliary is second most common

other routes - lung (through exhalation, think breathalyzer test), skin (through perspiration) etc.

Question 51

______ type of drugs may require several metabolism steps before they are excreted

In the kidney, ____ compounds are largely reabsorbed back into systemic circulation during passage through renal tubules

Answer 51

lipophilic x2

Question 52

t or f ionized and unionized moecules can pass thru glomerular filtration

Answer 52

true

Question 53

are

• drugs bound to plama proteins
• monoclonal antibodies
• conjugated metabolites excreted easily

Answer 53

no, these may not pass the glomerulus.

Question 54

t or f tubular secretion does not require energy

why

Answer 54

false. it does

There are pumps (in the epithelial cells of the proximal tubule) that “grab” drug molecules from the plasma water and move them into the nephron (renal tubule). There are separate pumps for acids and bases.

Question 55

if taking two acidic drugs does this affect excretion of them

Answer 55

Two acid drugs may compete with each other for the “acid pump” and two basic drugs may compete for the “base pump”.

Question 56

during what renal process would drug be reabsorbed into bloodstream

why? (what is happening at this time)

Answer 56

during Passive reabsorption. occurs because the nephron removes water from the glomerular filtrate.

Question 57

how would removing water fro the glomerular filtrate cause reabsorption of the drug?

what qualities would a drug need to have to be reabsorbed

Answer 57

As the water is removed, the concentration of drug molecules in the filtrate increases. The concentration of the drug becomes HIGHER in the tubule than in the plasma water.

IF the molecules are lipid soluble enough and small enough, they may diffuse back into the plasma. Drug molecules that move from the tubule back into the bloodstream are not eliminated

Un-ionised drug can undergo passive reabsorption from urine into blood along the length of the nephron (net excretion may be zero)

Question 58

in what section of the kidneys woud a drug be actively secreted

Answer 58

Some compounds are actively secreted into urine along the proximal tubule

Question 59

what differentiates allergic rxn from adverse rxn

Answer 59

immune response is present in allergic

Question 60

what are the most common side effects of oral drugs

Answer 60

N, V, gi upset

Question 61

what is reportable according to FDA

Answer 61

Death
Life-threatening
Disability or permanent damage
Congenital anomaly/birth defect
Intervention required to prevent permanent disability or damage
Other serious important medical events
Canadian serious event reporting

Question 62

what kind of meds can give you agranulocytosis

Answer 62

antipsychotics esp clozapine

rare

Question 63

what meds can give you rhabdomylosis

Answer 63

caused by a number of drugs, ex. Antipsychotics, statins, SSRIs (statins are direct myotoxins), statins plus antibiotics have caused this

Question 64

prob not important what med caused pulmonary HTN

Answer 64

famous diet medication fen-phen case from 1990’s taken off market due to this, many people required heart valve replacements