module 1-6 Flashcards
(86 cards)
1
Q
what can happen to the drug once released into the intestine?
A
either exctreted in feces or potentially enteroheptic recylcing
2
Q
what are characteristics of low ER drugs?
A
- high oral bioavail (>80%)
- PO dose usually similar to IV dose
- small changes in hepatic enzyme activity little effect on bioavail
- not very susceptible to drug-drug interactions
- require many passes through liver before completely metabolized
3
Q
what is first pass metabolism?
A
- metabolism before entering systemic circulation
- PO drugs
- result = decreased amount of parent drug that enters systemic circulation
4
Q
what are the 3 drug classifications?
A
- drugs i.e. chemical agents
- biologics eg. hormones, antibodies
- natural health products eg. herbs, vitamins, minerals
5
Q
what happens to a drug with large Vd when it’s displaced?
A
it distributes into the tissues
plasma concentration decreases
6
Q
what are characteristics of drugs with large Vd?
A
low molecular weight (pass through fenestrations)
lipophilic (pass over membrane)
minimal protein binding
predominantly in the intracellular fluid (but also present in the ECF [plasma + interstitial])
7
Q
what are characteristics of drugs with intermediate Vd?
A
low molecular weight (can pass through fenestrations very hydrophilic (can't cross membrane) intermediate protein binding enter interstitial space but not cells, but they are present in the ECF (plasma + interstitial)
8
Q
explain rate of dissolution
A
the faster the dissolution = the faster the onset
9
Q
what is extraction ratio?
A
the amount of metabolism that occurs on the first pass through the liver (has impact on bioavailability)
high ER = lots of metabolism
low ER = minimal metabolism
10
Q
what are the differences in blood flow for sites of IM injection?
A
blood flow in deltoid greater than vastus lateralis greater than gluteal
11
Q
explain disease state re: drug metabolism
A
diseases that decrease CYP activity include:
- liver disease
- kidney disease
- inflammatory diseases
- infection
12
Q
what are factors affecting renal excretion
A
glomerular filtration
tubular secretion
tubular reabsorption
13
Q
What is pharmacokinetics?
A
the study of drug movement in the body
What the body does to the drug
encompasses ADME
absorption, distrib, metab, excretion
14
Q
what is drug displacement from protein?
A
protein binding is reversible
if two drugs are present, one may displace the other from the protein
15
Q
explain enzyme inhibition (drug interactions) re: drug metabolism
A
inhibition of CYPs consequence is decreased drug metabolism consequences of decreased drug metabolism: higher plasma drug concentration increased therapeutic effect of drugs increased drug toxicity
16
Q
explain surface area r/t absorption
A
small intestine has more surface area than the stomach
17
Q
What is drug absorption?
A
the movement of the drug from the site of admin into the blood
18
Q
what is the pharmaceutical phase?
A
occurs after patient swallows tablet and includes disintegration phase and dissolution phase
disintegration - from tablet to granules to smaller particles
dissolution - drug particles dissolve in gastric fluid
19
Q
What is pharmacology?
A
the study of drugs
20
Q
what is first order kinetics?
A
- the concentration of drug is much lower than he metabolic capacity of the body
- drug metabolism directly proportional to the concentration of the free drug
- a constant fraction of drug is metabolized per unit time
- much more enzyme than drug
21
Q
what are some factors that affect albumin concentration?
A
malnutrition, trauma, aging, liver disease, and kidney disease DECREASE albumin concentration
Result = more free drug in plasma, possible toxicity
22
Q
what are the impacts of the rate of absorption and the amount of drug absoprtion?
A
rate of absorption - how quickly the effect of drug occurs
amt of absorption - the intensity of the effect
23
Q
what is enteric coating?
A
prevents dissolution of drug in acidic environ of stomach
*useful for drugs that are destroyed by stomach acid or cause damage to stomach
24
Q
what are the three categories of routes of admin and what falls under each category?
A
Enteral - (GI) oral, rectal
Parenteral - (INJECTION) IV, IM, Subq
Other - (no GI or injection) transdermal, sublingual, pulmonary
25
explain clinical pharmacokinetics
a relship exists b/w the effects of a drug and the concentration of drug in the body
26
what patient pop'n in the lifespan has limited blood flow?
neonates
27
name some other routes of drug excretion
hair - can see how long a person has been exposed
saliva - usually swallowed and either absorbed in intestine or excreted in feces
sweat - mostly washed away
28
explain ionizable molecules
they are either weak acids or weak bases
uncharged in like environments and charged in unlike environs
eg. weak acid is uncharged in acidic environ and charged in alkaline environ
29
what is bioavailability?
the fraction of the dose of drug that reaches systemic circulation unchanged
30
what are the factors affecting drug metabolism?
age
drug interactions (enzyme inducers and enzyme inhibitors)
disease state
genetic polymorphisms
31
explain IM route r/t bioavailability
absorption determined by avail of drug to pass throough fenestrations in capillaries
primary determinants of rate of absoprtion are blood flow and water solubility
advantages - can be used for poorly soluble drugs, can be used to admin depot preparations
disadvantages - pain/discomfort, may cause local tissue and or nerve damage if done improperly
32
how are drug concentrations measured?
in plasma
1) relatively non-invasive
2) good correlation b/w plasma concentration and therapeutic and toxic drug effects
33
what are some of the therapeutic consequences of drug metabolism?
1) increase water solubility of drugs to promote their excretion (lipophilic > hydrophilic)
2) inactivate drugs (active > inactive)
3) Increase drug effectiveness (active > more active)
4) activate pro drugs [prodrug (inactive) > active drug]
5) increase drug toxicity (non-toxic > toxic)
34
what is drug metabolism?
the enzyme mediated alteration of a drug's structure
| A.K.A. biotransformation
35
what are two types of plasma proteins that bind drugs?
albumin (high affinity for lipophilic and anionic (weak acids)
**albumin = majority of protein binding
Alpha 1 acid glycoprotein - primarily cationic (weak base) and very hydrophilic drugs
36
what is the impact of pH on Drug movement?
non-ionized drugs can cross the cell membrane
| therefore, a weak acid in an acidic environ can cross the membrane whereas a weak base cannot
37
what are characteristics of high ER drugs?
- low oral bioavail
- PO dose higher than IV dose
- small changes in hepatic enzyme activity produce large changes in bioavail
- susceptible to drug-drug interactions
38
what is a depot preparation?
preparations in which drug is absorbed slowly over time
39
where does phase II metabolism occur?
in the cytosol [except glucuronidation (smooth ER)]
40
explain blood flow r/t absorption, what increases and decreases blood flow
faster absorption in areas of high blood flow because the concentration gradient is maintained
* exercise increases blood flow and can increase drug absorption
* blood flow is decreased in heart failure, severe hypotension, hypothermia, circulatory shock
41
what are characteristics of drugs with small Vd?
highly protein bound (retained in plasma)
large molecular weight (can't fit through fenestrations)
tend to distrib in plasma volume (bc can't leave vascular space)
42
what are sites of drug metabolism?
```
liver - primary
intestine
stomach - alcohol metabolism
kidney
intestinal bacteria
```
43
what are 4 ways drugs are studied?
1. route of admin
2. mechanism of action
3. therapeutic effects
4. adverse effects
44
what is gastric emptying?
movement of stomach contents into intestine
| *things that affect gastric emptying affect rate of absoprtion as great absorption occurs in the intestine
45
drug distribution is determined by
blood flow to tissues eg. well perfused tissues (liver, kidney, brain) = rapid, tissues with lower blood flow (skin, fat, bone) = slower
ability of drug to move out of capillaries
ability of drug to move into cells
46
explain pH partitioning r/t absoprtion
drug absorption higher when there's a diff between the pH at site of admin and blood
eg. if a drug becomes ionized in the blood
47
discuss bile re: excretion
- some drugs eliminated into bile then ultimately through feces
- drugs that are excreted through bile...
1) molecular weight >300 Da - larger
2) amphipathic (have both polar and lipophilic)
3) glucuronidated
48
how do hdyrophilic and lipophilic drugs leave capillaries?
hydrophilic - only through fenestrations
lipophilic - through fenestrations or over membrane
*if tight junctions are present any drug that is not lipophilic will need to have transport proteins bring drug into tissue eg. brain
49
what are factors affecting pulmonary drug excretion?
Respiratory rate
Cardiac output
solubility of drug in blood (high= low pulmonary excretion and vice versa)
50
what do you need to know about quaternary ammonium compounds?
have at least one nitrogen and always have a positive charge
51
explain sublingual r/t bioavailability
absorbed accross oral mucosa
venous drainage from oral mucosa is to superior vena cava taking blood directly to heart
*doesn't have first pass metab through liver
*drug must be lipophilic and uncharged
52
what is p-glycoprotein?
A.K.A. P-GP
an efflux drug transporter
-it protects cells against drugs as it removes thems
-it is active (i.e. requires ATP) - transporting against concentration gradient
53
explain genetic polymorphisms re: drug metabolism
genes for some of the enzymes have genetic polymorphisms or single nucleotide polymorphisms (SNPs)
change of single nucleotide (A, T, G, or C)
-affects response of drug
54
what is bioavailability influenced by?
1. drug formulation
2. route of admin
3. degree of metab
55
what are some physiological barriers to drug transport?
intestinal villi
| tight junctions
56
explain age re: drug metabolism
infants (no CYP activity) - takes up to one year for reasonable level of enzymes, by age 2 same as adults
from age 2 through adulthood levels off then decreases slightly when elderly
57
what are sites of excretion?
kidney
bile
lung
breast milk
58
where is P-GP in the kidney?
proximal tubule cells - pumps drug into lumen of nephron
59
first pass metabolism can occur via...
hepatocytes in liver
intestinal enterocytes
stomach
intestinal bacteria
60
explain drug transport proteins r/t absorption
uptake transporters - increase absorption
| efflux transporters - decrease absorption
61
what are some factors that affect Alpha 1 Acidic Glycoprotein concentration?
aging, trauma, and hepatic inflammation (i.e. hepatitis) INCREASE Alpha 1 Acidic Glycoprotein concentration
Result = decreased free drug concetration, ineffective therapy
62
what are some trends across the lifespan re: body composition and drug distribution?
the proportion of body water to weight decreases as we age (and obese & elderly have lowest)
muscles mass (% of total weight) is lowest as baby, highest in adult, then obese, then elderly
the fraction of lipophilic drug in fat tissue is lowest in babies, then adults, then elderly, then obese
63
explain transdermal r/t bioavailability
must be both lipophilic enough and relatively hydrophilic because must pass through lipid barrier in skin but maneouver ECF
* usually small molecules
* this route of admin provides constant plasma drug levels
64
what is zero order kinetics?
- the plasma drug concentration is much higher than the metabolic capacity of the body
- drug metabolism is constant over time
- a constant amount of drug is metabolized per unit time
- more drug than enzyme
65
what is another name for cytochrome p-450 enzymes?
CYPs
66
what is measured when sampling plasma for drug concentration
total plasma concentration (free + protein bound)
67
what are the effects of age on renal function?
low in infants (until 2 where it is rate of adult)
then slowly decreases as we age
*lower renal function means excretion decreased
68
discuss kidney re: excretion
majority of excretion
| decreased kidney function prolongs the duration of action and intensity of drug effects, doses need to be reduced
69
explain enzyme induction (drug interactions) re: drug metabolism
Inducer- cell synthesizes enzyme in response to drug or other chem
some CYP isozymes susceptible
consequence is increased metabolism
consequences of increased drug metabolism:
decreased plasma drug concentration
decreased drug activity (if metabolite is inactive)
increased drug activity (if metabolite is active)
70
what are factors affecting gastric emptying?
increases - taking meds on empty stomach, taking meds with cold water, lying on right side, high osmolality feeding (tube feeding), taking a prokinetic drug (drug that increases motility)
decreases - high fat meal, heavy exercise, lying on left side, taking drugs that inhibit vagus nerve (anticholinergic drugs)
71
what are phase II SNPs?
NAT2
- acetylates isoniazid (for TB), caffeine, and various cancer causing chemicals
- pts. are either rapid or slow acetylators
- slow acetylators more susceptible to isoniazid toxicity (neuropathy, hepatotoxicity) and have higher risk for developing certain cancers
72
how many names do drugs have?
3 - chemical name, generic name, trade name
**generic name should be used by HCPs
73
Are oral drugs better absorbed in the stomach or the intestine?
INTESTINE
a) due to surface area
b) stomach small surface area and thick layer of mucous
* so even if drugs are weak acids (and ionized in the intestine), they will be better absorbed by the intestine
74
discuss breast milk re: excretion
- drugs excreted this way usually have
1) low protein binding
2) low molecular weight (small)
3) high lipophilicity
- BCRP transports drugs into breast milk
- breast milk = lower pH & higher lipid than plasma
75
what are the most important parameters determining drug disposition in humans?
clearance - efficiency in drug elimination
Vd - apparent space in body avail to contain drug
Elimination half life (T1/2) -measure of rate of removal of drug from body
bioavail - amount of drug reaching systemic circulation unchanged
76
what is enterohepatic recycling?
the drug is in the intestine and intestinal bacteria cleave the conjugate metabolite leaving the original parent drug
the original drug can be reaborbed and re-enter the body
drugs that undergo this stay in body for long time
77
what happens to a drug with small Vd when it's displaced?
the drug remains in the plasma therefore free drug concentration increases
78
what is ion trapping
when an unionized molecule crosses from a like pH environ to and unlike pH environ where it becomes ionized and therefore stays in the in new environ
ex. a weak acid is unionized in an acidic environment but then it crosses membrane into alkaline environ and becomes ionized (charged) and therefore unable to cross membrane becoming trapped in the basic environ
79
what is the most common CYP?
CYP3A4
80
Routes of admin
enteral - oral, rectal
parenteral - IV, IM, subq (doesn't go to liver before going into systemic circ)
topical - creams, patches
81
What is volume of distrib? (Vd)
APPARENT volume that the drug distrib into
82
what are the factors affecting absorption?
```
rate of dissolution
surface area
blood flow
lipid solubility
pH partitioning
activity of drug transport proteins
```
83
discuss lung re: excretion
drugs elminated this way are gaseous and volatile
eg. general anesthetic
not heavily reliant on metabolism
84
explain IV route r/t bioavailability
advantages - 100% bioavail, precise control of drug dosage and duration of action, allows injection of drugs that are irritants
disadvantages - expensive, invasive, inconvenient, drug can't be removed once admin, risk of infection and fluid overload, risk of injecting wrong formulation
85
what are some examples of poor blood flow/limited drug distrib in adults?
heart failure or shock
solid tumours have progressively decreased blood flow toward the middle
abscesses have no blood supply and therefore difficult to treat with antibiotics
86
what are the factors affecting transdermal absoprtion?
thickness of skin (thicker skin = slower absorption)
hydration - better absoprtion with better hydration
hair follicles - more = better absorption
application area - i.e. surface area
integrity of the barrier - absorption increased with poorer skin integrity
