Drug Products TEST 1 Flashcards
(225 cards)
1
Q
Equation
AUC =
A
F(dose)/Clt
2
Q
Equation
Css =
A
AUC/tau
tau = dose interval
3
Q
Equation
F relative =
fm =
A
(AUCgeneric)/(AUCstd) = Xugeneric/Xusdt
fm = 1 - fe
4
Q
Equation
F =
A
(AUCoral)(DoseIV)/(AUCIV)(Doseoral)
=
(Xuoral)(DoseIV)/(XuIV)(Doseoral)
5
Q
AUC is
A
the area under the curve
is useful to assess the total amount of unaltered drug that reaches the systemic circulation
AUC is directly proportional to F
AUC is proportional to Xu
AUC is unaffected by Ka which is rate of absorption
6
Q
tp is
A
time of peak
it is a function of Ka and KE
Shows which is absorbed more quickly
7
Q
F is
A
Extent of absorption
Extent to which the active drug reaches the general circulation
It affects Cmax
It affects AUC
8
Q
Low F can be attributed to
A
degradation of drug in stomach acid, acid labile drug = ampicillin, penicillin G, erythromycin
significant first pass = propranolol
drug binds GI component = tetracycline
Low water solubility meaning poor dissolution = digoxin
complexation with Ca2+ and Mg2+ = tetracycline
9
Q
Ka determines
A
the rate at which the active drug reaches the general circulation
it effects cmax and tp
10
Q
F for IV drug =
A
1, because the drug is injected directly into the systemic circulation. Absorption is by passed.
11
Q
AUC is determined by
A
equation
planimeter
cut and weigh
trapezoidal rule
12
Q
F oral =
A
F absolute = F physiologic
AUCoral/AUCIV
13
Q
F relative =
A
F generic/ F std
extent of absorption of a drug product compared to a recognized standard
14
Q
Fe =
A
fraction excreted unchanged
15
Q
Xu =
A
amount you collect in urine
16
Q
Function of bioavailability testing
A
to determine which drugs possess bioavailability problems
to evaluate physiologic and formulation factors which may alter bioavailability
To establish interchangeability of multisource drugs
17
Q
Pharmaceutical equivalents
A
rate and extent of absorption may not show a significant difference when administered at the same dose of the therapeutic moeity under similar conditions
18
Q
Latin square
A
design for experiment
do not want same sequence in any group
experiment cancels the carry over phase, which is assured because there are 10 half lives between phases.
19
Q
methods of evaluation of comparative bioavailability studies
From a single dose plasma data
A
superimposition - to compare bioavailability
Computer fitting - modeling - Ka, F relative, F/Vd
Bioequivalence = no difference at any concentration
= no significant difference in tmax, Cmax, and AUC
20
Q
Cmax reflects
A
maximum (or peak) concentration that a drug achieves in tested area after the drug has been administrated and prior to the administration of a second dose
rate of absorption
Extent of absorption
21
Q
(Cmax)(Clrenal) =
A
rate of drug excretion in the urine
22
Q
(Clrenal)(AUC) =
A
cumulative amount of drug excreted in the urine
23
Q
Therapeutic equivalence
A
same therapeutic effects and have equal potential for adverse effects under the conditions set forth on the labels of these drug products
24
Q
Rule of thumb for therapeutic equivalence
A
significant difference in means of all measured parameters are less than plus or minus 20% of the standard’s mean, therapeutic equivalence is assumed.
AUCgeneric/AUCstd
should fall between 0.8-1.2 if ratio is calculated
25
Variations in extent of absorption of digoxin
Increase by 30% = 150% increase in cardiac arrhythmia
| Decrease by 30% = 50% increase in chance of losing the desired effect of drug
26
Rapid absorption is a primary interest in ...
analgesic drugs, hypnotic drugs
Sustained release drugs want slow rate of absorption ex theophylline
27
Extent of absorption is a primary interest in...
maintenance drugs such as phenytoin, digoxin
28
Maintaining levels of MIC (minimum inhibitory concentration) would be important for...
antibiotics
29
bioequivalency may lead to serious alterations in clinical effects for:
```
Bishydroxycoumarin
dexamethasone
digoxin
digitoxin
nitroglycerin
p-amino salicylic acid
phenytoin
prednisolone
prednisone
quinidine
triamcinolone
warfarin
```
30
FDA ratings
AP - parenteral
AB - approved to be substituted for (levothyroxin is not interchangeable)
BC - not approved, hasn't been tested
RLD - reference listed drug, standard drug
31
FDA basis for determining bioavailability
bioavail of drug product is demonstrated if the product's rate and extent of absorption are not significantly different from the reference materials
Statistical techniques used should be of sufficient sensitivity to direct differences in rate and extent of absorption that are not attributable to subject variability
drug product that differs from reference material in rate but NOT extent may be considered bioavail if the difference in rate is intentional and reflected in labeling
32
Bioequivalence requirement maybe imposed by the FDA
- drug products do not give comparable therapeutic effects
- drug products exhibit a narrow therapeutic ratio and MEC in the blood. Safe and effective titration of drug product should be used
- lack of bioequiv would have a serious adverse effect
33
Bioequivalence requirement maybe imposed by the FDA: physiochemical evidence
- Active ingredient has low H2O solubility(< 50% in 30 min)
- particle size or surface area of active ingredient is critical in determining bioavail
- structural forms that poorly dissolve
- have a high ratio of excipients to active ingredients
- specific inactive ingredients may be required for abs of active ingredient or therapeutic moiety or may interfere with abs
34
Bioequivalence requirement maybe imposed by the FDA: Pharmacokinetic evidence
- active ingredient, therapeutic moiety, or precursor is abs in large part of GIT
- active ingredient, therapeutic moiety, or precursor degree of abs is poor (< 50%)
- rapid 1st pass
- rapid dissolution and abs are required for effectiveness of active ingredient
- Unstable in GIT and requires special coating
- drug product is subject to dose dependent kinetics
35
Waived evidence of in vivo bioavail when product meets one of the following
- drug product is a solution intended solely for IV and contains active ingredient combined with same solvent and in same concentration as in an IV soluntion that is subect of an approved all new drug application
- drug product is a topically applied preparation intended for local effect
- product is an oral dosage form that is not intended to be abs (antacid)
- drug product is administered by inhalation and contains an active ingredient in the same dosage form as a drug product hat is the subject of an approved full new drug application
- drug product is an oral solution, elixir, tincuture and contains an active drug ingredient in the same concentration as a drug product hat is the subject of an approved full new drug application and contains no inactive ingredient that is known to significantly affect abs of active ingredient
36
salicylate, aniline, and salicylamide
have low water solubility so that can get through lipid membrane
37
riboflavin, methyl orange, methylene blue
have high water solubility so they have a hard time crossing lipid membrane
38
low molecular weight
has fastest rate of relative absorption ex glyceraldehyde, ribose
39
Passive diffusion
rate of diffusion is proportional to the concentration gradient across the membrane
40
Increasing thickness of the membrane
decreases effect of K
| K is proportionality constant
41
increasing the area of the membrane
increases effect of K
42
Increasing partition of drug between membrane and solution
increases effect of K
43
Increasing diffusion coefficient
increases effect of K
44
Characteristics of passive transfer
-percentage of initial drug absorbed is independent of initial dose
-rate of abs is proportional to drug concentration
passive transfer = to 1 = no gradient
45
Active transport
- carrier mediated membrane transfer
- Against concentration gradient
- Ka effected by membrane transfer, gastric emptying, and dissolution
- Active transport > 1 = gradient
- Requires energy: Na - K ATPase, sodium gradient
- Process is capacity limited (saturable)
- competition between two similar substances for same carrier = dec F ie uracil and 5-flurouracil
- carrier systems may be localized in small intestines
- Inhibition of abs by cyanide, dinitropheol, sodium fluoride, neomycin (blocks Na/K ATPase)
46
Secreted =
less than 1
47
When C << Km
rate of abs is proportional to C (passive abs)
48
When C >> Km
rate of abs approaches Vmax
***remember smaller Km = higher affiniity
49
Iron has dec F when
taking heavy metals = Aluminum, magnesium, calcium
50
high diet of phenylalanine will dec abs
of L dopa because of competition
51
Facilitated diffusion
carrier mediated transport system but drug is NOT abs against concentration gradient
Ex. Vit B12 (riboflavin), need intrinsic factor for enhanced abs
Decrease can be seen as dose increases because carriers only have a certain capability
52
Vit B 12 deficient
take nascobal (nasal spray)
53
A carrier mediated absorbed drug with a low passive abs across GI
has an optimum dose
Due to site specificity, drug needs to be available at site. Sustained release products are irrational because of absorption site. Food can enhance drug abs.
54
On an empty stomach, tablet taken with H20, whole tablet dissolves in small volume of liquid, as stomach empties out in 30 min,
only so much riboflavin is abs because carriers are saturated
55
With food, tablet taken, stomach exposed to riboflavin for 2 hours
more drug abs
56
Alcohol - Displays carrier mediated GI transport
decreases absorption of thiamine, glucose, folic acid
| -damages brush border, carriers don't work as well
57
neomycin - displays carrier mediated GI transport
decreases absorption of amino acid, vit B12, and digoxin
| -poison to Na/K ATPase
58
PAS = para amino salicyclic acid - displays carrier mediated GI transport
decreases abs of xylose
| decreases surface area of Vit B12
59
Cholchicine - displays carrier mediated GI transport
decreases cell division
| decreases surface area of GI
60
Methotrexate - displays carrier mediated GI transport
decreases abs of folic acid (competes)
| decreases surface area
61
Folic acid abs is impaired by
**requires conjugation to monoglutamate folic acid
phenytoin, primidone, phenylbutzone, Birth control, isoniazid - displays carrier mediated GI transport.
they impair deconjugase (enzyme) synthesis
impair abs of monoglutamate form of folic acid
62
MRD1 (multi resistant drug transport system)
| AKA p glycoprotein - displays carrier mediated GI transport
competes with digoxin
| and pumps digoxin out and so when digoxin is given with drugs that block this transport system its F increases
63
Pinocytosis
engulfment of macromolecules by phagocytic cells
Oil soluble vit A, D, K, E are taken across membrane by pinocytosis
** radiation and long term use of antibiotics can damage phagocytic cells
64
absorption of fats
fats are converted into Fatty acids and glycerol by lipase then cross membrane into lymph system
emulsions = accumulation of fat in lymph system
Fatty acid gets caught up in micelles
**cyclosporin (emulsion) gets abs into lymph system
**fatty drug or emulsion gets abs into lymph system
65
Factors influencing drug abs
gastric emptying
drug interaction
intestinal motility
pH
66
Degrade in stomach acid
increase gastric emptying = increase abs
take on empty stomach
Do not take with fruit juice
```
ampicillin
Penicillin G
erythromycin base
bisphosphonate
L-dopa
```
67
Forms complexes with Mg2+ and Ca2+
| Do not take with milk/dairy
tetracycline
68
High first pass
propranolol
69
dose-dependent kinetics
phenytoin
70
lipophilic drugs
aniline
| salicyclamide
71
gets through membrane pores
salicylate
72
MW above 150 (no passive diffusion)
starch
inulin
lactose
73
MW less than 150 (passive diffusion)
ribose
| glyceraldehyde
74
secreted (<1)
uric acid
75
absorbed by active transport
5-flurouracil (uracil = competition)
5-bromouracil
L-dopa (phenylalanine = competition)
Amino acids
76
carriers found in upper small intestine
sugars
amino acids
folic acid
IRON
77
carriers found in lower smaller intestines
bile salts
| iron
78
metabolic poisons (inhibit active transport)
cyanide
dinitrophenol
sodium fluoride
neomycin (inhibits Na/K ATPase)
79
Absorption decreased with alcohol
thiamine
glucose
folic acid
80
absorption decreased with neomycin
amino acids
vit B12
digoxin
81
absorption decreased with PAS (Tb drug)
vit B 12
82
absorption decreased iwth colchicine (gout)
xylose
83
decrease abs of folic acid
```
methotrexate
phenytoin
primidone
oral contraceptive
ioniazid
alcohol
```
84
substrates for p glycoprotein (MDR)
- inhibited by ketoconazole - increase F
- induced by st john wart - decrease F
digoxin
morphine
verapamil
85
absorbed by pincytosis
oil soluble vit
86
drugs that increase GIT pH
```
antacid
antisposmatic (propantheline)
H2 blocker (cimetidine)
PPI (omeprazole)
fats and FA
```
87
food decreases abs
cloxacillin (RATE only - F, AUC not effected)
| erythromycin (rate and extent)
88
Decrease Gastric emptying and IM
| diseases: constipation, hypothyroidism, hypoglycemia, aging, pain
```
anticholinergic (propantheline, detrol, homatropine)
TCA
antihistamine
phenothiazine
narcotics
```
89
increase gastric emptying and IM
| diseases: diarrhea, hyperthyroidism, hyperglycemia, celiac disease
laxative (bisacodyl)
| metoclopramide
90
DRLAs
decrease in gastric empyting - increase abs
food increase abs
digoxin
nitrofurantoin
griseofulvin
91
affected by crohn's disease
| musin thickens, complexes with drugs
HTN drugs
| stepromycin
92
inactivated by bile salts
neomycin
kanamycin
nyastatin
93
take one hour before meal
librax
| anti-cholinergic (propantheline)
94
without antacid
bisacodyl
ferrous salts
tetracyclines
95
without mineral oil
oil soluble vitamins
| diocylsulfosuccinate
96
without grapefruit juice
lovastatin (pravastatin is fine)
nifedipine (calcium channel blocker)
cyclosporin
97
absorption decreased with crohn's disease
sulfa drugs
| lincomycin
98
abs decreased with malaria
vit b12
| xylose
99
abs decreased with irradiation and chemo (decrease in surface area)
digoxin
| cephalaxin
100
weak acid
sulfa drug
101
weak base
lincomycin
102
concentrated in breast milk
lodine
| thiouracil
103
rapid abs (tp)
hypnotics, analgesic
104
extent of abs (AUC)
maintenance drugs - digoxin, phenytoin, warfarin
105
AUC and MIC (cmax)
antibiotics, penicillin, nitrofurantoin
106
slow abs (tp)
extended release products
107
Stomach
pH 1-3
negative for villi
secretes HCL, lipase, pepsin
108
Duodenum
pH 4-5
positive for villi
Secretes bile, trypsin, chymotrypsin, amylase, maltose, lipase, nuclease
109
jejunum
pH 6-7.4
positive for villi, has high surface area
secretes amylase, maltase, lactase, sucrase
Has brush border which is a transport system and has enzymes
Drug most absorbed here
110
Ileum
pH 7.6
positive for villi, has high surface area
secretes lipase, nuclease, nucleotides
Drug most absorbed here
111
Colon
pH 8
negative for villi
Doesn't absorb drug
Does absorb water
112
weak Acid Drugs existing in non-ionized form
in the stomach favored for absorption
113
weak Base drugs existing in the non-ionized form
in the small intestines favored for absorption
**All drugs predominately absorbed in small intestine due to large surface area and longer residence time
114
Factors affecting gastric pH
Antacid
antispasmodic = propantheline
H2 blockers = cimetidine, ranitidine, famotidine
PPI = omeprazole, esomeprazole, pantoprazole
Fats
Fatty acids
All supress gastric secretions and raise pH
115
Cyclic manner of gastric pH
Normal pH 2
Pre meal pH 1
Meal pH 3
116
Factors that accelerate gastric emptying
increase absorption rate of drugs, because you want to get out of stomach faster and get to small intestines where most drugs are absorbed
117
Delayed gastric emptying
delays onset of therapeutic effect
| May also mean lower bioavailability for unstable drugs L dopa, alondionate
118
Rate of gastric emptying is proportional to
volume of gastric content to be emptied
| **difficult to observe due to vast number of factors influencing gastric emptying
119
Contribute to Ka
membrane transport, gastric emptying, intestinal motility
120
Volume of meal increases
t1/2 of gastric emptying
121
normal low bulk or liquid intake
needs about 20-60 minutes to completely empty
122
Effect of food on abs of cloxacillin
```
AUC of fasting and fed are same
F of fasting and fed are same
tp has shifted right for fed
Cmax is lower
Fed slows Ka
```
123
Effect of food on uncoated and enteric coated erythromycin tablets
When taking uncoated erythromycin under fasting conditions, we lose some drug but not much.
When taking the uncoated erythromycin with food, the drug stayed in the stomach longer so more was acid degraded and less was available for abs
When taking enteric coated erythromycin, it is unaffected by stomach acid. When taken with food there is a delay in time of peak because food delays gastric emptying. When taken with food enteric has higher F than uncoated product
124
Viscosity of meal
Can decrease gastric emptying rate
125
Diets rich in fats, fatty acids, protein, hypertonic liquids/food
slow gastric emptying rate
126
Duodenal contents has receptors that detect
Acidity too high the pyloric sphincter closes
127
Cold contents
increase rate of gastric emptying
128
Hot contents
decrease rate of gastric emptying
129
Laying on your left side
decreases rate of gastric emptying
130
Laying on your right side
increases rate of gastric emptying
131
Physical stress and exercise
decrease rate of gastric emptying
132
Women in late labor
decreases rate of absorption = shift right in tp and lower cmax
133
Each peristaltic movement passes material
6-8 cm
134
Anticholinergics: propantheline, atropine, hematropine, tolterodine
TCA, antihistamine, penothiazine
decrease gastric emptying and intestinal motility
135
Narcotic analgesics (causes constipation), loperamide (used to treat diarrhea)
decrease gastric emptying and intestinal motility by acting directly on GIT and CNS
136
Bisacodyl (enteric coated laxative that stimulates peristalsis) and metoclopramide
increase gastric emptying and intestinal motility
137
oral Chloroquine
anti malarial drug that affects its own bioavailability
| It slows its own gastric emptying rate
138
APAP given with metoclopramide
```
increases rate of abs
increases GE
Shorten tp
higher cmax
Reaches MEC
```
139
APAP given with propantheline (anticholinergic)
```
decreases rate of abs
decreases GE
increases tp
lower cmax
doesn't reach MEC = no therapeutic effect
```
140
Digoxin paired with propatheline (anticholinergic)
Digoxin is poorly water soluble and is a DRLA (dissolution rate limited absorption) drug
When given with propantheline, digoxin has a greater chance of getting abs because propantheline slows intestinal motility and therefore increases F and bioavailability
141
Digoxin paired with metoclopramide
When given with metoclopramide, digoxin has a lower F because metoclopramide increases rate at which drug passes through and there for less is abs
Css of digoxin decreased when given with metoclopramide because increases rate at which digoxin passes through and therefore less is absorbed
142
Riboflavin (carrier mediated drugs) taken with propantheline (anticholinergic)
increases extent of absorption and bioavailability of riboflavin because propatheline slows rate of gastric emptying. Riboflavin will be around longer due to longer contact time in carrier area.
143
Drugs that degrade in the stomach
L dopa, penicillin G, erythromycin, bisphosphonate, alendronate
144
L Dopa given with metoclopramide
has better bioavailability and extent of absorption
| Increased AUC
145
Mucin: polysaccharide
Disease: Crohn's disease which thickens mucin layer which leads to decrease in F
Complexes: drugs with amines have decreased F because they form complexes with mucin.
146
Enzymes and proteins that have potential to alter bioavailability of drugs
Peptide drugs - most dont survive GI
N-acetyl sufisoxazole (low water solubility) - masks taste of drug, it is prodrug, used in suspension, esterases in GI (pancreatic secretion, intestinal wal, liver) release sufisoxazole
Chloramphenicol - used in suspension, esterases release drug
Antacid - decrease activity in presence of enzymes
147
Bile salts (aliphatic) can inactivate drugs by complexing with them
neomycin, kanamycin, nystatin, tubocurarine, polymyxin
148
Food - viscosity
slows diffusion, slows dissolution, slows gastric emptying
| Slow GE is good for carrier mediated drugs and DRLA
149
Food - acid labile
Slow GE decreases acid labile drugs such as erythromycin, bisphosphonate, penicillin G, L - dopa. Eating with food is not good for acid labile drugs
150
Food - complexes
tetracycline with calcium, magnesium, iron
151
Nitrofurantoin (DRLA) given with food
enhances bioavailability and extent of abs
152
Griseofulvin (DRLA) given with high fat meal
Have increase in AUC
| Fat causes release of bile which forms micelles which solubilizes drug and then drug can be abs
153
7 Drugs to be administered on an empty stomach
ampicillin, erythromycin, lincomycin, penicillin G, tetracycline ( NOT doxycycline), Isoniazid, bisphosphonate
154
3 Drugs to be administered one hour before meal
librax, propantheline, anticholinergics, H2 blockers
155
3 Drugs to be administered without antacid
bisacodyl, ferrous salt, tetracycline
156
2 Drugs to be administered without milk
tetracycline (except Doxycycline), KCL, KI,
157
3 Drugs to be administered without mineral oil
multivitamins, dioctylsufosuccinate salts, stool softener
158
6 Drugs to be administered without grapefruit juice
lovastatin, calcium channel blocker (nifedipine), cispride, triazolam, cyclosporine, oral contraceptives, verapamil, carbamazepine
159
1 Drug that may be administered with food or milk to reduce GI irritation
nitrofurantoin
160
Drugs that have better systemic availability and accelerated abs when administered with food
DRLA drugs: nitrofurantoin, propranolol, griseofulvin, carbamazepine
161
grapefruit juice contains
flavanoid glycoside which inhibits CYP 3A4 leading to increase in F of certain drugs
**cyclosporin, verapamil, carbamazepine, arithromycin, felodipine
162
Pravastatin and pitavastatin not affected by
glycosides, Not affected by CYP 3A4
163
Diarrhea, hyperthyroidism, hyperglycemia, celiac disease
increase gastric emptying and intestinal motility, which is good for acid labile drugs. Not good for DRLA and carrier mediated
164
Constipation, hypothyroidism, hypoglycemia, aging, pain
decrease gastric emptying and intestinal motility, which is good for carrier mediated and DRLA. Bad for acid labile drugs
165
Celiac disease decreases
abs of carrier mediated drugs
| and increases abs of passive drugs
166
malaria decreases
| Hyperthyroidism decreases
abs of vitamin B12
167
Shock, CHF
decrease total cardiac output which decreases blood flow to GI, so drugs accumulate in tissues, which decreases F
168
Drug induced malabsorption - laxatives
low aqueous solubility
increase GE, increase intestinal motility
Not good for DRLA, carrier
169
Mineral oil and dioctylsulfosuccinate
decrease F
170
Irradiation and cancer chemotherapy with digoxin, cephalexin
decrease surface area of GI caused by chemotherapy
| Decreases F for digoxin and cephalexin
171
Ki =
Ku =
Kapp
Ki = rate constant for absorption of ionized drug
Ku = rate constant for absorption of unionized drug
Ku >> Ki
Kapp = apparent absorption rate constant. Fxn of pH and pka
172
When ph = pka
50% ionized and 50% unionized
173
Base with high pka means stronger base which means more ionization
Which would mean NH+ favored
has low absorption
| think quat amine
174
base with low pka means weaker base which means more unionized
Which would mean N favored
**codeine is a base
has good absorption
175
Acid with high pka means weaker acid means more unionized
Which would mean HA favored
**aspirin is a weak acid
has good absorption, graph shifts right
176
Acid with low pka means stronger acid means more ionized form
Which would mean A- favored
has low absorption, graph shifts left
177
When a drug is rapidly abs its passage through membrane is no longer the rate limiting step
Its rate of diffusion through the fluid layer at the surface of membrane is the rate limiting step
178
In the small intestines, weak acids of pka > 3
are well abs
179
In small intestine, weak base of pka < 8
are well abs
180
partition coefficient
measure of lipophilicity
High coefficient = greater abs
Example: barbital vs hexethal or secobarbital
181
Erythromycin propionyl has lower pka which leads to more drug in unionized state
thus greater abs and greater parition coefficient
| Another example is ampicillin ester
182
Unbound drug can partition into these body fluids
milk pH 6.5
saliva pH 6.5
sweat pH 4.5
bile
183
If you have a weak acid of pka = 6, where is it more rapidly absorbed, pH 4 or 8?
pH of 4
184
76% unionized for acids
pH = pKa - 0.5
185
99% unionized for acids
pH = pKa - 2.0
186
76% unionized for bases
pH = pka + 0.5
187
99% unionized for bases
pH = pka + 2.0
188
The lower the pKa, the stronger the acid
the more likely it will be ionized
189
When Acid drug partitions into pH 6.5
more is unionized HA
| C milk/ C plasma water is less than or equal to 1
190
When base drug partitions into pH 6.5
more is ionized
| C milk/ C plasma water is greater than or equal to 1
191
Higher pKa
higher C milk,saliva/C plasma water for bases and acids
| **higher partitioning into acidic compartments
192
Binding to albumin and inability to pass membrane
ionized
193
weak bases have a Vd that is
larger, a decrease in concentration - do concentrate in milk, have big compartment
194
weak acids have a Vd that is
smaller, an increase in concentration - does not concentrate in milk, have a smaller compartment
195
For sulfa drugs, the degree of unionization increases with increase in
pKa
| Concentration ratio in saliva also increases
196
For acids with pKa greater than 9.4
the concentration in compartment/ concentration in plasma water is about equal to one
197
For acids with pKa less than 9.4
the concentration in compartment/ concentration in plasma water is less than 1.0.
198
For bases with pka less than pHc -2
the concentration in compartment/ concentration in plasma water is about equal to one. Unionized in compartment
199
For bases with pka greater than pHc -2
the concentration in compartment/ concentration in plasma water is greater than one. ionized in compartment
200
For unionized drugs, the concentration in compartment/ concentration in plasma water is
equal to one
201
Concentration of durg in milk depends on
concentration in maternal blood
lipid solubility
degree of ionization
plasma protein binding
202
Four factors determine amount of drug entering infant through milk
free fraction
partitioning
milk intake
pharmacokinetics of mother
203
Less than 5% of mother's dose will
ever get into baby
204
Clinical significance of drug partitioning into breast milk
% of mother's dose
Therapeutic index of drug
elimination capabilities of infant - It takes 0.5 to 1.5 years for CYP systems (2C9, 3A4) to fully develop
205
Ergot alkaloids cause
nausea and vomit in babies
206
Morphine can cause what in babies
addiction
207
Laxative can cause what in babies
diarrhea
208
Phenytoin in mother can cause what in kid
cyanosis
209
Lodine and thiouracil have a higher what with in milk
concentration
210
Inc dose of passively abs drug does what to F
NC think ampicillin
211
Take food with passively abs drug does what to F
NC
212
Inc GE and IM with passively abs drug does what to F
NC
213
Dec GE and IM with passively abs drug does what to F
NC
214
Inc dose of carrier mediated abs drug does what to F
Dec F, think riboflavin
215
Take food with carrier mediated abs drug does what to F
Inc F
216
Inc GE and IM with carrier mediated abs drug does what to F
Dec F, shorter window of opportunity
217
Dec GE and IM with carrier mediated abs drug does what to F
Inc F
218
Inc dose of DRLA abs drug does what to F
NC
219
Take food with DRLA abs drug does what to F
Inc, think nitrofurantoin. Bile salts are released
220
Inc GE and IM with DRLA abs drug does what to F
Dec, think diarrhea
221
Dec GE and IM with DRLA abs drug does what to F
inc
222
Inc dose of acid labile drug abs drug does what to F
NC
223
Take food with acid labile drug abs drug does what to F
Dec, think degradation in stomach
224
Inc GE and IM with abs drug does what to F
inc
225
Dec GE and IM with acid labile drugs abs drug does what to F
dec
