Pharmaceutics Flashcards
1
Q
5 uses for excipients
A
- dosing control
- rate of absorption
- bioavailability and stability
- product identification
- safety and effectiveness
2
Q
5 types of excipients?
A
- diluents
- binders
- glidants
- dry-lubricants
- disintegrants
3
Q
What is a brønsted-lowry acid?
A
a proton donor
4
Q
What is a brønsted-lowry base?
A
a proton acceptor
5
Q
Equilibrium constant of a weak acid
A
[H3O+][A-]
Ka = ————–
[HA]
6
Q
pKa =
A
-log Ka
7
Q
The lower the pKa…
A
the stronger the acid
8
Q
Equilibrium constant of weak base
A
[OH-][BH+]
Kb = ————–
[B]
9
Q
The lower the pKb…
A
the stronger the base
10
Q
pKa + pKb =
A
pKw
11
Q
What are amphoteric electrolytes?
A
electrolytes which can function as acids or bases
12
Q
What is polyprotic?
A
Capable of donating more than one proton
13
Q
What is the henderson-hasselbalch equation?
A
pH = pKa + log([A-]/[HA])
14
Q
([A-]/[HA]) =
A
antilog (pH-pKa)
15
Q
What is the buffer equation for acid?
A
[salt]
pH = pKa + log ———–
[acid]
16
Q
What is the buffer equation for base?
A
[base]
pH = pKw - pKb + log ———–
[salt]
17
Q
What is the equation for buffer capacity?
A
β = Δ[acid/base] / ΔpH
18
Q
What is the integrated rate equation for a 1st order reaction?
A
ln[A]t = ln[A]0 - kt
19
Q
What is the half life equation for a first order reaction?
A
t1/2 = 0.693/k
20
Q
What is the shelf life equation for a first order reaction?
A
t95% = 0.0513/k
21
Q
What is the integrated rate equation for a zero order reaction?
A
[A]t = [A]0 -kt
22
Q
What is the half life equation for a zero order reaction?
A
t1/2 = [A]0 / 2k
23
Q
What is the shelf life equation for a zero order reaction?
A
t95% = [A]0 / 20k
24
Q
What is the integrated rate equation for a 2nd order reaction?
A
1 1
—- = —- + kt
[A]t [A]0
25
What is the half life equation for a 2nd order reaction?
t1/2 = 1 / [A]0k
26
What is the shelf life equation for a first order reaction?
t95% = 1 / 19[A]0k
27
What is the arrhenius equation?
k = A exp -Ea/RT
28
What is the pre exponential factor A?
The fraction of molecules with sufficient energy
29
How is the arrhenius equation rearranged for graphs?
lnk = lnA - Ea/RT
30
What is hepatic first pass effect?
When a drug is goes through the portal vein to the liver and is metabolised beofre it has a chance to reach general circulation
31
What is enterohepatic recycling?
When a drug is excreted into bile, used to digest food and then reabsorbed into general circulation
32
3 advantages of topical application?
- sustained concentration
- reduced dosing frequency
- bypasses liver
33
2 advantages of inhalation?
- bypasses liver
- straight to bloodstream
34
3 advantages of nasal delivery?
- bypass blood brain barrier
- straight to bloodstream
- bypass liver
35
2 advantages of vaginal delivery?
- bypasses liver
- long term controlled release
36
3 advantages of rectal delivery?
- high bioavailability
- by-passes liver
- advantage for those unable to take oraly
37
If the pH of the solution is higher than the drugs pKa value...
the drug tends to be more ionised
38
What is drug distribution?
The reversible transfer of drug from one site to another within the body
39
What are the stats of an average subject?
70kg
5L of blood (3L plasma)
cardiac output 5.5L/min
40
What is paracellular movement?
movement influenced by the tightness of intercellular junctions
41
What is transcellular movement?
- passage by simple diffusion
or
- facilitative methods like transporters
42
Which 4 factors affect passive diffusion?
- smaller MW diffuses faster
- lipid-water partion coefficient
- plasma binding
- membrane thickness
43
Why do some drugs rely on transporters?
They have poor passive permeability
44
Which 3 membranes are the most particular to cross?
- blood-brain barrier
- renal tubules
- hepatocyte
45
Membrane transport for charged drugs is
Slower
46
Bound fraction?
Fbound =
[drug]bound / [drug]total
47
Unbound/free fraction?
Ffree
[drug]free / [drug]total
48
Unbound/free concentration?
Ctotal x Fu
49
Amount of drug in the body (A) =
V . Cp
50
Volume of distribution in terms of amount in body wrt free fractions (V) =
Vp + Vt x ( fu/fu,tissue)
51
What is the partion coefficient when plasma-tissue equilibrium has been achieved?
P = Ct/Cp
52
Volume of distribution in terms of amount in body wrt the partition coefficient (V) =
Vp + ΣVt x P
53
Percentage of drug present in plasma
%plasma = (Vp/V) x 100
54
Percentage of drug present in tissue
%tissue = (V-Vp/V) x 100
55
What are the two parts of permeability rate-limited distribution?
- membrane permeability changes modify distribution
- distribution kinetics dependent on drug properties
56
What is perfusion rate-limited distribution?
- occurs when tissues don't affect distribution
- access to tissues limited by blood flow
- changes in blood flow modify distribution
57
What is the rate of dug uptake in tissues
= Q(Ca - Cv)
58
What is the tissue distribution rate constant (Kt)?
(Q/Vt)
= --------
P
59
What is perfusion rate?
Q/Vt
60
The larger the Kt...
The faster the distribution
61
Drug distribution is faster when?
- tissues have low perfusion
- tissues have low affinity for the drug
62
What is elimination?
The irreversible loss of drug by excretion or metabolism
63
What are the two definitions of clearance?
1. The factor relating elimination rate with the drug conc in plasma
2. Volume of fluid cleared of drug per unit of time
64
Rate of elimination =
Cl x Cdrug
65
Rate in = Rate out
dose/time = Cl x Css
66
How does the liver metabolise drugs?
Lipophilic chemicals metabolised into hydrophilic then excreted in urine or bile
67
What is the michaelis-menten equation?
Vmax x C
elim rate = ---------
Km + C
68
What are Vmax and Km in the michaelis-menton?
Vmax - max elimination rate
Km - michaelis constant / conc at which rate equals 1/2 Vmax
69
What is the extraction ratio (E)?
C entering - C leaving
Eh = ---------
C entering
70
What is hepatic clearance (Clh)?
= Qh x Eh
| same for renal clearance
71
What is the maximum hepatic clearance rate?
90 L/h aka hepatic blood flow
72
What can be an issue of high hepatic clearance?
high loss of drug to hepatic first pass effect
73
What is the maximum renal clearance rate?
72L/h aka renal blood flow
74
Which three processes contribute to renal excretion?
- glomerular filtration
- active tubular secretion
- passive and active reabsorbtion
75
How much water in the kidney is reabsorbed?
99%
76
How does passive reabsorbtion work?
When the water is reabsorbed, it creates a higher Cdrug in the urine which can then diffuse back into the plasma, reduces renal elimination
77
What is tubular renal secretion?
substances can be transported into tubules if not filtered
78
What is glomerular filtration?
Waste products are squeezed out of the blood into the bowmans capsule. Most is reabsorbed in tubules but wastes makes urine
79
How do you work out renal clearance?
Clfiltration + Clsecretion - Clreabsorption
80
Why is Clcreatinine used as a standard?
It is unbound in plasma and only eliminated by glomerular filtration
81
How can you work out renal clearance with Clcr
funbound x Clcr
82
The renal clearance of a drug filtered **and** secreted...
will exceed rate of filtration
83
The renal clearance of a drug filtered **and** reabsorbed...
will be less than rate of filtration
84
When urine is more acidic...
weakly basic drugs more ionised, less reabsorbed, more renal clearance
85
When urine is more alkaline...
weakly acidic drugs more ionised, less reabsorbed, so more renal clearance
86
What is the one-compartment model?
drug is assumed to instantaneously distribute into homogenous fluid, only accounts for drug elimination
87
What is k in the one compartment model equations?
the elimination rate constant, can also be considered the fractional rate of drug removal, eg 0.14h-1means 14% of drug per hour
88
How are A, V and C related in one compartment model equations
A = amount in body
V = volume of distribution
C = concentration
A / V = C
89
How can we estimate k from one compartment model equations?
plot ln of equation against time, the gradient of slope is -k
90
How do you explain if the one compartment model is a good fit?
plot lnC v time and it should be a straight line
91
How do you work out loading dose?
V x desired Co x body weight
92
How can you estimate V with IV bolus data?
V = dose/Co
93
Which equation links volume of distribution, clearance and k?
Cl = V x k
94
How do you change the lnC equation to account for half life?
lnCo /2 = lnCo - k x t1/2
95
C =
wrt to t1/2 and n
Co(1/2)n
n = number of half lives elapsed
96
AUCo for IV =
Co / k
and
D / (k x V)
and
D / Cl
97
How do you estimate AUC?
trapezoidal rule
98
What is the trapezoidal area equation?
(B+b) x h /2
99
What is absolute bioavailability?
the ratio of AUC obtained with extravascular formation and AUCiv of the same dose, e.g.
AUC syrup / Dosesyrup
Fabsolute = ----------------------------------
AUCiv / Doseiv
100
What are three advantages of IV infusion?
- drug plasma levels easily controlled by adjusting infusion rate
- constant drug plasma levels can be achieved
- less problems of irritation/toxicity
101
What are three disadvantages of IV infusion?
- continous monitoring
- solubility and stability of drugs
- fluid restricted patients
102
What are the three assumptions of the one compartment model for IV infusion?
- elimination is first order
- drug input is zero order
- linear kinetics
103
How can we calculate concentration for an IV bolus followed by IV infusion?
Just add together
C = Co x e-kt + Css (1-e-kt)
104
How can you find B graphically?
plot the elimination phase lnC over time and extrapolate to the y axis, you have lnB
105
AUCo for extravascular?
F x D / Cl
106
What is bioavailability?
The rate and extent to which the active ingredient is absorbed and becomes available at the site of drug action
107
What is relative bioavailability?
AUCcapsules / Dose capsules
Frelative = ---------------------
AUCsyrup / Dose syrup
108
What must be remebered when dealing with extravascular doses?
F!
109
What is Css mean for extravascular doses?
F x D
Css = -----------
Cl x tau
