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SOM 2 > parental administrations > Flashcards

parental administrations Flashcards

1
Q

what is the equation for dx/dt for sampling during infusion? after integration what is the equation then?

A

dx/dt= Q -kx
Q- infusion flow rate
k- elimination rate constant

after integration
X= Q/k (1-e^-kt)
X is influenced by infusion rate, elimination rate constant, duration of infusion

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2
Q

what is the equation for plasma conc.? what is this influenced by?

A 
Cp= Q/Vk(1-e^-kt)
Cp is influenced by:
- infusion rate
- elimination rate constant 
- Vd
- clearance
- infusion duration
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3
Q

what is the equation of the clearance?

A

clearance = Vd x k

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4
Q

what is the plasma conc at steady called? and what is the equation? when is this reached?

A

the plasma conc. is Css and is reached when time = infinity

Css x Vk = Q

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5
Q

if a drug has a short or long half-life how long will it take to reach the steady state?

A

a long half-life means it may take days to reach Steady-state
a short half-life means it may take hours to reach steady state

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6
Q

which type of dosing allows the therapeutic window to be reached?

A

frequent small doses will allow this
a continuous infusion allows this as well but at some point the plasma drug conc. will plateau so only a certain amount of drug will be present

infrequent large doses means a rapid drug conc. is reached quickly before it decreases quite steeply

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7
Q

how can we reach Css quickly?

A

loading dose + infusion

Xt= Q/Vk (1-e^-kt) + X0e^-kt
Cpt= Q/Vk(1-e^-kt) + (D2/V)e-kt
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8
Q

what is Wagners method?

A

allow high infusion rate for t=t1/2 intially

at t=t1/2 Q is changed to a slower rate

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9
Q

what are IV administration advantages?

A

100% bioavailability
no first-pass metabolism
direct to blood circulation
no absorption phase

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10
Q

what does the initial conc. will depend on?

A
  • the dose; increase initial dose increases in initial conc.
  • the volume of distribution
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11
Q

what is Vd affected by and what’s it used to estimate?

A

affected by physico-chemical properties of the drug
- lipophilicty
- binding to proteins
used to estimate blood conc./decide on loading dose

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12
Q

if the Vd is LARGE?

A
  • distribution is important
  • > drug will leave systemic circulation to go elsewhere in the body
  • plasma conc. is low
  • longer half-life for elimination; increase in Vd will increase t1/2
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13
Q

having a high plasma level means for Vd?

A

a low Vd

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14
Q

what is the equation for Cp(0)?

A

Cp(0)= dose/Vd

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15
Q

equation for plasma conc.- time curve?

A

C= Coe^-kt

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16
Q

what happens if there is an increase in clearance?

A
  • faster rate of elimination
  • faster decline in plasma conc.
  • shorter half-life
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17
Q

what is the equation for total clearance?

A

total clearance (CLtotal)= Clrenal + Clhepatic + Clother

Cltotal= kel x Vd units is L/time^-1

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18
Q

what is t1/2?

A

it is the time for Co to be 50% of Co

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19
Q

what is the equation for t1/2?

A 
t1/2 = ln2/k
t1/2= ln2/(Cltotal/Vd) 
t1/2= (ln2 x Vd)/Cltotal
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20
Q

how to find initial plasma conc.?

A

Co= D/Vd

D= loading dose

21
Q

with multiple injections, what type of order is it?

A

it is first order kinetics

it has one compartment system; distribution phase is negligible

22
Q

what can you do to keep the plasma conc. within the therapeutic window?

A

change the dose

add a dosing interval or change it

23
Q

how would you calculate the loading dose?

A

LD = Vd x Css

24
Q

if you increase loading dose, what happens to to concentration?

A

it will increase

25
Q

what is the benefit of a loading dose?

A

it gives a conc within the range immediately
allows first dose efficacy
allows therapeutic window to be reached

26
Q

what is vancomycin and how is it given?

A

vancomycin is a glycopeptide antibiotic and its treatment is for MRSA
it has poor oral absorptions so administered by IV
narrow therapeutic window
its ototoxicity has serum drug levels of 80-100mg/L
about 90% is excereted by glomerular filtration
initial dose is 1g

27
Q

what type of dosing is less than ideal?

A 
infrequent large dosing 
wrong dosing and wrong interval 
- continuous is better 
- can use LD 
- want to reach Css ASAP
28
Q

what is parental administration?

A
  • sterile preparations for administration by injection, infusion or implantation into humans or animals
  • > should be terminally sterilised or aseptically prepared
  • > ensure sterility and avoid contaminants
29
Q

why is parental administration used?

A
  • GI has poor drug stability
  • allows local admin.
  • quick onset of action
  • delayed/prolonged release
  • some drugs can be inactivated or degraded in GI tract and PA allows this to be avoided
  • allows reduced injections frequency
30
Q

main routes of PA?

A
  • IV -> want to reach the veins
  • IM
  • SC -> want them to reach under the fatty tissue under skin
  1. intra-arterial; into artery
  2. intracameral; into anterior/posterior chamber of the eye
  3. intra-articular; into the joints
31
Q

how is IV parental administrations given? what formulations should we get?

A
  • single dose and continuous infusion
  • peripheral or central vein
  • aqueous; solutions, emulsions, nanosuspensions
  • given via the central vein; frequent access required and limited peripheral access
  • central line inserted through chest to get bigger vein
  • dilutes the solution quickly and a lot
32
Q

advantages and disadvantages of IV route?

A 
Advantages
1. 100% bioavailability 
2. rapid onset of action 
3. rapid dilution in circulation 
4. self-admin possible 
5. useful 
Disadvantages 
1. higher costs 
2. invasive, restrictive 
3. aseptic techniques needed
4. hard to reverse
5. risk of embolism, extravasation
33
Q

what is SC administration and what is the formulation?

A
  • fatty tissues under dermis injection; upper arm, anterior thigh, lower abdomen
  • proximity of capillaries
  • small of 1-2mL or large divided doses
  • aqueous/oily solutions or suspension or
34
Q

why is hyaluronidase given as SC?

A
  • breaks down connective tissue

- allows admin of larger volumes

35
Q

what are the advantages and disadvantages of SC?

A 
advantages
1. more patient friendly 
2. self-injectable 
3. can be suspension
disadvantages 
1. invasive, restrictive 
2. < 100% bioavailability 
3. not predictable 
4. can be painful and hard to reverse 
5. some enzymatic activity
36
Q

where is IM administered and what formulations?

A
  • skeletal muscle; below SC tissue and farm from nerves and blood vessels
  • small <4mL
  • up to 10mL in divided doses
  • can be given aqueous solutions/suspensions
37
Q

what are the advantages and disadvantages of IM?

A 
advantages 
- more patient friendly 
- rapid onset of action
- variety of formulations 
- possible controlled release 
disadvantages 
- invasive, restrictive 
- aseptic techniques needed
- hard to reverse 
- difficult to self-administer
- impact of blood supply on absorption 
- high costs
38
Q

what do we need to think about when making parental formulations?

A
  1. sterility; avoids mechanisms of defence and barriers
  2. excipients; can play diff roles but nontoxic and compatible
  3. containers; can be made of glass/plastic but clear, should avoid contamination and should be tamper-evident
  4. endotoxins; they can cause fever or shock
  5. particulates; need to be free of visible particles
39
Q

what is included in formulating solutions, emulsions and suspensions?

A 
Solutions
- water for injection
- co solvents; ethanol, glycerol 
- solubilising agents surfactants 
- suitable oil 
Emulsions 
- water injections 
- emulsifiers; lecithin 
- suitable oils ; arachis oils, sesame oils
Suspension 
- water for injection 
- suspending agents; methylcellulose
- wetting agents ; surfactants 
- suitable oils
40
Q

what are preservatives used for?

A

multi-dose injections

41
Q

what can be used to prevent oxidation?

A

antioxidants can be added e.g ascorbic acid

to prevent oxidation nitrogen can be bubbled into preparation or can fill the vial instead of oxygen
- VC for aqueous and VE for oils

42
Q

what kind of pH should parental formulation have?

A

ideal pH ca. 7.4
it can impact solubility
acceptable range is 3-9

43
Q

what can u use to control pH?

A

acidifying (HCl, sulphuric acid) or alkalinising agents ( sodium bicarbonate, sodium citrate, sodium hydroxide

buffers can change pH due to interaction with container or change in storage
e.g. citric acid, sodium citrate, sodium lactate, mono basic sodium phospjate

44
Q

what should normal blood osmolality be?

A

around 280-296mmol/kg

45
Q

what is tonicity?

A

measure of the effective osmotic pressure gradient
Isotonic; osmotic pressure = plasma
Hypotonic; osmotic pressure< plasma
Hypertonic; osmotic pressure > plasma

46
Q

what are categories of parental preparations?

A
  1. injections and infusions; ready to inject can be pre-filled
  2. gels for injections
  3. implants
47
Q

how are injections and infusions prepared and used?

A
  • > can be single dose or multi dose injections
  • > infusions can be aqueous solutions or emulsions and isotonic to blood. must be sterile solutions or emulsions and clear and free of particulates and no preservatives for large volume
  • > there should be no creaming or cracking for sterile emulsions
  • > small micrometer should be used to avoid embolism risk
  • > e.g. diazemuls, propofol, parental nutrition
  • > no caking and SC/IM for sterile suspensions
  • > powders for injections should be reconstituted and in a suitable vehicle
  • > drug needs to be dissolved to be absorbed and particle size matters
  • > colloidal suspensions avoid embolism risk in small vessels
  • > require additional handling prior to administration
48
Q

how are gels for injections prepared and used?

A
  • sterile semi-solid preparation
  • MR
  • e.g. somatuline autogel
49
Q

how are implants prepared and used?

A
  • > SC or IM
  • > pellets or rods used as sterile and biodegradable
  • > e.g zoladex or nexaplanon or oxudurex
  • > other examples are gliadel wafer which is local delivery of carmustine and is a biodegradable polymer
  • > reservoirs
  • drug released by osmotic pressure
  • requires removal
  • drug encapsulated within metal/plastic or non-biodegradable polymer
  • special injection device

SOM 2 (10 decks)

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