parental administrations

Question 1

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

Answer 1

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

Question 2

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

Answer 2

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

Question 3

what is the equation of the clearance?

Answer 3

clearance = Vd x k

Question 4

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

Answer 4

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

Css x Vk = Q

Question 5

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

Answer 5

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

Question 6

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

Answer 6

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

Question 7

how can we reach Css quickly?

Answer 7

loading dose + infusion

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

Question 8

what is Wagners method?

Answer 8

allow high infusion rate for t=t1/2 intially

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

Question 9

what are IV administration advantages?

Answer 9

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

Question 10

what does the initial conc. will depend on?

Answer 10

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

Question 11

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

Answer 11

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

Question 12

if the Vd is LARGE?

Answer 12

• 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

Question 13

having a high plasma level means for Vd?

Answer 13

a low Vd

Question 14

what is the equation for Cp(0)?

Answer 14

Cp(0)= dose/Vd

Question 15

equation for plasma conc.- time curve?

Answer 15

C= Coe^-kt

Question 16

what happens if there is an increase in clearance?

Answer 16

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

Question 17

what is the equation for total clearance?

Answer 17

total clearance (CLtotal)= Clrenal + Clhepatic + Clother

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

Question 18

what is t1/2?

Answer 18

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

Question 19

what is the equation for t1/2?

Answer 19

t1/2 = ln2/k
t1/2= ln2/(Cltotal/Vd) 
t1/2= (ln2 x Vd)/Cltotal

Question 20

how to find initial plasma conc.?

Answer 20

Co= D/Vd

D= loading dose

Question 21

with multiple injections, what type of order is it?

Answer 21

it is first order kinetics

it has one compartment system; distribution phase is negligible

Question 22

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

Answer 22

change the dose

add a dosing interval or change it

Question 23

how would you calculate the loading dose?

Answer 23

LD = Vd x Css

Question 24

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

Answer 24

it will increase

Question 25

what is the benefit of a loading dose?

Answer 25

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

Question 26

what is vancomycin and how is it given?

Answer 26

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

Question 27

what type of dosing is less than ideal?

Answer 27

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

Question 28

what is parental administration?

Answer 28

- 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

Question 29

why is parental administration used?

Answer 29

- 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

Question 30

main routes of PA?

Answer 30

- 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

Question 31

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

Answer 31

- 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

Question 32

advantages and disadvantages of IV route?

Answer 32

``` 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 ```

Question 33

what is SC administration and what is the formulation?

Answer 33

- 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

Question 34

why is hyaluronidase given as SC?

Answer 34

- breaks down connective tissue | - allows admin of larger volumes

Question 35

what are the advantages and disadvantages of SC?

Answer 35

``` 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 ```

Question 36

where is IM administered and what formulations?

Answer 36

- 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

Question 37

what are the advantages and disadvantages of IM?

Answer 37

``` 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 ```

Question 38

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

Answer 38

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

Question 39

what is included in formulating solutions, emulsions and suspensions?

Answer 39

``` 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 ```

Question 40

what are preservatives used for?

Answer 40

multi-dose injections

Question 41

what can be used to prevent oxidation?

Answer 41

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

Question 42

what kind of pH should parental formulation have?

Answer 42

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

Question 43

what can u use to control pH?

Answer 43

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

Question 44

what should normal blood osmolality be?

Answer 44

around 280-296mmol/kg

Question 45

what is tonicity?

Answer 45

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

Question 46

what are categories of parental preparations?

Answer 46

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

Question 47

how are injections and infusions prepared and used?

Answer 47

- > 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

Question 48

how are gels for injections prepared and used?

Answer 48

- sterile semi-solid preparation - MR - e.g. somatuline autogel

Question 49

how are implants prepared and used?

Answer 49

- > 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