Chemotherapy drug delivery

Question 1

What is targeted chemotherapy

Answer 1

targeted to where the cancer is

Question 2

What is the issue with oral drug delivery?

Answer 2

issue of absorption - lose more drug, reduced bioavailability and subject to first pass metabolism and we want as much drug getting to the cancer as possible. Side effects and interactions with other meds
Cant give biologics orally as degraded by proteases and too big for absorption

Question 3

Why can side effects still occur with targeted chemo?

Answer 3

Partial distribution can occur

Question 4

What is IM delivery and its onset of action?

Answer 4

Into the muscle 90 degree angle - larger needle with deeper penetrtation - absorption is quicker than oral but not. as. quick as IV

Question 5

Is IM delivery commonly. used in chemo?

Answer 5

Not common, usually used for anti-emetics

Question 6

What condition should IM delivery be avoided in?

Answer 6

People with low platelets or increased risk due to risk of haemorrhage (high blood supply)

Question 7

What the SC used for?

Answer 7

Some types of biological response modifiers and chemo support drugs. Used to give biologics. over. time

Question 8

What is SC delivery?

Answer 8

short needle 45 degree angle, onset slower. good for low platelets and reduces irritation

Question 9

what. is. the most common route. of chemotherapy administration?

Answer 9

IV. route - 100% bioavailability

Question 10

Why is IV the most common route of chemo administration?

Answer 10

100% bioavailability
Minimises GI. irritation and mucositis
Can give doses as IV. bolus over mins-hours
Can get continuous. infusion for a few days/hrs
Can get pumps

Question 11

What are formulation aspects of. formulating chemo?

Answer 11

Must be sterile and pyrogen free (heat and. filtration)
Low viscosity to avoid irritation 
Isotonicity 
pH. adjustment 
avoid suspensions

Question 12

Why avoid suspensions. in IV?

Answer 12

Particles can occlude the veins

Question 13

If the IV fluid is hypertonic / isotonicity. is not. accounted for - what can happen?

Answer 13

Extravastation injury - unintentional installation or leakage of the drug out of the blood vessel into surrounding tissue. - affects the nerves, tendons, joints.
Can range from a mild skin reaction to necrosis.

Question 14

What are. the methods of IV administration of chemo?

Answer 14

Angiocatheter or central line into vein in arm/ hand (temporary)
Peripherally inserted central catheter. longer term
Porth a cath - through skin into middle of chest
Intrathecal into the CSF brain/spinal cord
Intraperitoneal - into abdominal cavity
Intravesicular - into bladder. with urinary catheter
Intra arterial - into the artery supplying the blood to the tumour
Inra pleural - into pleural cavity in lungs

Question 15

What are risk factors. for extravasation injury?

Answer 15

formulation factors e.g. viscosity, pH, osmolarity
Device related e.g. clot formation above. cannula or placed in an area prone to movement

Patient: age, impaired communication, sedation
HCP: skills, lack of IV therapy skills

Question 16

What are drug related risk factors for extravasation injury?

Answer 16

vesicant potential which destroys tissue
volume of liquid - need very low 
concentration of vesicant drug 
repeated use of the same vein 
pH of the drug/fluids <5 or > 9 = corrosive
co-solevnts e.g. alcohol, PEG

Question 17

What is the risk of using PEG ?

Answer 17

adverse effects if elimination impaired

Question 18

How do you reduce the risk of. vasoconstrictive potential?

Answer 18

Adjust. pH and osmolarity, reduce volume and concentration

Question 19

Why. can. some extravasation injuries present later. with extensive tissue destruction?

Answer 19

Some anti-cancer drugs e.g. Doxorubicin can. remain in tissue for ~5 months after extravasation so then it will present late with significant damage

Question 20

What antidotes are used for extravasation?

Answer 20

Hyaluronidase
DMSO
Sodium Thiosulfate
Local corticosteroids

Question 21

What does hyaluronidase do in extravasation injury?

Answer 21

Stops hyaluronic acid degrading the ECM tissue - counteracts it.

Question 22

Are chemo drugs irritant or vesicant or both?

Answer 22

Both - some are irritant, some are vesicant, some are both

Question 23

What is the role of polysorbate in formulations

Answer 23

Non-ionic surfactant prevents adsorption of drug to the surface = often used in Mabs because they diffuse slower as they are bigger, and thus may adsorb to the surface. This stops this from happening

Question 24

What is the role of alpha-alpha trehalose dihydrate in MAB formulations?

Answer 24

Prevents the collapse of the protein into aggregates - forms. hydrogen. bonds to stabilise it