L20 - Hormone drug delivery

Question 1

Types of hormones

Answer 1

Modified amino acid derivatives - dopamine, thyroxine

Peptide and proteins - insulin, vasopressin

steroids - testosterone, hydrocortisone

eicosanoids
prostaglandins and leukotrienes

Question 2

When might you not want systemic delivery?

Answer 2

side effects

low bioavailability

Question 3

Modified amino acid derivative factors

Answer 3

Drug factors - low dose required
biopharmaceutical factors - which route? - orally bioavailable
therapeutic factors: local vs systemic delivery
excipients for small dose like thyroxine 25 micrograms

Question 4

what are excipients

Answer 4

An excipient is a substance formulated alongside the active ingredient of a medication, included for the purpose of long-term stabilization, bulking up solid formulations that contain potent active ingredients in small amounts (thus often referred to as “bulking agents”, “fillers”, or “diluents”)

Types of excipients; 
diluents  - lactose, water
surfactants - polysorbates
lubricants - mg stearate 
disintegrants - starch 
sweetening agents 
preservatives 
viscosity enhancing agents - cellulose derivatives

Question 5

How can corticosteroids be delivered locally?

Answer 5

intra-articular injection - tennis elow 
creams - eczema 
inhalers  - asthma 
eye drops - inflammation 
suppositories - haemorrhoids

Question 6

Factors for peptide hormone INSULIN

Answer 6

drug factor: peptide hormone large molecule
biopharmaceutical factors - not absorbed after oral administration because of Enzymatic degradation in lumen of GIT

therapeutic factors - need systemic circulation

Question 7

How are insulins characterisd?

Answer 7

differences in:
onset - how quick they act
peak - how quick they achieve max impact
duration - how long they act
route of delivery - subcutaneous, inhaled

Question 8

What are long acting insulin analogs?

Answer 8

Long-acting injected insulin analog
replace background, or basal, insulin needs. They provide relatively constant insulin levels that plateau for many hours after injection. These insulins are sometimes called “peakless” insulins. The two commercially available insulins are insulin detemir (Levemir®) and insulin glargine (Lantus®).

Question 9

Rapid acting insulin

Answer 9

Rapid-acting insulins are used in insulin pumps, also known as continuous subcutaneous insulin infusion (CSII) devices. When delivered through a CSII pump, the rapid-acting insulins provide the basal insulin replacement, as well as the mealtime and high blood sugar correction insulin replacement.

Question 10

why is the pulmonary route good?

Answer 10

large surface area 
thin epithelial barrier 
good blood supply 
avoids harsh environment of GI tract 
avoids first pass hepatic metabolism

Question 11

Sex hormones factors

Answer 11

drug factors - steroid lipophilic

Biopharmacetuical factors -variable absorption after oral administration
extensive first pass hepatic metabolism - short t1/2

Therapeutic factors - systemic delivery required but try to avoid oral route
either cyclical or continuous administration required

Question 12

why do we need alternatives to oral route?

Answer 12

to increase bioavailability and offer sustained release

 IM injection 
transdermal route 
patch/gel 
intranasal spray 
buccal route
vaginal gel

Question 13

Give an example of routes that gives sustained release

Answer 13

IM injection - oily injection for testosterone

implants - nexplanon - prog only contraception

Question 14

why does oily injection have sustained action?

Answer 14

action because of lower rate of partition from oily vehicle into aqueous environment of tissue.

Question 15

Testosterone

ester at position 17

Answer 15

decreases water solubility
increases oil solubility
deactivates the molecule so it can’t bind to androgen receptor
the ester is cleaved in blood and restores -OH so can attach to receptor

Question 16

Release of steroid molecule from oily depots of long-chain esters in muscle tissue

Answer 16

oil has some affinity for water thus allows penetration of water.
the ester is hydrolysed at the surface of the droplet

Question 17

Subdermal implant of etonogestrol - Nexplanon

Answer 17

nexplanon is a progestogen only contraception

contraception up to 3 yrs

Question 18

Is intranasal administration systemic or local?

Answer 18

systemic

Question 19

what are the advantages of intranasal administration?

Answer 19

large surface area
highly vascularised
avoids first pass
good bioavailability for LMW compounds

Question 20

Disadvantages of intranasal administration?

Answer 20

mucociliary clearance
metabolic activity
poor bioavailability for HMW compounds

Question 21

is buccal administration systemic or local ?

Answer 21

systemic

Question 22

Can you administer testosterone buccally?

Answer 22

yes -
Mucoadhesive testosterone buccal delivery system
Sustained release of testosterone
through buccal mucosa

avoids first pass -
Venous drainage from mouth is to superior vena cava, therefore avoids first-pass hepatic metabolism.

Question 23

is vaginal administration local or systemic?

Answer 23

systemic

Question 24

vaginal administration - systemic

Answer 24

Crinone - bioadhesive vaginal gel 
progesterone released over 25-50 hours
good patient compliance 
continous release 
self insertion / removal

Question 25

vaginal administration - local

Answer 25

Vaginal ring - Estring

Pessary - oestradiol 10 mcg vaginal tablet insert - Vagifem

Question 26

Mirena

Answer 26

Intra-uterine progestogen -only device
levonorgestrel (52 mg) released into uterine cavity over 3 or 5 years – local action

T shaped device

How does it work?
thickens cervical mucus to prevent sperm entering uterus
inhibits sperm from reaching egg
thins the uterine lining

Question 27

Eicosanoid hormones

Local action of PGE2

Answer 27

Prostaglandin E2 - Indicated for the initiation and/or continuation of cervical ripening at or near term when need to induce birth.