Nasal Delivery

Question 1

Why is nasal delivery used

Answer 1

1. local effects
2. systemic effects
   - where oral route is not available

Question 2

what is the main nasal passage

Answer 2

turbinates and meatuses (air spaces)

Question 3

what are the functions of the nasal passage

Answer 3

1. air conditioning
   - can increase temperature from 23 degrees to about 32
2. can increase humidity
3. filtration by vibrissae and mucociliary clearance
4. olfaction

Question 4

describe the deposition and clearance of a nasal spray from the nasopharynx

Answer 4

deposition increases as time increases
- platueu

Question 5

describe the deposition and clearance of a nasal spray from the turbinates

Answer 5

deposition decreases as time increases
- platueus

Question 6

what is systemic delivery

Answer 6

a route of administration into the circulatory system so that the entire body is affected

Question 7

what are the anatomical and physiological factors affecting nasal absorption

Answer 7

1. large surface area
2. highly vascularized so avoids first pass hepatic metabolism
3. mucociliary clearance decreases contact time
4. metabolic activity
5. immunological clearance
6. mucus barrier
7. epithelial barrier

Question 8

what is transcellular transport

Answer 8

active transport mechanism where solutes pass through the cell passing through both the apical membrane and basolateral membrane

Question 9

what is paracellular transport

Answer 9

transfer of substances across an epithelium by passing through the intercellular space (tight junctions) between the cells

Question 10

what are the drug factors affecting nasal absorption

Answer 10

1. molecular weight
   - absorption decreases when molecular weight >1000Da
   - limited diffusion of molecules >3.6 Angstroms
   - negligible diffusion of molecules >15 angstroms
2. lipophilicity- absorption increases with increased lipophilicity
3. charge- absorption best if molecules are unionised

Question 11

what is breakthrough pain

Answer 11

A sudden increase in pain that may occur in patients who already have chronic pain
- usually lasts a short period of time
- can be given rescue dose of a rapid acting opioid of relatively short duration

Question 12

give an example of a drug that can be used for breakthrough pain

Answer 12

fentanyl/pecfent

Question 13

what is the half life of fentanyl

Answer 13

12-15 mins

Question 14

describe the effectiveness of PecFent

Answer 14

1. more effective than placebo in reducing pain 30 min after use
2. patients satisfied or very satisfied with 90% of breakthrough pain episodes

Question 15

what can be used as treatment of accidental overdose of opioid

Answer 15

IV and IM naloxone
Narcan nasal spray

Question 16

describe when overdose occurs

Answer 16

occurs when too much of an opioid fits in too many receptors slowing and then stopping the breathing

Question 17

describe how naloxone reverses an overdose

Answer 17

naloxone has a stronger affinity to the opioid receptors than opioids, so it knocks the opioids off the receptors for a short time
- this allows the person to breathe again and reverse the overdose

Question 18

describe how naloxone nasal spray can be used

Answer 18

used by many first responders and primary caregivers
- nasal spray formulation of naloxone is easier to deliver, and eliminates the risk of a contaminated needle stick

Question 19

which people are likely to witness an opioid overdose

Answer 19

1. people at risk of an opioid overdose, their friends and families
2. people whose work brings them into contact with people who overdose
   - healthcare workers, police, emergency service workers

Question 20

when is a nasal spray recommended

Answer 20

opioid overdose in non medical and medical settings

Question 21

compare the nasal and oral bioavailability of desmopressin

Answer 21

oral bioavailability= 0.08-0.16%
nasal bioavailability= 10%

Question 22

what are the formulation factors affecting nasal absorption

Answer 22

1. pH
2. osmolarity
3. viscosity
4. concentration
5. volume
6. dosage form
7. penetration enhancers

Question 23

give an example of a penetration enhancer

Answer 23

chitosan
- cationic polysaccharide
- increases the absorption of polar molecules and acts as a bioadhesive
- transiently opens tight junction

Question 24

give examples of therapeutic areas suitable for IN administration

Answer 24

1. breakthrough cancer pain- fentanyl, morphine
2. emergency situation medicines- naloxone for opioid overdose

Question 25

what are the patient factors affecting nasal absorption

Answer 25

1. acceptable to patient
   - non invasive, comfort and compliance
   - simple dosage forms, drops and sprays
2. variability of dosing
3. disease
   - inflammation
   - common cold