buccal sublingual and rectal administration

Question 1

what might topical drug delivery to the mouth be used for?

Answer 1

treatment of ulcers fungal infections and periodontal disease

Question 2

how are drugs deliverd systemically via the mouth?

Answer 2

drugs can be delivered accross the mucosal lining of the mouth via buccal and sublingual administration.

Question 3

what are the different anatomys of the mouth named?

Answer 3

buccal - gum
sublingual - under tongue
gingival - behind the lip
labial - lining of the inner lip
palatal - roof of mouth

Question 4

describe the anatomy of the oral mucosa

Answer 4

the oral mucosa consists of many layers of stratefied squamous cells. the epithelium is separated by a basement membrane from the lamina propria

Question 5

describ ethe anatomy of the masticatory mucosa

Answer 5

the masticatory mucosa consists of the gingiva and palatal, it is keratinised meaning they have an outer keratin layer providing a protective layer from the strong mechanical forces of eating - this howeer make it poorly permeable to drugs

Question 6

describe the anatomy of the lining mucosa

Answer 6

the lining mucosa consists of the buccal and sublingual membranes - this is non keratinised so they have good permeability. however the buccal tissue is quite thick but it does have good residence time, the sublingual tissue is very thin but its residence time is very poor.

Question 7

what are the pathways of drug absorption?

Answer 7

transcellular - this is the main route and involves crossing through cells - its particularly good for small lipophilic drugs
- paracellular - minor pathway - crossing between cells - good for small hydrophilic molecules due to the polar lipids between the cells

Question 8

the ph of the mouth is around 5.6 to 7.6, what logP do drugs usually have?

Answer 8

drugs usually have a log p of 1 to 5.

Question 9

what is saliva composed of?

Answer 9

saliva consists of water, mucus electrolytes and enzymes.

Question 10

what enzymes are present in the saliva?

Answer 10

aminopeptidase, carboxypeptidase, esterase, carbohydrase and lysozyme. although there are fewer enzymes than the GI tract metabolism of drugs is still possible.

Question 11

other than metabolism, how may saliva negatively impact drug absorption?

Answer 11

the amount of saliva present will affect drug absorption. an increased amount of saliva makes it easier for the drug to get into solution although it can also make it easier for the drug to be swallowed via saliva washout.

Question 12

how can the mucus in the mouth affect drug absorption?

Answer 12

the mucus can be both a physical and chemical barrier:

• its negatively charged so may react with positively charged drugs
• its viscous so drugs must diffuse through to get to the epithelium for absorption

Question 13

what are some of the benefits of buccal/sublingual drug administration?

Answer 13

• the mouth has a good blood supply enhancing absorption
• once absorbed across the oral mucosa it directly enters systemic circulation so it bypasses the hepatic first pass metabolism
• a high residence time can be achieved , making sustained delivery possible

Question 14

what are some of the downsides of buccal/sublingual drug delivery?

Answer 14

• could have an unpleasant tast - this can reduce compliance
• could cause irritation to the oral mucosa
• compliance can be difficult as it interferes with eating talking drinking etc.

Question 15

how is nitrglycerin used sublingually?

Answer 15

nitroglycerin is given sublingually for acute attacks of angina as it is rapidly absorbed so the effects are quick - it would then be given as tablets for maintenance.

Question 16

what happens after oral administration of nitroglycerin tablets?

Answer 16

there would be a very small peak in plasma concentration due to absorption across the oral mucosa before swallowing, there would then be a higher peak following absorption in the gi tract.

Question 17

patients with hypogonadism must take testosterone supllements, why must an alternative route to oral administration be found?

Answer 17

testosterone taken orally has poor bioavailability and the alternatives with better bioavailability are toxic to the liver. it therefore must be administered another way like IM, dermal patches, subcutaneous implant or via the oral mucosa.

Question 18

what drug delivers testosterone acrross the oral mucosa?

Answer 18

striant are buccal tablets taken every 12 hours to maintain a sustained testosterone level thats within the MIC and MTC. however striant can cause local irritation and dysguesia (unpleasant flavout)

Question 19

what is used for breakthrough pain in cancer patients?

Answer 19

backgrounf==d pain caused by cancer is treated with background anaesthesis. when break through pain occurs you give a buccal sublingual tablet for rapid pain relief - this will have quicker onset and shorter duration compared to treatment with a normal release opioid
fentanyl citrate can be sucked as a lollipop during episodes of breakthrough pain as this will have a rapid peak - a shoulder peak may be present due to absorption in the gi tract due to some being swallowed.

Question 20

what can be given to treat opiod addiction?

Answer 20

buprenorphine is an oipiod aganoist, it binds to the receptors replacing the opiods the patient is addicted to. it is as effective as methdone but safer and better tolerated. it is taken as a once daily sublingual tablet.

Question 21

how can abuse of buprenorphine be avoided?

Answer 21

sublingual beprenophine tablets are sometimes abused as they can be dissolved then injected - naloxone is therefore placed in the tablets too. naloxone is an opiod antagonist - it will block opioid receptors so that buprenorphine cannot bind and therefore cannot cause an effect.

Question 22

whats an alternative way of administering insulin rather than by injection?

Answer 22

insulin can be taken with a metered dose pump to obtain quicker effects then with injection. within the pump there is insulin, surfactant, solubiliser, micelle creating agent and emulsifying agents - this punches holes in the epithelium so its less viscous, forcing insulin through. although some may be swallowed most is absorbed in the back of the throat. it is non invasive has a rapid onset, no lung deposition an established safety profile, precise dose control, improved complieanse, easy self aministartion and is easy to carry. the only drwaback is it can require many puffs.

Question 23

what are the advantages of buccal/sublingual administration?

Answer 23

access and ease, rich blood supply, low metabolism, avoids first pass effect, low variability, prolonged contact

Question 24

what are the disadvantages of buccal/sublingual drug administration?

Answer 24

adverse reactions, saliva and mucus, can be inconvenient, expensive to develop.

Question 25

what are the different rectal dosage forms?

Answer 25

suppositories, capsules,tablets, ointments/creams/gels or solutions/emulsions and suspensions.

Question 26

whats the anatomy of the rectum like?

Answer 26

no villi, 300cm SA, normally empty, ph of 7.5 - therefore has low buffering capacity so we want an uncharged drug, simple epithelium (one cell thick), sustained release is possible, bacteria may metabolise some drugs, no peptidase makes it suitable for protein delivery.

Question 27

what can be used for sustained delivery via the rectum?

Answer 27

mucoadhesives can keep the drug in place on the mucosa for sustained delivery.

Question 28

describe the highly vascularised structure of the rectum.

Answer 28

from the rectum the drug goes into venous drainage, if this occurs in the higher region it will go to the liver but if the drug enters in the lower region it will go directly into the systemic circulation avoiding the first pass effect. however due to anastomases (cross linking blood vessels ) slight mixing can occur.

Question 29

lidocaine is metabolised by cyp3a4 in the liver to MEGX. how can you see the first pass effect varying with rectal administration?

Answer 29

by looking at the plasma profile of lidocaine you can see it has a higher cp with the rectal lidocaine infusion, howevere once the infusion is moved higher up more of the lidocaine starts entering venous drainage towards the liver so its metabolised by CYP3A4 to MEGX therefore causing the CP of lidocaine to reduce while that of MEGX increases.

Question 30

how is diazepam used rectally?

Answer 30

diazepam is administered rectally to control bouts of increased seizure activity for management of selected refractory epileptic patients. however diazepam is extensively metabolised to desmethyldiazepam by CYP2C19 and CYP3A4 hence to avoid the first pass effect diazepam rectal gel is used.

Question 31

what are the advantages of rectal administration?

Answer 31

safe and painless, avoids degradation in gi tract, potential extended absorption, good alternative for certain patient groups, potential for protein deliery.

Question 32

what are the disadvantages of rectal administration?

Answer 32

low acceptability, upwards movement can lead to first pass effect, insertion issues, leakage, slow absoprion compared to oral and intravenous.