L32 - Absorption: sublingual, buccal and rectal

• parenteral vs enteral delivery


  enteral = via intestineparenteral = other routes eg buccal/rectal
• How can drugs be administered to the mouth?

  - most drugs are swallowed: brief contact with oral cavity- Topical, eg to treat ulcers/fungal infections- Sublingual (under tongue)- Buccal (other epithelial linings)
• Describe the anatomy of the oral cavity

  lining = oral mucosabuccal, sublingual, gingival, labial, palatal mucosae
• Describe the structure of the oral mucosa- what are the epithelial layers?- where is the capillary bed?- what do prickle cells secrete?


  - stratified squamous layer (layers of cells thick)- Epithelium: basal, intermediate, superficial. (cells become larger and flatter going up)location of capillary bed = lamina propriaprickle cells secrete lipids

  
• Why is the masticatory mucosa keratinised?What's a downside of this?

  to protect when eatingpoor permeability

  
• Define residence time

  the time you can keep a dosage form in place in the mouth
• What's the best way to deliver drugs in the mouth?Pros/cons?

  = via buccal/sublingual linings- very high permeabilityBUT- poor residence time as can get washed away by saliva

  
• What are the most common drug paths across epithelium?What type of molecules use these?

  Transcellular path: lipophilic moleculesParacellular: hydrophilic. More viable in mouth than in GI tract

  
• What's the approximate pH of the oral cavity?

  5.6-7.6
• Saliva- What does it do?- What does it contain?

  water, mucus, electrolytes, enzymes (eg salivary amylase)saliva aids/hinders drug absorptionEg sublingually, drug can be washed down by saliva and swallowed, so could undergo hepatic first pass effect

  
• Mucuswhat is it? what does it do?

  = viscous physical barrier to drug absorption- lines epithelium in mouth-vely charged, so can interact with +vely charged drugs

  
• What is blood supply like in the mouth?

  - Very good blood supply- blood vessels in lamina propria- avoids hepatic first pass metabolism

  
• What factors affect drug absorption in mouth?


  saliva, mucus, taste, irritation, pt compliance, residence timeEg don't eat/drink an hour after taking sublingual dosage form to avoid hepatic first pass
• Eg Sublingual Nitroglycerin

  - rapid absorption for relief of acute angina symptoms- relatively high bioavailability

  
• What is hypogonadism?

  low testosterone
• How can we treat hypogonadism?How is this administered? Why?

  - Testosterne- Testosterone is highly metabolised by hepatic first pass- so given bucally/sublingually/transdermally- on skin, can transfer between partners- can cause dysgeusia

  
• What is dysgeusia?

  distortion of taste (oft metallic)
• Eg how can sublingual delivery be used for Breakthrough Cancer Pain?

  opiod delivery:- lag time between taking normal analgesic and its effect- absorption in mouth rapid, so better to deal with BCP

  
• Eg how can sublingual tablets be used to treat opioid addiction?What's it given with?

  Buprenorphine = od sublingual tablet- opiod agonist- given w/naloxone to remove potential for abuse- naloxone not absorbed well in mouth: passes to GI tract and is metabolisedNaloxone = Antagonist

  
• How can insulin be delivered orally?What does the inhaler contain?How does it work?

  via Pressured Metred Dose Inhaler (MDI)Contains surfactant (to prevent aggregation), solubiliser, emulsifying agents, micelle-creating agentMicelles punch holes in membranes at the back of the throat so insulin can pass through mucosa

  
• What are some advantages to oral transmucosal insulin delivery?

  non-invasive, safe, rapid onset of action, precise dose control, ease of administration, convenient, similar timing of release into systematic circulation

  
• What are some disadvantages to oral transmucosal insulin delivery?

  Needed 20+ puffs to get decent response to glucose.Not convenient

  
• What are some advantages of oral administration eg buccal/sublingual?

  - large SA- ease of access- highly vascularised- avoids hepatic first pass

  
• What are some disadvantages of oral administration eg buccal/sublingual?

  - High Mw drugs must be potent- saliva/mucus barriers- acceptance- development costs eg RapidMist insulin

  
• In what situations is rectal delivery benficial?

  unconscious pts, children, vomiting, drugs that are degraded via oral delivery
• How do rectal suppositories work?

  Fatty covering layer melts at body temp, releasing drug

  
• Describe rectal anatomy

  - end of colon- pH 7.5- no specialisations- metabolism by bacteria- no esterase/peptidae activity: possible protein delivery route

  
• What are anastomoses?

  links/junctions between blood vessels
• Describe rectal blood supply

  - highly vascularised- avoids hepatic first pass if drug enters inferior/middle haemorrhoidal artery- BUT susceptible to hepatic first pass if drug goes further up, eg to superior arteryEg lidocaine is metabolised by cytochrome P450 in liver if infusion is high in rectum

  
• Eg why is diazepam gel commonly used?

  Diazepam is extesively metabolised to active metabolite in liver- used for management of acute seizures- diffusion of rectal gel is slower, so can maintain [drug] for longer time period- low levels of metabolite as bypasses liver

  
• What are advantages of using diazepam rectal gel?What's an issue?

  - low incidences of respiratory depression- low potential for abuse- rare serious overdose consequencesIssue = underadministration
• What are advantages of rectal dosage forms?

  - avoids hepatic first pass if low- safe, painless- avoids degradation in GI tract- good alternative to oral delivery in some pt groups- extended absorption possible

  
• What are disadvantages of rectal dosage forms?

  - acceptability: ew!- upwards movement leads to hepatic first pass- leakage