Booklet 9: Routes of Admin 2 Flashcards
(23 cards)
1
Q
What is the buccal and sublingual route?
A
Administration via oral cavity drugs are placed under the tongue or retained in the mouth
2
Q
What is the purpose of the buccal and sublingual route?
A
Provides route for systemic administration which avoids exposure to the GI tract and liver
- most area well perfused with blood
- oral mucusa is a barrier so not highly permeable
- most substances absorbed by simple diffusion
- log P 1.6-3.3 optimal
3
Q
What are the advantages of the buccal route?
A
- Avoids first pass effect
- Abundance of blood vessel
- Less hostile environment than the GIT
- Fast cellular recovery
- Directly and easily modify microenvironment
- Lower intersubject variability as compared with transdermal patches
- For drugs extensively metabolised in liver or unstable in the GIT
- No stratum corneum
- Can achieve sustained release
4
Q
What are the disadvantages of the buccal route?
A
- Small absorption surface area
- Movement affects mucoadhesive systems
- Less permeable than the small intestine
- Salivation and swallowing
- Drug can’t be masked
5
Q
Applications for buccal delivery
A
- Treat local and systemic conditions (eg. deliver Trinitrin for local treatment such as sore throat and other buccal infections
- Delivery of large, hydrophilic and unstable proteins, oligonucleotides and polysaccharide
- Alternative route for insulin delivery
6
Q
Anatomy and physiology of the nose
A
For smelling
- ofactory membrane approx 5% of total nasal area
- heats and humidifies inspired air
- 2 mucus layers 5-20mm thick
- surface pH of mucosal cells: 7.39
- mucous layer pH: 5.5-6.5
- back 2/3 covered with cilia -> mucociliary clearance
- facilitate movement mucus from nasal cavity to the nasopharynx
7
Q
3 classes of nasal delivery drugs
A
- Alleviation of nasal symptoms
- Alternative to injection for drugs inactivated by the GIT
- Vaccines, peptides, insulin, interferon, buserelin, nafarelin
8
Q
Advantages of nasal delivery
A
- Avoids hepatic first pass metabolism
- Extremely rapid absorption, so only short exposure time for enzymatic activity to take place
- Level of enzymes in the tissue low, can easily saturate with the drug
9
Q
Ideal properties of drug candidate
A
- Appropriate aq solubility to provide desired dose per nostril
- Low molecular weight (smaller better, cut off 20000 Da)
- Low dose (<25mg/dose)
- No nasal irritation
- No toxic nasal metabolites
- No offensive odors
- Suitable stability
10
Q
Ideal nasal absorption enhancers
A
- Increase absorption if drug
- Not cause permanent damage or alteration to the tissues
- Should not be irritant or toxic, either to local or rest of body
- Be effective in small quantities
- Enhancing effect should be temporary and reversible
- Should be stable and compatible
11
Q
Types of parenteral drug administration
A
- Intradermal
- Subcutaneous
- Intravenous
- Intramuscular
12
Q
Intravenous admin
A
- Immediate total access to bloodstream
- Max conc reached in approx 4 mins
- Duration of action depends on dose, timescale of admin (bolus or infusion) and distribution, metabolism and excretion
- Large or small volumes can be given
13
Q
Intramuscular admin
A
- Weak electrolytes: increased absorption w increased lipophilicity, may be binding to muscle protein
- Hydrophilic neutral compounds
- disperse from IM sites according to size
- diffuse through muscle fibres through pores of capillary walls to blood
- Pores only account for 1% of available surface of the capillary wall
- Transport through capillary wall is the rate limiting step
14
Q
Subcutaneous admin
A
- Dissolution and absorption phases occur slower than IM as blood supply is not good
- Greater patient to patient variation in time to Cmax
- Max volume approx 1mL
Eg. Insulin, adrenalin
15
Q
Intrathecal drug admin (inserted into area under spinal cord)
A
Admin of drugs in solution by intrathecal catheter
- > drugs to brain and spinal cord
- more invasive than IV, IM or SC
- implanted catheters and pumps have been used to reduce risk of infection on repeated puncture
16
Q
Rectal drug delivery: advantages and disadvantages
A
- local effect
- systemic effect: when patients cannot use oral route, not stable, pH, drug not suitable for oral
- avoidance of first pass
Disadvantages: aversion (nationality dependent), slow and sometimes incomplete absorption, considerable inter- and intra- subject variation
17
Q
Anatomy and physiology of rectum
A
- Last 150-200mm of the GIT
- Essentially hallow, flat wall surface
- Rectal mucosa normal lipoidal barrier, total surface area approx 300cm2
- Mucous volume approx 3mL
- Mucous pH approx 7.5, little buffering capacity
- 3 systemic veins -> direct to circulation
- No esterase or peptidase activity
- No active transport mechanisms
18
Q
How does rectal absorption occur?
A
- Drug molecules enter general circulation directly (lower and middle veins) or via liver (upper vein)
- Avoidance of first pass is possible but the extent will depend on site of absorption
- Depending on vehicle, a suppository will either dissolve in rectal fluid or melt on mucous layer
19
Q
Vaginal drug delivery
A
- Generally for local effects
- Can achieve systemic absorption
- > drug enters systemic system and avoids first pass
- > wide network of blood vessels
eg. steroids, prostaglandins, some antibiotics
20
Q
How does vaginal absorption occur?
A
- Epithelial layer increases in thickness after puberty and menopause
- SA increased by folds and microridges
- pH decreases after puberty to 4-5
- Little fluid in the vagina
- Absorption tends to be variable
- Dosage from : pessaries
21
Q
Pulmonary drug delivert
A
- treatment or prophylaxis of airways diseases : asthma and cystic fibrosis
- rapid onset of activity for local action
- smaller doses can be administered for oral and parenteral routes
- useful where drug is poorly absorbed orally
Systemic: large SA, abundance of capillaries
22
Q
Advantages of pulmonary drug delivery
A
- direct admin to site of action
- smaller quantities of drug required
- rapid onset of action
- reduced side effects
23
Q
Disadvantages of pulmonary drug delivery
A
- seeking to defeat natural body defense
- demands on patient (educated)
- deposition is technically inefficient
