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Lecture 17: Flashcards

0
Q

Which drugs are administered via the buccal cavity?

A

Used traditionally with drugs, but also with recreational substances.

Nitroglycerine (tablet) to treat cardiac diseases

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1
Q

What is the buccal cavity?

A

This route of administration involves placing drugs under the tongue or retained in the mouth

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2
Q

What can be achieved by using polymers which are bioacidic?

A

We can retain the medication in the buccal cavity, giving us more options for drug delivery

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3
Q

Can the buccal route be used as means of administration for system effects?

A

Yes. This is due to the extensive capillary network in the oral cavity

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4
Q

What is the buccal route especially good for?

A

The administration of drugs which are susceptible to mass degradation in the stomach and in the GIT

This is because the buccal cavity is not very acidic

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5
Q

What difficulties does the mucous in the cavity pose?

A

The mucous is not very permeable so it is not designed for absorbing drugs.

However some chemicals like sugars can be absorbed significantly through here

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6
Q

What is the main difference between transport mechanisms in the buccal cavity and the GIT?

A

In the GIT we had lots of mechanisms of transport, however in the buccal cavity, simple passive diffusion is the only transport

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7
Q

What kind of criteria must drugs meet to be absorbed via the buccal cavity?

A

Although many different drugs can be administered through this route, it is ideal that the drug has a logP value of 1.6-3.3 to undergo maximum absorption

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8
Q

Why does the ideal drug have to have a high log P value to be best absorbed through the buccal cavity?

A

The drug needs to be lipophilic because the mucous of the buccal cavity is lipophilic. However it also cannot have a log P too high (greater than 3.3) or else it wont be absorbed

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9
Q

What are the advantages with absorption via the buccal cavity?

A

It avoids first pass metabolism
There are lots of blood vessels, so it goes directly through the systemic circulation
There is rapid absorption
The environment is not as hostile
Administration of devices like tablets is easy, termination is also easy
There is a lower individual variability as sub tissues, mucosa and adipose tissue do not vary as much in the buccal cavity

The stratum corneum is absent (tight layer of skin tightly joined together) so absorption is maximised?

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10
Q

What are the disadvantages of drug administration via the buccal route?

A

Small surface area
Movement of tongue affects mucoadhesive system
Movement in oral cavity causes viscosity to decrease.
Oral cavity is less permeable than SI
Salivation could dissolve some of the drug
Sometimes drug could be swallowed by mistake
The taste of the drug is VERY important

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11
Q

What is a main application of the buccal cavity used to treat local conditions?

A

Oral infection or sore throat.

There are medicines to relieve cold symptoms which are administered via the buccal cavity

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12
Q

What is a main application of drugs administered via the buccal cavity used to treat systemic conditions?

A

The buccal cavity is suitable for the delivery of water soluble drugs, polysaccharides and sugars.

It could be an alternative route for insulin delivery in type I diabetes

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13
Q

What is the structure of the nose?

A

Nostrils about 1.5cm, next to nasal valve.
Nasal cavity up and behind nostrils.
Mucous layer about 5-20mm thick (there are actually two layers)
Cilia in the back 2/3rds of the nose, for defence

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14
Q

What is the nasal cavity?

A

A region behind the nostrils

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15
Q

Why is the nasal cavity a drug target for administration?

A

The nasal cavity has a large volume and is abundant in terms of capillary networks

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16
Q

What is the structure of the nasal cavity?

A

2ml and 6cm in length, with 3 foldings on each side

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17
Q

What is the nasal cavity divided by?

A

It is divided in half by the nasal seltum

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18
Q

What are turbinates?

A

Shelf like things, they circulate the air in the nasal cavity and also humidify and heat the air we breathe in

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19
Q

What are the main functions of the nose?

A

Main function is to smell, the nose also heats and humidifies inspired air

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20
Q

What is the pH of the mucous layer?

A

The surface is quite neutral. 7.39

However this can drop to 5.5 and 6.5 for microbial protction

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21
Q

What does a drug adminstered via the nasal cavity have to overcome?

A

Although the nasal cavity provides opportunities by its large surface area and capillary network, the drug will still need to overcome defence mechanisms set by the cilia and changing pH of the nose

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22
Q

What are the advantages of the nasal cavity?

A

It bypasses the first pass effect
There is rapid absoprtion
There is some enzymatic activity (especially nasal CYP P450 enzymes)
However absorption is so quick enzymatic degradation can be neglected.

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23
Q

Why can enzymatic degradation be neglected in the nasal cavity?

A

There are so few enzymes there they are unlikely to be saturated, so wont affect drug absorption too much.

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24
What are the three classes of drugs that can be delivered via the nasal cavity?
1) drugs for the alleviation of nasal symptoms 2) drugs which are inactivated by the GIT and need an alternative route, 3) some vaccines can also be given through this route Another area of research is the opportunity for peptides, proteins and insulin to be adminstered through this route.
25
Which drug is always being researched for new ways of development?
We are always looking for new routes to administer insulin as it is the only treatment for type I diabetes patients
26
What does the ideal drug candidate for the nasal route require?
Appropriate aqueous solubility to provide desired dose per nostril, No nasal irritation No toxic nasal metabolites No offensive smells No instability It also must have a low molecular weight (20,000 atoms or under)
27
How is dynamics and engineering airflow important for nasal administration?
Initially some drugs given as a nasal spray only deposited in the lower parts of the nasal cavity, so they ended up in the GIT However by studying dynamics and doing some airflow engineering of the cavity, they came up with new devices which could deposit nasal medication on the upper parts of the cavity which is more ideal as it is rapidly absorbed and can therefore reduce the dose to achieve a certain therapeutic effect
28
What can be done to enhance nasal absorption?
Absorption ehancers: these increase the gap between the capillary and blood vessel cells.
29
What are the qualities of a good nasalabsorption enhancer?
It has to increase the solubility of the drug significantly with very little dose At the same time, the effects on the cellular membrane should be reversible, and not permanent
30
What is the parenteral route?
This route refers to injections and the adminstration of drugs through hollow needles
31
What routes does parenteral route include?
Intradermal- used with syringes to admin below the skin within the dermis Subcutaneous- within the subcutaneous layer IV - directly into the veins IM- into muscular tissue
32
What are the advantages of IV administration?
It is the most efficient administration route, The bioavailability is 100% as it is directly into the bloodstream It is very good for emergency situations (takes an average of 4 mins for most drugs to take effect) Duration of drug action is dependent on dose administered. This can be adjusted accordingly We can have a bolus injection or infusion Can give both large or small volumes (e.g. Vaccines, electrolytes,) Accepts both hydrophilic and lipophilic drugs
33
What are factors in intravenous administration rely on a time scale to control?
Distribution, metabolism, excretion
34
What happens if a drug is too lipophilic for the intravenous route?
The intramuscular route is a better choice
35
What are the advantages of the intramuscular route?
Useful for weak electrolytes Ideal for lipophilic compounds Drugs can bind to proteins - good if drug targets muscular tissue Can also give hydrophilic and neutral compounds
36
What are the disadvantages of intramuscular administration?
The onset of action is not as fast as the drug is injected into muscular tissue, needs to diffuse through muscular cells, membrane and then into the blood stream. Drugs can bind to proteins - this is a limiting factor for drugs targeting systemic effects Size of particles plays an important part as drugs have to go through muscular fibres, through capillary pores to enter the systemic circulation. Smaller particles diffuse faster
37
What is the rate limiting factor in intramuscular administration?
Transport through capillary and muscle
38
What is the brief history of subcutaneous administration?
Has been used for as long as the pharmacy profession has existed. More recently, has been used for drugs like insulin and adrenaline
39
What are the disadvantages of subcutaneous administration?
Dissolution of drug through the skin is much slower due to nature and physiology of the skin (which is more lipophilic in nature) Absorption is very patient dependent - time required to reach C max varies due to dissolution difference and distribution and variance of adipose tissue Thickness of skin also varies a lot between individuals
40
What is the intrathecal route?
Refers to the placement of a catheter through the spinal cord and giving the drug as solutions
41
What are the advantages of the intrathecal route?
Provides opportunity to administer drugs to brain, CNS and spinal cord
42
What are some disadvantages of the intrathecal route?
It is very invasive, but could be the last resort in some cases As we are dealing with the spinal cord, there are likely to becomplications
43
What kinds of patients may require drug administration via the intrathecal route?
In severe cases e.g. Patients with extreme back pain | Cancer patients
44
What two different categories can intrathecal administration fall under?
Hospital and clinical. There have been recent developments on delivery systems which can be inserted into the body as implants, and provide most of the painkillers
45
What are the advantages of the rectal route?
Can be used for local effects (mostly) and systemic effects It is an alternative option for patients who cannot take the drug orally It is a possible route of administration that may bypass the first pass metabolism - due to physiology of the rectum
46
What are the disadvantages of the rectal route?
Aversion - dislike by patient, depending on ethnicity or personal preference Drug absorption could be slow Sometimes incomplete absorption could occur There is lack of control over drug administration Patient variability will be a big issue Potent drugs are not a good candidate Need to be careful when giving drugs of lower pH due to limiting buffer capacity in the rectum
47
What is an example of a local condition that could be treated with drugs administered rectally?
Haemorrhage, pain, can also administrate drugs as a laxative
48
What are examples of system conditions which drugs administered rectally could be used to treat?
Fever etc, if patients cannot take oral routes due to GIT instability, and pH of stomach
49
What is the basic physiology of the rectum?
It is part of the colon, about 25-20cm, hollow with flat wall surfaces Only 3 folds in the rectum Rectal mucosa is a barrier to hydrophilic drugs Volume of mucosa is much smaller (~3mL) PH = 7.5, not acidic like stomach There are 3 separate veins called haemorrhoids situated in different levels of the rectum There is no active transport mechanism
50
What are the differences between the three haemorrhoids?
The lower and middle haemorrhoids go directly to the system circulation so for the drug to bypass first pass metabolism, it needs to target the lower rectum Any drugs ending up in the higher rectum are subjected to metabolism in the liver
51
What could not having active transport mechanisms in the rectum be a rate limiting factor for?
Some biologically active molecules like antibodies which have specific receptors in order to be absorbed
52
What is the most common dosage form for the rectal route.
The suppository. This can designed to retain the drug in the rectum Depending on the vehicle, it can be dissolved in rectal fluid or meltd in the mucous layer
53
What is vaginal administration mostly used for?
Local effects, e.g. To treat infections, although it can have some systemic absorption
54
What are some advantages of vaginal administration?
Drugs entering via this route bypasses first pass metabolism Surface area is increased by vaginal folds Wide network of capillaries to aid absorption Could be an opportunity for specific conditions in women
55
What are some disadvantages with using the vaginal route?
The thickness of the epithelial layer increases after puberty and menopause, resulting in variation in absorption among women. PH can decrease to 4.5-5 after puberty (defensive mechanism) Little fluid in vagina, so need to be aware that if administering a tablet, needs excipients which aid disintegration and dissolution
56
What kind of drugs are administered via the vaginal route?
Steroids, prostaglandins
57
What are some common dosage forms for medications administered via the vaginal route?
Tablets, capsules, pessaries, solutions, foam, cream, ointments
58
Why is the transdermal route not discussed?
It does not have both local and systemic applications
59
What is pulmonary drug delivery used for?
Conditions like asthma, cystic fibrosis
60
What are advantages of pulmonary drug delivery?
Due to such rapid action, smaller doses can be taken Useful for poorly absorbed drugs like sodium cromoglycate Lungs have a large surface area which can be utilised It is another potential route for proteins and peptides It offers direct administration to the site of action (in the case of treating conditions like asthma and CF) Drugs have a rapid onset of action, and reduced side effects
61
What are disadvantages of using pulmonary drug delivery?
Use of drugs this way defeats bodys natural defence mechanisms, Patient needs to be educated and trained to use device Deposition of the drug into the lungs required a lot of efforts from engineers

Pharm202 (22 decks)

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