1. Routes of Drug Administration

2. The “Right” ways of administering drugs
Right patient
Right drug
Right dose
Right route
Right time
Right documentation

3. Significance of Drug Administration
Input of drug in the Human body.
Permits entry of the therapeutic agent either Directly or Indirectly into the Plasma.
A drug once taken in any form has to be then distributed, metabolized and finally eliminated from the body.

4. How do we choose the right route of administration
The route of administration is determined primarily by the properties of the drug (such as water or lipid solubility, ionization, etc.) and by the therapeutic objectives
(for example, the desirability of a rapid onset of action or the need for  long-term administration or restriction to a local site).
The route of administration (ROA) that is chosen may have a profound effect upon the speed and efficiency with which the drug acts.

5. Routes Otic Vaginal Intradermal Subcutaneous Intramuscular Intravenous
Enteral/paraentral
Oral
Buccal
Rectal
Sublingual
Topical
Transdermal
Inhalant
Ophthalmic
Intranasal
Otic
Vaginal
Intradermal
Subcutaneous
Intramuscular
Intravenous
Intraosseous
Intrathecal

6. Enteral routes Drug placed directly in the GI tract: Oral - swallowing
Sublingual- placed under the tongue
Buccal route
Rectum- absorption through the rectum (suppositories, anemas)
GI tubes (e.g. nasogastric, gastrotomy)

7. Oral Route

8. Oral Route
Giving a drug by mouth is the most common route of  administration but it is also the most variable , and requires the most complicated pathway to the tissues.
Little absorption occurs until the drug enters the small intestine.
Oral
Giving a drug by mouth is the most common route of  administration but it is also the most variable , and requires the most complicated pathway to the tissues.
Little absorption occurs until the drug enters the small intestine.
Drug absorption from the intestine:
The drug absorbed by passive transport mechanism in intestine at a rate determined by the ionization and lipid solubility of the drug molecules.
Strong bases of pKa 10 or higher are poorly absorbed, as are strong acids of pKa less than 3, because they are fully ionized

9. Drugs are absorbed by:
Passive Diffusion:
Determined by the lipophilcity of the drug compound
Ionized drugs are poorly absorbed (Strong bases of pKa 10 or higher are poorly absorbed, as are strong acids of pKa less than 3, because they are fully ionized)
Active Diffusion:
By carrier proteins
Example: ca+2 is carried by V.t-D dependent carrier system

10. Why most of the drugs are absorbed from the small intestine?
Small intestine has a much larger surface area for  absorption (~200 m2) as compared to the stomach (~1-3 m2).
Drug spends more time in the small intestine (~4 hrs) than the stomach (~0.5-1 hrs).
Can food in stomach decrease absorption of drugs?
Food may delays gastric emptying time so that drugs may destroyed by acid.
Interactions between drug and food particles.
Most of the drug is absorbed in the small intestine, Why?
Small intestine has a much larger surface area for  absorption (~200 m2) as compared to the stomach (~1-3 m2).
2. Drug spends more time in the small intestine (~4 hrs) than the stomach (~0.5-1 hrs).
Food in the stomach can decrease absorption
Food may delays gastric emptying time so that drugs may destroyed by acid.
Interactions between drug and food particles.
- Exception: propranolol- due to ↑ blood flow.

11. Factors affecting GI absorption
1- Altered gastric motility e.g. diarrhea 2- Splanchnic blood flow (it decreases in shock) 3- Particle size and formulation 4- Physiochemical Factors: i.e. ions that affect the absorption of some drugs. e.g. Tetracycline: it binds to ca and ca containing food

12. Advantages of Oral Route
Convenient
can be self-administered
pain free
Easy to take
It is safe
Absorption takes place along the whole length of the GI tract
Cheap compared to most other parenteral routes
There are a few instances where intestinal absorption depends oncarrier-mediated transport mechanism rather than simple lipid diffusion.
For example levodopa, iron, calcium.
Advantages:
Convenient
can be self-administered
pain free
Easy to take
It is safe
Absorption
takes place along the whole length of the GI tract
Cheap
compared to most other parenteral routes

13. Disadvantages:
Some drugs have an Unpleasant taste
Irritation to gastric mucosa can cause nausea and vomiting
Destruction of drugs by gastric acid and digestive juices
Absorption is sometimes inefficient, only part of the drug may be absorbed
Effect too slow for emergencies
Unable to use in unconscious patient or who have had GI surgery
First-pass effect

14. Portal Circulation
Systemic Circulation

15. First Pass Effect
When a drug is absorbed across the GI tract, it enters the portal circulation before entering the systemic circulation.
A drug can be metabolized in the gut wall or even in the portal blood, but most commonly it is the liver that is responsible for metabolism before the drug reaches the systemic circulation (plasma). In addition, the liver can excrete the drug into the bile.
Any of these sites can contribute to this reduction in bioavailability , and the overall process is known as first-pass effect or first-pass elimination.
First-pass effect
When a drug is absorbed across the GI tract, it enters the portal circulation before entering the systemic circulation.
A drug can be metabolized in the gut wall or even in the portal blood, but most commonly it is the liver that is responsible for metabolism before the drug reaches the systemic circulation (plasma). In addition, the liver can excrete the drug into the bile (fluid secreted by liver).
Any of these sites can contribute to this reduction in bioavailability , and the overall process is known as first-pass effect or first-pass elimination.

16. The greater the first-pass effect, the less the agent will reach the systemic circulation when the agent is administered orally.
Lidocaine (anesthetic agent) is a drug with a first-pass effect that is so great that oral administration is not practical.
Propranolol: significant portion of the orally administered dose is metabolized through a first-pass effect.
Nitroglycerin: More than 90% of nitroglycerin is cleared during a single passage through the liver.
Therefore, a much larger oral dose is required to achieve the same therapeutic response as that obtained from a dose administered intravenously.

17. The oral route should generally be used when possible, considering the patient’s condition and ability to take or tolerate oral drugs

18. Sublingual Route Sublingual/Buccal
Placement under the tongue allows the drug to diffuse into the capillary network and therefore to enter the systemic circulation directly.
When only small amounts of drugs are required to gain access to the blood, the sublingual route may be very satisfactory.
For example, nitroglycerin in angina pectoris.
Because the stomach is bypassed, acid-liability and gut-permeability is not important.
Drugs are absorbed from the mouth straight into the systemic circulation without entering the portal system and so escape first-pass metabolism by the liver.

19. Buccal Route
The drug is placed in between gum and inner lining of the check
Delivery of insulin to the buccal mucosa utilizing the RapidMist ™ system

20. Sublingual and Buccal Routes
Advantages
Rapid absorption
Drug stability
Avoid first-pass effect
Glyceryl trinitrate
Disadvantages
Inconvenient
Small doses
Unpleasant taste of some drugs
Advantages
-rapid absorption
-drug stability
-avoid first-pass effect
Disadvantages
-inconvenient
-small doses
-unpleasant taste of some drugs

21. Rectal route
50% of the drainage of the rectal region bypasses the portal circulation; thus the biotransformation of drugs by the liver is minimized.

22. Advantages of Rectal Route
Devoid of destruction of the drug by intestinal enzymes or by low pH in the stomach
Unconscious patients (postoperative)
Children
If patient is nauseous or vomiting
Good for drugs affecting the bowel such as laxatives
Irritating drugs contraindicated
Can be used for both local effects and systemic effects
Absorption may vary
Venous Drainage of the Rectum and Anal Canal—There are two main routes of venous drainage in this area. The superior rectal vein drains into the inferior mesenteric vein. The IMV joins the splenic vein which drains into the hepatic portal vein. The middle and inferior rectal veins drain into the inferior iliac vein. This drains into the common iliac vein and from there into the IVC. There are anastamoses that form between the internal and external plexus of these veins. The internal plexuses are found in the anal columns and the external plexues are located just beneath the skin. (Netter 379, 302, 248, 241).
Devoid of destruction of the drug by intestinal
enzymes or by low pH in the stomach
- Unconscious patients (postoperative) and children
- If patient is nauseous or vomiting
- Absorption may vary
- Good for drugs affecting the bowel such as laxatives
- Irritating drugs contraindicated
- Can be used for both local effects and systemic
effects

23. GI Tubes (e.g. nasogastric, gastrostomy)

24. Liquid preparations are preferred over crushed tablets and emptied capsules, when available
Tube should be rinsed before and after instilling medication

25. GI tubes Disadvantages Advantages
Allows use of GI tract in patients who cannot take oral drugs
Can be used over long periods of time, if necessary
May avoid or decrease injections
Disadvantages
With nasogastric tubes, medications may be aspirated into the lungs
Small bore tubes often become clogged
Requires special precautions to give correctly and avoid complications

26. Parenteral Routes

27. Parenteral administration is used for drugs that are poorly absorbed from the gastrointestinal tract, and for agents such as insulin that are unstable in the GI tract
Parenteral administration is also used for treatment of  unconscious patients and under circumstances that require a rapid onset of action

28. Intravascular: Intravenous, Intra-arterial
Intraosseous (infusion - bone marrow drains directly into the venous system.)
Intramuscular
Subcutaneous
Intracerebral (into the brain parenchyma)
Intra-cerebro-ventricular (in the cerebral ventricular system)
Intracthecal (an injection into the spinal canal) e.g. anesthesia, methotrexate

29. Intrathecal injection (subaracnoid space)

30. Synovial cavity (containing synovial fluid)
Intra-articular
Femur
(hip bone)
Joint capsule
Synovium
Corticosteroids are injected into the joint cavity to relieve pain and inflammation
Pelvic bone
Synovial cavity (containing synovial fluid)

31. INTRAOSSEOUS
Tibia

32. Intraosseous infusion is used commonly when there is failure to locate a suitable veinous site, particularly in babies. This procedure is generally performed in the Emergency Department or the Intensive Care Unit by a qualified practitioner.

33. Useful in emergencies and in patients that are unconscious
Intravenous (IV)
Injection is the most common parenteral route. For drugs that are not absorbed orally, there is often no other choice.
Benefits
Rapid onset of action because the drug is injected directly into the bloodstream
Useful in emergencies and in patients that are unconscious
The drug avoids the GI tract and first-pass metabolism by the liver 
Smaller doses generally are required than the other routes but cost is high
Intravenous (IV) injection is the most common parenteral route. For drugs that are not absorbed orally, there is often no other choice.
Rapid onset of action because the drug is injected directly into the bloodstream
Useful in emergencies and in patients that are unconscious
The drug avoids the GI tract and first-pass metabolism by the liver 
Smaller doses generally are required than the other routes but cost is high

34. Disadvantages of Intravenous Route
Greater risk of adverse effects as:
High concentration attained rapidly
The amount injected cannot be recalled by strategies such as emesis or binding to activated charcoal
Risk of embolism (obstruction of blood vessel)
May introduce bacteria through contamination
Pain at application site
No self administration facility

35. Advantages Disadvantages Extremely rapid action Most dangerous route
Bypasses barriers to absorption
Drug levels are more accurately controlled
Good for administering irritant drugs
Suitable for large volumes
Can be administered to conscious / unconscious patients
Disadvantages
Most dangerous route
Phlebitis commonly occurs and increases risk of thrombosis.
Phlebitis / thrombosis may take many days to subside
Must be performed slowly
Once injected, drug cannot be removed
It may be difficult to find a suitable vein.
Requires trained personnel .
Expensive - Sterility, pyrogen testing and larger volume of solvent means greater cost for preparation, transport and storage

36. Intra-arterial
Similar properties, advantages and disadvantages of intravenous route.
Intra-artery route is specially used when high drug concentration in specific tissue is required: Diagnostic purpose and for chemotherapy

37. Intramuscular Injection

38. Intramuscular
Drugs administered intramuscularly can be aqueous solutions or specialized depot preparations
It is often a suspension of drug in a non-aqueous vehicle, such as ethylene glycol or peanut oil.
Absorption of drugs in aqueous solution is fast,
whereas that from depot preparations is slow. Drug
passes through
capillary walls
to enter the blood
stream. -
Pain at injection sites for certain drugs
- This parenteral route may be used when an
immediate effect is not required but a prompt effect is
Desirable
Absorption from an intramuscular depot is more
predictable and uniform than from a subcutaneous site

40. Intramuscular Administration
Dorsal Gluteal
Locate the posterior iliac spine.
Locate the greater trochanter.
Draw an imaginary line between these two landmarks. Injection site is above and lateral to the line.
Most dangerous site because of sciatic nerve location

41. Intramuscular Administration
Ventral Gluteal
Palm of hand on greater trochanter of femur.
Index finger on anterior superior iliac spine (hip bone).
Middle finger extended.
Injection site lies within the triangle formed by the index and middle fingers

42. Subcutaneous
Drug is injected beneath the skin and permeates capillary walls to enter blood stream.
Absorption from the site of injection is dependent on local blood flow
Concurrent administration of vasoconstrictor will slow absorption. Epinephrine acts as a local vasoconstrictor and decreases removal of a drug, such as lidocaine (local anesthetic), from the site of administration.
Examples of drugs given by this route are Insulin and sodium heparin, neither of which is absorbed orally, and both of which should be absorbed slowly over many hours.
subcutaneous
Drug is injected beneath the skin and permeates
capillary walls to enter blood stream.
Absorption from the site of injection is dependent on
local blood flow
. Concurrent administration of 
vasoconstrictor will slow absorption.
For example, minute amount of 
epinephrine is
sometime used in combination with a drug to restrict
its area of action. Epinephrine acts as a
local
vasoconstrictor 
and decreases removal of a drug,
such as lidocaine (local anesthetic), from the site of 
administration.
Examples of drugs given by this route are
insulin
and
sodium heparin
, neither of which is absorbed orally,
and both of which should be absorbed slowly over 
many hours.

44. Subcutaneous Administration
Why does he have a circle around his umbilicus?
Which side absorbs the quickest? What is the preferred site?
Adapted from Smith, S.F., Duell, D.J., Martin, B.C. (2004) Clinical Nursing Skills Basic to Advanced, 6th Ed. Pg New Jersey: Prentice Hall

45. INTRADERMAL SITES Intradermal injection:
Inject directly below the surface of the skin. The injection should produce a wheal or fluid-filled bump that can be seen beneath the skin at the injection site. Skin on the back of the forearm is the usual site for these injections. The area should be marked or mapped for reading tests in h.

46. Inhalational
Inhalation provides the rapid delivery of a drug across the large surface area of the mucous membranes of the respiratory tract and pulmonary epithelium, producing an effect almost as rapidly as by intravenous injection.
This route of administration is used for drugs that are gases and volatile agents (for example, some anesthetics), or those that can be dispersed in an aerosol.
The route is particularly effective and convenient for  patients with respiratory complaints (for example, asthma or chronic obstructive pulmonary disease) as drug is delivered directly to the site of action and systemic side effects are minimized.
Inhalation
Inhalation provides the rapid delivery of a drug across
the large surface area of the mucous membranes of 
the respiratory tract and pulmonary epithelium,
producing an effect almost as rapidly as by
intravenous injection.
This route of administration is used for drugs that are
gases and volatile agents
(for example, some
anesthetics), or those that can be
dispersed in an
aerosol .
The route is particularly effective and convenient for 
patients with respiratory complaints (for example,
asthma or chronic obstructive pulmonary disease) as
drug is delivered directly to the site of action and
systemic side effects are minimized.

47. Topical
Topical application is used when a local effect of the drug is desired.
Used for most dermatologic and ophthalmologic preparations.
Clotrimazole is applied as a cream to the skin in the treatment of dermatophytosis.
Atropine is instilled directly into the eye to dilate the pupil and permit measurement of refractive errors.
Topical
Topical application is used when a local effect of the
drug is desired.
Used for most
dermatologic
and
ophthalmologic
preparations.
Clotrimazole
is applied as a cream to the skin in the
treatment of dermatophytosis.
Atropine
is instilled directly into the eye to dilate the
pupil and permit measurement of refractive errors.

48. Transdermal
This route of administration achieves systemic effects by application of drugs to the skin, usually via a transdermal patch.
The rate of absorption can vary markedly depending upon the physical characteristics of the skin at the site of application.
Small lipid soluble molecule.
This route is most often used for the sustained delivery of drugs, such as the antianginal drug, nitroglycerin.
Transdermal
This route of administration achieves systemic effects
by application of drugs to the skin, usually via a
transdermal patch .
The rate of absorption can vary markedly depending
upon the
physical characteristics of the skin
at the site
of application.
Small lipid soluble molecule
This route is most often used for the sustained delivery
of drugs, such as the antianginal drug, nitroglycerin.

49. Route for administration
-Time until effect-
intravenous seconds
intraosseous seconds
endotracheal 2-3 minutes
inhalation 2-3 minutes
sublingual 3-5 minutes
intramuscular minutes
subcutaneous minutes
rectal 5-30 minutes
ingestion minutes
transdermal (topical) variable (mins to hrs)