First pass metabolism
the movement of a drug molecule from the site of administration into the liver before going into the bloodstream
-typically with oral administration
-liver contains enzymes that can break down the drug
Bioavailability
fraction of administered drug, that reaches the bloodstream unchanged
- formula: fraction of drug in the bloodstream divided by what you initially started out with
Example of how to determine bioavailability: 100 mg of the drug is administered, 70 mg enters the bloodstream
70 mg/100 mg= 0.7 mg
List common dosage forms of drugs
solids, semi-solids, liquids, and gases
solids
tablets, capsules, lozenges (cough drops)
semi-solids
creams, gels, ointment, & lotions
liquids
syrups, solutions, suspensions, & emulsions
gases
nebulizer (inhaler) & general anesthesia
Systemic drug delivery
directly brings the drug into the system, bloodstream, and effects are seen throughout the entire body
Examples of systemic drug delievery
oral, sublingual, transdermal, intranasal, inhalation, rectal, parenteral (intravenous, intramuscular, subcutaneous)
Local drug delivery
drug is restricted to one part of the body
Examples of local drug delivery
topical, ophthalmic, otic, intranasal, inhalation, intrathecal
Oral route
put pill in mouth, ingested in GI track and gets into the body
Oral Route:
1. Is it common/convenient?
2. Painful to administer?
3. Chance of infection (safety)?
1. yes
2. no
3. no chance of infection, safe route
Oral Route:
1. Is it expensive?
2. Does it require help to administer?
3. Once administered, can it be recalled?
1. no
2. no
3. yes, it can be recalled
How do you recall orally administered drugs?
- vomit
- activated charcoal (powder) --> poop it out
NOTE: timing is important, need to get drug out of the body before it enters the bloodstream
Oral Route:
1. How big is the surface area available for absorption?
2. Presence of food/bacteria in stomach?
3. Is patient compliance important?
1. pretty big/high; due to microvilli on the GI track
2. both; with food to prevent irritation and without for absorption
3. yes
Oral Route:
1. Does it use first pass metabolism?
2. Gastric and intestinal pH?
1. yes; bioavailability will decrease and drug will lose concentration
2. yes, gastric and intestinal pH play a role in how well the drug is absorbed
Problem with gastric and intestinal pH with orally administered drugs
- the stomach is acidic and the intestines are basic
- some drugs are better absorbed in basic pH vs acidic pH
- basic drugs have to pass through the stomach which is acidic in order to get to the small intestine
Enteric coated tablets
chemically coated tablets that allow the drug to not be destroyed in the gastric pH
EX: Aspirin
Extended- release tablets
the drug that's in the tablet will not be immediately released, instead it will be released slowly
- increase patient compliance since patients take less pills
EX: Tylenol 8 hr
Conventional tablet vs extended
Plasma level of a drug from a conventional tablet containing 50 mg of drug given at 0, 4, and 8 hours (A) compared to a single 150-mg drug dose given in an extended-release dosage form (B).
Sublingual route:
Drug placed under the tongue, enters the systemic circulation directly.
Buccal route:
Drug placed in the buccal pouch, enters the systemic circulation directly.
Sublingual route & Buccal route:
1. Speed of absorption?
2. First-pass metabolism?
3. Gastric and intestinal pH?
1. fast; directly going through mucosa to bloodstream
2. not first-pass metabolism; directly enters the blood stream
3. no gastric and intestinal pH
Sublingual route & Buccal route:
1. Used for small- or large-sized drug particles?
2. What about the drug portion which is swallowed instead?
1. small sized particles
2. the drug will go to the stomach and then the liver for the first-pass metabolism; therefore, the drug won't have the same effect/ the amount of drug in the bloodstream will go down
Transdermal route:
Application of drug to skin, via a transdermal patch
(ideal for lipophilic drugs requiring prolonged administration).
EX: nicotine & hormonal (testosterone and estrogen)
Intranasal inhalation and Oral inhalation routes:
Rapid drug delivery through the respiratory and
pulmonary epithelium
Intranasal inhalation and Oral inhalation routes:
1. Surface area available for absorption?
2. Onset of action similar to?
3. First pass metabolism
1. large surface area for absorption
2. fast, IV
3. no
Intranasal inhalation and Oral inhalation routes:
1. Common in patients with which type of disorders?
2. Ideal for which type of drugs? Solid/liquid/gas?
1. pulmonary issues such as asthma
2. gas is the most ideal for this type of administration
Why is Intranasal inhalation and Oral inhalation routes common route for substance abuse?
inhalation is commonly used because onset of action is very quick, immediate effect ("high") of drug
Rectal route is used for
laxatives & ulcerative colitis
Rectal route:
1. Surface area available for absorption?
2. First-pass metabolism
3. Use in unconscious patients
1. high surface area
2. 50% chance
3. yes
Rectal route:
1. Ideal for which type of drugs?
2. Example: Suppositories -
1. drug types that induce vomiting
2. Suppositories- can be inserted into the rectum or vagina to get effect in lower part of the body
Types of Parenteral administration
intramuscular, subcutaneous, intravenous, and intradermal
Intravenous route:
injected into a vein (most common)
Intravenous route:
1. Onset of action?
2. Use in unconscious/uncooperative/vomiting patients?
3. First-pass metabolism?
1. one of the quickest onset
2. yes
3. no
Intravenous route:
1. Bioavailability?
2. Is it painful?
3. Chances of infection?
1. 100%
2. yes
3. yes
Intravenous route:
1. Can it be self-administered?
2. Onset of adverse effects
3. Can the administered drug be recalled?
1. no
2. fast (disadvantage)
3. no
Subcutaneous route:
Injected directly below the skin under the epidermis and dermis layers (fat tissue)
Subcutaneous route:
1. Onset of action?
2. Example
3. Can it be self-administered?
4. safe?
1. provides extended slow release by simple drug diffusion
2. insulin pumps
3. yes
4. concern for infection (less safe)
Intramuscular route:
injected into a muscle
Intramuscular route:
1. immediate (aqueous) and depot (non-aqueous) preparations available
2. painful
3. can it be self-administered?
1. aqueous = waters soluble --> immediately into bloodstream
non-aqueous = oil soluble --> slow release into bloodstream
2. most painful; perpendicular
3. no
Intradermal route:
Injected into the outer epidermis
-used commonly for allergy tests and local anesthesia
Intradermal route:
1. onset of action?
1. quick
Local routes of absorption:
stays at the site, doesn't go throughout the body
Topical route:
on the surface of the skin
Ophthalmic route:
in the eye
Otic route:
in the ear
Intranasal route:
in the nose
Intraventricular route:
Drug administration directly into the cerebrospinal fluid (brain)
-bypasses the BBB
Intrathecal route:
Drug administration directly into the cerebrospinal fluid (spinal cord)
-bypasses the BBB