Pharmacokinetics is the study of the behaviour and time course of the following features of a drug:
· Administration · When the drug is given
· Absorption· When the drug is taken up by the body
· Distribution. When the drug spreads through the body
· Elimination· When the drug is removed from the body
DRUG ADMINISTRATION
· When drugs are administered, they can have either local or systemic effects.
· A local effect is one which acts near the site of administration
· A systemic effect occurs when the drug gets into the systemic circulation and is distributed throughout the
whole body.
Local administration
· The main advantage of a local administration is that it minimises the systemic side effects. Because the drug does not enter the systemic circulation, the drug only acts where we want it to act, and not at any other, less desirable places.
· Examples of some common sites of local administration are:
· Skin: Rubbing ointments, corticosteroids to decrease inflammation, antihistamines to prevent an allergic
reaction
· Nose: Decongestants
· Vagina: Antifungals
· Rectum: Vasoconstrictors to treat hemorrhoids
· Lung: Bronchodilators (salbutamol, a beta agonist). If this drug enters the systemic circulation (which
sometimes happens), then it can have side effects on the heart.
· Eye: Atropine/homatropine which causes dilation of the pupil during eye inspections and surgery.
Systemic administration
· Systemic administration is used if we want a drug to act on hard to reach places such as the heart or brain. We
cannot administer a drug locally (which would be good) because it would be too traumatic (e.g. sticking a needle
into your heart or chest).
· Sites of systemic administration are:
· Skin
· e.g. Glycerol trinitrate which is applied via a patch on the skin, allows the drug to diffuse through the
skin.
· An advantage of this sort of administration is that it avoids the first pass effect by not having to pass
through the gut (explained later).
· Nose
· Also bypasses the gut because the veins in the nasal mucosa drain into the vena cava. e.g. cocaine
· Vagina/rectum
· The blood vessels in the mucosal lining drain into the systemic circulation, thus bypassing the gut.
· Lung
· Ideal for gaseous. The large surface area and high vascularity of the drugs makes it ideal for
absorption of drugs. e.g. general anaesthetics - halothane
· Orally
· Parenterally
· Note that these sites are identical to the ones used in local administration (except the last two). It is the
physicochemical properties of the drug which determine whether it will stay at that site and act locally or be
absorbed and act systemically.
Oral administration
· The most common route of systemic administration
· Most of the absorption of drugs occurs in the small intestine because it is specialised for absorption (large surface area due to villi and microvilli)
· If a drug is to be absorbed effectively, it has to be in solution (hence water soluble), but must also be able
to pass through cell membranes (lipid soluble as well).
· Drugs which are given in solid form (e.g. tablets) have their rate limiting step as the disintegration
and dissolution of the drug.
· e.g. Digitoxin is poorly soluble. The particle size used in the manufacture of the tablet needs to be
very tightly controlled because it has a very small therapeutic window.
· A therapeutic window is when the dose required to have a therapeutic effect is very
close to the dose required to have a toxic effect. You thus have a very small margin for
error.
· If the tablet is made up of small particle sizes it will dissolve easily and therefore get a
high dose. If the particle size is large, dissolution will be less and so result in a smaller
dose.
· A disadvantage of oral administration is that all blood from the gut must pass via the portal vein through the liver
first. The liver metabolises many drugs and so they are inactivated before entering the systemic circulation. This is
the first pass effect.
· There are some drugs/chemicals which are not toxic to the body, but when metabolised by the liver,
become toxic - e.g. carbon tetrachloride.
· Orally administered drugs cannot be proteins because the digestive enzymes of the gut break the protein into
useless amino acids. e.g. insulin cannot be given orally. The drug must also be able to withstand the acidic
conditions of the stomach.
· A special type of oral administration is sublingually. This is where the drug is placed under the tongue where the veins enter the systemic circulation.
Parenteral administration (via injection):
· The other common alternative to systemic administration
· There are 3 types of parenteral administration:
· Subcutaneous
· Good for non irritant drugs. Advantage being that injection is not too deep and painful.
Disadvantage is that only a small volume can be injected (max 2mL).
· Intramuscular
· Antibiotics are usually given this way (e.g. penicillin), often into the bum (gluteus maximus).
Larger volumes can be administered and the drug can be released slowly into the circulation,
while some of it being stored in the muscle (acting as a reservoir).
· Intravenous
· Though invasive and uncomfortable, this method provides accurate, reliable dosage of a drug
directly into the circulation. It means that the bioavailablity of the drug is 100%. More on
bioavailability later.
· There is a very rapid response because no absorption is required. The drug must be soluble.
· Injection into a vein can be a bolus (all at one go) dose or infused (slowly administered over a period of time).
Other, more exotic forms of administration
· For example, how do we get protein drugs into the CNS.
· Because of the blood brain barrier, only lipid soluble drugs are able to pass through the barrier and exert their
effects on the brain. Various solutions have been proposed:
· Pumps
· Implanted cells which produce the protein and release it into the surroundings
· Viruses, which work on the same principle, i.e. making a protein and releasing it
· Polymer Encapsulated Genetically Modified Cells
Polymer Encapsulated Genetically Modified Cells
· This (new and experimental) method has been tried to administer neurotrophic factors into the CSF which
prevents cell death.1997 Pharmacology Semester 1 page 3 of 3 By Duy Thai: www.geocities.com/d.thai
· A polymer capsule is filled with genetically modified cells. This capsule allows nutrients from the CSF to
pass into the cell, thus sustaining the cells inside, and also allows the neurotrophic factors produced by the
cells out into the surroundings.
· The capsule is implanted into the intrathecal space (in the spinal canal) and has the advantage of being able
to provide continuous administration of the drug. Another benefit is that the polymer capsule prevents an
immune response against the foreign cells, thus reducing the side effects (no allergic reaction for instance).
Abbreviations: IM, intramuscular; SQ, subcutaneous; GI, gastrointestinal.
· Administration · When the drug is given
· Absorption· When the drug is taken up by the body
· Distribution. When the drug spreads through the body
· Elimination· When the drug is removed from the body
DRUG ADMINISTRATION
· When drugs are administered, they can have either local or systemic effects.
· A local effect is one which acts near the site of administration
· A systemic effect occurs when the drug gets into the systemic circulation and is distributed throughout the
whole body.
Local administration
· The main advantage of a local administration is that it minimises the systemic side effects. Because the drug does not enter the systemic circulation, the drug only acts where we want it to act, and not at any other, less desirable places.
· Examples of some common sites of local administration are:
· Skin: Rubbing ointments, corticosteroids to decrease inflammation, antihistamines to prevent an allergic
reaction
· Nose: Decongestants
· Vagina: Antifungals
· Rectum: Vasoconstrictors to treat hemorrhoids
· Lung: Bronchodilators (salbutamol, a beta agonist). If this drug enters the systemic circulation (which
sometimes happens), then it can have side effects on the heart.
· Eye: Atropine/homatropine which causes dilation of the pupil during eye inspections and surgery.
Systemic administration
· Systemic administration is used if we want a drug to act on hard to reach places such as the heart or brain. We
cannot administer a drug locally (which would be good) because it would be too traumatic (e.g. sticking a needle
into your heart or chest).
· Sites of systemic administration are:
· Skin
· e.g. Glycerol trinitrate which is applied via a patch on the skin, allows the drug to diffuse through the
skin.
· An advantage of this sort of administration is that it avoids the first pass effect by not having to pass
through the gut (explained later).
· Nose
· Also bypasses the gut because the veins in the nasal mucosa drain into the vena cava. e.g. cocaine
· Vagina/rectum
· The blood vessels in the mucosal lining drain into the systemic circulation, thus bypassing the gut.
· Lung
· Ideal for gaseous. The large surface area and high vascularity of the drugs makes it ideal for
absorption of drugs. e.g. general anaesthetics - halothane
· Orally
· Parenterally
· Note that these sites are identical to the ones used in local administration (except the last two). It is the
physicochemical properties of the drug which determine whether it will stay at that site and act locally or be
absorbed and act systemically.
Oral administration
· The most common route of systemic administration
· Most of the absorption of drugs occurs in the small intestine because it is specialised for absorption (large surface area due to villi and microvilli)
· If a drug is to be absorbed effectively, it has to be in solution (hence water soluble), but must also be able
to pass through cell membranes (lipid soluble as well).
· Drugs which are given in solid form (e.g. tablets) have their rate limiting step as the disintegration
and dissolution of the drug.
· e.g. Digitoxin is poorly soluble. The particle size used in the manufacture of the tablet needs to be
very tightly controlled because it has a very small therapeutic window.
· A therapeutic window is when the dose required to have a therapeutic effect is very
close to the dose required to have a toxic effect. You thus have a very small margin for
error.
· If the tablet is made up of small particle sizes it will dissolve easily and therefore get a
high dose. If the particle size is large, dissolution will be less and so result in a smaller
dose.
· A disadvantage of oral administration is that all blood from the gut must pass via the portal vein through the liver
first. The liver metabolises many drugs and so they are inactivated before entering the systemic circulation. This is
the first pass effect.
· There are some drugs/chemicals which are not toxic to the body, but when metabolised by the liver,
become toxic - e.g. carbon tetrachloride.
· Orally administered drugs cannot be proteins because the digestive enzymes of the gut break the protein into
useless amino acids. e.g. insulin cannot be given orally. The drug must also be able to withstand the acidic
conditions of the stomach.
· A special type of oral administration is sublingually. This is where the drug is placed under the tongue where the veins enter the systemic circulation.
Parenteral administration (via injection):
· The other common alternative to systemic administration
· There are 3 types of parenteral administration:
· Subcutaneous
· Good for non irritant drugs. Advantage being that injection is not too deep and painful.
Disadvantage is that only a small volume can be injected (max 2mL).
· Intramuscular
· Antibiotics are usually given this way (e.g. penicillin), often into the bum (gluteus maximus).
Larger volumes can be administered and the drug can be released slowly into the circulation,
while some of it being stored in the muscle (acting as a reservoir).
· Intravenous
· Though invasive and uncomfortable, this method provides accurate, reliable dosage of a drug
directly into the circulation. It means that the bioavailablity of the drug is 100%. More on
bioavailability later.
· There is a very rapid response because no absorption is required. The drug must be soluble.
· Injection into a vein can be a bolus (all at one go) dose or infused (slowly administered over a period of time).
Other, more exotic forms of administration
· For example, how do we get protein drugs into the CNS.
· Because of the blood brain barrier, only lipid soluble drugs are able to pass through the barrier and exert their
effects on the brain. Various solutions have been proposed:
· Pumps
· Implanted cells which produce the protein and release it into the surroundings
· Viruses, which work on the same principle, i.e. making a protein and releasing it
· Polymer Encapsulated Genetically Modified Cells
Polymer Encapsulated Genetically Modified Cells
· This (new and experimental) method has been tried to administer neurotrophic factors into the CSF which
prevents cell death.1997 Pharmacology Semester 1 page 3 of 3 By Duy Thai: www.geocities.com/d.thai
· A polymer capsule is filled with genetically modified cells. This capsule allows nutrients from the CSF to
pass into the cell, thus sustaining the cells inside, and also allows the neurotrophic factors produced by the
cells out into the surroundings.
· The capsule is implanted into the intrathecal space (in the spinal canal) and has the advantage of being able
to provide continuous administration of the drug. Another benefit is that the polymer capsule prevents an
immune response against the foreign cells, thus reducing the side effects (no allergic reaction for instance).
Route | Bioavailability | Advantages | Disadvantages |
Parenteral IV bolus IV infusio IM SQ | Systemic absorption(100%) Systemic absorption (100%);rate of absorption controlled Variable absorption (<100%) Variable absorption (<100%) | Immediate effect Drug levels more precisely controlled; tissue damage at injection site Simpler therapy than IV infusion Self-administration | Increased risk of adverse effect Difficulty in administration;infection risk Irritating or painful Irritating or painful |
Enteral Buccal Oral Rectal | Rapid absorption of lipid-soluble drugs Absorption variable; slower rate of absorption than IV or IM Variable absorption; more reliable absorption with enema | No first-pass effect; useful if patient cannot swallow Safest and easiest route; may use immediate and slow-release drugs Useful when patient cannot swallow; local and systemic effects achieved | Drug may be swallowed Possible erratic absorption; first- pass (liver or GI) Erratic absorption; suppository migration and discomfort |
Transdermal | Slow absorption; variabl rate of absorption | Simple to use; useful for patients who cannot swallow | Irritation possible; permeability of skin variable |
inhalation | Rapid absorption(<100%) | Useful for local or systemic effects | Particle size determines lung distribution |
Abbreviations: IM, intramuscular; SQ, subcutaneous; GI, gastrointestinal.
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