1.4 Pharmacokinetics Flashcards
Pharmacokinetics
Movement of a drug into, through and out of the body
Four major processes involved
One absorption
Two distribution
Lthree metabolism
four excretion
Routes of administration
- Before drug can be absorbed it must be administered
- topical administration
- Enteral administration
- parenteral administration
Topical Administration - ON THE SKIN
-Large number of drugs can be applied to the skin to treat mild to moderate severity skin condition such as eczema acne and infections
Topical Administration- THROUGH THE SKIN
-Transdermal drug delivery is the application of a drug to the skin for absorption into the general circulation for a systemic affect this method is
-convenient
End it delivers a study drug supply for several days eliminating frequent oral dosing
-Bypasses the enzymes of the stomach intestines and liver
-Disadvantages it’s expensive and can cause local irritation
Topical Administration- INHALATION
- Drugs are rapidly absorbed from the lungs and a number of both prescription and recreational drugs are administered this way
- Drugs are administered through the lungs for both local and systemic affects
- Gaseous anaesthetics administered by inhalation for a systemic affect
- Steroids and other drugs for lung disease is administered for local effect in the lungs
- Advantages the quantity of the drugs are small does avoiding the toxicity associated with oral ministration of the drug
- disadvantage is that the method requires proper use by the patient
Enteral Administration
-Enter the blood through the gastrointestinal tract
Enteral administration – mouth
- The mouth is commonly used to administer drugs for a number of reasons
- Most convenient and least expensive
- Noninvasive and can be self administered
- More than 90% of all drugs are taking this way
- Slow 30-min to > 1 hour
- 5%-10% bioavailability
Enteral administration – rectum
- Can be for systemic or local effect
- can be used in patients who were nauseated or vomiting, or as a less invasive route for those who are comatose
- Digestive enzymes of the stomach and intestine are bypassed
- Disadvantages not all drugs are available as suppositories and absorption from the rectal mucosa is slow, incomplete, and variable, depending on the time the suppository is retained
- slow and incomplete
- 30-100% bioavailability
Enteral administration – sublingual and Buccal
- Sublingual is under the tongue and buccal refers to in the cheek
- Enzymes of the stomach, intestines and liver are bypassed by this route
- Disadvantages not all drugs are adequately absorbed by this route and drugs may be swallowed and then the drug behaves as if it was taken orally
- under the tongue, rapid 1-2 min, 30-100% bioavailability
- in the cheek, intermediate 3-4min, 30-100% bioavailability
Parenteral administration
Injected into the body and enter the bloodstream
Parental Administration- Intravenous
- The drug is placed directly into the blood
- Can be used for drugs that are poorly absorbed providing that they can be made into a solution in water for injection
- Disadvantages response is immediate, intense an irreversible (highest risk for drug reactions)
- costly
- Preparation must be sterile and free of fever producing substances (pyrogens)
Parenteral administration-intramuscular
- The drug is injected deep into a muscle
- Volume of drug is limited to 5 to 10 mL in an adult
Parental administration-subcutaneous
- The drug is injected into the deepest layer of the skin
- Drug preparations can be modified to control the timing of the release of the drug from SC injection sites
Absorption
-Movement of a drug from the site of administration into the blood
Endfor a drug to be absorbed and distributed to the sites of action, storage and excretion, it must be able to cross biological membranes
Transfer across membranes- DIFFUSION THROUGH AQUEOUS PORES
- Drugs with small molecular weights of 150 or less that are water soluable can move across membranes by first resolving in the aqueous fluids surrounding cells and then by passing through the small openings between cells
- drugs flow down these water passages from an area of higher concentration to an area of lower concentration
Transfer across membranes- DIFFUSION THROUGH LIPIDS
- biological membranes are composed of a lipid bilayer structure which consists of proteins interspersed throughout a double layer of lipid the fast majority of drugs have molecular weights greater than 150 and do not pass through aqueous pores but rather pass through the membrane by dissolving in the lipid portion of the membrane these drugs still flow down a concentration gradient to the other side of the cell membrane the ability of a drug to cross a membrane and be absorbed depends on its lipid solubility diffusion through lipid is the most important process that drugs use to cross membranes
transport across membranes - Active Transport
-a number of drugs bind to proteins termed carried proteins or transporters which carry molecules across a membrane once bound the drug carrier complex moves across the membrane and releases the drug on the other side of the membrane transporter mediated drug transfers can move down a concentration gradient but can also be an active process requiring energy and can move a drug against a concentration gradient these carrier proteins for drugs and their matobilites play an important role in removal of metabolites from the liver and kidney
Distribution/redistribution
-The movement of a drug from the blood to the site of action and other tissues
Most drugs reach all tissues and organs regardless of the target site of action
-Concentrations of drug at the sites of distribution equilibrium with its concentration in the blood
-If the concentration in the blood drops below the concentration of any of the distribution sites the drug will move from that site to the blood to maintain the equilibrium
-The greater the blood flow to an organ in the more rapidly drugs reach that organ and vice versa
Metabolism
- Conversion of a drug to a different chemical compound
- Products are called metabolites, and they are usually, but not always, devoid of pharmacological action
- To be eliminated from the body by the kidneys a drug must be water soluble
- Without metabolism some chemicals that are very lipid soluble will never be excreted from the body
- The liver is the organ where most metabolism reactions occur but some metabolism also occurs in the kidneys, intestine, lungs, skin, and most other organs
- Divided into phase 1 and phase 2 reactions
Phase 1 bio transformation reactions
-Purpose is to add or unmask a functional group on the drug so that the phase 2 reactions can add a large water soluble molecule, usually glucuronic acid or sulfate, making the product more water soluble for excretion by the kidney
P450
- Enzymes capable of bio transforming drugs are found in most tissues, but are present in high concentrations in the liver
- The liver is the organ that is responsible for the majority of drug biotransformation
- The cytochrome P450 family of enzymes by transforms the vast majority of clinically used drugs
Phase 2 bio transformation reactions
-Add a large water soluble part or functional group or a molecule (moiety) To the product resulting from phase 1, making him a tablet water soluble for excretion by the kidney
Excretion
-Moving the dragon it’s metabolites out of the body
