Pharm Ch. 2 and 3: Pharmacokinetics I and II Flashcards
Administration, Absorption, Distribution, and Elimination
Alimentary Canal
Enteral administration
Non-alimentary routes
Parenteral administration
Oral
-High degree of lipid solubility to pass through GI mucosa
-Drugs enter system in controlled manner
-Final amount and rate are less predictable
First Pass
Drug is transported directly to liver via portal vein and may be metabolized before it can be used/effective
Sublingual and Buccal
Drugs can reach systemic circulation without being subjected to first pass. Faster than swallowing drug
Rectal
-Good for when patient is unconscious or vomiting and can’t take oral drugs
-Poorly absorbed, can irritate mucosa
-Best for treating local issues
Parenteral
-More direct
-More predictable quantity
-Not subject to first pass
Inhalation
-Rapid entry into bloodstream through diffusion to pulmonary circulation
-Can’t predict exactly how much will reach lungs due to compliance/other things in lungs
IV injection
-Frequently resulting in peak levels almost instantaneously and reach target site rapidly
-Lines allow prolonged and steady infusion
Intra-arterial injection
-Difficult and dangerous
-Occasionally used in chemo
Subcutaneous Injection
-Slower more prolonged release into systemic circulation
-Patients can perform on themselves
Intramuscular Injection
-Easily accessible
-Steady and prolonged release
-Relatively rapid effect without rapid plasma level spikes seen with IV
Intrathecal Injection
-Deliver medication in a sheath
-Bypass blood-brain barrier and reach CNS
Topical medications
-Direct to skin
-Absorbed poorly thru epidermis
-Also includes mucous membranes (eyedrops, etc)
Transdermal
-Absorbed thru dermal layers and into subcutaneous tissue or peripheral circulation
-Slow and controlled release, maintain constant level for prolonged period of time
Iontophoresis
Drives ionized form of medication into skin (like estim)
Phonophoresis
Uses ultrasound to enhance transmission of medication through dermis
Bioavailability
-Extent to which drug reaches systemic circulation
-Depends on route of administration and the drug’s ability to cross membrane barriers
Passive Diffusion
-Made possible through electrical, chemical, and pressure differences on either side of membrane
-Rate depends on magnitude of gradient, size, distance, and temperature
Drugs diffuse more easily if they are in
Neutral, non ionized form
Weak acid is in neutral form if
in acidic environment
Weak base becomes non ionized in
duodenum, allows it to be absorbed into small intestine
Drug should remain ___ in urine so it will be excreted
Ionized
Active transport
Use membrane proteins to transport substances across cell membrane
-Carrier specificity
-Expenditure of energy
-Ability to transport substances against a gradient
Facilitated diffusion
-Assisting protein carrier is present, but no energy expended
-Ex: skeletal muscle glucose uptake
Factors affecting distribution: blood flow
Organs with rich blood flow will make distribution easier
Factors affecting distribution: binding to plasma proteins
Ex: albumin
Only unbound drug can reach the target tissue and exert an effect
Factors affecting distribution: binding to subcelluar components
Several drugs bound to organelles can’t be distributed to other compartments
Volume of distribution
Amount of drug administered/concentration of drug in plasma
Drug storage: adipose tissue
Primary site since most drugs are lipid soluble
Drug storage: bone
Toxic agents and heavy metals
Drug storage: muscle
May lead to long term storage
Drug storage: organs
Ex: liver and kidneys
Enters passively or actively and forms bonds to subcellular components
Adverse consequences of drug storage
-High concentrations can cause local damage
-Reservoir “soaks up” a drug and prevents it from reaching target site
-Can leak out and reintroduce drug long after dose should have been eliminated
Biotransformation
Chemically altering a compound usually in liver so it is no longer active. Fast (minutes/hours)
Excretion
Active form is excreted, slow and not very effective (good for removing byproducts of biotransformation)
Phase 1 Reactions
Oxidation, reduction, hydrolysis. Conjugation happens afterwards
Phase 2 Reactions
Conjugation
Oxidation
Oxygen added or hydrogen removed
Reduction
Oxygen removed or hydrogen added
Hydrolysis
Original compound broken into 2 parts
Conjugation
Intact drug or metabolite from one of earlier actions is coupled to endogenous substance
Enzyme Induction
-Prolonged use of certain drugs induces body to adjust and destroy drug more rapidly than expected
-More enzymes being manufactured or less degraded
-Can lead to tolerance
Excretion in Kidneys
-Traps ionized water soluble compounds for elimination via urine
-Can be reabsorbed back via passive diffusion
Clearance
Organ/tissue ability to eliminate drug
-Depends on ability to extract drug and flow of blood (Q)
Half-Life
-Amount of time it takes for 50% of drug remaining to be eliminated
-Function of both clearance and volume of distribution
Dosing Schedules
Larger doses given further apart result in greater plasma fluctuations
