01&02 - Drug Absorption&Administration Flashcards
what is pharmacology
the study of substances that interact with living systems through chemical processes
what s medical pharmacology
the science of substances used to prevent, diagnose and treat disease
types of medical pharmacology
PHARMACOGENOMICS
PHARMACOEPIDEMIOLOGY
PHARMACOECONOMICS
TOXICOLOGY
what is pharmacokinetics
- relationship between drug dosage and time-course of drug concentration in the body, usually as reflected in plasma drug concentrations
- what the body does to the drug
pharmacodynamics
- concerned with the mechanism of drug action, including the relationship btwn drug concentration and the magnitude of effect (dose-response)
- what the drug goes to the body
describe the pathways of a drug
dose of drug administered–> (absorption)–>drug concentration in systemic circulation –> (distributed OR Elimination) –> drug concentration at site of action –> pharmacological effect –> clinical response –> toxicity OR Efficacy
what happens during distribution of the drug
drug in extracellular fluid & intracellular sites
what happens during elimination of the drug
drug metabolized or exerted
what 3 factors affect the pharmacological effect
- regimen specific
- drug specific
- patient specific
regimen specific
dose
frequency
route
drug specific
Dose-response relationship Site of Biological Effect Disposition of the Drug Potency of the Drug Dosage Form
patient specific
Environmental/Dietary Exposures Psychological Condition Genetic Constitution Organ Function Enzyme Activity Age/Sex
different plasma concentration of phenytoin can cause what
mental changes
ataxia
nystagmus
routes of drug administration
topical
enteral
parenteral
specific sites/cavities
topical
skin, mucous membranes, oral pharynx, eye, inside of ear, pulmonary
enteral
oral route, putting directly into GI
parenteral
- by injection (ie. subcutaneous, intramuscular and IV), patches
- bypass GI?
specific sites/cavities
intra-articular (ie. into joint, bladder irrigation)
-implants that rleease AB at a certain time
intravenous route absorption
100%; potentially immediate onset
intravenous route special utility
emergency use: permits dosage titration; may be the only suitable route; suitable for larger volumes & irritating substances when diluted
intravenous route limitations
increase risk of ADRs; not suitable for oily or insoluble substances
subcutaneous absorptions
may be prompt or sustained
subcutaneous special utility
may be used for suspensions or slow-release implants
subcutaneous limitations
not suitable for large volumes or irritating substances
oral ingestion absorption
variable, depends on many factors
oral ingestion special utility
convenient; economical; generally safe
oral ingestion limitations
dependent on patient compliance, bioavailability potentially erratic
mechanisms of drug transport
Passive diffusion Facilitated/Active transport Filtration Endocytosis Ion-pair transport
name a few drug transporters
- membrane proteins
2. superfamilies - ABC and SLC
what are membrane proteins
that control the influx of essential nutrients, ions (and certain drugs) and the efflux of toxins and certain drugs
what are the 2 major superfamilies of drug transporters
- ABC
2. SLC
what is ABC
ATP binding cassette
what is SLC
- solute carrier
- transport polypeptides (OATP), organic anions (OAT), and cations (OCT)
what are drug transporters
- play protective roles
- reducing drug absorption from the GI tract
- enhancing drug elimination into bile and urine
- impeding access of drugs to the brain and placenta
some drug transporters serve as
- drug targets (eg. neurotransmitters uptake; cholesterol uptake; Na+-H+ exchange) and can be a source of drug interactions
- drug resistance (antivirals; anticancer agents)
pharmaceutical factors of GI absorption and passive diffusion
dosage form must first dissolve into solution
chemical properties of the drug that affect GI absorption and passive diffusion
molecular size
lipid solubility
ionization coefficient (pKa)
Fick’s Law of Diffusion
Flux = (C1-C2) x [(Area x perm Coefficient)/Membrane Thickness]
Gastrointestinal Factors
Gastric emptying time; intestinal transit
Presence of food
Local blood flow
Local pH
Ionization and Effect of pH
- most drugs are weak electrolytes
- the mucosal lining of the GI tract is largely impermeable* to the ionized form of a weak acid or base
*ionized forms may be candidates for some transporters
the degree of ionization depends on what
the pKa of the drug and the local pH
Henderson-Hasselback Equation
pH – pKa = log (base)/(acid)
weak acid H-H equation
pH-pKa= log [RCOO-] / [RCOOH}
weak base H-H equation
pH-pKa = log [RNH2] / [RNH3+]
lipid solubility
for a given pKa (and therefore relative degree of ionization) the larger the lipid solubility, the more rapid is absorption
importance of absorptive surface area
drug absorption is fastest from the small intestine
absorption is facilitated at sites where
ionization is suppressed/unionized
the rate at which the stomach empties has a significant effect on
the overall rate of drug absorption
the absorption of weak bases is particularly dependent on
arrival in the small intestine
drugs tend to accumulate in
fluid/tissue compartments where the degree of ionization is the greatest (ion trapping)
what factors play a role in oral drug absorption
- drug instability
- food
- gastric emptying
- intestinal transit
- transporters
- villous blood flow
- drug-drug interactions
transporters can be a source of what
drug interactions affecting the rate of drug absorption and distribution
what 3 fluid compartments do drugs distribute into
- vascular
- interstitial
- intracellular
volume of distribution (Vd) relates to what
relates the amount of drug in the body to the plasma concentration (simple dilution principle)
equation for Vd
dose/ [plasma]
Vd values exceeding total body water indicated what
binding or sequestration at an extravascular site
along with clearance (Cl), Vd determines what
the pharmacokinetic behaviour of a drug (Ke= Cl/Vd)
changes in Vd can be explained by what
drug interactions and differences in drug response
drugs binding to plasma proteins, are they reversible or irreversible?
usually reversible
drugs binding to plasma proteins are governed by what law
law of mass action
what are the main protein targets drugs bind to
- albumin
- α1-acid glycoprotein
- lipoproteins
what does albumin bind to
binds mostly to weak acids
what does α1-acid glycoprotein bind to
mostly organic bases
what do lipoproteins bind to
lipid soluble drugs
what are consequences of plasma protein binding
- reduces the concentration of unbound free (drug)
- may slow the distribution and/or elimination of the drug (functioning as a depot)
- represents a potential site of drug interaction
the risk of an adverse effect from drug interaction/displacement based on protein binding is increased with the presence of?
- high degree of protein binding
- low Vd for displaced drug
- slow elimination kinetics of displaced drug
absorption of intramuscular
similar absorption characteristics as subcuatenous (may be prompt or sustained)
special utility of intramuscular
can accept large volumes than subcuatneous as well as some irritating substances
limitations of intramuscular use
not for use on patients on anticoagulants; may release muscle enzymes temporarily interfering with some diagnostic tests
