Lecture 2 Flashcards
Pharmacokinetics
study of movement of drugs throughout body
-ADME
oral administration
safe, self-administered, economical, must be resistant to stomach enzmes and acid
-absoprtion affected by food intake, physcial activity
-harmful chemical processed by the liver
Intravenous
most rapid and accurate, cannot be removed from body easily if overdosed or allergic
Intramuscular
slower, more even absorption
Rectal administration
may avoid first-pass liver metabolism, used for vominting or those unable to take oral medication, or infants
Intraperitoneal
common for lab animals, injetion through abdominal wall into spce surrounding organs, used for cancer drugs
Subcuteaneous
injection just below skin, slow and varibale absorption, can be slowed with oil or impant
Inhalation
abosroption through lungs, rapid due to large surfae area
Topical
applied to mucous membranes, local effect, could be absorbed into bloodstream
Intranasal
Can pass blood-brain barrier, or for local effects in nasal passage
Transdermal
through the skin using patches, controlled and sustained delivery of drug
Epidural
spinal anesthetis to cerebrospinal fluid, pass blood-brain barrier
Infusion pump
impant under skin of scalp, constant antibiotic dose into cerebral ventricles
Gene therapy
application of DNA that encodes specific protein, used to increase or block gene expression to correct clinical condition, vectr needed to carry gene to cell nuclei, often viral vectors
Absorption factors (3)
primarily dictated by rate of passage into blood stream of drug through cell membrane. Phospholipids of the membrne have a hydrophilic head and two hydrophobic tails in a bilayer. Only lipid soluble drugs can pass freely, others need receptor or channel or pores in capillaries
-also affected by rate stomach empties and size and sex of the person
CSF
cerebralspinal fluid, fills subarachnoid space around brain and spinal cord. Many drugs cannot enter the CSF from the bloodstream
Brain capillaries
have distinct morphology that limits movement of water soluble molecules
blood brain barrier
separation between the brain capillaries and the brain/CSF
Distribution
drug is distributed fastest to tissues with high blood flow and are vascular
slowe to low blood flow (muscle) and fat
slowest to tissues with lowest bloodflow (bone) and tendons
Distribution depends on (3)
-cardiac blood flow
-degree of protein building
-volume of distribution
sometimes biological barriers such as blood brain barrier
Drug transport
transporter proteins on cell membrane mediate drug concentrations in cells, uptake or efflux
efflux transporters
remove drug from inside the cell, critical determinant of drug conentration inside cell, source of multii drug resistance
uptake transporters
bring drugs into cell, critical determinant of drug concentration inside cell
Drug depots
binding at inactive sites where no biological effect is initiated
-plasma proteins, fat, muscle
-cannot reach active sites or metabolism by liver
-reversible
-affects magnitude and duration of drug action -delays effects
-people vary in amount of depot binding
-nonselective, can bind different drugs
-can cause overdose, or higher expected blood levels of drug
-drugs reamin detectable in body for long times
three routes of clearing drug from body
-hepatic metabolism
-bile
-urine
drug metabolism
process of turning drug into its metabolites
-increase water solubility and prepare for elimination
-takes place in liver, minor metabolism in kidney, brain, skin and lungs
Cytochrome p (CYP) 450
major role in drug metabolism
variable acitivity between people
cause of many drug drug interactions
different types of CYP 450
CYP 3A4
most abundant p450, metabolism of about half of drugs on the market
CYP 450 induction and inhibition
drugs can induce or inhibit CYP enzymes, increasing or decreasing metabolism
drug activation
sometimes metabolism actives a drug (prodrug)
biotransformation into active compound
kidneys
elimnation of drugs from blood into urine, pH of urine affects reabosrtion into kidney, also removes waste and excess salts from blood
other routes of elimination
faeces, bile into faeces, lungs in air, breast milk, sweat
Clearance (Cl)
total body clearance is sum of clearance from various metabolism pathways
Pharmacodynamics
study of physiological and biochemical interaction of drug molecules with cell receptors in target tissue
Neuropharmacology
drugs act on neurotransmitter receptors to enhance or reduce normal functioning of cell
hormones
most hormones act on brain by binding receptors in cytoplasm or nucleus. alters cell function by triggering changes in gene expression
receptor agonist
highest affinity for receptor and produce significant biologicl effect
receptor antagonist
fits receptors but produces no cellular effect
partial agonists hgave intermediate efficacy (partially bind receptor)
inverse agonsis initiate biological affect that is opposite to agonist
dose-response curve
describe extent of effect produced by given drug concentration
threshold dose
smallest dose that exhibits measurable effect
ED50
dose that produces half the maximal effect (50% effective dose)
-tell you about potency of a drug
maximum response
assume all receptors are bound to drug (ED100)
drug tolerance
diminished response to drug after repeated exposure
-increasing dosage needed to see same magnitude of biologial effect
cross tolerance: tolerance to one drug an diminish effectiveness of other drugs
pharmacogenetics
study of genetic basis of variability in drug response amoung individuals
-goal: genetics that affect side effects and predict therpeutic response
-i.e. differences in p450 enzyme genes, recpetors, transporters, signalling cascade proteins
-some people may require different doses
