Chapter 4 - Properties of Drugs Flashcards
What is pharmacokinetics?
study of how drugs pass through the body (absorption in blood stream to elimination)
steps: absorption, distribution, metabolism, elimination
Absorption stage
refers to passage of a drug into the bloodstream; in most cases drug must pass through cell membrane(s); depends of route of administration
ex. intravenous goes to blood directly, orally must pass through mucous membranes in mouth or wall of intestine
Route of administration
affects how much drug reaches blood stream and the speed of absorption (may contribute to abuse)
common routes: inhalation, intramuscular, intravenous, oral
Absorption into body depends on
how well pH of an environment matches the drug’s pKa (acidity of drug)
Henderson-Hasselbalch equation
the closer the pKa and pH, the more non-ionized particles (better diffusion into blood stream)
ex. pKa=3 better absorbed in the stomach (pH=1) than intestine (pH=7)
Liberation (process during absorption)
the process of drug molecules separating form the pill or solution it was dissolved in; many oral drugs are meant to be liberated in small intestines
Distribution stage
after absorption into blood stream, passage of drug from bloodstream into intended body sites
Bioavailability
ability of a drug to reach its intended target
blood-brain barrier
protective layer of cells surrounding blood capillaries in brain that prevent many substances in blood from entering brain; nutrients and some molecules can penetrate it through passive diffusion or active transport
Passive diffusion
fat soluble, neutrally charged, and small in size chemicals can diffuse across the blood brain barrier
Active Transport
consists of membrane channels or transporters that facilitate passage of chemicals through cell membranes
ex. glucose transporter, large amino-acid transporter
Non-specific binding
drugs can sometimes bind to other unintended targets which reduces amount delivered to intended targets
Protein binding
drug may bind to proteins in blood stream (not free to cross blood-brain barrier)
Depot binding
drug may bind to other tissues which reduces amount in blood available to intended target (ex. TCH in fatty tissues)
Metabolizing stage (biotransformation)
process of converting a drug into one or more metabolites
metabolites
products resulting from transformation of a drug via enzymes
mostly smaller molecules; water soluble; may be active or inactive
Individual differences
rapid metabolizers: more metabolic enzymes; decreased amount of drug (have to use high dose or use different class of drugs)
poor metabolizers: fewer metabolic enzymes; prolongs drug life-span
Personalized medicine
prescribe treatments based on patient’s unique biological make up
Elimination stage
process by which drug leaves the body; final stage of pharmacokinetics; several channels, depends on drug (urine/sweat/breath/feces)
Elimination rate
amount of drug eliminated from the body over time
Half life
amount of time required to eliminate half the amount of drug; amount eliminated per unit of time varies; can vary considerably; determines dosing frequency; used if drugs follow first-order kinetics
Zero-order kinetics
drug is eliminated at a fixed amount per unit time (ex. alcohol is eliminated at about 10-14mg per hour)
Pharmacodynamics
mechanisms of action for drug which accounts for its (psychological) effects; some alter neurotransmission directly; some may interfere with neurotransmitter storage/reuptake mechanisms/metabolic enzymes
Binding affinity
The drug’s strength of binding to a receptor; some drugs have a stronger binding to a receptor than a neurotransmitter
Receptor efficacy
The drugs ability to activate a receptor; some drugs exert weak effects, others exert strong effects
Agonist
Binds to a receptor and exerts actions similar to the neurotransmitter
Partial agonist
Binds to the same receptor that the neurotransmitter binds to but has a weaker effect than the NT; functionally reduces the action of the NT
Antagonist
Binds to a receptor and blocks the action of a NT
Competitive antagonist
Binds to the same receptor that the neurotransmitter binds to and blocks the action of the NT; direct competition for receptor
Non-competitive antagonist
Binds to a different receptor than the NT (usually on a complex) and blocks action of NT
Allosteric regulators
Bind to a receptor other than a NT and affects action of NT; usually receptor for drug is part of a larger receptor complex
Positive modulator
Drug enhances the action of the NT
Negative modulator
Drug decreases the action of the NT
A good example of allosteric regulation is ____ because ____
GABAA receptors; several drugs increase GABA binding to GABAA receptors which enhances action of GABA (benzodiazepines, barbiturates, alcohol)
Sensitization (chronic drug use)
Increased effects of drugs; lower dose necessary for a given level of effect; dose-response curve shifted left
Tolerance (chronic drug use)
Decreased effect of a drug; larger dose necessary for a given level of effect; dose-response curve shifted right
Pharmacokinetic tolerance (types of tolerance)
Reduction in the amount of drug reaching target
Ex. Increased production of metabolic enzymes
Pharmacodynamic tolerance
Changes in the number of neurotransmitter receptors
Down-regulation
Decreased number of receptors
Behavioural tolerance (types of tolerance)
Decreased behavioural response (learn to perform tasks better under effects of drug)
Conditioned/contingent tolerance (types of tolerance)
Tolerance due to conditioned physiological responses that counteract the drug effects; stimuli associated with drug use may activate a pharmacokinetic response that reduces drug’s effect; in presence of conditioned stimulus, drug effect decreases; in absence of CS, drug affect is much stronger
Cross tolerance (types of tolerance)
Tolerance to one drug may result in tolerance to another drug
Ex. Someone with high tolerance to heroin may be tolerant to methadone
Withdrawal syndrome
Collection of responses that occur when a drug is no longer administered; severity of physical effects depends on length/amount of use; psychological effects commonly include drug cravings or mood changes
Ex. Alcohol withdrawal can lead to seizures; heroin withdrawal can lead to increased pain sensitivity
