Pharmacology: pharmokinetics Flashcards
(101 cards)
1
Q
Neuro-psychopharmacology
A
the study of the actions of drugs on the CNS and their effects on human behavior
2
Q
Drug actions
A
specific molecular changes resulting from drug binding to the target site receptor
3
Q
Drug effects
A
widespread alterations in physiology or psychology resulting from drug action
4
Q
Therapeutic effects
A
drug-target interactions producing the desired physiological or behavioral changes
5
Q
Side effects
A
any effect that isn’t the therapeutic effect
6
Q
Adverse effects
A
undesirable or harmful drug effects
7
Q
Specific effects
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biochemical interaction between the drug and the receptor
8
Q
Non-specific effects
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interactions that go beyond the interaction between the drug and the receptor
9
Q
Placebo
A
Measurable therapeutic effect of a treatment without specific activity for the receptive condition
10
Q
Pharmacokinetics
A
factors contributing to bioavailability and efficacy of drugs in the human body. Provides performance guidelines for efficacy, efficiency, and drug use in clinical settings
11
Q
ADME
A
Absorption, distribution, metabolism, excretion
12
Q
Absorption
A
movement of the drug from site of administration to the circulatory system
13
Q
Distribution
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dispersal of the drug through body fluids to the target tissues of the body
14
Q
Depot binding
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when the drug binds to non-target tissues
15
Q
Metabolism
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biotransformation or inactivation of drugs in the body into metabolites
16
Q
Excretion
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removal of substances or metabolites from the body
17
Q
First pass effect
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blood flow from the stomach/intestines goes directly to the liver for detox, drug gets metabolised into a usable form for the body
18
Q
the more of a drug you take the more
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adverse the effects become
19
Q
Nonspecific effects may occur as a result of
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unique characteristics of the individual or an individuals state
20
Q
Placebo effect is affected by
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expectancy and conditioning
21
Q
Placebo is a
A
confound in neuropsychopharmacology
22
Q
PO =
A
oral administration
23
Q
IV =
A
intravenous
24
Q
IM =
A
intramuscular
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Inhalation
intake of drugs through the nose
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Advantages and disadvantages of oral Administration
Advantages: self administered, economical
Disadvantages: slow, variable absorption, subject to first pass metabolism
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Advantages and disadvantages of intravenous Administration
advantages: Rapid, accurate blood concentration
Disadvantage: overdose danger, cannot be readily reversed, sterility
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Advantages and disadvantages of intramuscular Administration
Advantages: slow and even absorption
Disadvantages: irritation at injection site, sterility
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Advantages and disadvantages of subcutaneous Administration
Advantages: slow and prolonged absorption
Disadvantages: variable absorption depending on blood flow
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Advantages and disadvantages of inhilation Administration
Advantages: most rapid, large absorption surface
Disadvantages: irritation of nasal passages, could damage lungs
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Advantages and disadvantages of topical Administration
Advantages: localized action and effects, easy to self-administer
Disadvantages: may be absorbed into general circulation
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Advantages and disadvantages of transdermal Administration
Advantages: controlled and prolonged absorption
Disadvantages: local irritation, useful only for lipid soluble drugs
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Advantages and disadvantages of epidural Administration
Advantages: bypass blood brain barrier, very rapid effects of the CNS
Disadvantages: not reversible, need a trained anesthesiologist, possible nerve damage
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Oral rout has the greatest
breakdown of a drug
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Absorption is affected by
drug concentration, breakdown by metabolic or digestive processes, solubility and ionizing of the drug
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Absorption is dependent on
passive diffusion
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Drug concentration is affected by
age, sex, body size, body fat content
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Polar molecules
Water soluble
Hydrophilic - water loving
Lipophobic - fat hating
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Non-polar molecules
Lipid-soluble Hydrophobic - fear water
Lipophilic - fat loving
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polar molecules are transported through
aqueous compartments
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Non-polar molecules freely diffuse across
semi-permeable membranes
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aqueous compartments
blood, CSF, ECF
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semi-permeable membranes
intestinal wall, BBB, cell membranes
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Non-polar molecules tend to be
less soluble in water
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Polar or charged (ionized) drugs are prevented from
diffusing through membranes
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Many orally administered drugs are weak acids or bases
gaining or losing charges based on the pH of the external environment
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How aspirin moved through the system
stomach - around the same acidity to freely moves across the cell membrane - becomes ionized in the blood and is readily soluble - in the intestines' it alternates between ionized and non-ionized forms and diffuseness more slowly across the membranes
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Surface area of body compartments
surface area affects drug absorption
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Stomach has a relatively small surface area
slow absorption
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Intestines have relatively large surface area
(fast absorption) and are the site of most (oral) drug absorption
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Once in the bloodstream drugs circulate to the entire body within
minutes
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Drug concentration is highest in tissues with
greatest blood flow
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Drug concentration is highest in tissues with greatest blood flow
Heart, brain, kidneys, liver
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Peripheral capillaries are highly
porous allowing ready distribution of drugs (lipophilic or hydrophilic) into tissues
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Blood-brain barrier
permits passive diffusion of only lipophilic drugs
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Three main compartments affect drug concentration in the brain
Blood plasma, Cerebral spinal fluid, extracellular fluid
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Blood plasma
Permeates entire brain
Carries soluble drugs and nutrients (glucose, oxygen, amino acids)
Removes waste products and gases
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Cerebral spinal fluid (CSF)
Fills subarachnoid space, ventricles, cisternae
Highly regulated concentration of solutes, glucose, very low protein
Isolated from systemic circulation
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Extracellular fluid (ECF)
Interstitial space between cells in the brain
Similar composition to CSF but more varied between brain regions
Isolated from systemic circulation by the blood-brain barrier (BBB)
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Astrocytes are to blame for
hydrophilic substances being unable to pass through the blood brain barrier
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typical capillary
capillaries are porous, allowing hydrophilic drugs to freely enter tissues
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Brain capillaries are
are coupled by tight junctions and lined by astrocyte endfeet creating a highly impermeable barrier
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The BBB limits access to
98% of small molecule pharmaceuticals (and 100% of large molecule pharmaceuticals
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Passage of solutes through the BBB often occurs at
specific transporters (e.g. glucose and amino acid transporters)
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Some drugs are actively removed from the ECF by
efflux transporters (i.e. p-glycoprotein, a.k.a. multidrug resistance protein-1)
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BBB is not a complete barrier
certain sites have direct access to the circulatory system
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Chemoreceptor trigger zone
allows direct detection of toxins in the blood
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where is the Chemoreceptor trigger zone located
the medulla (vomit center)`
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Hypothalamus
allows direct access to capillaries for secretion of neurohormones and hormone-releasing factors
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some drugs get into the brain Via the
passage way the hypothalamus uses
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Drugs (licit and illicit), alcohol, gaseous anaesthetics, and gases (e.g. carbon monoxide) readily cross the placental barrier and can cause
acute toxicity or teratogenic effects to the fetus
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the placenta is
Slightly more permeable than the BBB
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drug depot sites
Adipose tissue (lipid-soluble drugs)
Muscle tissue
Albumin (plasma protein)
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drug depot sites and circulation
Decreases circulating drug concentration
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drug depot sites and Prolongs drug action
Can function as reservoirs for drug release
Protects stored drug from metabolism
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depot binding and drug efficacy
Can explain individual differences in drug efficacy
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rapid binding to depot before reaching target tissue = what therapeutic effect
slower onset and reduced effects
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individual differences in the amount of binding = what therapeutic effect?
less free drug, so some need higher doses, low binding means more free drug so some individuals are more sensitive
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competition among drugs for depot binding sites = what therapeutic effect
higher than expected blood levels of the displaced drug, possibly causing greater side effects even toxicity
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bound drug is not metabolized = what therapeutic effect?
drug remains in the body for prolonged action
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binding to depots follows the rapid action at targets (redistribution) = what therapeutic effect?
rapid termination of drug action
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Metabolism occurs primarily in the
the liver under control of microsomal enzymes
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cytochrome P450 family (CYP ~ 57 in total)
oxidize the majority of psychoactive drugs (incl. opioids, antidepressants, amphetamines, nicotine)
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CYP1A2
metabolizes many antidepressants and antipsychotics – induced by smoking
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CYP3A4
metabolizes many opioids, antidepressants, statins, anxiolytics – inhibited by grapefruit juice
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Metabolism is a non-specific
detoxification process that occurs in two distinct types or phases
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Metabolism is a non-specific detoxification process that occurs in two distinct types or phases (type 1)
non-synthetic modifications, oxidation, reduction, and hydrolysis
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Metabolism is a non-specific detoxification process that occurs in two distinct types or phases (type 2)
synthetic modifications. conjugation with glucuronide, sulfate, or methyl groups
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Type I metabolism during first pass can produce
active metabolites of the pharmaceutical preparation of drugs
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Metabolic products (active and inactive) are returned to circulation from
the liver and can reach target sites of action or sites for excretion (kidneys, biliary, or fecal excretion)
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4 factors that influence metabolism
Enzyme induction
Enzyme inhibition
Drug competition
Individual differences (age, sex, genetics)
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Enzyme induction
repeated use results in increase in liver enzymes (contributes to tolerance and cross tolerance)
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Enzyme inhibition
drugs targeting enzymes (e.g. monoamine oxidase inhibitors - MAOI) decrease their own clearance and other drugs
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Drug competition
competition for enzymes may prevent some drugs being metabolized in a safe fashion
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Individual differences
genetic polymorphisms have been identified in metabolic enzymes
different individuals have different rates of clearance for drugs
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Routes of excretion include
breath, sweat, saliva, feces, breast milk, and urine
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Primary means of excretion is
filtration by kidney and excretion through urine
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Most drugs are excreted by
first-order kinetics
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Exponential elimination
constant fraction removed in a given time
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Half-life (t½)
describes the interval required to eliminate half of the drug from circulation
101
Very few drugs removed by
zero-order kinetics (constant rate)
- alcohol is
