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222 Cards in this Set
- Front
- Back
What are the 3 types of drug names?
|
1. chemical
2. generic 3. trade |
|
why is it important to know the generic names of drugs?
|
Generic names are the same everywhere.
|
|
Define pharmacokinetics
|
The study of the movement of drugs through the body
(i.e. what the body does to the drug) |
|
Define pharmacodynamics
|
The study of the mechanisms of action & physiological effects of drugs
(i.e. what the drug does to the body) |
|
Where do drugs come from?
|
1. A naturally-occuring substance
2. a modification of a naturally-occuring chemical |
|
What does ADME stand for?
|
A-absorption
D-distribution M-metabolism E-excretion |
|
What does ADME describe?
|
the processes affecting the movement of drugs through the body. PHARMACOKINETICS
|
|
Following administration, a drug must reach _______
|
systemic circulation
|
|
To be effective, drugs must _________ before reaching the target tissue
|
not be inactivated
|
|
What is bioavailability?
|
The FRACTION of administered dose of drug that reaches the SYSTEMIC circulation UNCHANGED
|
|
What is enteral administration?
|
"via the intestine"
usually oral |
|
What is parenteral administration?
|
Routes that involve absorption of drug from sites other that the stomach or intestine.
|
|
what are the advantages of oral administration?
|
- simple; most convenient for self-administration
- usually safer than injection |
|
What are the disadvantages of oral administration
|
- erratic absorption
- patient complience - not for unconscious patients - "first pass" effect - too slow for some emergency situations |
|
What is the first pass effect?
|
Drugs administered orally are absorbed into the portal vein and delivered first to the liver where metabolism my inactivate a percentage of the drug.
|
|
What is subligual administration?
|
Drugs placed inder the tongue. Absorption is across oral mucosa
|
|
what are the advantages of sublingual administration?
|
- no first-pass metabolism
|
|
Disadvantages of subligual administration?
|
- patient must cooperate (not swallow the drug)
- significant proportion of dose may be swallowed dispite efforts not to swallow |
|
What is subcutaneous injection?
|
an injection of a drug uner the skin
|
|
Advantages of subcutaneous injection?
|
- suitable for solid pellets, insoluble suspensions, oily vehicles ("depot" formulations)
- easier the IV - absorption slower than by IV or IM routes (may also be a disadvantage) |
|
Disadvantages of subcutaneous injection?
|
- not for large volumes
- pain or necrosis with irritating drugs - absorption can be very slow - possible infection |
|
What is intramuscular injection?
|
injection of a drug into the muscle of a patient.
|
|
Advantages of intramuscular injection?
|
- suitable for moderate volumes and oily vehicles ('depot" formulas)
- safer and easier that IV |
|
Disadvantages of intramuscular injection?
|
- local pain, swelling, possibe infection
- avoid during anticoagulant treatment (extensive hemorrhage/bruising may occur) |
|
What is intravenous administration?
|
- injection directly into the vein of a patient
|
|
advantages of IV?
|
- emergency use, rapid drug availability
- large volumes (slowly) - irritating drugs (when diluted) |
|
disadvantages of IV?
|
- higher risk o adverse effects
often must inject slowly due to cardiax toxicity risk - not for oily or insoluble drugs - requires more skill |
|
what is topical administration?
|
drugs placed on the suface
- eye, ear, skin, mucous membranes (conjuctiva, nasopharynx, oropharynx, vagina, colon, urethra) |
|
advantages of topical administration?
|
- drug delivered to site of need
- can achieve very high concentrations |
|
disadvantages of topical administration?
|
-may be absobed systemically
- may not remain in place/messy |
|
what is drug "formulation"?
|
the physical form of a medication as well as its chemical ingredients
|
|
what do the inactive ingredients in drugs do?
|
- balance pH
- alter flavour - produce the desireable physical form |
|
most drug are found as _____
|
weak acids or weak bases
|
|
non-ionized form = more _______ solube
|
lipid
|
|
ionized form = more _______ soluble
|
water
|
|
________ molecules can diffuse accross membranes
|
non-ionized
|
|
diffusion rate depends on _______
|
lipid solubility
|
|
what determines the ionization state of a drug?
|
the pKa
|
|
what is the pKa?
|
pH when 50% of drug is ionized
|
|
pKa is usually between ___ and ____
|
pH 3 and pH 11
|
|
what is the pKa of acetaminophen?
|
9.5
|
|
what is the pKa of aspirin?
|
3.5
|
|
what is "ion trapping"?
|
when drug accumulates on side of membrane where ionization is highest
(basic accumulate in acidic and acidic accumulate in basic) |
|
distibution usually begins _______ absorption is finished
|
before
|
|
most drugs goes where it is not needed, only a small fraction reaches ________
|
receptor sites
|
|
what 3 factors effect drug distribution?
|
1. Physicochemical properties of drug
2. anatomy and physiology of patient (tissue perfusion, blood brain barrier) 3. plasma protein binding |
|
examples of physicochemical properties of drug
|
- lipid solubility
- degree of ionization - size, molecular weight |
|
once drug enters blood, it distributes to entire blood volume in _____
|
1-2 min
|
|
organs with ______ blood flow get more drug
|
higher
|
|
what organs have higher blood flow? (20% of cardiac output)
|
- brain, kidney, heart, liver
|
|
what is the blood brain barrier?
|
- capillaries in the brain are much less permeable to som water-soluble substances due to glial cells
|
|
the blood brain barrier is totally impermeable to ________
|
plasma proteins
|
|
water soluble substances will enter the CNS ______
|
very slowly
|
|
_______ administration is useless if intended site of action is the CNS
|
systermic
|
|
which drugs cross the blood brain barrier well?
|
high lipid soluble, low protein drugs
|
|
what is the main plasma binding protein?
|
albumin
|
|
what percentage of the total plasma protein is albumin?
|
50%
|
|
_______ drugs connot enter tissues and cannot be eliminated via kidneys
|
protein-bound
|
|
infected tissue is more _____ than healthy tissue
|
acidic
|
|
is lidocane a weak acid or a weak base?
|
weak base
|
|
true/false: drugs distribute equally to all tissues
|
false
-some remain almost exclusively in blood (~7% of body volume) - some distribute readily to other tissues |
|
what is volume of distribution ?
|
a rough estimate of th extent to which the drug leaves the bloodstream and enters other tissues
|
|
what factors effect the volume of distribution?
|
- ion trapping
- highly lipid-soluble drug - irreversilble receptor binding - incorporation into tissue |
|
what is biotransformation or metabolism?
|
a change in the chemical structure of an absorbed drug within a living organism, usually by nzyme-catalyzed reaction
|
|
why is drug metabolism important?
|
-enzymes play a pivotal role in terminating drug action
- metabolism makes drugs more excretable and inactivates many drugs |
|
why are lipid soluble drugs not readily excreted?
|
- cross out of urine through membranes back into the blood
|
|
where are drug metabolized?
|
- in the liver
- but also in lungs, GI tract, skin, kidneys, brain |
|
the enzymes resonsible for biotransformation are located in______________
|
- *endoplasmic reticulum
- * cytoplasm - mitocondria - nuclear or cell membrane - lysosomes |
|
following differential centrifugation of cell homogenates, drug metabolizing enzymes are present mainly in _______ and _______
|
microsomes and cytosol
|
|
what are microsomes?
|
- visicle consisting of membranes of ER which contain membrane-bound P450 enzymes (mediate Phase l metabolism)
|
|
what is the cytosol?
|
supernatant consisting of cytoplamic fluid and soluble Phase ll enzymes
|
|
how are drugs metabolized?
|
phase l and phase ll reactions
|
|
what is a phase l reaction?
|
- drugs are converted to more polar metabolites
- then they are either excreted or they go to phase ll reactions |
|
what is a phase ll reaction?
|
conjugation or synthesis reactions in which endogenous sustance combines with the functional group derived from phase 1 reaction
- polar = excretable |
|
what are the characteristics of phase l reactions?
|
1. makes drugs moore reactive, capable of combining with polar conjugate bodies
2. substrates are lipid soluble, of widely varied chemical structure 3. metabolites are more water-soluble, either excreted or go to phase ll reactions 4. involve one or more cytochrome P450 enzyme found in smooth ER |
|
what are P450 enzymes called P450 enzymes?
|
they are heme-containing proteins (P) that maximally absorb light at 450 nm
|
|
what are the other names for P450 enzymes?
|
- microsomal
- CYP enzymes system - mixed-function oxidases (MFOs) |
|
what are the different types o Phase l reactions?
|
1. oxidation
2. reduction 3. hydrolysis |
|
what is the most common type of phase l reaction?
|
oxidation
|
|
what is an oxidation reaction?
|
involves the addition of oxygen or removal of hydrogen from the drug
- involves P450 enzymes |
|
what are the characteristics of phase ll reactions?
|
1. couple drug (or phase l metabolite) with substrates from diet to produce conjugates
2. conjugates are often polar, inactive and readily excretable |
|
what are some conjugating substances?
|
- glucuronic acid
- sulfate - glutathione - methl groups - glycine - cysteine - methionine - acetic acid |
|
what are the different types of phase ll reactions?
|
1. glucuronic acid conjugation
2. sulphate conjugation 3. acetylation 4. glutathione conjugation |
|
what are the features of glucuronic acid conjugation?
|
- very important
- enterohepatic recirculation - individuals deficient in glucuronide synthesis are slow to metabolize certain drugs (e.g. neonates, cats) |
|
what is enterohepatic recirculation?
|
large drugs (>500 MW) are excreted in bile for elimination in feces, but glucuronidases in gut bacteria can hydrolyze conjugate and free drug, which can be reabsorbed
|
|
what drugs are metabolized using glucuronic acid conjugation?
|
- morphiine
- acetaminophen - salicylic acid - chloramphenicol |
|
what types of drugs are metabolized using sulphate conjugation?
|
- phenol and alcohol
- e.g. acepaminophen, morphine |
|
what types of drugs are metabolized by acetylation?
|
- occurs in drugs with -NH2 group conjugated to COCH3
- e.g. most sulfonamide antimicrobial drugs |
|
whaat types of drugs are metabolized using glutathione conjugation?
|
- epoxides, arene oxides conjugated to glutathione (GSH)
- e..g. some anticancer drugs (alkylating agents) |
|
in the metabolism of acetaminophen (Ac), what three pathway does it follow?
|
1. Ac to Ac-glucuronide
2. Ac to Ac-sulfate 3. Ac to reactive electrophilic compound (Ac*) - uses P450 |
|
what happens in acetaminophen overdose?
|
1. acetaminophen gets turned into a reactive electrophilic compound by P450 enzyme
2. this then gets turned into acetaminophen bound to protein by cell macromolecules 3. this causes cell death 4. leading to liver failure |
|
what factors effect drug metabolism?
|
1. enzyme induction and inhibition
2. multidrug therapy 3. distribution 4. age 5. genetics 6. disease |
|
what is induction?
|
- many drug metabolizing enzymes can increase in amount and activity in response to chemical inducers
- induction can increase drug metabolism and decrease drug action - can increase drug-related toxicity depending on whether phase l or ll enzymes are induced |
|
what is inhibition?
|
- certain drugs may inhibit P450 activity mostly by competing for the same isozyme
|
|
what is multi-drug therapy?
|
- there is a finite number of hepatic enzymes
- systems can be saturated - most comon when multiple drugs requiring the same metabolic enzyme are taken at once - drugs compete for, or inhibit, metabolizing enzymes |
|
what is distribution?
|
- drugs bound to plasma proteins or stored in fat not available for metabolism
|
|
how does age effect metabolism?
|
- neonates, geriatric patients deficient in metabolc capacity
|
|
how does genetic effect drug metabolism?
|
- drug metabolizing enzyme levels may vary between individuals due to genetic polymorphisms
|
|
how does health and disease effect drug metabolism?
|
- poor nutrition can lead to deficiency in substances needed for conjugation
- endocrine diseases, liver diseases, infectious/inflammatory diseases can inhibit drug metabolism - heart disease can cause impaired blood flow to liver |
|
how can acetaminophen overdose be treated?
|
- glutathione conjugation can inactivate the reactive intermediate (NAPQI)
- a physician will administer a source of glutathione (n-acetyllcysteine), which minimizes hepatic damage |
|
what is elimination?
|
the tranfer for drugs to the external environment
|
|
what organs are involved in elimination?
|
- *kidney
- * liver - lungs (volatile drugs) - intestinal tract - other (milk, sweat, tears, etc.) |
|
what can be used to describe elimination?
|
half life
|
|
how many half lives does it take for 99.9% of a dose to be eliminated?
|
10 half lives
|
|
for practical purposes, drug is essentially eliminated after________
|
4-5 half lives
|
|
what is a loading dose?
|
an initial dose that is larger then subsequent doeses
|
|
if excretion decreases, drug half-life ________
|
increases
|
|
hte most benificial way to administer drugs is?
|
small doses more frequently
|
|
what are the mechanisms of renal elimination?
|
1. glomerular filtration
2. tubular secretion 3. tubular reabsorption (passive) - working against excretion |
|
what are the characteristics of glomerular filtration?
|
- passive
- non-selective - non-saturable - drug with MW< 68 000 goes into urine - drugs bound to albumin dont get filtered (slow elimination) |
|
what are the characteristics of tubular secretion?
|
- active transport and passive diffusion
non-specific secretory mechanism for acids (e.g. penicillin) and bases (e.g. morphine) - may saturate if [drug] is high - competition by different drugs for same active transport mechanism, individual excretion rates may decrease (longer T1/2) |
|
what are the characteristics of tubular reabsorption?
|
- works against excretion
- follows filtration or secretion - many lipid-soluble drugs simply diffuse from tubule back into plasma - aided by continuous re-absorption of water mainly passive (rare active processes) |
|
what is tubular reabsorption affected by?
|
a) physiochemical properties of drug
b) rate of urine flow |
|
what are the physiochemical properties of a drug?
|
- degree of ionization (affected by diet: pH 5.5 - 8.0; can alkalinize for weak acid OD e.g. aspirin)
- acid vs. base - molecular size - |
|
how does the rate os urine flow effect elimination?
|
- increased flow means increased elimination
can use fluids, diuretics to increase elimination |
|
what is hepatic elimination?
|
- only drug not bound to plasma proteins
metabolism in hepatocytes - excretion into bile (ative transport to gut to feces |
|
what is enertohepatic recycling?
|
-drug reabsorbed in small intestine gets returned to liver in portal blood
|
|
gut microbes may ________
|
reactivate drug
|
|
drugs that are conjugated get excreted into ____
|
bile
|
|
what are the characteristics of hepatic elimination?
|
- active process, against conc gradient
- once in bile drug moves to intestine then to feces - some conjugated drugs can be deconjugated and reabsorbed into blood - important if recycling prolongs drug action |
|
what is the therapeutic margin?
|
- drug response is essentially proportional to the concentration of free drug at the target organ
|
|
what is drug clearance?
|
a concept used to compare rates of elimination of drugs
|
|
what is pharmacodynamics?
|
what drugs do to the body
|
|
what are the 2 sub-sections of pharmacodynamics?
|
1. what the drug does to individual cells
2. what the drug does to the entire body |
|
most drugs exert their effects by binding to _______ proteins in the plasma membrane of cells
|
receptor
|
|
drugs can _____ or ______ receptors
|
stimulate or block
|
|
receptors are normally modulated by ______________
|
endogenous ligands
|
|
examples of endogenous ligands
|
neurotransmitters, hormones, endorphines, leukotrienes and other intra-cellular signalling chemicals produced by the body
|
|
the fracion o drug receptors occupied by drug is dependent on _________
|
drug concentration in extracellular fluid
|
|
drug effect is generally proportional to the __________ by drug
|
percentage of receptors occupied
|
|
where are drug receptors located?
|
cell membranes
|
|
lipid soluble drugs can have receptors located in_______
|
the nuclear membrane
|
|
most drugs are receptor ______ or ______
|
agonists or antagonists
|
|
what is a agonist?
|
- activates receptor
|
|
what is an antagonist?
|
- bind to but do not activate the receptor
- blocks physiological response |
|
most receptors are ______
|
proteins
|
|
many receptors have ______ binding sites
|
several
|
|
advantages of multiple binding sites on a receptor ?
|
- different abilities to dissociate
- critical for response - continued response requires repeated binding and unbinding |
|
irreversible binding generally produces _________
|
toxicity
|
|
what are the different types of bond for receptor-drug complexes.
|
1. covalent bonds
2. ionic or electrostatic bonds 3. hydrogen bond 4. van der waal's forces 5. hydrophobic bond |
|
what are the characteristics of a covalent bond?
|
- high energy
- cannot be broken - recovery from drug depends on new receptor production - e.g. phenoxybenamine (irreversable blocker of alpha receptors) |
|
what are the characteristics of a ionic bond?
|
- medium energy
- occurs between opposite charges - reversible - may attract drug to receptor over a distance |
|
what are the characteristics of hydrogen bonds?
|
- medium energy
- e.g. between amino acids |
|
what are the characteristics of van der waals forces?
|
- low energy
- drug and receptor close together, increases dipole - may be many dipoles, increases drug receptor selectivity |
|
what are the chracteristics of a hydrophobic bond?
|
- low energy
between fat soluble (hydrophobic) regions - usually very selective D-R binding |
|
what effect can drugs have on a receptor?
|
- initiate
- enhance - diminish - terminate (block) |
|
the magnitude of response depends on ______?
|
the percentage os receptors occupied bu the drug
|
|
what are the 5 important signal transduction mechanisms?
|
1. lipid-soluble drug binds intracellular receptor (enzyme, gene regulator)
2. D-R complex activates cytoplasmic enzymatic activity 3.D-R complex activates tyrosine kinase 4. Drug binds to and opens or block ion channel 5. D-R acts through G-protein to activate effector enzyme |
|
what is an effector?
|
- molecule that translate D-R interaction into a change in cellular activity
- drug R usually extracellular and effector intracellular - therefore signal crosses cell membrane |
|
what important signal transduction mechanisms are essential for action of drugs?
|
- ion channels
- second messengers - DNA/RNA synthesis |
|
what are the characteristics of intracellular receptors?
|
- lipid soluble of diffusible ligands (e.g. steriod hormones, nitric oxide)
- cross membrane and bind to intracellular R that affects an intracellular effector molecule - no specialized transmembrane signaling device required - ultimately increases transcription and expression of regulator genes (e.g. estrogen, glucocorticoids, Vit D) |
|
what are the characteristics of receptors that activate cytoplasmic enzymatic activity?
|
- R have extrcellular and intracellular domains
- membrane-spanning Rs bind separate kinase molecules |
|
what are the chracteristics of receptors with membrane-spanning enzymes?
|
- drugs bind R on extrcellular portion os enzyme and modify intracellular activity
- when activated, Rs dimerize and kinases phosphorylate tyrosine residues on the cytoplasmic domain (e.g. insulin or EGF acts on receptor tyrosine kinase located in membrane which increases glucose uptake) |
|
what are the characteristsics of receptors that act as ion channels?
|
- receptors regulate pore-forming transmembrane proteins causing the opening of an ion channel
- regulate ion flow across membrane producing depolarization or hyperpolarization |
|
what is a ion channel?
|
- type on ligand-gated ion channel (e.g. nicotinic acetylcholine R NAChR)
|
|
where are ion channels located?
|
- motor end plates of NMJ
- CNS - autonomic ganglia |
|
what is the structure of an ion channel?
|
- 5 subunits: 2 alpha, 1 beta, 1 gamma, 1 delta
|
|
what are the characteristics of receptors linked to G proteins?
|
- R linked by coupling proteins (G proteins) to intracellular or membrane effectors
- guanosine triphosphate (GTP) proteins amplify signal - activated G protein the changes the activity of an effector element (e.g. enzyme or ion channel) - this element then changes the concentration of second messenger |
|
what does a does response curve show?
|
response is related to drug concentration and affinity of drug for receptor
|
|
when on a drug response curve does a drug produce half-maximal effect?
|
at EC50
|
|
when does a drug produce half maximal receptor occupancy?
|
at KD
|
|
Competitive antagonists can be completely overcome by ________
|
increasing the concentration of the agonist
|
|
irreversible antagonists reduce_____
|
Emax
|
|
what is allosteric antagonism?
|
results from the binding of a chemical (antagonsist) to a site on the receptor different from the agonist binging site ( the antagonist reduces the receptors affinity for the drug)
|
|
what is potency?
|
the relative ability to different drugs that are agonists at the same receptor to produce half-maximal effect
|
|
the drug that produces ______ at the lowest concentration is the most potent drug
|
Emax/2
|
|
what is efficacy?
|
the magnitude of the maximum response that a drug produces
|
|
the most efficacious drug produces quantitatively the ______ response
|
largest
|
|
what is tachyphylaxis?
|
the rapid loss of response of an organ to receptor activation by a drug e.g. after a few days or weeks
|
|
what is desenitization?
|
refers to tachyphylaxis at the receptor level
|
|
what is receptor down-regulation?
|
occurs when a receptor type has been excessively stimulated for an exended period of time - the number of receptor (and therefore the response tot he drug) is decreased
|
|
what is up-regulation?
|
occurs when a drug has been restricted for an extended period of time and the response to the drug increasses due to increases receptor numbers
|
|
what are inert receptors?
|
do not produce a pharmacological responce when drug binds e.g. plasma protein binding sites
|
|
"rest and digest"
|
parasympathetic nervous system
|
|
"fight or flight"
|
sympathetic nervous system
|
|
what organs do not receive input from both PSNS and the SNS
|
- adrenal gland, sweat gland, pilomotor muscles, blood vessels
|
|
in general, the PSNS and SNS mediate _______ responses in effector organ
|
opposing
|
|
what is ganglia?
|
aggregation of cell bodies of postganglionic neurons
|
|
what are preganglionic fibers?
|
brain and spinal cord to ganglia
|
|
what are postganglionic fibers?
|
axons from ganglia to effector organs
|
|
what are the characteristics of the PSNS?
|
- leaves CNS via cranial an sacral nerves
- ganglia close to or within end organ - long preganglionic and short postganglionic fibers - one preganglionic to one postganglionic fiber |
|
what are the characteristics of the SNS?
|
- cell bodies in thoracic and lumbar spinal cord
- ganglia near spinal cord - short preganglionic and long postganglionic fibers one preganglionic to many post ganglionic fibers |
|
what are the main neurotransmitters in the ANS?
|
- acetylcholine (ACh)
- norepinepherine (NE) - epinepherine (EP) |
|
what are the 2 types of cholinergic receptors?
|
1. muscarinic (M1-M5)
2. Nicotinic (Nn, Nm) |
|
what are the characteristics of muscarinic receptors?
|
- found in organs innervated by PSNS (M1-M3)
- found on endothelial cells (M3 and M5) - found in sweat glands innervate by cholinergic SNS fibers (M3) |
|
what are the characteristics of nicotinic receptors?
|
-Nn found in all ganglia (PSNS and SNS)
- Nm found on skeletal muscle (somatic nervous system innervation) |
|
what are the characteristics of adrenergic receptors?
|
- found in organs innervaated by SNS
- location and subtype determine tissue response |
|
what are the 2 types of adrenergic receptors?
|
1 alpha (1 and 2)
- activated by NE and EP 2. beta (1,2,3) - activation of B2: EP>>>>>NE |
|
acteylcholine is synthesized by the enzyme ________
|
choline acetyltransferase (ChAT)
|
|
acetylcholine is degraded by the enzyme _____________
|
acetylcholinesterase (AChE)
|
|
muscarinic receptors activate ________
|
second messengers (G proteins)
|
|
in muscarinic receptors increasing IP3 and DAG =
|
stimulatory
|
|
in muscarinic receptors, decreasing cAMP =
|
inhibitory
|
|
nicotinic receptors open _____
|
ion channels
|
|
where are M1 receptors located and what is there action?
|
- gastric mucosa
- increase secretion |
|
where are M2 receptors located and what is there action?
|
- heart
- decrease rate/force of contraction AND - adrenergic nerve - decrease NE release |
|
where are M3 receptors located and what is there action?
|
- smooth muscle glands
- contracts AND - endothelial cells - increase EDRF release |
|
where are M5 receptors located and what is there action?
|
- endothelial cells
- increase EDRF release |
|
what is EDRF?
|
- endothelial derived relaxing factor (nitric oxide)
|
|
where are Nn receptors and what is there action?
|
- postganglionic neurons
- opens Na+ and K+ channels AND - CNS - excitation |
|
where are the Nm receptors located and what is there action?
|
- skeletal muscles
- opens Na+ and K+ channels |
|
what does ion influx cause?
|
depolarization / contraction
|
|
what are the 3 steps in norepinepherine synthesis?
|
1. tyrosine hydroxylase
2. dopa decarboxylase 3. dopamine beta-hydroxylase |
|
what are the 2 steps in the termination of NE?
|
1. re-uptake
2. diffusion away from synapse - metabolized by: monoamine oxidase (MAO) or catechol-O-methyltransferase (COMT) |
|
dopamine transported into synaptic vescles and converted to NE by ________
|
beta-hydroxylase
|
|
all adrenoreceptors are linked to _____________
|
G-protein second messenger systems
|
|
where are a1 receptors located and what is there action?
|
- smooth muscles cells (eye, vascular (organs and skin), pilomotor, GI and urinary sphincters)
- contraction |
|
where are a2 receptors located and what is there action?
|
- SNS nerve terminals
- decrease NE AND - PSNS nerve terminals in GI tract - decrease ACh AND - Platelets - aggregation - |
|
where are B1 receptors located and what is their action?
|
- heart
- increase rate/force of contraction |
|
where are B2 receptors located and what is their action?
|
- smooth muscle cells (skeletal muscle vessels, bronchial tree, uterine, GI and bladder walls)
- relaxation |
|
where are B3 receptors located and what is their function?
|
- fat cells
- increase lipolysis |
|
what are the effects of the direct acting receptor agonists have on the heart?
|
M2 - decrease heart rate
B1 - increase heart rate |
|
what are the effects of the direct acting receptor agonists have on the blood vessels?
|
M3 - vasodilation
a1 - vasoconstriction |
|
what are the effects of the direct acting receptor agonists have on the blood vessels in skeletal muscles?
|
B2 - vasodilation
|
|
what are the effects of the direct acting receptor agonists have on most organ sysems/glands?
|
M3 - contraction - increase activity - increase secretion
B2 - relaxation of smooth muscle a1 - constriction of sphincters |
|
autonomic transmission can be inhibited or stimulated by chemicals that affect?
|
- neurotransmitter synthesis
- neurotransmitter storage - neurotransmitter release - receptor activation - neurotransmitter re-uptake or inactivation |
|
what are cholinomimetics?
|
mimic action of ACh
- direct (receptor agonists) - indirect (AChE inhibitors) |
|
what are the 2 types of cholinergic antagonists?
|
1. antimuscarinic
2. antinicotinic |
|
what are th examples of direct acting cholinergic agonists?
|
1. acetylcholine
2. bethanechol 3. muscarinic 4. pilocarpine 5. nicotine |
|
what agonists are AChE susceptible?
|
acetylcholine
|
|
what are the examples of indirect acting cholinergic agonists (AChE inhibitors)
|
- physostigmine
- echothiophate - carbamate - organophosphate |
|
what are the examples of cholinergic antagonists?
|
- atropine (M-)
- trimethaphan (Nn-) - D-tubocurarine (Nm-) |