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123 Cards in this Set
- Front
- Back
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Qualitative pharmakodynamics have 3 properties:
(hint: pharmocology big pic) |
1. drug receptors properties
2. drug properties 3. drug-receptor interactions (blind date) |
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inportant drug receptor properties are the interface of drugs, usually Membrane bound protein, 2 properties include:
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1. selectivity (why do what do & act where they act, ie. soft tissue R's)
2. binding (reversibe, irreversible) |
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what do you know about reversible vs. irreversible rxn's
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rev: weak bonds (ionic, H, van der waals)
irrev: rare, rule: covalent (NO & aspirin) |
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all drugs are chemicals that ionize at biol pH, they're:
a)weak acids b)weak bases c) strong acids and bases d) a & b |
d.
and has preference for h2o or lipid. more ionization = more water solubility |
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drug receptor interactions must have complementary binding. besides luck, what aids binding?
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steric factors (lock and key) & charges.
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a big division of pharmaceutical chemistry is structure-activty relcationsip, t/f. what is this?
p6 |
T. change molecular structure to increase/decrease biol activity to receptor. ie 3 vs. 2 pt contact
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what are the theories of drug action?
hint: there's 2. p7 |
occupation theory
perturbation theory |
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what's the difference between Action and Effect, when talking pharacology?
p7 |
Action - biological chagned initated by durg/receptor interaction
Effect - Endpoint of these chagnes (measurable) |
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what's the occupation theory?
p7 |
magnitude of dug effect is Proportional to # of receptors occupied (more R's = greater effect)
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What's the perturbation theory?
p7 |
signal transduction. drug physically binds to protein R & causes protein to change 3', change microenvironment and ultimately change in Cell (sum) ie muscle & Ca+
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drug Receptor interactions: what is efficacy?
another word for efficacy? p8 |
the ability of a drug to produced SPECIFIED effect, AKA intrinsic activity
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difference between the vocab:
Agonist/Antagonist/Partial Agonist p8 |
Agonist: = monitored effect
antag = no efficacy, inhibit Agoni Partial A = efficacy, <max effect |
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one drug, one receptor. T/F?
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F. drugs show degrees of selectivity over range of receptors
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What are acceptors?
hint: related to nonselectivity of drugs p8 |
show lowest oreder of selectivity. bind many unrelated drugs, usually b/c ionic attractions. (side effects) bind plasma proteins
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drugs must have a receptor to induce a response, weather it is occupational or perturbational. T/F
p8 |
F. drugs with no receptors. ie. antacides, anestetic gases
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quantitative aspects of drug action include looking at what interaction?
p 8-11 |
magnitude of response (& why), type of responses, dose response curves, and variability of population responses
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what determines the Magnitude of a drug?
hint: 4 p9 |
concentration (magnitude of effect = dose), efficacy, responsiveness (of target tissue), reflex actions
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what's the efficacy of a drug?
p9 |
max effect achievable by the agonist under immediate circumstances
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atropene not effecting kids hearts as much as adults is a good example of what?
p9 |
responsiveness of target tissue. kids already have high sympathetics going on (atropene blocks parasympathetic)
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net effect =______ - _______
p9 |
net effect=
gross effects - reflex effects |
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"types of responses" include what?
hint: good, bad, other p9 |
1. therapeutic response
2. side effects 3. placebo response |
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therapeutic responses are rationalized because they are?
p9 |
-dose related
-resulting from drug-receptor interaction (usually for dental) -occurs in ever patient (no drug 1 drug 1 effect) |
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t/f
there are beneficial side effects and adverse side effects. p9 |
beneficial "icing on the cake" (but don't add to the terapeutic usefulness).
adverse - toxic, harmful, unwanted, necessary often |
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% of placebo effect?
p10 |
25% of feeling better is from the anticipation of the beneficial effect.
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dose response curves:
what's the difference between graded dose resonse curves and quantal dose-response curves? |
graded (discrete units, measurable response, affinity, potency) Quantal (all or none, populations, info from quantal curves: ED50, LD50 TI)
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_ _ _ _ _ _ dose response curves
1.discrete units 2. 1 subject 3. X-axis is ___, Y axis is _____. 4. affinity (drug to receptor) 5. potency aka ______ p 10 |
graded dose response curve:
Y axis - response in units X axis - Log units - creates sigmoidal shape Threshold. (often measured at the midpoint of the dose- response curve) |
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T/F
High affinity = high efficacy p10 |
Affinity is force of attraction b/w drug and receptor, shape dependent. Threshold (potency) is the midpoint of the dose-response curve Not a measure of the MAx effect (which would be the efficacy of the drug)
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_ _ _ _ _ _ _ dose response curves
1. all or none (arbitraty endpoint) 2. population measure (0-100%) 3. X axis - 4. obtainable information 1, 2, 3? p11 |
Quantal Dose Response Curve
x axis - log units (as with graded) obtainable: 1. ED50 2. LD 50 3. Therapeutic Index |
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What's the difference b/w ED50 and LD 50?
p11 |
ED 50 - desired effect in 50% of study population
LD 50 - death produced in 50% of the population (toxicity related) |
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t i ?
p11 |
Therapeutic Index --> LD50/ED50
crude indicator of safety of a drug. LARGER TI = safer drug |
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there's at least 2 quantal dose-response curves for every drug, explain
p 12 |
one is for therapeutic effects, the other for toxic effects. compare and you have the MARGIN OF SAFETY
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what's the difference b/w ED99 and TD1?
p12 |
the margin of safety
(no drug actually has a margin of safety) |
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what does one call LD1-ED99?
p13 |
Certain Safety Factor - ultimate margin of safety
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_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ - sum of all intangibles that influence an individuals response to a drug. sometimes called "innate variability" b/c not well understood and unpredictable
p13 |
biological variation
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what's the % of people a drug company serves, and why?
p13 |
90%, because 5% hyperresponders and 5% hyporesponders, 90% get the general effect. This is seen on a Bell Curve.
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what's the difference between caution and contraindication?
p 14 |
caution - risk may outweigh benefit
contraindication - risk definitely outweighs benefit and MUST not use |
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what is antagonism, and what are the 4 types of antagonism?
p14 |
effects of one drug inhibiting the effects of a 2nd drug.
1. chemical 2. biochemical 3. physiological 4. pharmacological |
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what's the difference b/w chemical, biochemical, physiological and pharmacological antagonisms?
p14 |
Chemical - physical or chem properties altered by antagonist
Biochemical - 1 drug increases metabolism of excretion of 2nd drug (ie antibiotics and birth control) Physiological - 2 drugs, on different R's produce opposite effects Pharmacological - 2 drugs for one R, but only one displays efficacy |
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Competetive Antagonism vs. Noncompetetive Angagonism?
p 14-15 |
competitive - agonist & antagonist 1 R, reversible binding.
noncompetetive - bind same receptor, but irreversibly or Binds to a Different site that alters access to the agonist to its receptor. |
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competitive antagonists in a dose response curve show a shift to the right ... what's happening to the agonist?
p15 |
losing potency but not efficacy
(thus it takes more drug to see the threshold effects) |
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T/F
Antagonism is surmountable p15 |
T, just put enough agonist into system & the antagonist can be overcome
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name three augmentation effects
augmentation effect - the actions of on drug increasing the effects of another drug p15 |
1. additive effects
2. potentiation 3. synergism |
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what's the difference between additive effects, potentiation & synergism?
p 16 |
additive - the combined effect of 2+ drugs acting simultaneously is equal to the sum of the expected individual effects
potentiation - nonagonist enhances agonist (ie, A blocks elimination of B, so B's effects UP) Synergism - 2 agonists make greater than sum of 2 individual effects (alcohol & sedatives) |
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_____ ____ - the delay b/w administration of the drug and first observable effects
p16 |
onset time
dependent largely on route of administration |
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_____ ____ - delay b/w admiistration of drug and time of greatest effect
p16 |
time to peak effect
increase can cause slight increase in this parameter |
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_____ ____ - timed point from where effect first seen (threshold)until effect no longer measurable.
p16 |
Duration of Effect
most effected by change in dose |
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_____________ - the study of how drugs move in the body, incl. absorption, distribution, biotansformation (metablolism) & excretion
p18 |
pharmacokinetics
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according to picture, where are the locations of where absorption of a drug take place?
p18 |
Free Drug --> Tissue Depots
--> bind lasma proteins (stays in blood) --> site of action (the Receptor) --> biotransformation (metablolites) --> excretion |
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what determines the best route to be used when administering a drug?
p18-19 |
1. therapeutic characteristics
2. drug characteristics |
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whats the difference b/w therapetic and drug characteristics with administering a drug?
p18-19 |
therapeutic - pt specifics. ie location of where drug is needed, convenience of use, compliance, severity of situation
Drug - physical characteristics, like if drug is destroyed by stomach acid, or damage muscle if injected |
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big picture: the ways, or "routes" of drug administration include
p19 |
enteral - absorbed via GI system
oral route - swallow tablet topical route - on oral mucosa parenteral - given outside GI tract |
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T/F
absorption - the movement of Drug from site of Administration into Blood p19 |
T
or not blood, but for local anaestetic, whatever the site of action is |
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is absorption a passive or active process?
p 19 - 20 |
both. by far most commin is passive thru lipid and water barriers (into blood) Active's are ionized Against conc gradient, requires E
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how does henderson hasselbach play into absorption?
p19 |
drugs are weak electrolytes (ionized/nonionized forms) relative amnt of either depends on the pKa of a drugh and pH of environment
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how can one utilize concentration gradient to get more drug to target?
p19 |
just add more molecules at site of administration. passive diffusion (random motion) bring more drug through
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T/F
noncharged forms penetrate through the membrane surface covered by hydrophilic phospholipid heads p19 |
true
ionized (water soluble) can pass too - through pres/gaps (<200 gm) |
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what's a good way to think about facilitated diffusion - where ionided drugs passive cross membranes?
p20 |
a cat on a buey
charged drug binds to carrier causing conformational change, pulls binding site inside and drug drops off. can be saturated process |
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the greater the amnt of _______ around site of administration, greater likelihood will find its way into the blood stream
p21 |
vasculature
surface area also effects how fast drugs get in (lungs - smoke), villi |
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distribution of drugs to body tissues relies on 3 factors
p21 |
1.binding
2. compartmental pH 3. relative blood flow |
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T/F
bound drugs can pass through membranes to move towards receptors ... can utilize a concentration gradient |
F
only free drugs can pass through membranes. 1:1 binding, 1:9 binding. |
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define: biotransformation
p22 |
altering the molecular structure of a parent drug, usually by enzymatic actions that add moieties of cleave off sections of molecule (often to get rid of it)
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nonsynthetic rxn: referred to as ____ _ rxn b/c they occur first and procure changes in molecular structure tha facilitate the later ____ _ rxn
p23 |
phase I/II
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most common fate of drugs is what?
hint: molecule reacts with drug p23 |
oxidation. cytochrome p450 system. requires reducing agent NADPH
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what's the difference b/w reduction and hydrolysis?
p23 |
reduction - add H
hydrolysis - involves cleaving of molecule |
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synthetic rxn - referred to as ___ _ rxn. add organic groups, ie glycine rendering the drug inactive
p23 |
phase II
oftena 2' rxn w/ a phase I matabolite |
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define: altering biotransformation rate
p23 |
responses to drugs that're frequently influence by changesin biotransformation caused by disease and drugs
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what is "induction of drug metabolizing system?"
p24 |
increase in # of biotransfmormation enzymes in liver and elsewhere.
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"induction of drug metabolizing system", are seen significantly when?
p24 |
1. with tolerance. tolerance b/c more enzymes to drug
2. enymes of other drugs lead to biochem antagonism |
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how might biotransformation be interefered with?
p24 |
1. if liver's damaged (hepatocytes can't metabolize).
2. competeing substrates for same enzymes (synergism/potentiation) 3. 1 drug intereferes with enzyme of 2nd drug (2 agaonists/agonist,nonagaonist) |
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renal excretion, 4 steps: glomerular filtration (into collecting tubules), passive diffusion (uncharged form of drug move passively down conc gradient, how else?
p25 |
active secretion and reabsorption
ion trapping |
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catch phras for ion trapping is what?
p25 |
"an acid in an acid crosses"
a weak acid in an acid environment is noncharged, so it moves thorugh lipid membranes into blood |
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T/F
changing acidity of urine can influence excretion fo drugs and their metabolites p26 |
T.
heroin users eat baking soda to get things basic, to keep the acidic drugs in bloodstream |
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what is the "cycling" called which leaves drugs in the feces mostly?
p26 |
enterohepatic cycling
lipid soluble drugs that're metabolized slowly are recycled a few times |
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how does enterohepatic cycling work?
p27 |
drug absorbed GI to hepatic portal blood --> most to bile (b/c lipid soluble drug) Small intestine (s.o.oddi) cycles again
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besides feces and urine, how might excretion exist?
p27 |
mothers milk, sweat
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define:
elimination half-life p27 |
time for amount of drug in body to be reduced 50%.
Considered eliminated after 4 1/2 lives have passed |
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what's the difference b/w PSNS and SNS (fibers and ramifications)?
p32 |
PSNS: ganglia next to organs. local changes. pre-post = closer to 1:1. (GI 1:1800).
SNS: discrete & general fx. transverse more ganglia, then 1:20. Postganglionic can get input from more than 1 preganglionic N |
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PSNS or SNS?
interested in conserving energy and maintaining baseline organ fxn p32 |
PSNS
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what is unit firing?
p 32 |
SNS has genralized activation of all parts of SNS to stress, even Adrenal medulla fires epi off (modified sympathetic ganglion)
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PNS & PSNS usally work against eachother, however there is an example of when they work cooperatively, when is this?
p33 |
sexual function
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what is the preganglionic neurotransmitter for SNS? how about PSNS?
p33 |
both use Ach
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neurotransmitter postganglionically? exceptions?
p33 |
PSNS - Ach (all)
SNS - NE (most) - EPI (adrenal medulla) - ACh (blood vessels of skeletal Muscles) |
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table p 35 - autonomic innervation of effector organs. which uses muscarinic receptors?
p35 |
PSNS
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cholinergic vs adrenergic?
p35 |
cholinergic - ach
adrenergic - e/ ne |
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biosynthesis of ACh?
p34 |
within cytoplasm of cholinergic nerve, choline acetylase catalyzes transfer of actyl group from actyl coA to choline
choline is actively transported into nerves (limiting step) |
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storage and release of Ach?
p34 |
stored in vesicles in nerve varicosities. depolarization of varicosity in intracellular Ca++ = movement of coalescence of storage vesicles with nerve membrane. exocytosis
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termination after release of Ach?
p34 |
all ACh rapidly hydrolyzed into acetate and choline by acetylcholinesterase (from effector cell memB)
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what if ACh reaces the blood, regarding termination?
p34 |
hydrolyzed via butyrylcholinersterase (pseudocholinesterase) that's found free inplasma
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what's difference b/w nicotinic R's and Muscarinic R's?
p35 |
Nicotinic: R's respond similar to how nicotine on autonimic ganglia react. postganglionic N's of skeletal M's
Muscarinic: those similar to muscarine response. all effector cells postglanglionic, cholinergic S & PSNS |
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pilocarpine is a prototypical agonist. effects salivation, blood flow, how? indications.
p36 |
increased salivation for xerostomia - copious, watery saliva formed. more blood flow to glands. Muscarinic R's activated.
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contraindications of Pilocarpine?
p37 |
asthma - muscarinic R's on bronchial smooth M - constriction (bad). secretions block too.
Ulcers - more HCl secretion, exacerbates gastric ulcerations |
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warning for pilocarpine?
p37 |
can decrease viual acuity (contraction of ciliary M). rounding of lens.
bradycardia occurs with stimulation of muscarinic R's on AV node. Hypotension b/c vasodilation in periphereal vessels having muscarinic R's (noninervated) pulmonary disease - emphysema too |
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a _____ blocking agent is used in dentistry for a dry field for an impression, for example.
p38 |
cholinergic blocking agent. such as Atropine Sulfate, Propantheiline, Glycopyrrolate, and Hyoscyamine
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how does the mechanism of cholinergic blocking agents work?
p38 |
agents are competetive, pharmalogical antagonists of ACh. block ACh in salivary gland production and secretion of saliva down.
higher Affinity for muscarinic R's than nicotinic |
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Cholinergic Blocking Agents used in Dentistry? hint - there's four, chemical and common names
p38 |
1. Atropine sulfate (SAL TROPINE)
2. Propantheline (PRO-BANTHINE) 3. Glycopyrrolate (ROBINUL) 4. Hyoscyamine (CYTOSPAZ) |
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contraindications of Cholinergic Blocking Agents in dentistry
p38-39 |
1. glaucoma (blindness) Y
2. heart patients' 3. young patients 4. elderly 5. prosthatic hypertrophy Y 6. Ulcerative colitis Y 7. Asthma |
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_____ is the mj role of SNS. it is involedi n the moment to moment physological adjustments necessary for normal fxning. especially important for regualting ____ system.
p40 |
SNS
cardiovascular system` |
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Phenylanaline and tyrosine are the starting blocks of what neurotransmitter?
p40 |
for biosynthesis of NE and epi, the adrenergic transmitters. made from food, transported from the blood into nerves.
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Tyrosine hydroxylase is rate limiting. TH and DBH are upregulated by _____.
what process are we talking about? p40 |
cortisol
process of biosyntehsis of NE/Epi |
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T/F
40% of all NE in nerve varicosity is located in Mobile pool #1, what's that? where's the rest? p40 |
Mobile pool #1 is NE floating free as molecules in the axoplasm.
the remainder (60%) is located in the granules |
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describe release of NE
p41 |
depolarization of varicosity membrane -> increased intracellular Ca++ -> movement and coalescence of stroage granules with nerve memB & exocytosis in "quantum"
(NE, ATP, DBH dopamineBeta Hydroxylase) |
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how does termination of adrenergic nerves (ie NE)occur (after released from nerve varicosities)?
p41 |
back into cytoplasm of varicosity via transporter (active). then it's repackaged (via active transport proteins).
Some is metabolized via MAO (mitochondria) |
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how does termination of Epi, NE (exongenous) occur after being released from adrenal medulla?
p42 |
reaches some receptors via blood. termination when goes through liver, via COMT. Because lower transmitters, conc. gradient changes and stops action
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adrenergic R's are in 2 groups, __ & ___ based on affinity of standard seris of adrenergic agonists. contain how many transmembrane segments linked to G proteins?
p43 |
Alpha and Beta adrenergic Receptors.
7 transmembrane segments are linked to G-proteins |
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difference between alpha 1 and beta 1?
p 43 |
alpha 1 - adrenoR activation = excitiatory (intracellular Ca++). the R's are postjxnal
Beta 1 - adrenoR activation = excitatory in Heart. also post jxnal R's |
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difference b/w alpa 2 and beta 2 Receptors?
p43 |
alpha 2 - adrenoR = inhibitory effectsb/c opening of K+ channels = depolarization (either post, pre, or nonjxnal)
beta 2 - inhibitory effects too. also post jxnal, prejxnal or nonjxnal |
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____ receptors - are linked to stimulation of denylate cyclase activity
p43 |
beta receptors
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T/F Direct acting agonists are agents that bind to adenoR's to initate their pharmacological activity.
p43 |
T
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adrenergic stimulants Smimetics
phenylephrine (NEO-SYNEPHRINE) - agonist? NE (LEVO-PHED) agonist? levonordefrin (NEO-COBEFRIN)? p43 |
phenylephrine (NEO-SYNEPHRINE) - pure Alpha agonist 99:1
NE (LEVO-PHED): mixed a/b 85:15 levonordefrin (NEO-COBEFRIN) mixed a/b 75:25 |
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adrenergic stimulants Smimetics
Epi(ADRENALINE) agonist? isoproterenol (ISUPREL) ? Albuterol (PROVENTIL) ? |
Epi(ADRENALINE) - a/b 50:50
isoproterenol (ISUPREL) - b 1:99 Albuterol (PROVENTIL) pure Beta |
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____ acting agents - agents with no affinity for adrenoreceptors but can elicit S effects by causing increase in amnt of NE in vicity of ___ R's
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Indirect acting agents -
increase NE in vicinity of adrenergic R's |
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what are 2 examples of indrect acting agents of Adrenergic stimulus (sympathomimetics)?
p43 |
amphetamine - increase of normal NE leakage = activates significant amnt of R's
Cocaine - blocks actions of NE transporters, slowing reuptake. longer R occupation and frequency |
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phenylephrine likes what kind of R's? response?
p44 |
alpha 1 adrenoR's (excitatory) = contraction of muscles and secretion of glands
phenylephrine is sympathomimetic |
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alpha 1 adrenorecepotrs are excitatory, so if one injects phenylephrine, the radial muscle of the eye will react how?
p44 |
radial Muscle of the eye will contract, causing a widening of the pupil (mydriasis) = night vision
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alpha 1 adrenorecepotrs are excitatory, so if one injects phenylephrine, the blood and savlivary glands will react how?
p45 |
smooth muscle in skin & salivary glands blood undergo Contraction. (blood to brain & muscles). The salivary Glands secrete thick ropey, (^ resp)
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if albuterol cuases relation of smooth M and decrease in glandular secretions, what type of receptor is it working on?
p45 |
beta 2 receptor, b2 adrenoreceptor, leads to inhibitory responses
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if one takes albuterol, what is the effect on ciliary m of eye, hepatic blood vessels, and bronchioles?
p45 |
albuterol - b2 adrenoreceptor
ciliary - relax, lens flattens = far vision hepatics - relax, ^ blood in liver, helps ^ glc from liver (for brain/muscles) broncholes - relax, opening cirularly, more O2 intake |
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what's the effector with predominate bea 1 receptors? fx?
p45 |
the heart has predominately beta 1 receptors = excitation. atrial & ventricular M = ^ automaticity and force of contraction.
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beta 1 R's on nodal cells?
p46 |
stimulation of the R's on the SA node will lead to an ^ in atrial contraction & ^ HR, b/c AV node and conduction sys is also excited so that they will carry increased activity to the ventricles
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both Sympathetic postganglionic adrenergic and cholinergic N's innervate smooth m. of blood vessels. At rest tone dictated by which?
p46 |
by adrenergic input
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alpha 1 adrenorecptors are the ___ abundant and are associated with the sympathetic postganglionic adrenergic nerves, stimulated by _ _ released from the Nerves
p46 |
alpha 1 adrenorecptors are the *least abundant and are associated with the sympathetic postganglionic adrenergic nerves, stimulated by *NE released from the Nerves
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muscarinic R's are ____ abundant and are associated with sympathetic postganglionic n's. stimulated by _ _ release.
p46 |
muscarinic R's are more abundant and are associated with sympathetic postganglionic n's. stimulated by ACh release.
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beta 2 adrenoreceptors are ____ abundant and are not associated with ____ (nonjunctional). stimulated by _ _ released from ____ during stress.
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beta 2 adrenoreceptors are *Most abundant and are not associated with *nerves (nonjunctional). stimulated by EPI released from *adrenal medulla during stress.
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