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363 Cards in this Set

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any substance that brings about change in biologicfuncFon through its chemical acFons; used for the treatment,cure, prevenFon or diagnosis of specific diseases or clinicalcondiFons

drug

an inactive form of a drug that is converted to anactive form in the body

prodrug

any chemical that is considered foreign to abiological system (e.g. a drug in a patient); can be a naturalcompound if it is not expected to be present but usually refersto drugs, pollutants or other toxic compounds that get into thebody

xenobiotic

qualitative description of how the bodyhandles the drug; includes how the drug is absorbed, where it isdistributed, how it’s metabolized, and how it’s eliminated fromthe body (ADME)

drug disposition

quantitative description of drug disposition

pharmacokinetics

the actions of the drug on teh body; usually mediated through drug actions on specific cellular receptor proteins

pharmacodynamics

the study of drugs

pharmacoloty

the preparation of dispensation of medications

pharmacy

the study of the harmful effects of chemicals including drugs

toxicology

what are the three main routes of drug administration?

enteral (through the GI tract)


paraenteral (into the body by any route other than the GI tract, initially bypasses the liver)


topical

what are the three forms of enteral drug administration?

sublingual, oral, rectal

for oral drug administration, teh drug must first disolve in __

GI fluids

what is the major site of oral drug absorption?

small intestine

how are rectal drugs administered?

suppository preparations

what are the three kinds of paraenteral drug admnistration?

injection, inhalation, intranasal

what are the 4 kinds of injection drug administration?

subcutaneous, intramuscular, intravenous, intrathecal

kind of injection that has instantaneous delivery to systemic circulation

intravenous

kind of injection that bypasses the blood brain barrier

intrathecal

volitile anethetics, aerosols, and dry (micronized powders) are all methods of __ drug administration

inhalation

drugs that have a local action on nasal mucosa (decongestant, anti-allergy); vaccines are administered via __

intranasal

what are the two kinds of topical drug administration?

ophthalmic, dermal

drug administration route that uses the instillation of drops into the eye for a local effect

ophthalmic

topical drug administration route that has a local action, and a possible systemic action via transdermal patches applied for a prolonged effect

dermal

the __ affects time to onset of the therapeutic effect

rate of absorption

the rate of absorption of intravenous drugs

30-60 seconds

rate of absorption of inhalation

2-3 min

rate of absorption for sublingual

3-5

rate of absorption for intramuscular

10-20 min

rate of absorption for subcutaneous

15-30 min

rate of absorption for rectal

5-30 min

rate of absorption for ingestion

30-90 min

rate of absorptoin for trasdermal

variable (min-hr)

the process of getting a drug from teh point of administration into teh systemic circulation

drug absorption

getting drugs into the body

absorption

moving drugs witin the body

distribution

removing drugs from teh body

excretion

in order to get drugs into, around, and out of teh body drugs must be able to __

cross biological membranes

what are two mechanisms of passive transfer?

filtration, passive diffusion

passive transfer of drug molecules by passage through membrane pores. this is the process for getting drugs out of circulation and into tissues in all areas EXCEPT the CNS; includes glomerular filtration of drugs into renal tubules for excretion

filtration

the most important proces for getting drugs across cell layers

passive diffusion

the passage of drugs by dissolving in and diffusing across the phospholipid bilayer

passive diffusion

what must happen to allow for passive diffusion to occur?

the drug must be sufficiently "lipid soluble" due to te hydrophobic nature of teh interor of the phospholipid bilayer

what happens to a drug in regards to passive diffusion if it is ionized or it contains water soluble functional groups?

it will not diffuse easily

in passive diffusion, net transfer is dependent on teh exisitence of a __ across the membrane

concentration gradient

drug transfer during passive diffusion will proceed until the __

concentration is the same on both sides of the membrane (equillibrium)

what maintains the concentration gradient in passive diffusion?

tissue blood flow

what are the three methods of carrier-mediated transfer?

active transport, facilitated diffusion, uptake transporters

kind of carrier mediated transfer where the drug is transfered across membranes by specific transporter proteins.


these are structurally selective and saturable; amenable to competitive inhibition.

active transport

active transport is energy dependent. it transports drugs __

against concentration gradients

in active transport, drug transfer proceeds until __ or __ is depleted

drug stubstrate, ATP

kind of carrier mediated transfer that is energy independent, it transports drugs WITH their concentration gradients. drug transfer proceeds until equilibrium is reached

facilitated diffusion

in carrier mediated transfer, __ move drugs in to cells, __ move drugs out of cells and tisseus

uptake transporters, efflux transporters

the percentage of administered drug that reaches the systemic circulation by any route

bioavailability

what are the bioabailability of drugs given IV?

100%

what 3 things does bioavailability depend on?

1. chemical form of drug




2. amoutn of contact time with absorbing surface




3. presence fo drug metabolizing enzymes and efflux transporters that may eliminate the drug before it reaches the systemic circulation

what are 3 effects of exercise on drug absorption?

1. reduced splanchnic blood flow during or after exercise may reduce oral absorption




2. increased absorption for SC, transdermal, IM and inhalation due to increased blood flow




3. increased skin temp increases transdermal absortpoion of antianginal agent, nitroglycerin

why is it important that tissue distrubtion of drugs throughout the body is not uniform?

becuase drug concentration at the anatomical site of action determines the pharmacological effect

what are three factors that determine drug distribution?

1. blood flow and tissue mass/volume




2. capillary permeability


-periperal capillaries are porous (filtration into interstitial fluid is rapid)


-CNS and placental capillaries are non-porous; provides some limits to distribution to these tissues




3. lipid solubility of the drug vs lipid content of teh tissue (highly lipophilic drugs can accumulate in adipose tissue)

defined as the volume (in liters per kg body weight) a drug appears to be containedin, relative to the concentration of drug in teh blood

volume of distribution

what is the equation of volume distribution

Vd=amount of drug in teh body/concentration of drug in the blood

what does volume distribution really tell you?

is the drug mainly in tissues or in the blood

what does a low Vd mean?

the drug is confined to teh circulation and will be eliminated rapidly by teh kidnes

what does a high Vd mean?

drug will remain in teh body longer. kidneys will have difficulty eliminating the drug (unless it is metabolized)

any drug in teh blood is present both __ and __

free in solution, reversiblty "bound" to plasma protiens (mainly serum albumin)

binding to plasma proteins are __

saturable (when all binding sites are occupied, free drug concentration increases

what is the basic purpose of drug metabolism?

drugs that enter the body are usually too lipid soluble to be excreted rapidly enough to prevent toxicity. drug metabolizng enzymes turn these into more water soluble metabolites that can be excreted.

enzymes that metabolize and transport drugs are concentrated at the __. this ___

portals of entry; decreases the likelihood that chemicials will reach systemic circulation ina form which they might accumulate

where are teh locations of enzymes that metabolize and transport drugs and which is teh most important, and initial

liver (most important


small intestine (initial site of drug metabolism after oral dosing; conributes to 1st pass effect)


nasal epithelium and lung


skin


plasma


kidney


CNS

what is the first pass effect?

when metabolism of drugs by liver enzymes can be high enought ot remove most of teh drug from teh portal system passing through the liver

what do phase 1 enzymes do?

oxidizes drugs, product may be active, inactive, toxic, or nontoxic.

what is the most important phase 1 enzyme?

cytochrome p450

what three CYP subfamilies account for teh metabolism of most drugs?

3A, 2C, 2D

what phase one enzyme is involved in the metabolism of >50% of all drugs?

CYP3A4

what do phase 2 enzymes do?

convert drugs to inactive metabolites

phase 2 enzyme that adds glucuronic acid to produces of phase 1; product is termed a glucuronide conjugate

UDP glucuronyltransferase (UGT)

phase 2 enzyme that adds sulfate; product is sulfate conjugate

sulfotransferases (SULT)

what are the 5 phase 2 enzymes?

UGT, SULT, GST, NAT, MT

phase 2 enzyme that acetylates drugs

N-acetyltransferase (NAT)

phase 2 enzyme that methylates drugs

methyltransferase (MT)

enzymes that act in concert with pahse 1 and 2 enzymes to trasnfer drugs and their metabolites across membranes

pahse 3 (efflux transporter proteins)

explain what ATP binding cassette (ABC) transporters are

MDR! (P-glycoprotein)




pumps drugs from cells itno urine, bile, and intestinal lumen




pumps drugs out of the brain




pumps anti-cancer drugs out of cancer cells

what happens if a drug is metabolized too rapidly or too slowly?

rapidly: may never reach a therapeutic blood level




slowly: accumulates and causes an excessive clinical response/toxicity

what three things effect drug metabolism?

enzyme induction


enzyme inhibition


pharmacogenetics

what is enzyme induction and how does it affect metabolizing?

a reversible, adaptive response that INCREASES the rate of drug metabolism and or transport





how can enzyme induction affect the body by increasing drug metabolism?

reduces therapeutic blood levels necessitating an increase in dosage




may increase the production of toxic metabolits

how does enzyme inhbition decrease the rate of drug metabolism?

decreases the rate of drug metabolism and or transport

how does enzyme inhibition occur?

when two or more drugs compete for the same drug metabolizing enzyme

__ is the major cause of drug interactions in patient taking multiple drugs

enzyme inhibition

grapefruit juice causes the enzyme CYP3A4 in GI epithelium to increase oral bioavailability of many drugs. this is an example of __

enzyme inhibition

tobacco smoke increasing CYP1A1, Charcoal broiled foods increasing CYP1A2, ethanol incresaaing CYP2E1, and st. johns wort increassing CYP3A$ and PgP are all examples of __

enzyme induction

the individual variability in drug responses

pharacogenetics

ethinic subpopulations with faster or slower raes of drug metabolism like CYP2D6 causing poor, extensive, and ultra-rapid metabolizers of certian drugs and NAT-2 causing fast and slow acetylators of certain drugs (TB drug isoniazid) are examoples of __

pharmacogenetics

genetic variation accounting for pharmacogenetics can occur from __, __, and __

SNP (polymorphisms), duplications, or deletions

how does overall excretion of drugs occur?

can be removed by kidneys if sufficiently hydrophilic. lipophilic drugs are eliminated by metabolism but their hydrophilic metabolitse must be revomed by the body by teh kidneys

what are the components of total urinary excretion?

glomerular filtration+(passive diffusion-passive reabroption)+ (carrier mediated efflux-carrier mediated reuptake)

how does biliary excretion occur?

active transport of comparatively large mostly anionic molecules from liver or bile, which is secreted itno the duodenum.




the glucoronide metabolizes the drug in the bile back to the free drug and be reabsorbed (enterohepatic recirculation)

how does enterohepatic recirculation occur?

gluconruonide conjugates excreted into the bile can be metabolized to the free drug by GI bacterial B-glucuronidase; free drug can then be reabsorbed.

what are thee other(minor) routes of excretion?

pulomonary (volitile comounds ie ethanol/anesthetic gases)


sweat and saliva


breast milk

any drug taken via the stomach-proximal colon goes to the __ vien

portal. to the liver to be processed

__ and __ and entereal rounts of admnistration which avoid the liver.

sublingual, rectal

what does intrathecal injection mean?

injection into sub-arachnoid space

what route of administration might be better for a drug that needs slow distribution?

dermal

blood with drugs from teh stomach/proximal colon go into the __ into the liver to be metabolize

portal vein

what does intrathecal mean?

injecting a drug into the subarachnoid space

how does the body maintain a concentration gradient from the blood to itssues?

the blood washes drugs away maintaining the gradient

carrier mediated transfer can become __ and has an __ for certain drugs

saturated, affinity

efflux transporters are important for __ functions

barrier

explain volume of distribution

its a ration of teh amount of drug in teh tissues to the amount of drug in teh blood. the higher the Vd, the more in the tissues. the lower the Vd, the more in the blood

most important phase 2 enzyme

UGT

drug metabolizing enzymes that conjugate drugs to make them inactive

phase 2 enzymes

allows metabolites to leave cells b/c they’re too hydrophillic to do so on their own.

phase 3 enzymes

most important phase 3 enzyme

ABC (ATP binding cassette)

drug inhibition occurs when __

two drugs are competing for the same enzyme

how do you find the therapeutic range?

its the difference between the minimal effective does and the minimal toxic dose.

why is it more effective to use an infusion than a bolus?

an infusion accumulates to a constant level whereas a bolus is continually eliminated

what is the clinical significance of drug levels in teh blood?

although the blood is not the site of action for ost drugs, there is a direct correlation between therapeutic and toxic responses in tissues and teh amount of drugs in teh blood. thus, a minimum effective level in teh blood can be defined for most drugs

a period of latency between drug adminisration and onset of teh desired effect; depends on teh rate of absorption

time to onset

the maximal level attained after drug administration; usually correlates with the intesnity of the pharmacological effect

peak drug level (Cmax)

the amount of time spent above teh minimal effective level

duration of action

what determines the duration of action?

the rate of elimination (metabolism+excretion)

when drug levels fall below the __, the drug response ceases

minimal effective limit

what is the execption to the rule of drug effects ceasing after the drug level falls below the MEL?

if drug action persists after drug levels fall below MEL when the response is due to irreversible binding of the drug to its target (eg aspirin effects on platelets). once the drugs effect a tissue, that tissues stays that way permenantly.

indicate how cautious clinicians should be in using and instructing pts to use a drug. incorporates a margin of saftey.

therapeutic range

at therapeutic doses, most elimination processes (renal, hepatic metabolism) are __; ie the rate of elimination is proportional to the amount of drug present

1st order

what does it mean if an elimination process is 1st order?

the more the drug there is, the faster the eliminatino

explain how you can get information on first order kinetics of drugs elmination from a blood concentration curve?

you take the log of the y axis to get a linear curve.

what does teh beta from teh log curve for 1st order kinetics elimination tell you?

how fast the drug is eliminated

how can you use the the log curve for the drug concentration graph to find half life?

you find how much drug is present at time 0 and see how long it takes for half the drug to be eliminated.

half life is always the same b/c its a __ reaction

1st order

it takes __ half lives for a drug to efficently leave teh body

4-5

what is the equation fro volume of distribution?

Vd=dose/concentration at time 0

what do you do if volume of distribution is expressed in liters/kg body weight?

you multiply by body weight (ie 70 kg)

the volume of fluid from which a drug is completely removed in a given period of time (mL/min or L/hr) as it flows through teh body or through an individual organ

clearance (CL)

what can clearance be conceptualized as?

the rate of drug elimination (liver metabolism + renal excretion) relative to drug concentration in teh blood

what is the equation for clearnace?

metabolism + excretion/drug concentration

drugs with long half lives and large volumes of distribution have __ clearance and are __ soluble

long, lipid

what are 2 factors that affect volume of distrubtion?

aging: reduced muscle mass->decreases Vd->decreases half life




obesity: increased adipose ->increased half life





what are 3 factors taht affect clearance?

CYP induction: increases CL->decreases half life->need dose elevation




CYP inhibition: decreases CL->increases half life-> dose reduction




hepatic/renal failure ->decreases CL -> increases half life -> dose reduction

how is the clearance of creatinine used to adjust doses of drugs eliminated by the kidneys in pts with renal insufficiency?

if creatinine drops, it means kidney function isn't as high

explain the principle of multiple dosing regimins

the 2nd does is taken before teh first does is eliminated. each next dose is taken at the same interval. accumulation of the drug up to a steady state level occurs when DRUG INTAKE = DRUG ELIMINATION. drug levels will then always be in the therapeutic range

what factors affect steady state of multiple dose drug regimins?

if CL of teh drug is 1st order and teh dose interval =half life, then it will take 4-5 half lives to reach steady state

if a drug has a very long half life and its a multiple dose regimin, you may need a __

loading dose

drugs acting on enzymes usually try to __ them

inhibit

drugs that activate receptors (stimulates the receptors)

agonists

drugs that block receptors and prevent their activation preventing endogenous ligands binding to it

antagonists

determines how much drug it takes to bind to the receptor

affininty

what does a high or low affinity mean?

high affinity means you don't need much drug, low affinity means you need a lot of drugs

what are the four superfamilies of receptors?

ligand-gated ion channels-opened by ligand, lets ions in. ie nicotininc ACh




G protein coupled receptors-largest class on surface of cells. bind to ligand, activate signalling cascade to activate protein synthesis




kinase linked receptors




nuclear receptors-receptor not on cell surface, in nucleus ie steroid receptors

explain the drug response relationship

drug receptor binding is reversible




the number of recetpors in finite




at some drug dose, all teh binding sites will be occupied and the response is "maximal"

what does Kd on teh linear dose response curves represent?

teh dose of agonist that occupies 50% of teh recetpors

a measure of the affinity of the drug for teh receptor

Kd (the lower the Kd, the higher the affinity)

the dose that produces an "effective response" that is 50% of maximal

ED50 (on log dose response curves)

if antagonists bind to teh receptor, but do not activate it, their efects are produced by __

preventing the agonists form binding

the amount of drug required to generate a given fractional response aka how little/how much do you need to give for a response?

potency

how well the drug activates the receptor when its bound

efficiacy

produces 100% response when all teh receptors are bound

full agonsit

produces <100% response when all receptors are bound

partial agonist

the curve closest to the Y axis is the most __

potent

the curve that is higest is teh most __

efficacious

the __ the Kd, the more potent

lower

drugs that bind reversibly to the receptor and thus compete with agonists for binding

competitive antagonists

what is the effect of competative agonists?

decrease teh potency of teh agonist

in teh presence of a competitive antagonist, the agonist does response curve shifts to the __

right

the effect of a competitive antagonist can be reversed by __ the concentration of the agonist

raising

bind irreversibly to the receptor; no other agonists can "compete" for teh receptor

non-competitive antagonists

what is the effect of non competitive antagonists?

decrease the efficacy of teh agonist

in teh presence of a non-competitive antagonist, the agonist dose-response curve shifts __

down

the effect of the non-competitive antagonist __ be reversed

cannot

how do quantal dose response curves differ from "graded dose response curves?

in that it measures discrete outcomes

drug curve used to assess efficacy and safety of drugs in teh clinical trials

quantal dose response curves

how are quantal dose response curves recorded?

for each dose, teh number of patients in a population who respond to the drug is recorded

what is the equation for the therapeutic index?

TD50/ED50

waht is the equation for the margin of safety?

TD01/ED99

drug effect known from pharmacology and are dose-related; seldom fatal and are common

augmented pharmacological effects

drug effect that is unpredictable with high morbidity/mortality; uncommon

bizarre effects (idiosyncratic)

drug effects that only occur with prolonged treatment

chronic effects

drug effects that occur months to years after treatment; can occur in children of treated parents

delayed effects

drug effects that occur when drug is stopped suddenly (withdrawl)

end of treatment effects

the official FDA aproved name of a drug. every drug has 1 of these

generic name

the name each manufacturer gives its product; a drug can have many of these. first letter is capitalized

trade name

superfamily of receptor that uses the flow of ions that causes hyper/de polarization to cause cellular effects. takes milliseconds. examples are nicotinic and ACh receptors

ligand gated ion channels

superfamily of drug receptor that uses second messengers that causes phosphorylation and cellular effects. takes seconds. examples are muscarinic ACh

g protein coupled receptors

superfamily of drug receptors that cause protein phosphorylation, gene transcription, protein sysnthesis, and cellular effects. takes hours. examples cytokine receptors

kinase linked receptors

superfamily of drug receptor that occurs in teh nucleus, cuases gene transcription, protein synthesis, and cellular effects. takes hours. examples estrogen receptor

nuclear receptors

sympathetic nerves exit from the __ and __

thoracic and lumbar spine

parasympathetic nerves exit from the __ and __

cranium and sacrum

compare/contrast somatic and ANS nerves

somatic: ganglia in CNS, 1 effert fiber, used for skeletal muscle, NT: ACh, denervation cuases muscle atrophy




ANS: gnglia outside CNS, 2 efferent nerve fivers (pre/post ganglionic (non-myelinated), smooth muscle/heart/exocrine glands, function: homeostasis, NT: NE and ACh, denervation reveals intrinic activity

contrast sympathetic and parasympathetic pre/postganglioiic fibers

SNS: short pre, long post


PNS: long pre, short post

what is the importance of the multiple postganglionic fibers innervated by 1 SNS preganglionc?

you can mobilize everything at once for fight/flight.

what doesn't have dual innervation?

blood vessels, sweat glands, and adrenal glands (only SNS)

what physiological function is mediated by a cooporation of the SNS and PNS nervous system?

sex

describe the anatomical arrangement of the PNS

long preganglionic, releases ACh, stimulates nicotinic subtype receptor.




short post ganglionic, releases ACh to affect muscarinic recepotr

describe the anatomical arrangement of the 3 SNS nerves

short preganglionic, releases ACh, affects nicotinic recepotr; long postganglionic, releases NE to affect alpha or beta recepotrs




short preganglionic, releases ACh, affects nicotinic recepotr. long post ganglionic, releases ACh, affects muscarninc recepotrs on SWEAT GLANDS




short preganglionic, releases ACh, affects adreneal medulla. releases epinephrine. binds to alpha and beta receptpors

the PNS affect on teh SA node, AV node, atria, and ventricles of the heart use a __ receptor and cause __ response

M2, decreased HR, decreased conduction velocity, decreased contractility

the PNS affect on the VSM and endothelium of teh blood vessels use a __ receptor and cause __ response

M3, constriction (NO release-dilation)

teh PNS affect on the broncial muscle and glands of teh respiatory tract use a __ receptor and cause __ response

M3, bronchiole constriction/secretion

the PNS affect on the moltility and tone, sphincters, and proton pumps of the GI tract use a __ receptor and cause __ response

M3, increase motility/tone, relax sphincters, secreted protons

the PNS affect on the genitoruniiary tract uses a use a __ receptor and cause __ responses in bladder detrusor, trigone and shpincter, and penis respectively

M3, contraction, relaxation, erection

the PNS affect on teh sphincter muclse of the iris, and ciliary muscle of the lens use a __ receptor and cause __ response

M3, contraction (miosis), contraction (near focus)

the PNS affect on the salivary glands uses a __ receptor and causes a __ response

M3, salaivation

the SNS affect on sweat glands uses a __ receptor and cuases a __ response

M, perspiration

the SNS affect on the adrenal medulla uses a __ receptor and causes a __ response

nictoinc, epinephrine release

the SNS and PNS affect on autonomic ganglia use a __ receptor and cuase _

nicotinic, stimulation

the somatic affect on skeletal muscle uses a __ receptor and cuases __

nicotinic, contractoin

what is the SNS effect on the SA node, AV node, and atria/venticles of the heart and what receptor is used?

inc HR, inc conduction velocity, inc contractility; beta 1

what is the SNS affect on the BV of the skeletal muscle and skin/mucosa? what receptors are used?

contriction/dilation of skeletal muscle, constriction of skin/mucosal; alpha 1 and beta 2 for skeletal muscle, alpha 1 for skin/mucosa

what is the SNS affect on brinciole muscle and what receptor is used?

relaxation; beta 2

what is the affect on teh bladder detrusor muscle by the sns and what is the receptor used?

relaxation; beta 2

what is the effect on the trigone and sphincter muscles by teh SNS and what recetpor is used?

contraction, alpha 1

what is the effects of SNS on the penis and what recetpor is used?

ejactulation; alpha 1

what is the effect of the sns on the radial muscle of the iris and what receptor is used?

contraction (mydriasis); alpha 1

what is the effect of the sns on the cilliary muscle (lens) and what recetpro is used?

relaxation (far focus), beta 2

what is the effect of the sns on the ciliary body and what recetpor is used?

aqueous humor secretion; beta

what is the effect of the sns on the uterus and what are the recetptors

contraction/relaxation; alpha 1/beta 2

what is the effect of the sns on the kidney and what recetpor is used?

inc release of renin; beta 1

explain the basics of synaptic neurotransmission

nerve impulse arrives a terminal button; opens Ca channels, Ca couses NT vessicles to exocytose and release NT into synaptic cleft.

onabotulinumtoxinA, muscarine, atropoine, noicotine, tubocurarine, mehtyldopa, and cocaine all affect teh __ fuction

presynaptic termianl function

what characteristic of ACh makes it very transportable in the body?

a postive charge on teh N atom, making it hydrophilic

what enzyme breaks down ACH into acetate and choline

acetycholine esterase

how does botulinum toxin work?

botulinum is a protein which gets inot the nerve terminal. prevents fusion of storage vessicle with terminal membrane. prevents release of ACh from nerve. causes flacid paralysis.

used for therapeutically treat muscle spasms/dystonias; facial wrinkles; hyperhidrosis, and urge incontinence by causing temporary cholinergic denervation

onabotulinumtoxinA

what are the side effects of botulinum?

if drug spreads beyond site of injection, dyphagia, breating difficulties; muscle weakness (ptosis), allergic reaction (rash)

teh duration of action for botulinum toxin is __. you may get an allergic reaction from it b/c its a __

3-6 months, forgein protein

what are two important points to educate PT pts on botlinum toxin use?

may have allergic reaction b/c its a foreign protein, effects are temporary

what are the effects of muscarine and atropine?

muscarine (stimulates muscarinic recepotrs)




atropoine (blocks muscarinnc recepotrs, leaves sympathetic nerves unopposed)

muscarine is a muscarinic __

agonist

atropine is a muscarininc __

antagonist

muscarinine __ activate nocotininc recepotrs

DOESN'T

substance found in amanita muscaria, a mushroom that produces all cholinergic responses, worst of all in GI tract

muscarine

found in deadly night shade, which roman women used to cause pupillary dilation

atropine

muscarine and atropoine are selective for the __ recepotr

muscarinic

compare teh two nicotininc recepotrs

Nn (ganglia): nictoine stimulates this receptor. Mecamylamine is an antagonist of this recepotr subtype




Nm (neuromuscular): nictoine stimulates this recepotr (tubocurarine is a competitive antagonists)

_ is an antagonist for Nn recepotrs

mecamylamine

__ is a competitive antagonists for Nm recepotrs

tubocurarine

__ is used as a neuromuscular blocking drug by copetitively antagonising the Nm recepotrs

tubocurarine

how does nicotine affect nictoinc recepotrs?

nicotine is selective for nicotinic receptors at teh NM junction and ganglia (Nm and Nn). it DOES NOT ACTIVATE TEH MUSCARININC RECEPTOR!!!. nictoine activates teh nicotinic receptors

explain the synthesis of catecholamine NT

all adrenergic NT come from tyrosine. then it gets converted to specific NT based on the tissues. tryosine->DOPA->dopinine (in BG)-.NE (SNS post-ganglionic neurons)->epinephrine (adrenal medulla)

explain the differences between how NT action in a synapse is decrease in cholinergic and andrenergic transmission?

cholinergic=enzyme


adrenergic=NET transporter

explain andrenergic transmission

NE is created in teh cell by converting tyrosine->DOPA->dopamine->NE. it is then packeaged into vessicles.




MAO (monoamine oxidase) is an enzyme in teh mitochondira that degrades dopamine/NE in teh cytosol)




once NE is released into the synapse, it is either removed by NET (pumps it back into teh presynaptic neruonr), it may stimulate alpha 2 recepotrs on teh Presyn cell which negatively feed back to decrease exocytosis. if NE gets to teh blood it will be removed by the ENT transporter

tranporter in teh blood which can have an affect on IV given NE like drugs

ENT

tranposrter in teh presynaptic cell that pumps NE back inot it

NET

receptor on the presynaptic andrenergic cell that negatively feeds back to inhibit NE release

alpha 2

how does dyramine affect the presynaptic cell?

tyramine is a dietary substance found in ceratin foods that gets into the nerve and dumps NT from teh cessicles into the cytosol. this reverses the concentration gradient for NET making the transporter dump NE into the synapse.

drug found in aged cheeses, beer/wine, smoked meats, etc, that deplaces all the NE form nerve terminals at once, changing the concentation gradient for NET, reversing its flow.

tyramine

why do we not get advers affects from tyramine normally?

its normally degraded byMAO in teh GI tract. systemic absorption can occur with pts taking MAOIS for depression

what is an adverse effect for people taking MOAI's which allow tyrosine to have affect?

hypetensive crisis

hwo does methydopa work?

it insertes itself into the biochemical pathway for NE/E production. it creates methyl'ed dopaine, NE< and E. these do not stimulates postsynaptic receptors but DOES HAVE AN AFFINITY FOR THE A2 RECEPTOR. this increases the negative feedback to decrease NE release.




you get decreased alpa 1 recepotrs in BV and B recepotrs in the heart. this decreases blood pressure.

what was methy-dopa used for, what are its adverse effects, and what is it used for now?

used as an antihypertensive, gave you parkinsons like symptoms b/c it got into dopminergic nerves in teh brain. its now used to treat high bp in pregnant women b/c its safe for the fetus

methydopa is __ which is converted to methyl-NE in adrenergic nerves

prodrug

what is teh mechanism of action of methyldopa?

agonist at alpha 2 adrenergic recepotrs, reducing sympathetic outflow from CNS

what is methyldopa used for?

antihypertensive

waht are the side effects for methydopa?

parkinsons like symptoms, sedation, dry mouth

what do you need to keep in mind as a PT iwth pts who are on methydopa? (2)

check BP, stay away from interventions that would increase vasodilation

how does cocaine affect the nerves?

it blocks the NET tranposrter. causing excess stimulation of post-synatpic recepors.




also has periphery affects: causes heart problems b/c of inceased B1 stimulation (increases HR)




blocks NA channels on axons, giving it local anesthtic affect

what is the mechanism of actin for cocaine?

blocks NET leaving NT in synapse.




blocks Na channels in sensory nerves

what are the therepueitc uses for cocaine?

local anesthetic for ENT

all adrenergic receptor subtypes are __

coupled to G proteins

alpha 1 receptpors are on __ and cuase __

smooth muscle, contraction

alpha 2 receptors are on __ and cause __

nerves, inhibitory effects (negative feedback)

beta 1 receptors are in teh __ and __ and cause __/__ effects

heart, kidney, excitatory/contraction

beta 2 receptors are in the __ , __, and __ and cause __

lung, skeletal muscle vasculature, uterus, relaxation

alpha 1's are on teh __ synaptic cel; alpha 2's are on teh __synaptic

post, pre

beta 1's cause and increase in __ and __

HR, contractility

beta 2 recepotrs cause __

relaxation

metabolzer of catecholamines that degrades NE/E, tyramine, histamine.




clears catecholamines in teh nere terminals




inhibitors elevate transmitter leves in neruons

monoamine oxidase (MAO)

metabolizer of catecolamines, cleasrs circualting catecholaines in teh liver/kidney.




inhibitors are used for parkinsons disease

catecholo O methytransferase (COMT)

what are teh pharmacokinetics of the drug acetylcholine?

IV administration: poor lipid solubility (bad bioavailability; short duration of action (<10) due to lots of cholinesterase in tissues; non selective (acts on both nicotinic and muscarininc recepotrs

acetylcholine is __, meaning it acts on both nicotinic and muscarinic recepotrs

non-selective

what are the 2 cardiovascular effects of aceytlcholine?

vasodilation (sitmulates muscarinic recetpors an vascular endothelium




stimulation of these receptors releases NO




NO diffuses inot vascular smooth muscels and cuases relaxation

what are 2 cardiac effects of acytelcholine?

negative rate (chronotropic) effects




negative contractility (inotropic) effects





what are teh smooth muscel effects of acetylcholine?

increases tone, amplitude of contraction, peristalitic activity, and secretory activity of GI.




contracts bronchiolar, uterine, urinary smooth muscles

what are the glandular effects of aceytlcholine?

salivary, lacrimal, diestive, and tracaeobronchial secreation




sweat gland stimulation (sympathetic)

what are teh occular effects of acytelcholine?

contraction of sphincter mucle of iris, produces miosis (pupil constirction)




contraction of ciliary muscle (focuses eyes for near vision)

what is the clinical use for acytelcholine?

opthalmic

how do synthetic choline esters and alkoloids differ from acytelcholine?

there are more selective and have a more prolonged action

synthetic choline esters and alkaloids act via __ of __ receptors

direct stimulation; muscarinic

what are the main differeces between synthetic choline esters and alkoloids?

esters do not penetrate the blood brain barrier. alkaloids do.

what is bethanechol?

a choline ester that is resistant to hydrolysis by AChE; has a longer action than ACh

with oral dosing of bethanechol, there is a selectvity for __ and __ muscarinic receptors

GI, bladder

what is the effect of bethanechol when administered orally?

increased smooth muscle contraction of urinary bladder (detrusser muscle) whcih helps people pee. reduces need for catheters

the therapeutic use for bethanechol are __

postoperative and postpartum urinary retetion

what is cevimeline?

an alkaloid that is a selective muscarnic agonist. used to stimulate muscarinic receptors in salivitory glands.

what is cevimeline used to treat?

xerstomia from sjogrens syndrome and head/neck radiation

name a synthetic choline ester and allkoloid

bethanechol, cevimeline

what are teh main adverse effects from muscarinic agonists?

you get the full range of muscarinic effects. most comon are sweating, hypotension, and upset stomach.

name 2 antidotes for muscarinic agonist poisoning

atropine, epinephrine

name 3 muscarninc agonists

bethanacol, cevimeline, aceytlcholine

what are 4 muscarinic antagonists?

atropine, ipratropium bromide, scopolamine, tolterodine

what is the mechanism of action of atropoine?

competitively blocks muscarinic receptors, produces the opposite effect of muscarinic stimulation

atropine is a lipophilic drug that can cross teh __

blood brain barrier

atropine has no effect on the __ becuase theres no receptors there

blood vessels

what are the central nervous system effects of atropine?

mild intoxication at low doses




toxic doses produce hallucinations and psychosis

what are teh occular effects of atropine?

mydriasis (blocks sphincter muscle)




cycloplegia (blocks ciliary muscle)

what are the cardiovascular effects of atropine?

tachycardia (blocks vagal nerve)




NO EFFECT ON CIRCULATION B/C IT HAS NO PNS INNERVATION

what are the genitourinary effects of atropione?

suppresses detrusor muscle contraction, contracts trigone and sphincter (urinary retention, need to go but can't)




antispasmodic for pts with overactive bladder

what are the respiratory effects of atropine?

decreases bronchial secretions




relaxes bronchial smooth muscle (asthma)

what are teh GI effects of atropine?

inhibits salivation




reduces tone and motility of GI (constipation)




reduced GI acid secretion

what are 3 therapeutic uses for atropine?

bradycardia during surgery




mydriasis for opthalmic procedure




poison antidote for amanita mushrooms and organophosphate insectides

dry mouth, blurred vision, photophobia, tachycardia, GI distress, hot and dry skin are adverse effects of __

atropine

when is atropine contraindicated?

urinary retention (males with BPG)

what is a drug interaction you must be mindful with atropine?

additive anticholinergic effects with antihistamines, antipsychotic, and antidepressant

what is a main PT concern for atropine?

pts will be at cardiac risk and have altered thermoregulation

a drug similar to atropine but used as a sedative at low doses

scopolamine

what is scopolamine used for?

suppresses emesis and motion sickness (atropine does not)

used as a preventative treatment for motion sickness and nausea/vomitting associated with recovery from anethesia

scopolamine

quaternary amine that is always charged so it does not diffuse across cell membranes. approved as a bronchodilator in treatment of COPD and asthma. limited absorption when inhaled, so atropine like side effets are minimal

ipratropium bromide

a muscarinic antagonist administered by inhalationto treat asthma. allows teh SNS to take over and dilate the bronchiols

ipratropium bromide

muscarinic antagonist used to treat frequenc or uncontrolled urination (urge incontinence). effects are modest, atropine like effects

tolterodine

name 5 anticholinesterase agents

nestigmine, physostigmine, doneqezil, malathoid, pralidoxime

what is the mechanism of action of the acytelcholine esterase inhibitors?

competitive inhibition of AChE. enhances effects of ACh.

in therapeutic doses, AChE inhibitor effects are limited to __ receptors and __ receptors

M, N (at NMJ)

AChE inhibitor that is used to treat myesthenia gravis.

neostigmine

explain the neuromuscular effects of neostigmine at low and high doses

low: increased force of contraction




high doses: reduced force of contraction b/c receptors are sensitized

neostigmine is used to treat __ and __

myesthenia gravis, glaucoma

neostigmine has adverse effects by causing __ like respiratory depression. these can be treated with __

excessive muscarinic stimulation. atropine

AChE inhibitor that has an action similar to neostigmine; but crosses the blood brain barrier. used to treat poisoning by atropine and other drugs that cause muscarinic blockade. reverses muscarnic blockade in CNS

physostigmine

AChE inhibitor used to counteract the cognitive decline from alzheimers disease.

donepezil

is a more selective AChE inhibitor that targets AChE in the brain, rather than in the periphery

donepezil

what is an important drug interaction to know for donepezil?

anticholinergics can cause an ultimate decline in cognitive function

an irreversible AChE inhibitor that is an insecticide. its a highly lipid souble compound absorbed from all routes including the skin. is a common source of accidental and agricultural poisoning. therapeutically used to treat head lice

malathion

profuse sweating, salivation, miosis, bronchorrea/bronchospasm, bradycardia involuntary urination and defecation (muscarinic)




muscle weakness, fasciculation, paralysis (nicotinic)




confusion, ataxia, convulsions, coma, respiratory depression (CNS) are all sings of a __ caused by exposure of irreversible AChE inhibitors

cholinergic chrisis

what are 2 treatments for a cholinergic chrisis

atropine, pralidoxime

used to treat cholinergic crisis, give in large repeated doses; antagonizes muscarinic effects

atropine

used to treat a choliergic crisis. reactivates AChE at the NMJ. must be administed before aging occurs

pralidoxime

name 4 andrenergic agonists

epinephrine, phenyephrine, terbutaline, methylphenidate

what are 4 adrenergic antagonists?

prazosin, tamsulosin, propranolol, metoprolol

what are 4 mechanisms of action of sympathomimetics?

direct receptor stimulation (agonist)




promotion of NE release (tyramine)




inhibition of NE reuptake (cocaine)






inhibition of NE inactivation (MAOI's)

what are teh differences between catecholamines and non-catecholamine sympathomimetics?

catecholamines: not orally active, short duration of action, doesn't cross teh BBB




non-catecholamines: don't have catechol, orally effective, longer duration, produce CNS effects

adrenergics have a strong __

selectivity

adrenergic selectiviey is __ related to dose. you can overcome a lack of affinity by having a lot of drug

inversley

what is a clinical affect of alpha 1 activation in the blood vessels, eye form adrenergics? (4,2)

vasoconstriction: hemostasis, nasal decongestion, prolonged action of anesthetics, elevation of blood pressure




mydriasis without cycloplegia (doesn't cause blurred vision)

what are the the A2 activation effects of andrenergic agonists in teh CNS and eye? (3)

reduced sympathetic outflow




antihypertensive effect




reduced gluacoma

what are the clinical applications of andrenergic agonists on teh Beta 1 receptors of teh heart? (2)

cardiac stimulation, treatment of shock

what are the clinical applications of Beta 2 activation by adrenergic agonists? (2)

asthma and COPD treatment




delay preterm labor

epinephrine activates __, __, __, and __ receptors

alpha 1, alpha 2, beta 1, beta 2

what are the cardiac effects of epinephrine?

increased SA node automaticty (chronotropism)




increased contractility (inotropism)

what are the vascular effects of epinephrine?

reduced cutaneous blood flow (alpha 1)




decreased/increased skeletal muscle blood flow (alpha 1 or beta 2)

when does epiephrine cause skeletal muscle vasculature to vasoconstrict or vasodilate?

if its a low dose: you get a B2 dilation effect




if its a high dose, alpha 1 receptors constriction effect

what are teh 2 respiratory effects of epinephrine?

relaxation of bronchial smooth muscle (B2)

epinephrine is used for a __, __, and __

anaphylactic shock, topical hemostasis, cardiac arrest

hypertensive crisis (alpha 1), dysrhthmias (B1), angina pectoris (B1), and hyperglycemia (B2) are all adverse effects of __

epinephrine

what are 3 drug interacitons to be aware of with epinephrine?

MAOI's (additive effect), cocaine (block NE reuptake, additive effect), alpha/beta blockers (antagonised effects)

phenylephrine is __ selective

A1

andrenergic agonist which acts on A1 receptors. cuases marked vasoconstirction, used as a nasal decongestant, pressor aganet, and mydriatic

phenylephrine

because it can cause reflex bradycardia, excitability, restlessness, hypertension, overdose, problems with geriatic pts, __ has FDA high alert status

phenylephrine

terbutaline is a __ selective drug

B2

what is teh cardiovascular effects of terbutaline?

little effect due to B2 selectivity

what are 2 therapeutic uses of terbutaline?

reduces airway resistances




tocolytic (supresses premature labor by relaxing uterine smooth muscle

indirectly promotes teh release of NE/DA and inhibits reuptake (amphetamine like CNS stimulant). used for ADHD in children and adults. also used as a narcoleptic.

methylphenidate

__ could have insomnia and appetitie supression as adverse effects

methylphenidate

what are the alpha 1 blockade effects from adrenergic antagonsits (4)

hypertension, BPH, pheochromocytoma (catecholamine secreting tumor), reynauds disease

what are 7 b1 blockade effects of adrenergic antagonists?

hypertension, angina, CHF, hyperthyroidism, glaucoma, stage fright, migraine headache prevention

prazosin is a __ selective drug

a1

an alpha 1 selective drug that blocks alpha 1 receptors, especially in teh vasculature. produces dilation of arteries and veins and relaxes smooth muscle of teh bladder neck and prostate capsule. used for hypertension

prazosin

the first dose effect (orthostatic hypotension), inhibitory ejaculation, nasal congestion are adverse effects of__

prazosin

tamsulosin is a __ selective drug

alpha 1a

a drug that selectively favors blockade of teh alpha 1A receptor in the prostate and bladder. has little effect on blood pressure and facilitates urination in males with BPH by reducing prostatic smooth muscle tone

tamsulosin

can cause abnromal (failed, decreased, retrograde) ejaculation

tamsulosin

what drug interactions are important for tamsulosin?

vasdilator drugs for ED, can cause dangerous drop in BP and precipate MI

the prototype beta blocker that nonselectively blocks beta receptors (B1 and B2). decreases HR and contractility, supresses impulse conduction through AV node, slowly developiong reduction in BP, supresses release of renin (blocks activation of renin-angiotension system), bronchoconstriction, and inhibits glycogenolysis in liver and skeletal muscle

propanolol

fatigue, lethargy, and coldness of extremities, exercise intolerance, sexual dysfunction, bradycardia/av block, and aggravation of asthma due to bronchoconstriction are all adverse effects of __

propanolol

what are 3 cases where propanolol is contraindicated/precautioned?

diabetes (supresses tachycardia warning sign)




heart failure: exacerbates symptoms




contraindicated in asthmatics

a b1 cardioselective drug that is used for hypertension, angina, CHF, and MI. less likely to cause bronchoconstriction and suppression of glycogenolysis

metoprolol