Exam 2 Flashcards
Catecholamines are named for their
structure
General term for neurotransmitters/hormones in sympathetic NS
Catecholamines
Three major catecholamines/neurotransmitters
Dopamine, Norepinephrine, + Epinephrine
Norepinephrine is located
On effector organs at adrenergic receptors of the sympathetic NS
Four basic categories of adrenergic receptors
- Alpha 1 type (a1a,b,c)
- Alpha 2 type (a2a,b,c)
- Beta type (b1,2,3)
- Dopamine type (d1,2,3,4,5)
Adrenergic receptors (alpha1, alpha2, beta, + dopamine) are all
G-protein coupled cell membrane bound receptors
What increases of complexity of the NS by adrenergic receptors (alpha1,alpha2,beta,dopamine)
Various subtypes differing by potency + type of response
Number of factors can alter degree to which any adrenergic receptors respond to a stimulus
- Selectivity
- Regulation
- Polymorphisms
- Catecholamines
- Why we see effect in one person but not others
Receptor selectivity allows
sympathomimetic drugs to bind to one subgroup of receptors w/out binding to others
-Drug X binds to a1 receptors but not a2/B
Selective binding results in
selective actions
Degree of binding in receptor selectivity is
concentration-dependent
Receptor selectivity at low concentrations allow for
selective binding
Receptor selectivity at high concentration cause
Non-selective binding
- larger concentration floods receptors that usually don’t bind drug
- high dose of drug X bind to both a + b
- more unintended effects
Receptor regulation
Response inc./dec. over time
*usually due to changes in number of receptors/Up-down regulation
Receptor regulation can result in
Changes of observed response to sympathomimetic drugs
Example of receptor regulation
Desensitization
Desensitization AKA
- Tolerance
- Refractoriness
- Tachyphylaxis
Desensitization occurs after
long term exposure to catecholamines/drugs
Desensitization results in
Dec. responsiveness of that cell/tissue to additional stimulation
Mechanisms of desensitization
- Altered transcription/translation of DNA+/RNA
- Modifications of receptors by interaction w/enzymes/other proteins
- Long term exposure to agonist often w/ long-term drug use
- Interactions/messages from other receptors
* Results in less effect
Sometimes desensitization of receptors is the
Desired effect of drug b/c increased response followed by the desired decreased physiologic action
Example of therapeutic desensitization
Drug z binds to a1 receptors + causes exaggeration of expected physiologic response but the body doesn’t like that and wants to maintain homeostasis so the body dec. production of a1 receptors in the target organ (down regulation) so less neurotransmitter available to bind to a1 receptors result in in desired effect of drug which is dec. in a1 activity in specific target organ
All people have a and B receptors but slight changes in ______can occur in different people
amino acid sequences
Amino acid differences in receptors can
Alter receptor response
- Inc./dec. risk to develop dz
- Degree of susceptibility to desensitization
- Degree of responsive to drug
- May be why some therapeutic drugs work in some patients but not others which is a key area of future genetic investigations
Termination of neurotransmitter action
- Norepinephrine transporter (NET) protein responsible for vaccum to suck up norepinephrine
- Movement NE out of synaptic cleft + into blood stream (diffusion to area w/out receptors)
- Metabolism by catecholamine-O-methyl transferase (COMT)
- Metabolism by monoamine oxidase (MAO)
Norepinephrine Transporter (NET) targets
norepinephrine released into synaptic cleft
Major method of NE clean-up
NET removes 90% of released NE
NET acts as
a pre-synaptic pump to move NE out of synapse + back into neuron (vacuum)
Therapeutic NET
- Some drugs bind + inhibit NET action (atomoxetine (ADHD), cocaine)
- NET inhibition prolongs presence of NE in synaptic cleft increasing stimulation of adrenergic receptors
- Reverse NET action and inc. release of NE that had been taken up leading to enhanced action of NE
What metabolizes all catecholamines
Catechol-O-Methyl transferase (COMT)
What assists in terminating the actions of NE, Epi, + DA?
Cetechol-O-methyl transferase
Example of drugs that inhibit COMT + prolong the effect of catecholamines
Entacapone
What drug is used in Parkinson’s + inhibits the metabolism of levodopa, which is the precursor drug for dopamine, which is deficient in patients with parkinson’s (increases dopamine)
Entacapone
What metabolizes endogenous monoamines?
Monoamine oxidase
Examples of monoamines
NE, epi, serotonin, DA
Two forms of monoamine Oxidase
A +B
Monoamine oxidase is susceptible to _____ by many drugs which leads to ____ levels of these neurotransmitters and the ____ levels can actually be very _______
inhibition, increased, increased , dangerous
What used to be used for depression but now use SSRI’s?
Monoamine oxidase
Drugs that mimic actions of norepinephrine, epinephrine, + dopamine the three neurotransmitters?
Sympathomimetics
Sympathomimetic direct agonists
structure allows for binding to adrenergic receptors resulting in activation
Indirect agonists of sympathomimetics
Multiple mechanisms: cause release of stored catecholamines + inhibit reuptake of catecholamines already released which interferes w/ metabolism of norepinephrine
Medical chemistry of direct sympathomimetics
Able to create drugs w/ similar structural highlights to catecholamines
Provide enough similarly o be able to bind to adrenergic receptors
_____ alter affinity for a/b receptors yielding compounds w/ various levels of ____ or ____ activity in sympathomimetic drugs. This is based on where the change is out of the four key areas
Modifications, agonist, antagonist
Four key areas of sympathomimetic drugs
Benzene ring
Beta carbon
Amino group
Alpha carbon
Key focus of the pharmocological effects of sympathomimetics
Cardiovascular
pulmonary, ocular, GU, Salivary glands, apocrine, metabolism, hormone release, + CNS
Cardiovascular effects of Sympathomimetics: ___ and ____ receptors are present in the heart, blood vessels, + other systems that regulate BP.
a, B
Cardiovascular effects of sympathomimetics: Outcome of a given drug is dependent upon ____ for a + b receptors, _____ action at the receptors, action of the _______ to maintain homeostasis (desensitization)
Selectivity, pharmacologic, body’s compensatory mechanisms
*This complicates our predictions of what effect is observed when administer a drug
Key sympathomimetic effects on the cardiovascular system
Heart rate
Cardiac output
Peripheral vascular resistance
Venous return
B2 receptors of sympathomimetics in the cardiovascular system is _____ and A1 receptors ____
vasodilation, vasoconstriction (decrease/increase BP)
a1 agonist cardiovascular effects of sympathomimetics causes _____ resulting in ____ BP _____ vascular resistance which may cause a reflex _____ of HR which should ____ CO but venous return also ____ which ___ stroke volume + _____ CO (CO=HR*SV)
vasoconstriction resulting in INC BP and INC peripheral vascular resistance w
Example of an a1 cardiovascular agonist
Phenylephrine
Used to maintain BP in a pt w/ poor organ perfusions like vascular shock (IV drip for very low BP) + also used for stuffy nose by constricting blood vessels in the nasal passage ways
Phenylephrine an a1 agonist
A1 receptors are present in _____ of the cardiovascular system
vascular beds
a2 receptors are present ____ and ___ in the cardiovascular system
vascular beds, CNS
Activation of PERIPHERAL receptors by a2 agonists cause _____ but only when given_____, ______, or in very _____ doses
vasoconstriction, locally, IV push, high
Systemic administration results in activation of _____ a2 receptors which _____ sympathetic vascular tone which causes a ____ in sympathetic activity and a ___ in BP which can treat ______ (Clonidine)
central, inhibits, decreases, decrease, hypertension
Effects of B cardiovascular sympathomimetic ______ depending on which ____ receptors are activated
vary, B
B1 receptors in the heart ______ contractility + ____ HR causing an ____ in cardiac output
increase, increase, increase
B2 receptors in the VASCULATURE _____ peripheral resistance (_______) resulting in ____ BP
decrease, vasodilation, dec.
Stimulation of D1 receptors causes ______ in some areas (renal, splanachnic,coronary, cerebral)
vasodilation
Dopamine also binds to ___and ___ receptors + response is ______
a, b, dose dependant
Low dose of dopamine (<5mcg/kg/min)
activates B2 receptors causing vasodilation
Medium doses of dopamine (5-10mcg/kg/min)
activates B1 receptors increasing HR + contractility
High doses of dopamine >10mcg/kg/min activates
a1 receptors causing vasoconstriction + inc. BP
____ receptors in the lung cause ______
B2, bronchodilation
A receptors in the radial muscle of the eye cause ____ and a agonists also cause _____ outflow of aqueous humor + can _____ IOP in glaucoma
Mydriasis, inc., reduce
____ receptors in the bladder, urethral sphincter, prostate + more _____ urine retention + ______ ejaculation
A, promote, mediate
___ receptors of salivary glands ____ saliva
B, inc.
Sympathomimetics: apocrine sweat glands (palms of hands) _____ sweat production in response to ____ (not temp.)
increase, stress
Sympathomimetics ___ glycogenolysis in the liver via ____ receptors that ___ serum glucose
inc., B, inc.
___ receptors inc. lipolysis + ____ receptors dec. lipolysis
a2, b
___ receptors promote K+ uptake into cells which can cause hypokalemia
B2
___ receptors increase insulin release from islet cells, ___ decrease insulin release from islet cells
Inc., dec.
Renin has an increased release by ____ and a decreased release by ___
b1, a2
*Renin mediate renal perfusion + intravascular volume
Hormones mediated by adrenergic receptors include
Insulin Renin Parathyroid hormone Calcitonin Thyroxine Gastrin
Sympathomimetics on the CNS create feelings such as
nervousness adrenaline rush feeling of impending disaster alertness + improved attention elevation of mood Euphoria Anorexia Psychosis
Endogenous catecholamines
Epinephrine, norepinephrine, dopamine
Direct sympathomimetics
a1, a2, b1, b2 agonists
Epinephrine aka
adrenaline
Epinephrine is an agonist at ___ and ___ receptors
a, b
Epinephrine is a potent ____ + ___ stimulant due to action on a1 receptors which ____ systolic BP and ___ HR+CO via B1 receptors
vasoconstrictor, cardiac, inc., inc.
Norepinephrine aka
Noradrenaline, Levophed
Norepinephrine agonist at ___, ___, and ____ (*Minimal ____)
a1, a2, B1, b2
Norepinephrine is a potent ___+_____ stimulant
vasoconstrictor, cardiac
Low dose of dopamine
b2 receptors vasodilation
Medium dose dopamine
B1 receptors inc. HR + CO
High dose dopamine
a1 receptors vasoconstriction
Phenylephrine (Neosynephrine)
direct a1 agonist
useful decongestant + to inc. BP
Midodrine (Amantine)
Increase BP + treat orthostatic hypotension
Examples of direct a2 agonists + what they do
Clonidine (Catapres) Methylopa (aidomet) pregnancy HTN Guanfacine (Tenex) Guanabenz (wytensin) *All act in CNS to reduce BP + treat HTN
Dexmedetomidine (Precedex)
Use to use clonidine but now use this
Acts in CNS + used for sedation of patients in the ICU setting
Direct a1 + a2 drug
Oxymetazoline
a1-vasoconstriction + used as a decongestant
a2-clonidine to dec. BP (don’t usually see effects b/c local)
Nonselective B1 + B2 agonists
Isoproterenol (Isuprel)
Isoproternol
B2- vasodilation dec. dystolic BP + mean arterial pressure
B1- positive chronotropic + inotropic effects on the heart inc. HR + CO
NO ____ specific agonist
B1
B1 selective agonists ____ CO + ____ HR. An example is ____
Inc., Inc., dobutamine
Dobutamine B1 selective agonist
+ isomer-potent B1 action + a1 antagonism (blocks vasoconstriction) allowing inc. CO w/out inc. BP
- isomer- potent a1 action which inc. BP
B1 selective agonists like dobutamine when given together
the results give positive inotropic action w/ little change in BP
B2 selective agonists
Causes bronchodilation + are useful to treat asthma + COPD
Examples of B2 selective agonists
Albuterol (Ventolin) Terbutaline (brethine) Metaproterenol (alupent) Pirbuterol (maxair) Salmeterol (serevent) formoterol (Foradil)
B2 selective agonists also ____ uterine smooth muscle during premature labor (aka tocolysis)
relax
B2 selective agonists to relax smooth uterine muscle
Ritodrine (yutopar)
Terulatine
Mixed acting sympathomimetics provide ___ and ___ effects
a, b
Examples of mixed-acting sympathomimetics effects
vasoconstriction, decongestion, bronchodilation, +CNS effects such as appetite suppression, stimulation, + more
Examples of mixed acting sympathomimetic drugs
Ephedrine (performance enhancing drug)
Pseudoephedrine (Sudafed)
Ephedrine
mixed acting sympathomimetic
Obtained from multiple plant sources-herbal product ma huang (ephedra) Performance enhancing banned by WADA
Provides bronchodilation in asthma pts (better agents preferred)
Ephedra sales banned in US since 2004 due to risk of death
Pseudoephedrine (Sudafed)
Decongestion-vasoconstriction
Contraindicated in high bp
Indirect acting sympathomimetics work via two potential mechanisms
Displace catecholamines increased norepinephrine,epinephrine, + dopamine
Inhibit Reuptake of released neurotransmitter by interfering w/ NET
Examples of indirect acting sympathomimetic drugs
Amphetamines
Tyramine containing compounds (aged meats, cheeses, fish)
Catecholamine reuptake inhibitors (doluxetine)
Amphetamine causes release of stored ___ and ____. It is a _____ stimulant and ___ mood + alertness and _____ appetite
Norepinephrine, dopamine, CNS, inc., dec.
Methamphetamine (crystal meth) has a similar action to ______ made from _____ and has ____ CNS actions
amphetamine, pseudoephedrine, POTENT
Phenmetrazine has actions similar to ______
amphetamine
Methylphenidate (ritalin) is a ____ derivative used in the treatment of ____ by ___ reuptake of ____ + ____ function of the brain (smooth out norepinephrine so everything can come into focus)
amphetamine, ADHD, reduces, norepinephrine, improves
Modafinial is an _____ sympathomimetic drug that ____ Norepinephrine + dopamine transporters in the CNS. The exact mechanism is more complex + poorly understood. It is used to _____ wakefulness in pts w/ _____, ___, and ____
indirect, inhibits, increase, narcolepsy, sleep apnea, shift work disorder
Armodafinil (Nuvigil) is an _____ sympathomimetic which is an _____ of modafinil and has ____ actions + uses to modafinil
indirect, R-enantiomer, similar
Tyramine is a ______ of ____ metabolism found in _____ concentrations of many foods like fermented foods like cheese, cured meats, soy sauce, red wine, etc. + causes _____ of stored catecholamines leading to similar actions to ______ (a1, a2, B1), + metabolized by _____.
product, tyrosine, high, release, norepinephrine, MAO
Patients taking an MAO inhibitor (pheneizine, linezolid, tranylcypromine, etc.) can get ______ sympathomimetic actions by _____ tyramine breakdown that causes ____ release of catecholamines + tyramine action—> ______ NE activity
intensified, preventing, extra, excessive
Patients on MAOIs (dec. tyramine + NE breakdown) should avoid ______ containing foods due to potentially dangerous ______
tyramine, hypertension
Catecholamine reuptake inhibitors vary in _____ of reuptake activity (block vacuum) due to imbalance btwn ____ + ____ leading to different actions and also acts at other _____ (serotonin)
selectivity, NE, DA receptors
Atomexetine (stratera) is a selective inhibitor of ____reuptake w/ mostly ____ effects + may cause some ____ in BP and is used to treat _____
norepinephrine, CNS, increase, ADHD
Sibutramine (Meridia) is a ___ + ___ reuptake inhibitor approves as an _______
serotonin, NE, appetite suppressant
Duloxetine (Cymbalta) is a ____ and ____ reuptake inhibitor used as an ________
serotonin, NE, antidepressent
Cocaine inhibits _____ reuptake of ___ by NET and enters the CNS + produces _____-like actions, but more _____. Key feature is inhibition of _____ reuptake in pleasure center of the brain which leads to a very ____ addiction
peripheral, amphetamine, intense, Dopamine, rapid
Therapeutic applications of sympathomimetics
Cardiovascular, pulmonary, anaphylaxis, opthalmic, GU, CNS, sedation
Therapeutic use of sympathomimetic on the cardiovascular system is for ______. The goal is to increase ____ and _____. The _____ could be due to severe blood loss, hypovolemia, arrhythmia’s, antihypertensive overdose, + shock. It needs to be maintained to ensure _____ of vital organs. May use ______ agonists to raise ____ like ____ + ____ and _____ agents in shock syndromes to increases _____ like ___ + _____
hypotension, BP, CO, low BP, perfusion, a1, BP, norepinephrine, phenylephrine, inotropic, CO, dopamine, dobutamine
Therapeutic effects of sympathomimetics on the cardiac system is to treat ______ by decreasing _____. Central acting____ agonist can be used to manage high ______. ____ is a drug that can do this and is available in ____ and ____.
hypertension, BP, a2 agonist, clonidine (catapres), oral tablets, topical patch
Sympathomimetic therapeutic treatment in the management of _____ hypotension (OH) has a goal _____. OH is a drop in ___ as a pt moves from a ____/___ position to a ____ position which can result in the ____ of consciousness + ____ due to a fall. Normal sympathetic reflex action prevents this (i.e. Inc. HR + peripheral vasoconstriction) + can be inhibited by ______ + other drugs that block autonomic function. You would treat w/ ____ agonists like ______.
inc. BP, BP, sitting/lying down, standing, loss, trauma, antihypertensives, a1, midodrine
Sympathomimetics can be used for emergency cardiac measures w/ a goal of ____. This is used in ____ heart block or cardiac arrest. ____ is part of resuscitation measures by redistributing blood flow from ____ important areas to ___ important areas like the brain + heart muscle using ____ and ___ mediated actions. Used in combo w/ other agents that try to jump start the heart back into action.
resuscitation, complete, Epinephrine, less, more, a1, b2
Two goals of surgical application of sympathomimetics based on ___ activity
a1, Reduce blood loss @ site w/ epinephrine/cocaine (used to prolong effect of lidocaine)
Slow diffusion of anesthetics away from site of administration like w/ epinephrine, norepinephrine, + phenylephrine
*A1 agonist dec. swelling by vasoconstriction
Sympathomimetics used for sinus decongestant. The goal is to _____ which is associated w/ hay fever/sinus colds. Use ____ in nasal sprays to cause _____. Two examples are ___ + _____. Use usually limited to no more than ____ days due to rebound effect b/c leads to ischemic changed followed by hyperemia when agents are discontinued
dec. nasal stuffiness, a1, vasoconstriction, phenylephrine (neosynephrine), oxymetazoline (12 hr afrin), 3
Pulmonary uses of sympathomimetics are used to improve _______. ____ effects used in patents w/ bronchoconstriction such as asthma + COPD. ____ selective agents are very commonly used in inhalers/nebulizers. These include 5 drugs:
pulmonary air flow, Bronchodilation, B2, albuterol (ventolin, proventil), metaproterenol (alupent), pirbuterol (maxair), salmeterol (serevent), + formoterol (perforomist)
Sympathomimetics used in anaphylactic reactions has a goal to ____. Exposure to allergens can cause shock due to cardiovascuar + respiratory hypersensitivity responses which have symptoms that include (bronchospasm, mucous membrane congestion, angioedema, + severe hypotension). ____ activates a1, B1, + B2 receptors to reverse symptoms and is often used in combo w/ a ___ or ____.
reverse vascular complications of immune hypersensitivity, Epinephrine (Epipen), steroid, antihistamine
Ophthalmic applications of sympathomimetics
Mydriasis to facilitate eye exam + decongestion to reduce eye redness in associated allergies(a1 agonist)
Reduce IOP of glaucoma (a2 agonists) (apraclonidine, lopidine, + brimonidine, alphagan)
GU applications of sympathomimetics goal is ____. _____ selective agents used to relax uterus in premature labor. Examples of drugs are
delay delivery of baby (tocolysis), B2
CNS applications of sympathomimetics are used in the treatment of ____ to increase ___ and ___ sleep. Some examples of drugs that do this are ___ and ____. They are also used in appetite _____ and management of _____. In ____ they improve attention span, reduce hyperkinetic behavior, + eliminate behavioral barriers to learning. Some examples of drugs are _____
narcolepsy, alertness, defer, amphetamine, modafinil, suppression, ADHD, ADHD, methylphenidate (ritalin), dextroamphetamine/amphetamine (adderall), lisdexamfetamine (prodrug for amphetamine)
Sympathomimetics for ICU sedation goal is to _____. Patients under sevre physiological stress like mechanical ventilation, post-op, often need to be sedated. Use ___ agonist in combo / agents of other classes like opioids, benzodiazepines, + propofol which help to ___ requirements of other drugs. An example is ___
improve pt comfort in ICU, a2, lower, Dexmedetomidine (precedex)
Adrenergic antagonists aka
sympatholytics
Cardiovascular a1 receptors
vasoconstriction
Cardiovascular B1 receptors
Increase HR + CO
Cardiovascular B2 receptors
vasodilation
Cardiovascular CENTRAL a2 receptors
vasodilation
Respiratory a1 recepetors
decongestion
Respiratory B2 receptors
bronchodilation
Ophthalmic a1 receptors
mydriasis, dec. redness
Ophthalmic a2 receptors
dec. IOP
GU B2 receptors
delay fetal delivery
Secretory glands B receptors
increase apocrine sweat glands + salivary glands
Metabolism B receptors
increase glycogenolysis + lipolysis (inc. energy availability)
Metabolism a2 receptors
dec. lipolysis + insulin release
Metabolism b2 receptors
increase insulin release
Adrenergic actions on the CNS
Feelings such as wakefulness, nervousness, anorexia, + euphoria
a-receptor reversible antagonists compete w/ ___ + _____. They are ____ to block receptor + then become dissociated if an agonist is present in high enough concentrations. Duration of action is dependent on drug’s ____ for the receptor + ______ of drug in the body.
agonists, endogenous catecholamines, able, affinity, half life
*Shorter half life
a-receptor irreversible antagonist for _____ with receptor + _____ block it. Duration of action is dependent on the ____ of new receptors (may take several days)
covalent bonds, completely, synthesis
*Longer half life
a-antagonists and the cardiovascular system: ____ a1-mediated vasoconstriction causing _____ which ____ peripheral vascular resistance and ___ bp. This can lead to ____ + reflex ____ as side effects. The drug blocks the bodies ability to adjust ___ vascular resistance when moving from ___ to ___. The reflex ___ develops in response by the body to maintain CO (CO=SV*HR); it’s the bodies compensatory mechanism to drop the BP
Block, vasodilation, dec., dec., orthostatic hypotension, tachycardia, peripheral, sitting, standing, tachycardia
A1 antagonists also block _____, nasal _____, and _____
mydriasis-miosis, vasoconstriction-sinus congestion, a-mediated urinary retention-facilitates urination
Phenoxybenzamine (Dibenzyline) is an ____ antagonist which has an ____ blockade a1>a2. Most significant effect is blockade of ____ which causes _____. It also blocks presynaptic _____ receptors which blocks reuptake of _____. It is used to treat conditions of excessive ____ release like phenochromocytoma (tumor of adrenal medulla/sympathetic ganglion cells. Oversecretion of NE + Epi cause hypertension, headaches palpitation, + sweating which could lead to a stroke) *Life saving
a, irreversible, a1>a2, vasoconstriction, vasodilation, a2, norepinephrine, catecholamine
Phentolamine (oraverse) is a _____ blockade of a1 and presynaptic ____ receptors. a1 blocking effects cause ___peripheral vascular resistance and may cause some ___ effects due to ___ cardiac stimulation (inc. Hr, potential for arrythmias, + inc. cardiac workload) which occurs due to enhanced ____ activity from blocking ____ reuptake. Also used in management of _____
reversible, dec., a2, inc., NE, NE, pheochromocytoma
Examples of a1 antagonists
Prazosin (minipress)
Terazosin (Hytrin)
Doxazosin (Cardura)
Tamsulosin (Flomax)
Tamsulosin is an a1 _____ and is highly _____ and results in ____ of arterial + venous smooth muscle which is useful for treating _____. ALso relax smooth muscle in ____ b/c it has more selectivity for ___ smooth muscle + is more potent so can be used to treat ____
antagonist, a1-selective, relaxation, hypertension, prostate, prostate, BPH
several drugs have a1 antagonism as a ___ mechanism of action which leads to side effects such as _____. Examples include
secondary, hypotension, haloperidol (Haldol;antipsychotic), chlorpromazine (Thorazine;antipsychotic), trazodone (sleep aid + antidepressant), Ergotamine + dihydroergotamine (migraine ha)
B-receptor antagonists bind _____. Most are ___antagonists, but some have partial ____ agonist activity which only occurs in low concentration of _______. Drugs differ is ___ + ___ for blocking B1 + B2 receptors and the selectivity tends to ___ w/higher doses. _____ differences also exist (distribution, half life, + elimination route). Some have local ____ properties but we don’t really use them for that.
reversibly, pure, B, endogenous catecholamines, affinity, selectivity, dec., Pharmacokinetic, anesthetic
B-antagonists + the cardiovascular system are usually referred to as ____
beta blockers
Beta blockers use to control ______ but is NOT the first line tx. Complex + unclear mechanism of ___ of renin release and ___ actions. Used more commonly in __, ___, + ____ in which it IS first line therapy. It ___ cardiac workload (negative inotropic + chronotropic effects) which doesn’t cure but makes it feel better. It also slows ______ to ___ HR, _____ renin release, and the net effect is to ____ peripheral vascular resistance + BP to ____ overall workload of a diseased heart
high BP, suppression, CNS, angina, CHF, + MI, reduces, av node conduction, dec., suppresses, dec., dec.
beta blockers block peripheral ___ receptors to cause vasodilation to reduce blood pressure…..this is ironic b/c you would think it would inhibit vasodilation but w/ long term use ____ decreases w/ b-blocker use (unclear mechanism) and the effect is enhanced by agents that also block ___ receptors
B2, BP, a1
Agents that block both a + b receptors cause a greater drop in BP by blocking _____. An example of this is _____
vasoconstriction, labetalol
Beta blockers help pts w/ angina by ____. They block the adrenergic effects that would occur under sympathetic conditions resulting in a ____ of cardiac workload which ____ the demand for ____. It also improves ____ tolerance by preventing the heart from working to hard. *Doesn’t clear _____ even though inc. cholesterol causes chest pain
improving the balance btwn oxygen supply + demand, reduction, reduces, oxygen, exercise, cholesterol
____ receptors in the lungs facilitate bronchodilation. You would use these to treat pts w/ asthma + COPD
B2
There is ___ pure B1 blockers available. Therefore, ___ blockers could theoretically ___ condition of asthma pts due to “dirty” actions
NO, B, worsen
Many textbooks suggest the use of ___ blockes in pts w/ lung dz is _____. Even though this is true some pts tolerate the drugs just fine so best to use w/ informed caution.
B, contraindicated
Beta blockers are used to treat _____ glaucoma. Other drug classes are also useful like cholinergic agents, a agonists, prostaglandin analogs, + diuretics. These all help to ______. B-blockers are given by _____ to reduce the production of _____. Some examples are ___, ____, + ____
open-angle, reduce IOP, eye drops, aqueous humor, Betaxolol (betoptic), timolol (Timoptic), + carteolol (ocupress)
Multiple unique actions of beta blockers occur: Block ____ mobilization, worsen high ____, intrinsic ______ activity, + local _______activity
glucose, cholesterol, sympathomimetic, anesthetic
B blockers block glucose mobilization + reduce energy availability. It does this by ____ sympathetic-mediated stimulation of lipolysis + partially ____ glycogenolysis. Therefore these drugs could ____ the bodies ability to make ____ available when needed like during hypoglycemia. Use w/ caution in patients @ risk of complications associated w/ hypoglycemia like ______ b/c it masks key signs like increased HR + dec. sweating, so could be a problem but NOT contraindicated
inhibiting, inhibition, block, glucose, insulin dependent diabetics
B blockers alter levels of some of stored _____ and ____ cardiovascular risk + CAD. It _____ VLDL ____HDL. The mechanism is unclear and these effects may be less likely w/ ____ agonists like ____.
cholesterol, inc., inc., dec., partial, labetolol
____ occurs when a B blocker has ____ agonist activity based on structure. Having some degree of this may ____ the likelihood of _____ features of B blockers like bronchoconstriction/bradycardia. It may also reduce the ____ of B blockers especially ____ benefits. Some examples of these are
Intrinsic sympathomimetic activity (ISA), dec., negative, therapeutic effects, cardioprotective (ineffective dec. BP), Labetalol, Pindolol, acebutolol
Local anesthetic action of B blockers aka ____ result from the blockade of ____ in axons of the nerves like lidocaine. This blockade prevents ____ of the nerves preventing ______ + subsequent transfer of _____ –> anesthesia. Some examples are: *They are typically NOT used for this effect since better agents are available.
membrane stabilization, sodium channels, electrolytic excitation, depolarization, sensation information, acebutolol, labetalol, pindolol, + propranolol (also ISA’s)
The use of B blockers include
hypertension, ischemic heart disease, arrythmias, heart failure, glaucoma, migraine headaches, + performance anxiety
B blockers for hypertension are considered ______ option (along w/ drugs of other classes) in pts w/ _______ (i.e. heart failure, post-MI, angina, diabetes, + more). Not considered 1st line in pts w/out these. Some examples are
1st line, “COMPELLING INDICATIONS”, atenolol (tenormin), Metoprolol (lopressor, toprol), bisoprolol (zabeta), nadolol (corgard), pindolol (visken), + several more
IHD occurs when ____ line cardiac arteries, ____ blood flow + ___ delivery. Leads to symptoms of ___ + ____. Beta blockers ____ cardiac workload by slowing ___ and ___ strength of heart squeeze resulting in less demand for ___ so the limited supply meets the less demand. *Considered _____ in pts @ risk/after MI/history of angina/left ventricular disfunction. Some examples are
cholesterol plaques, dec., oxygen, angina, poor exercise tolerance, dec., HR, dec., oxygen, *1st line, propranolol (inderal), metoprolol (lopressor)
Arrythmias are abnormal ____ w/in the heart. They ___ heart functionality + may be _____. B blockers can be used to suppress ____ + ____ arrythmias. Extend the resting period of ____ + _____ventricular response to electrical stimulation which hopefully _____ the abnormal rhythm. Useful to treat ___ + ___. used in some ____ ventricular arrythmias. SOme examples are ___ + ____
electrical rhythms, dec., fatal, supraventricular, ventricular, AV nodal cells, slows, stops, atrial fibrillation, atrial flutter, life-threatening, metoprolol (lopressor) + sotalol (betapace)
B blockers are useful in pts w/ ___ heart failure NOT ____ heart failure. Mechanism is unclear. This may contribute to changes in heart muscle (aka myocardial remodeling). Used to be ___ in patients w/ CHF but now used _____. Pts w/ ____ curve could make _____. Want to get pt to ____ of curve to optimize. Examples include
chronic, acute, contraindicated, commonly, flat line, worse, peak, metoprolol (lopressor), bisoprolol (zabeta), carvedilol (coreg)
B blockers in the use of glaucoma is instilled _____ into the eye to ____ IOP that ____ production of ______. Examples include: *Some systemic absorption can occur leading to ____ in the ___ and ___ but only usually occurs in the very sensitive patient.
directly, decrease, aqueous humor, timolol (timoptic), betaxolol (betopic), carteolol (ocupress), + levobunolol (betagan), unwanted side effects, heart, lungs
B blockers are also used in hyperthyroidism. Overactive thyroid glands can lead to _____ action which could lead to ___. B blockers help in two ways: . They are especially useful in ____. An example would be ___.
excessive catecholamine, tachycardia, dec. symptoms by blocking receptors, dec. conversion of thyroxine (T4) to triiodothyronine (T3), which is active thyroid hormone, proponolol
B blockers can be used in hepatic disease. Liver disease can lead to ___ and ___ including _____ which is an increased sign of mod-severe cirrhosis. Specific beta blockers can have a ____ effect to reduce the ____ BP. Some examples include _____ + _____
cirrhosis, multiple complications, portal vein hypertension, targeted, elevated, Nadolol (corgard), propanolol (inderal)
b blockers are also used in migraine headaches. Migraines are complex + often difficult to treat. Some examples are _____ + _____ which can reduce ____ and/or ______ of migraines. Exact mechanism is unknown. May be used for refractory cases since better drugs exist (triptan class of agents)
mtoprolol, propanolol, frequency, intensity
B blocker use in performance anxiety aka ______ useful for many people that are ___ speaking/performing in front of others. They eliminate many symptoms induced by ____ + ____. These ____ HR and ____ palmar sweating.
stage fright, nervous, stress, anxiety, slow, reduce
Many unwanted effects can occur using b blockers including ____ Some others are minor + less expected like ______You need to use beta blockers w/ caution due to unpredictability of how pts will respond
Bradycardia, worsening of asthma, may worsen CO in pts w/ heart failure, exacerbation of hypoglycemia in diabetics, mild sedation, vivid dreams, + depression
Cannot abruptly discontinue ____ blockers used in pts w/_____ or being treated for _____ b/c it can lead to rebound _____ probably associated w/ receptor up-regulation + sudden exposure to catecholamines upon withdrawal of agent (increased risk of stroke + heart attack) so you must ___ these pts off their B blocker
B, ischemic heart dz, hypertension, hypertension, taper
Lots of different characteristics of beta b activity include
safety issues (side effects)
Partial agonist activity
Differences in renal + hepatic metabolism
Differences in elimination half life
B blockers are _____ interchangeable + choice is based on ____,____, + ___
NOT, established guidelines, approved indications, clinical evidence
ACh is synthesized in ____ of neurons of ____ + ____NS catalyzed by the enzyme ______. It is stored + released in vesicles of these same neurons. In response to an ______, release ACh binds to ____ or ___ acetylcholine receptors. ACh is broken down in the _____ by the enzyme ______ + components recycled
mitochondria, parasympathetic, sympathetic, choline O-acetyltransferase, action potential, muscarinic, nicotinic, acetylcholinesterase
Cycle of acetylcholine
ACh is made from acetyl-CoA + choline ACh is stored in neurons Release of ACh when neurons stimulated by an action potential Bind to ACh-R AChE breaks down ACh Acetyl-CoA + choline recycled
2 types of ACh receptors named for their ability to bind either of 2 alkaloid compounds ____ + ______. They are distributed throughout the body in specific locations. Could be called “type1” + “type2” but researchers found that although each type binds ACh, they differ in their structure enough to have different abilities to bind exogenous compounds allowing clear determination of where they are located.
Muscarinic receptors
Nicotinic receptors
Muscarine + Nicotine produce actions that mimic those seen when ACh binds to _____ of the _____ nervous system. They also produce actions that mimic those seen when ACh binds to _____ of autonomic ganglia + skeletal muscle receptors
muscarinic, parasympathetic, nicotinic receptors
Five types of muscarinic receptors ____ to _____. ___, ___, + ___ lead to cellular excitation, ____ + ___ inhibit cellular excitability. They are found mainly on ______ effector organs including ___, ____, ___, + ____. Compounds exist that bind to muscarinic receptors as either agonists/antagonists.
M1, M5, M1,3,5, M2,4, autonomic, Heart, smooth muscle, brain, exocrine glands
Two key actions at muscarinic receptors sites
- Nerves in parasympathetic NS release ACh that ACTIVATES muscarinic receptors on target organs. Alters organ function by creating a POSITIVE stimulus.
- ACh released from nerves of parasympathetic NS bind to receptors on nerve terminals to INHIBIT release of the neurotransmitters. Also alters organ function by creating a NEGATIVE stimulus.
Nicotinic receptors are located at ____ level of BOTH parasympathetic + sympathetic sides of the autonomic NS. They bind ____ released from _____ neurons and pass message on to _____ neurons. There are No inhibitory capabilities. They only relay the efferent message sent from the CNS
ganglionic, ACh, pre-ganglionic, post-ganglionic
Two types of nicotonic receptors
NM are located at the neuromuscular junction
NN are located in any other location like CNS, adrenal medulla, + autonomic ganglia
Nicotinic receptors are primarily present at the ____. Binding of ACh/an agonist causes ____ of the nerve cell/neuromuscular end plate membrane creating a _____ stimulus (skeletal muscle contraction). Prolonged binding to the receptor causes the muscles to stop firing + causes skeletal muscle to ___. It also prevents further ___ that creates muscle paralysis creating a ____ stimulus.
neuromuscular junction of skeletal muscle, depolarization, positive, relax, depolarization, negative
Nonacetylcholine compounds that mimic actions of acetylcholine as ____ (direct agonist) by direct binding to ACh receptors. As _____ (indirect agonist) by indirect cholinergic action by inhibiting ACh hydrolysis preventing breakdown of ACh and if ACh doesn’t get broken down, it stays around longer in the synapse + allows it to continue to produce cholinergic actions.
stimulants, cholinesterase inhibitors
Two groups of direct acting cholinomimetics
Esters of choline (acetylcholine)
Alkaloids (muscarine + nicotine)
Choline esters are ____ ammoniums (methacholine, acetylcholine, carachol, + bethanechol). Insoluble in lipids but water soluble.
quaternary
Quaternary ammoniums are ___ + poorly penetrate into the CNS. They are hydrolyzed by _____ but vary in rate of hydrolysis which affects the _____ of the drug. Variations in chemical ____ alter characteristic such as ___ (i.e. binding affinity + fit to receptors hat determines degree of action elicited) and ____ to hydrolysis by AChE
hydrophilic, acetylcholinesterase (AChE), half-life, structure, potency, susceptibility
Four examples of cholinomimetic alkaloids
Muscarine, pilocarpine, nicotine, + lobeline which are typically tertiary amines but could also be quarternary like muscarine
Cholinomimetic alkaloids are _____ after oral administration. Lipid solubility allows for ____ volume of distribution. They cross blood-brain barrier into CNS (including muscarine). They are _____ susceptible to acetylcholinesterase + rely on other mechanisms of metabolism.
well-absorbed, larger, NOT
Normally, the action of ACh is terminated by _____. By inhibiting AChE prolongs the presence + actions of ACh at all ______ (M, N, NMJ, + brain). Indirect cholinomimetics act by inhibiting ____.
AChE, ACh-R, AChE
Three chemical groups of AChE inhibitors
Simple alcohols, carbamate esters, organophosphates
Simple alcohols w/ quartenary ammonium
Edrophonium
Carbamate esters of alcohols w/ quaternary/tertiary ammonium
Neostigmine, physostigmine, + pyridostigmine
Organophsophates
Echothiophate, isofluorophate
Binding affects duration of action: Simple alcohols bind ___ + ____ to AChE leading to a ___ half life of
weakly, reversibly, shorter, reversibly, tighter, prolongs, covalent, long
Effects of cholinomimetics on specific organ systems. Which organ systems are similar for direct/indirect cholinomimetics? Which organ systems differ for direct + indirect cholinomimetics?
Eye, respiratory system, GI, + GU tract
CV, secretory glands, CNS, peripheral NS, + neuromuscular jct.
Cholinomimetic effects on the eye are sensitive to ___ agonists + ____ inhibitors. Cause contraction of the ____ sphincter smooth muscle resulting in ____. ___ muscle resulting in accommodation. These effects ____ flow of aqueous humor out of the anterior chamber. Alter amount + focus of ___ reaching the retina.
muscarinic, AChE, Iris, Ciliary, facilitate, light
Cholinomimetics for glaucoma: ____ agonists + ____ inhibitors reduce _____ in narrow + wide angle glaucoma by allowing for the outflow of aqueous humor. Drug examples include ____ + ____
Muscarinic, IOP, pilocarpine (direct), physostigmine (indirect)
Cholinomimetic effects on the respiratory system cause ___ of smooth muscle in the bronchial tree restricting airflow. It stimulates secretions from tracheobronchial mucosa. ACh ____ aren’t much use in respiratory medicine but ___ help increase airflow in pts w/ respiratory dz like asthma
contraction, agonists, anti-cholinergics
Cholinomimetics on the GI tract ___ secretory + motor activity in the gut. It ____ salivary + gastric glands, pancreas, + small intestine, _____ peristalsis, ___ most of GI sphincters allowing GI contents to pass along the tract. Use agents to correct depressed smooth muscle activity + increase motility in post-op ileus (neostigmine) and congenital megacolon.
increase, stimulates, increases, relaxes
Cholinomimetics of the GU tract trigger ____ of bladder. ____ detrusor muscle (contraction) + ____ the trigone + sphincter muscles of the bladder. Use agents to correct depressed smooth muscle activity to treat ____ like post-op, post partum, spinal cord injury, or neurogenic bladder. Two examples of drugs are: ___ + ___
voiding, Stimulate, relax, urinary retention, bethanecol, nestigmine
Effects of DIRECT cholinomimetics to the cardiovascular system have two effects of muscarinic agonists: _____ peripheral vascular resistance. ____ reduces ___ and this drop can cause an ___ reflex increase in ____. ___ in heart rate from ___ in rate of firing @ sinoatrial node resulting in ___ and also reduces ____. It’s DIFFICULT to predict the outcome. ACh agonists aren’t used much in cardiovascular medicine b/c there are drugs that do these things better + more predictably.
Reduce, vasodilation, BP, indirect, HR, Decrease, decrease, bradycardia, CO
Effects of INDIRECT Cholinomimetics on the cardiovascular system: AChE inhibitors _____ cholinergic activity. Sympathetic + parasympathetic nerves in the heart: Negative chronotropic–> ____ and negative inotropic –>_____. Observations result from greater impact of AChE inhibitors on parasympathetic system. Cholinergic receptors in cardiac + vascular smooth muscle cause a ____ drop in BP
incrase, bradycardia, drop in CO, modest
Cholinomimetic effects on miscellaneous secretory glands. Acetylcholine mediates ____ glands causing _____ to help regulate ____, ____ glands, + ____ glands. Cholinomimetics can trigger all of these side effects.
sweat, diaphoresis, lacrimal, nasopharyngeal
DIRECT cholinomimetics on the CNS: Nicotinic receptors have been found to induce _____, and stimulate ___ + ____. Muscarinic receptors have also been found to induce _____,+ cause ____, + interfere w/ ______.
tremor, emesis, respiratory center, tremor, hypothermia, nociception
Effects of INDIRECT cholinomimetics on the CNS: Low concentrations cause ___ effect. Higher concentrations cause _____, ____. + _____.
little,, convulsions, coma, respiratory arrest
Use of Cholinomimetics for CNS conditions: ___ + _____
Alzheimer’s dz
Smoking cessation
Alzheimers dz is related to deficiency of ____ neurons in CNS and cannot be cured, but progression of cognitive dysfunction can be slowed w/ AChE ______. Some examples of drugs are ___
cholinergic, inhibitors, tacrine, donepezil, galantamine, + rivastigmine
ACh is released from ____
pre-synaptic neurons
ACh binds to ___ cholinergic receptors on muscle fiber and results in ____ of muscle fiber that leads to ___ of the skeletal muscle
nicotinic, depolarization, contraction
_____ doses of AChE inhibitors prolong the effects of ACh which ____ strength of muscle contraction
Low, increases
____ doses of AChE inhibitors may cause muscle to fibrillate making the muscles less effective
Medium
_____ doses of AChE inhibitors block muscle depolarization leading to paralysis
High
Use of cholinomimetics in disorders at the neuromuscular jct. on which dz’s?
Myasthenia gravis, + reversal of neuromuscular paralysis
Myasthenia gravis is an autoimmune process of antibodies targeting _____ receptors on skeletal muscle. These antibodies block binding of ___ to the receptors. Symptoms include ___, ____, + ____ . AChE inhibitors (pyridostigmine + neostigmine) are very effective as treatment.
nicotinic, ACh, ptosis, difficulty speaking, weakness
Reversal of neuromuscular paralysis by _____ following surgery (neostigmine)
cholinomimetics
Excessive anticholinergic action can be ____ in children or cause ____ in adults. Some examples are ____ + ____. Increasing the amount of ACh at receptor sites can overcome the anticholinergic action like AChE ___ (physotigmine)
lethal, arrythmias, atropine, tricyclic antidepressants (TCAs), inhibitors
Toxicity of cholinomimetics differs by ___ + ____
receptor type (muscarinic vs. nicotinic) Mechanism of action (direct cholinomimetic vs. AChE inhibitor)
Signs of muscarinic excess include: ____. Treat w/ ____ an _____
N+V, dirrhea, urinary urgency, salivation, sweating, cutaneous vasodilation, + bronchial constriction
atropine, anticholinergic
Acute nicotine toxicity is fatal at doses > ____ mg (1 drop pure nicotine liquid). ___ cigarettes contain about 40mg, but most of it is burned off or in smoke that’s not inhaled. Ingestion by infants can cause ____. Large doses can cause ___. Treatment is ____ until the drug is metabolized w/in a few hours (as long as brain damage or death hasn’t occurred)
40, 2, vomiting, central NS stimulation like convulsions, coma, + respiratory arrest, skeletal muscle depolarization leading to blockade+ respiratory paralysis, hypertension + cardiac arrythmias, supportive
Chronic nicotinic toxicity: ____ power of nicotine makes smoking cessation difficult. Unclear of health risks of chronic nicotine use.
Addictive
Toxicity of cholinesterase inhibitors are often related to exposure to _____. Organophosphates + carbamate cholinesterase inhibitors. Many organophosphates were developed as ___ agents. Symptoms show muscarinic excess: ___
pesticides, nerve, dirrhea, urination, miosis, bradycardia, bronchoconstriction, emesis, lacrimation, salvation, + sweating
Treatment of AChE toxicity: monitor ____, ____ if possible, _____ w/ parenteral atropine/pralidoxime (2-PAM). 2-PAM reactivates inhibited AChE before the full covalent bond forms through “aging”
VS, decontaminate, Antidote
Cholinomimetics are ___ absorbed for oral after oral administration. ____ solubility allows for larger volume of distribution. They cross the blood-brain barrier into CNS (including muscarine). _____ susceptible to acetylcholinesterase. They rely on other mechanisms of metabolism.
well, lipid, NOT
Normally, the action of ACh is terminated by _____. Inhibiting ____ prolongs the presence + actions of _____ at all ACh-R (M, N, NMJ, + brain). _____ cholinomimetics act by inhibiting AChE.
AChE, ACh, Indirect
Cholinergic agonists on the eye
miosis, accomodation
Cholinergic agonists on the lungs
bronchiolar constriction + inc. secretions
Cholinergic agonists on the GI tract
increased motility + secretions
Effects of cholinergic agonists on the GU tract
bladder emptying
Effects of cholinergic agonists on the cardiovascular system
dec. vascular resistance, bradycardia
Effects of cholinergic agonists on sweat glands
diaphoresis
Effects of cholinergic agonists on CNS
stimulation
Effects of cholinergic agonists on NMJ:
muscular contraction
Agonist
molecule found in nature or created in lab
Able to bind to a specific receptor
Elicits the same response as the endogenous compound for which the receptor was designed
Antagonist
molecule found in nature or created in a lab
Incompletely bind to a specific receptor
They usual response caused by agents fully binding to the receptor does not occur
Often observe the opposite response (dry mouth instead of salivation)
Two groups of cholinergic antagonists aka anticholinergics
Muscarinic antagonists and nicotinic antagonists
Muscarinic antagonists aka _____/_____. locks effects of parasympathetic autonomic discharge. Two examples are
parasympatholytic, antimuscarinic, atropine, scopolamine
Nicotinic antagonists are ____ blockers of the autonomic NS. Neuromuscular blockers NMJ induce paralysis. Three examples are
ganglionic, tetraethylammonium, tubocurarine, succinylcholine
Atropine comes from many plants including ____. Many laboratory derivatives have been synthesized. Drugs from other classes have similar structures + produce similar effects including ____, ___, + ___ which result in _____ from the intended benefits of these meds
Atropa belladonna, antihistamines, phenothiazine antipsychotics, tricyclic antidepressants, side effects
Atropine REVERSIBLY blocks ____ receptors + prevents ACh from binding to those sites. It typically blocks actions of ____ administered cholinergics>_______acetylcholine. Actions vary w/ _____ type. Most sensitive areas include ___, ____, + ____
muscarinic, exogenously, endogenous, tissue, salivary, bronchial, sweat glands
Tissues affected by atropine + other anticholinergic agents
CNS, eye, CV system, Respiratory system, GI tract, GU tract, + sweat glands
Atropine has _____ effect or use on the CNS. Scopolamine can produce ____ + _____. It’s toxicity can cause CNS ____, ____, ___, + ____.
minimal, drowsiness, amnesia, excitement, agitation, hallucinations, coma
Antimuscarinic agents may be used as adjuncts to treat tremor seen in ____ (Benztropine). Scopolamine used to treat/prevent ____ (injection, oral, or transdermal patch).
Parkinson’s dz, motion sickness
Antimuscarinic drugs such as _____ block anticholinergic stimulation of pupillary constrictor muscles resulting in ____ sympathetic dilation (mydriasis). Prevents contraction of ____ muscle, resulting in ___, which is the loss of accommodation which prevents focusing of the eye for ___ vision. It also reduces ___ secretion causing _____. Antimuscarinics can dangerously worsen _____ due to lack of outflow of aqueous humor.
atropine, unopposed, ciliary, cyclopegia, near, lacrimal, dry eyes, narrow angle glaucoma
____ + ____ are both useful to ophthalmologists to view the retina. These are caused my antimuscarinics. They are given as drops or ointment.Other drug classes are usually used first line.
Mydriasis, cycloplegia
Antimuscarinics: Low doses (<0.5) of atropine block ___ receptors only. You would observe ____ b/c ACh is still binding to ___ receptors on sinus node that result in ____ HR
M1, bradycardia, M3, dec.
Moderate to high doses of atropine (>0.5-5mg) block ___+____ receptors in SA + AV node that usually slow HR. This causes _____ due to the blockade of vagal slowing. Consider it like inhibiting brakes on heart rate. Used for ____ in _____ (0.5-3mg IV)
M2, M1, tachycardia, bradycardia, ACLS
Toxic doses (>10mg) of atropine cause ____ conduction block. It _____ electrical pulse generation in pacemaker nodes. Little effect on ____ due to minimal innervation from parasympathetic system.
intraventricular, inhibits, BP
Therapeutic uses in CV disorders: In acute MI, SA, + AV node function may be abnormally ____ resulting in unwanted ____ + impaired cardiac output. *_____ is the FIRST LINE recommendation for bradycardia in ACLS guidelines. Use of moderate doses of atropine/other antimuscarinics may correct his by blocking ____ receptors which triggers increased HR + CO which could save a pts life!
depressed, bradycardia, Atropine, M2
Effects of anticholinergics on respiratory system: Muscarinic receptors in respiratory smooth muscle + secretory glands are ______ to anticholinergics. Atropine + other anticholinergics cause _____ and reduce/dry up _____.
sensitive, bronchodilation, secretions
Therapeutic uses in respiratory disorders: ____ + ____ used in inhalers/nebulizers in the treatment of ___ + ____ to cause _____. Atropine/scopolamine are useful to dry upper + lower respiratory secretions prior to surgery/in mechanically vented pts
Ipratopium (atrovent), tiotropium (spiriva), asthma, COPD, bronchodilation
Effects of antimuscarinics on GI tract: Reduce motility by ____ tone of GI smooth muscle. ____ gastric emptying time + ____ intestinal transit time. Also reduce ____ secretion causing dry mouth (xerostomia) + ____ secretions
dec., Prolongs, slows, salivary, GI
Atropine is effective in reducing GI secretions + treating _____. ____ induced diarrhea, combo w/diphenoxylate to make ______. Note 1: Antimuscarinics do ____ affect acid secretion in the stomach. Note 2: Anticholinergic agents ____ cause significant constipation.
diarrhea, Irinotecan, Lomotil, NOT, CAN
Antimuscarinic agents cause ___ of smooth muscle in ureter + badder wall (detrusor muscle) + ____ vomiting. It can also ___ or cause urinary ____ in men w/ benign prostatic hyperplasia (BPH).
relaxation, reduces, worsen, urinary retention
Therapeutic uses in urinary disorders: Useful to treat urinary tract ____ w/ inflammation, surgery, or neurologic conditions. Some drugs include: *____ + others include
spasm, Oxybutinin (ditropan), trospium (sanctura), darifenacin (enablex), Solifenacin (vesicare), + tolterodine (detrol LA)
Oxybutinin (Ditropan) is a selective ___ receptor antagonist. Provides targeted relief for bladder ___ that causes ____ voiding.
M3, spasm, involuntary
Therapy for muscarinic toxicity: May result from ___ exposure (potent cholinomimetics…organophosphates). Potentially life threatening. Atropine effective for ___ + ___ NS symptoms. Doses may need to be ____ over several days for potent muscarinic agents like parathion + nerve gas agents. Use in addition to ____ (pralidoxime) which recycles _____ which allows for more breakdown of ___ to help reduce cholinergic activity
pesticide, central, peripheral, repeated, 2-PAM, acetylcholinesterase, ACh
Treatment of mushroom poisoning: May occur w/ ingestion of wild mushrooms which contains natural cholinergic agents. Two types of poisoning: ___ + ____
Rapid onset, delayed onset
Rapid onset mushroom poisoning: w/in ___ minutes after ingestion. Treat w/ ____
15-30, Atropine
Delayed onset mushroom poisoning (big problem) occurs ____ hours after ingestion. Includes ___ side effects as well as ___ + ___ toxicity. ____ is ineffective so must use ____.
6-12, muscarinic, renal, hepatic, atropine, SUPPORTIVE CARE
Effects of anticholinergics on sweat glands may be used to treat ____. Not always effective as there are different types of sweat glands eccrine>apocrine. Examples are ___, ___, ___, + ____ and also use ____ which reduces ACh release
hyperhydrosis, Glycopyrrolate (robinul), oxybutnin(ditropan), benztropine (cogentin), propantheline, botulinum toxin (botox)
Anticholinergic adverse effects: Related to ___ and ability to bind to ____. Examples are TCA’s, antihistamines, + phenothiazine antipsychotics. Side effects might include:
chemical structure, ACh-R, dry mouth, mydriasis, tachycardia, hot flushed skin, agitation, PLUS, urinary retention, visual changes, dry mouth, constipation
Contraindicated uses of anticholinergics: Pts w/ _____ especially NARROW ANGLE b/c causes angle closure preventing outflow of aqueous humor, elderly men w/ history of ____, + pts w/ ____ may have increased symptoms due to slow gastric emptying
glaucoma, BPH, gastric ulcers
Presynaptic inhibition of cholinergic action: Toxins from ____ target presynaptic proteins that block the release of ACh resulting in ____ of skeletal muscle, ____ activity at parasympathetic + sympathetic synapses, ___ lasts several wks to mo. Used to treat various conditions including _____ + other types of focal muscle spasms, ____ of palms + axillae, + cosmetic removal of ___. Some drugs include ___, ____, + ____.
Clostridium botulinum, paralysis, dec., inhibition, blepharospasm, hyperhydrosis, wrinkles, Onabotulinum toxin (botox), abobotullinum toxin (dysport), rimabotulinum toxin (myobloc)
Ganglionic blocking agents block ____ and its agonists at ___ receptors of parasympathetic + sympathetic ganglia. Also called ____. Able to block all autonomic outflow. This includes: ___, ____, ____, + ____.
ACh, nicotinic, nondepolarizing competitive antagonists, Tetraethylammonium (TEA), Hexamehonium (C6), Mecamylamine, Trimethaphan
Effects of ganglionic blockers: Mixed sympathetic + parasympathetic effects. CNS-___, Eye-___, CV-____, GI tract-____
sedation, tremor, choreiform movements, mental aberrations
cycloplegia, loss of accomodation, moderate dilation of pupil
tachycardia
dec. secretions + motility
There are ____ therapeutic uses of ganglionic blockers as better autonomic blockers are available + effects are difficult to predict. Major use is in ____ research
LIMITED, pharmacological
**Neuromuscular blockers block neuromuscular transmission btwn ___ + _____ receptors on skeletal muscle. Two groups work in opposite ways but cause same effects: ___ + ___
neuron, nicotinic, nondepolarizing antagonists, depolarizing agonists
Nondepolarizing neuromuscular blockers are true ____. They block ___ from binding to ___ receptors. Bind in a ____ fashion. Prevent ____ of muscle fibers + ____ contraction. Results in very ____ (paralyzed) muscle. Effect can be terminated w/ ____ inhibitors (neostigmine) that ___ ACh + overcome the competition for blockaded receptors.
antagonists, ACh, nicotinic, competitive, depolarization, inhibit, relaxed, AChe, inc.
Nondepolarizing neuromuscular blockers are used during ____ as adjuncts to anesthesia to produce muscle _____ (paralysis). Drugs differ by onset of ___, ____, + means of _____. Examples are:
surgery, relaxation, action, half-life, elimination, tunocurarine, mivacurium, atracurium, doxacurium, pancuronium, cisatracurium, vecuroium, + rocuronium
Depolarizing neuromuscular blockers: Example is ___ which binds to ____ receptors on skeletal muscle + act like ____ but the persistence of the agent @ adequate concentrations provides a ___ stimulation of the receptor. Initially, the agent causes ___ of the muscle by binding to the receptor + continued presence prevents transmission of further impulses. This causes a ___ to further depolarization + ____ results.
Succinylcholine, nicotinic, ACh, constant, depolarization, resistance, paralysis
Therapeutic uses of depolarizing neuromuscular blockers: Good characteristics include ___ onset + ___ duration of action. ____ is used to facilitate intubation + during electroconvulsive shock therapy
rapid, short, Succinylcholine
