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397 Cards in this Set

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what does activation of alpha-1 adrenoceptors mediate?
smooth muscle contraction
leading to vasoconstriction
dilation of pupils
contraction of bladder sphincter muscle
what does activation of alpha-2 adrenoceptors mediate?
inhibits the release of NE from sympathetic neurons
decreases the secretion of aqueous humor
decreases the secretion of insulin
what does the activation of beta-1 adrenoceptors mediate?
produces cardiac stimulation and increases secretion of renin
what does activation of beta-2 adrenoceptors mediate?
smooth muscle relaxation
what do the catecholamines include?
NE
epinephrine
isoproterenol
dopamine
dobutamine
how are catecholamines administered and why?
administered parenterally because they are rapidly metabolized
what are catecholamines primarily used to treat?
cardiac disorders
various types of shock
besides adrenoceptors what does dopamine activate?
D1-receptors and thereby increases renal blood flow
what are noncatecholamines?
Pheylephrine
Albuterol
are resistant to degradation by COMT
how does Phenylephrine work?
noncatecholamine
activates alpha-adrenoceptors and causes vasoconstriction
how does albuterol work?
activates b2-adrenoceptors and produces bronchodilation
what are imidazoline compounds?
agents that activate a-adrenoceptors and imidazoline receptors
Example of imidazoline compounds?
Oxymetazoline: decongestant
clonidine: antihypertensive agent
aproclonidine: agent used to treat glaucoma
how do indirect acting adrenoceptor agonist work?
increase the synaptic concentration of NE
what type of drug is amphetamine? how does it work?
Indirect acting adrenoceptor agonist
causes reverse transport of NE by the catecholamine transporter
what type of drug is cocaine? how does it work?
Indirect acting adrenoceptor agonist
blocks the reuptake of NE by the catecholamine transporter
what type of drug is pseudoephedrine?
both direct and indirect actions
- used as a nasal decongestant
what is the mechanism of signal transduction for alpha-1 adrenoceptors?
phospholipase C activation
increased IP3
release of calcium
what are the effects of alpha-1 stimulation?
contraction of smooth muscle
exocrine gland secretion
neuronal excitation
what is the mechanism of signal transduction for alpha-2 receptors?
inhibition of adenylyl cyclase and decreased cAMP
what is the effect of alpha-2 stimulation?
inhibition of NE release
decreases in aqueous humor
decrease in secretion of insulin, platelet degradation, and CNS system effects
what is the mechanism of action of B1-receptors?
adenyly cyclase activation
increased cAMP
protein kinase activation
what is the mechanism of signal transduction for alpha-1 adrenoceptors?
phospholipase C activation
increased IP3
release of calcium
what are the effects of alpha-1 stimulation?
contraction of smooth muscle
exocrine gland secretion
neuronal excitation
what is the mechanism of signal transduction for alpha-2 receptors?
inhibition of adenylyl cyclase and decreased cAMP
what is the effect of alpha-2 stimulation?
inhibition of NE release
decreases in aqueous humor
decrease in secretion of insulin, platelet degradation, and CNS system effects
what is the mechanism of action of B1-receptors?
adenyly cyclase activation
increased cAMP
protein kinase activation
what is the mechanism of signal transduction for alpha-1 adrenoceptors?
phospholipase C activation
increased IP3
release of calcium
what are the effects of alpha-1 stimulation?
contraction of smooth muscle
exocrine gland secretion
neuronal excitation
what is the mechanism of signal transduction for alpha-2 receptors?
inhibition of adenylyl cyclase and decreased cAMP
what is the effect of alpha-2 stimulation?
inhibition of NE release
decreases in aqueous humor
decrease in secretion of insulin, platelet degradation, and CNS system effects
what is the mechanism of action of B1-receptors?
adenyly cyclase activation
increased cAMP
protein kinase activation
what is the effect of B1-receptor activation?
increase in secretion of renin and increases in heart rate, contractility, and conduction
what is the effect of B2-receptor activation?
Glycogenolysis
relaxation of smooth muscle & uptake of potassium in skeletal muscle
what is the mechanism of action of B2-receptor activation ?
adenylyl cyclase activation
increased cAMP
protein kinase activation
what is the mechanism of signal transduction for B3 receptors?
adenylyl cyclase activation
increased cAMP
protein kinase activation
what is the effect of B3 receptor activation?
Lipolysis
what is the mechanism of signal transduction for D1 receptors?
increased cAMP
what is the effect of stimulation of D1 receptors?
relaxation of smooth muscle
what is the mechanism of signal transduction of D2 receptors?
decreased cAMP
increased potassium currents
decreased calcium influx
what is the effect of D2 receptor activation ?
modulation of NT in the sympathetic and CNS
what is the mechanism of action for Imidazoline receptor activation?
uncertain
what is the effect of activation of imidazoline receptors?
natriuresis
decreases sympathetic outflow from the CNS
where are alpha-1 receptors found?
primarily in the smooth muscle
where are B1-receptors found?
primarily in the smooth muscle
where are B2-receptors found?
predominately in the cardiac tissue
where are alpha-2 receptors found ?
some receptors are located on sympathetic neurons where they produce feedback inhibition of NT release
what receptors are found on platelets?
alpha-2
beta-2
what are the direct acting Catecholamines?
Dobutamine
Dopamine
Epinephrine
Isoproternol
Norepinephrine
describe receptor affinity for Dobutamine.
B1 > B2 >>> alpha
describe the receptor affinity for Dopamine.
D1=D2 >> B1 >> a1
describe the receptor affinity for Epinephrine.
a1 = a2 < B1=B2
describe the receptor affinity of Isoproterenol.
B1=B2 >>>>>> a
describe the receptor affinity of Norepinephrine
a1 = a2 > B1>>B2
what is the pharmacological effect of Dobutamine?
cardiac stimulation (B1)
Vasodilation (B2)
Not for septic shock
what is the clinical use for Dobutamine?
Cardiogenic shock
acute heart failure
Cardiac stimulation during heart surgery
what is the pharmacological effect of Dopamine?
Renal vasodilation (D1)
Cardiac stimulation (B1)
Increased blood pressure (B1 & a1)
what are the clinical uses of Dopamine?
cadiogenic shock
septic shock
heart failure
adjunct to fluid administration in hypovolemic shock
what are the pharmacological effects of Epinephrine?
vasoconstriction
increased blood pressure (a1)
cardiac stimulation (B1)
Bronchodilation (B2)
what are the clinical uses for Epinephrine?
Anaphylactic shock
Cardiac arrest
Ventricular fibrillation
Reduction in bleeding during surgery
Prolongation of the action of local anesthetics
what is the pharmacological effects of Isoproterenol?
Cardiac stimulation (B1)
Bronchodilation (B2)
what are the clinical uses for Isoproterenol?
Asthma
AV block
Bradycardia
what are the pharmacological effects of Norepinephrine?
Vasoconstriction and increased blood pressure (a1)
what are the clinical uses for Norepinephrine?
Hypotension
shock
Name the direct acting Noncatecholamine?
Albuterol
Apraclonidine
Clonidine
Midodrine
Oxymetazoline
Phenylephrine
Ritodrine
Terbutaline
describe the receptor affinity of Albuterol.
B2>> B1 >>>>> a
describe the receptor affinity of Apraclonidine.
a2 > a1 >>>>> B
describe the receptor affinity of Clonidine.
a2 > a1 >>>>>> B
describe the receptor affinity of Phenylephrine.
a1 > a2 >>>>>> B
describe the receptor affinity of Ritodrine.
B2 >> B1 >>>>> a
describe the receptor affinity of Terbutaline.
B2 >> B1 >>>>> a
what is the pharmacological effect of Albuterol?
bronchodilation (B2)
what is the clinical use of Albuterol?
asthma
what are the pharmacological effects of Apraclonidine?
decrease aqueous humor formation (a2)
what are the clinical uses of Apraclonidine?
short term control of intraocular pressure
what are the pharmacological effects of clonidine?
decreased sympathetic outflow from CNS (a2 & imidazoline)
what are the clinical uses of Clonidine?
hypertension
opiod dependence
what is the pharmacological effect of Midodrine?
Vasoconstriction (a1)
what are the clinical uses of Midodrine?
orthostatic hypotension in severe cases
what is the pharmacological effect of Oxymetazoline?
vasoconstriction (a1)
what is the clinical use of Oxymetazoline?
nasal and ocular decongestion
what are the pharmacological effects of Phenylephrine?
vasoconstriction, increased blood pressure, mydriasis (a1)
what are the clinical uses of Phenylephrine?
Nasal and ocular decongestion
mydriasis
maintenance of blood pressure and treatment of shock given via IV
what are the pharmacological effects of RItodrine?
uterine relaxation (b2)
what is the clinical use of Ritodrine?
premature labor
what is the pharmacological effects of Terbutaline?
Bronchodilation (B2)
what is the clinical use of Terbutaline?
Asthma
name the indirect acting agents that are adrenoceptor agonist.
Amphetamine
Cocaine
what are the pharmacological effects of Amphetamine?
increase in norepinephrine release
Central nervous system stimulation
what are the clinical uses of Amphetamine?
Narcolepsy
attention deficit disorder
what are the pharmacological effects of cocaine?
inhibition of norepinephrine uptake
what is the clinical use of cocaine?
local anesthesia
name something significant about mixed acting agents that are adrenoceptor agonist.
activate both a & b receptors
can cause tachycardia via B1
Name the mixed acting adrenoceptor agonist.
Ephedrine
Pseudoephedrine
what is the pharmacological effect of ephedrine?
vasoconstriction (a1)
what is the clinical use of ephedrine?
nasal decongestant
what is the pharmacological effect of pseudoephedrine?
vasoconstriction (a1)
what is the clinical use of pseudoephedrine?
nasal decongestant
Describe the cardiovascular effects of Norepinephrine.
increases peripheral resistance and blood pressure
leds to reflex bradycardia
describe the cardiovascular effects of Epinephrine.
increases heart rate while reducing peripheral resistance and the mean arterial pressure increases slightly
describe the cardiovascular effects of Isoproterenol.
increases heart rate
significantly lowers peripheral resistance
mean arterial pressure declines
describe the cardiovascular effects of Dopamine.
increase heart rate
increases cardiac output
lowers vascular resistance
Mean arterial pressure increases
what does Tyramine cause?
release of catecholamines
what normally breaks Tyramine down?
MAO rapidly breaks tyramine down
what happens if a person take an MAOI and eats certain foods?
it can cause acute hypertension because Tyramine is not broken down
what are the Genitourinary indications for sympathomimetic drugs?
Premature labor: Ritodrine or Terbutaline
Stress incontinence:
what are the cardiovascular indications for sympathomimetic drugs?
Congestive heart failure: sympathomimetic drugs that elicit a positive inotropic effect may be useful in the treatment of CHF.
Dobutamine & Dopamine are used most often
what are the respiratory indications of sympathomimetic drugs?
asthma: drugs that activate B2-adrenoceptors are useful in the treatment of asthma because they cause bronchial smooth muscle relaxation.
B2-selective agonist: Albuterol, metaproterenol, and terbutaline widely used because they have less cardiac effects than the non-selective adrenoceptor agonist Epinephrine
what are the adverse effects of sympathomimetic drugs?
Cardiovascular effects:
marked increase in blood pressure
- cerebral hemorrhage
- pulmonary edema
- angina or precipitation of MI
-Excessive vasoconstriction at the site of injection may cause ischemia
- can be reverse by a-receptor antagonist
- Sinus tachycardia
- LIfe threatening arrhythmias
what are the adverse effects of Epinephrine?
restlessness, throbbing headache, tremor, palpitations, cerebral hemorrhage, cardiac arrhythmias
what are the contraindications of Epinephrine?
not used in patients receiving non-selective-B-blockers
- can cause massive increase in BP with b-blockers
what are the adverse side effects of Norepinephrine?
similar to epinephrine with greater elevation of blood pressure, necrosis, and sloughing at injection site
what are the adverse effects of Isoproterenol?
palpitations
tachycardia
headache
flushed skin
arrhythmias
what are the adverse side effects of Clonidine?
drug mouth
sedation
sexual dysfunction
bradycardia
- reduced sympathetic outflow
what are the adverse side effects of Pheylephrine?
similar to NE
throbbing headache
tremor
palpitations
cerebral hemorrhage
cardiac arrhythmias
what are the adverse side effects of Albuterol?
skeletal muscle tremor
restlessness
apprehension
anxiety
tachycardia
arrhythmias
myocardial ischemia
what are the adverse side effects of Ritodrine and Terbutaline?
similar to albuterol
severe pulmonary edema in women receiving ritodrine for premature labor
what is the function of indirect acting sympathomimetics?
drugs that promote NT release
drugs that prevent NT release
what are adverse side effects of Amphetamine?
produces vasoconstriction, cardiac stimulation, increased BP, stimulant effect on mood and alertness, and depressant effect on appetite
what drugs prevent neurotransmitter reuptake?
Cocaine an indirect acting sympathomimetic
what drugs possess both direct and indirect actions on the release of NE?
Ephedrine
Pseudoephedrine
what is Ephedrine used for?
nasal decongestant
stress incontinence
what is psuedoephedrine used for?
nasal decongestant
stress incontinence
what are the adverse side effects of Ephedrine?
hypertension
insomnia
tachyphylaxis
urinary retention
adverse CV effects in susceptible individuals
what are the adverse effects of Pseudoephedrine?
similar to ephedrine
hypertension
insomnia
tachyphylaxis
urinary retention
adverse CV effects in susceptible individuals
should cough and cold products that can be purchased OTC be used in children less than 2 years of age?
NO
use caution with children under 6 years of age
what drugs are competitive a1-blockers?
Doxazosin
Prazosin
Terazosin
what is the pharmacological effect of competitive a1-blockers?
Doxazosin, Prazosin, Terazosin
- cause vasodilation and decrease blood pressure
- relax bladder, urethral, and prostate smooth muscle
what are the clinical uses for a1-blockers?
Hypertension
Urinary symptoms due to benign prostatic hyperplasia
Raynauds phenomenon & Systemic Sclerosis
off-label: PTSD - increase sleep and decrease nightmares
what type of drug are Alfuzosin and Tamsulosin, and Silodosin?
competitive a1-blockers
what are Alfuzosin, Tamsulosin, and Silodosin used clinically for?
- relax the bladder, urethral and prostate smooth muscle
- uroselective
- urinary symptoms due to BPH
what type of drug is Phenoxybenzamine?
noncompetitive a1 and a2-blocker
what is the pharmacological effects of phenoxybezamine?
causes vasodilation
decreases blood pressure
what is the clinical use of phenoxybenzamine?
hypertension in pheochromocytoma
Phentolamine
competitive a1 & a2-blocker
duration of action IV: 15 min
duration of action IM/SC: 3-7 hrs
what is the pharmacological effects of Phentolamine?
causes vasodilation
decreases vascular resistance and blood pressure
what is the clinical use of phentolamine?
hypertension due to pheochromocytoma
treat necrosis and ischemia after injection of an a-adrenoceptor agonist
what is Yohimbe?
competitive a2>>a1 blocker
OTC herbal preparation
sometimes taken to treat ED
could cause BP/HR abnormalities and sleep disturbances
what are the adverse effects of Phentolamine?
hypotension
tachycardia
cardiac arrhythmias
ischemic cardiac events
GI stimulation may result in abdominal pain, nausea, and exacerbation of peptic ulcer
what are the adverse side effects of Phenoxybenzamine?
postural hypotension accompanied by reflex tachycardia and arrhythmias
inhibition of ejaculation and aspermia after orgasm
what are the adverse side effects of Prazosin, Terazosin, Doxazosin?
first dose phenomenon
orthostatic hypotension
headache
dizziness
fainting
reflex tachycardia
edema
describe the negative feedback mechanism that decreases the amount of sympathetic stimulation to the heart.
NE activates presynaptic a2-adrenergic receptors and this inhibits formation of cAMP and decreases the release of NE
how does Phentolamine work?
blocks a2-receptor mediated inhibition of NE release. This increases the stimulation of cardiac b1-adrenergic receptors and results in tachycardia (blocking negative feedback)
why does Prazosin cause less tachycardia than phentolamine?
Prazosin, a selective a1-blocker does not block a2-receptor mediated inhibition of NE release therefore prazosin causes less tachycardia than does phentolamine
what are the clinical uses of b-blockers?
Neurological disease
Hypertension
Ischemic heart disease
Cardiac arrhythmias
Glaucoma
Hyperthyroidism
how doe b-blockers work in the treatment of neurological disease?
reduction in the frequency and intensity of migraine
reduction in somatic manifestation of anxiety
reduction in essential tremor
why do b-blockers work in treatment of hypertension?
effective and well tolerated
often used with diuretic or vasodilator
how do b-blockers work in the treatment of ischemic heart disease?
reduce the frequency of anginal episodes
improves exercise tolerance
how do b-blockers work in the treatment of cardiac arrhythmias?
effective in the treatment of both SVT and ventricular arrhythmias
Reduce ventricular ectopic beats, particularly if ectopic activity has been precipitated by catecholamines
Slow ventricular response rate in atrial flutter and fibrillation
what other cardiac disorders are b-blockers used to treat?
increase stroke volume in some patients with obstructive cardiomyopathy
useful in dissecting aortic aneurysm to decrease the rate of development of systolic pressure
why are b-blockers used in the treatment of Glaucoma?
reduction in intraocular pressure
why are b-blockers used in the treatment of hyperthyroidism?
decreases HR, BP, anxiety, and tremor
Name the B1-blockers.
Acebutolol
Atenolol
Esmolol
Metoprolol
what are the pharmacological effects of B-blockers?
decrease cardiac rate, output, AV node conduction, and oxygen demand
decreases blood pressure
what is the clinical use of Acebutolol?
hypertension
cardiac arrhythmias
NOT for migraines
what is the clinical use of Atenolol?
b1-blocker
hypertension
angina pectoris
acute MI
Essential tremor
what is the clinical use of Esmolol?
B1-blocker
administered via IV
Acute SVT
Acute Hypertension
what is the clinical use of Metoprolol?
B1-selective with MSA
Hypertension
angina pectoris
acute MI
what type of b-blocker is Nadolol?
B1 & B2-blocker
what is the clinical use of Nadolol?
non-selective b-blocker
hypertension
angina pectoris
migraine headache
what type of b-blocker is Pindolol?
b1 & b2-blocker
what is the clinical use of Pindolol?
Hypertension
NOT for MIGRAINES
Propanolol.
B1- and B2-blocker
hypertension
angina pectoris
hypertrophic subaortic stenosis
essential tremor
migraine headache
acute thyrotoxicosis
acute MI
Pheochromocytoma
Timolol
B1 & B2-blocker
what is the pharmacological effect of Timolol?
decreases cardiac rate, output, AV node conduction, and oxygen demand
decreases blood pressure
decreases intraocular pressure
what is the clinical use of Timolol?
Hypertension
Acute MI
Migraine headaches
Glaucoma: topical- reduce secretion of aqueous humor
Name the non-selective a- and b-blockers.
Carvedilol
Labetolol
Carvedilol
b1 & b2 blocker
a1-blocker
strong antioxidant properties
cardioprotective
causes vasodilation
decreases heart rate and blood pressure in patients with hypertension
increases CO in patients with heart failure
tx: hypertension & heart failure
Labetalol
B1& B2-blocker with MSA
a1-blocker
causes vasodilation
decreases heart rate and blood pressure
tx: hypertension
what non-selective b-blocker has intrinsic sympathomimetic activity?
Pindolol
what non-selective b-blocker has membrane stabilizing activity?
Pindolol: low
Propanolol: high
what b1-blocker has intrinsic sympathomimetic activity?
Acebutolol has low sympathomimetic activity
what b1-blocker must be administered via IV?
Esmolol
what are the adverse side effects of b-receptor blockers?
CNS: sedation, sleep disturbances, depression, psychotic reactions
Pulmonary fxn: worsening of pre-existing asthma and other forms of airway obstruction
CV: may cause or exacerbate heart failure, acute MI, or cardiomegaly. Bradycardia, life threatening bradyarrhythmias. Cold extremities, abrupt discontinuation can exacerbate angina and increase risk of sudden death
Metabolism: blunt recognition of hypoglycemia and may delay recovery from insulin induced hypoglycemia. USE b1-specific antagonist to avoid
Drug interactions: effects are additive to CCB and with other antihypertensive drugs
what is the CNS?
brain and spinal cord
what is the PNS?
ganglia outside of the spinal cord
what are the motor portions of the PNS divided into?
somatic motor division
autonomic motor division
what is the somatic motor division of the PNS?
motor axon that connects the brain and spinal cord to skeletal muscle
what is the autonomic motor division of the PNS?
cells and axons that innervate smooth muscle, cardiac muscle, and glands
what can the autonomic nervous system be divided into?
Sympathetic
Parasympathetic
Enteric
describe the sympathetic nervous system.
Fight or Flight
ganglia near spinal column and innervate various target organs
describe the parasympathetic NS.
ganglia found within organs they innervate
"Rest and Digest"
what is the Enteric nervous system?
neurons in the wall of the gut
Gastric motility and secretion
what inhibits the Enteric NS?
sympathetic NS
what activates the Enteric Nervous system?
Parasympathetic Nervous system
"rest and digest"
describe the anatomy of the Sympathetic NS?
from thoracic and lumbar of spinal cord to ganglia near the spinal cord and then from the ganglia to organs
- Short pre-ganglionic
- Long post-ganglionic
Describe the anatomy of the Parasympathetic NS?
Rest & digest
From brainstem (CN III, VII, IX, X) and sacral spinal cord to ganglia (near or in organs) and then from the ganglia to organs.
- Long pre-ganglionic
- short post-ganglionic
- ganglia often located in the target organs
what receptor do Preganglionic fibers synapse on?
Ionotropic
Fast
with Nicotinic receptor
what receptor do Post-ganglionic fibers synapse on?
metabotropic
slower with Muscarinic receptors
what NT acts on preganglionic receptors?
ACh acts on Nicotinic receptors
- muscle (somatic)
- Ganglia, CNS
what NT acts on Postganglionic receptors?
Parasympathetic: Muscuarinic receptor > ACh
Sympathetic: Adrenocreceptors (Epi/NE)
__________ is the primary NT at somatic (preganglionic nicotinic) and parasympathetic (postganglionic) receptors.
ACh
Norepinephrine is the primary NT at the _________ NS (postganglionic) junctions.
Norepinephrine
what are the non-adrenergic and non-cholingergic NTs found in the ANS?
Peptides
Nitric oxide
Serotonin
describe the functions of ACh.
Somatic & Parasympathetic NT
- Ionotropic receptors: excitatory
- Nicotinic receptors
- Metabotropic receptors
- Muscarinic receptors
what muscarinic receptors are excitatory?
M1, 3, 5
what muscarinic receptors are inhibitory?
M2 & 4
what breaks down ACh?
acetylcholinesterase
what type of neuron is Norepinephrine active on?
adrenergic neurons
Sympathetic neurons
where is dopamine concentrated in?
locus ceruleus
what are the excitatory adrenergic receptors?
alpha1
beta1,2,3
what breaks down ACh?
acetylcholinesterase
what breaks down Dopamine and NE?
MAO and COMT
what breaks down Serotonin?
MAO and ALDH
Hemicholinum
inhibits synthesis of ACh
Vesamicol
prevents vesicular storage of ACh by increasing the release of ACh
Botulinum Toxin
inhibits release of ACh
- inhibits muscle contraction
black widow spider venom
inhibits release of ACh
cholinesterase inhibitors: Physostigmine
inhibits breakdown of ACh = increased ACh
Name ACh agonist.
Acetylcholine
Bethanechol
Pilocarpine
- activate the postsynaptic receptor
Name ACh antagonist.
Atropine
Tubocrurarine
- blocks postsynaptic receptors
what type of receptor does atropine block?
Muscarinic receptors
What type of receptor does Tubocrurarine block?
Nicotinic receptors
if a drug is going to effect the sympathetic nervous system NT, what NT is it affecting?
Norepinephrine
Metyrosine
inhibits synthesis of NE by decreasing tyrosine hydroxylase
Reserpine
prevents vesicular storage of NE
Bretylium
inhibits release of NE
- neuronal blocking agent
Amphetamine
inhibits the release of NE
- increases NE in synapse
Cocaine
inhibits the reuptake of NE
decreased reuptake > increased NE
Phenelzine (MAOI)
inhibits the breakdown of NE
decreases breakdown = increased NE
Name direct acting b-agonist that cause NE release by activating the postsynpatic receptor.
Albuterol
Dobutamine
Epinephrine
Name NE receptor antagonist that block postsynaptic receptor.
Phentolamine
Propanolol
what type of receptors does Phentolamine block?
a-adrenoceptors (post synpatic)
what type of receptors does Propanolol block?
b-adrenoreceptor (pre-synaptic)
Anxiolytic
what type of receptors does Labetalol antagonize?
a- and b-adrenreceptors
when muscarinic (ACh) and a-adrenoreceptors are stimulated what is the action?
smooth muscle cell contraction
when b-adrenoreceptors (NE) are stimulated what is the action?
smooth muscle relaxation (b-2)
cardiac stimulation (b-1)
what modulates the baroreceptor reflex?
adrenoreceptor (NE) agonist and antagonist
Name the ACh receptors
Nicotinic
Muscarinic
describe Nicotinic receptors
Preganglionic
Somatic
Parasympathetic/Sympathetic
describe Muscarinic receptors
postganglionic
parasympathetic
where are nicotinic receptors found?
Nicotinic receptors are found at all autonomic ganglia, somatic neuromuscular junction, and CNS
what occurs with the activation of nicotinic receptors at autonomic ganglia by ACh?
activated nicotinic receptors = excitation of postganglionic neurons leading to release of NT at postganglionic neuroeffector junctions
what occurs with activation of the nicotinic receptor at somatic nerves and skeletal muscle.
activated nicotinic receptors = depolarization of motor end plate and leads to increase calcium from SR = muscle contraction
what occurs when nicotinic receptors are activated in the CNS?
activation of nicotinic receptors in the brain = excitation of pre and post synaptic neurons
describe a nicotinic receptor.
ionotropic
excitation
fast
what is the nicotinic receptor structure?
polypeptide pentamer with ACh binding sites
how does acetylcholine affect the channel that a nicotinic receptor controls?
ACh gated Na Channels: activation leads to increase sodium influx = depolarization
where are muscarinic receptors found in the body?
smooth muscle
cardiac tissue
glands at parasympathetic neuroeffector junctions
Presynaptic sympathetic and parasympathetic autonomic nerves
what occurs after a muscarinic receptor has been activated by ACh?
decreased NT release
how are the parasympathetic and sympathetic nervous systems connected?
Muscarinic receptors are present at sympathetic nerve terminal = connection between parasympathetic and sympathetic NS
- release of ACh from parasympathetic NS = decrease NE from sympathetic nerves
describe the Muscarinic receptor.
metabotropic (GPCR)
slow
M1-M5
M1,3,5: increase PLC = increase IP3 and DAG
M2,4: decrease cAMP
A nicotinic ACh receptor have neurotransmission and muscle contraction properties. Where are the three types of receptors found?
Muscle type: NM Junction: increases sodium influx: muscle contraction
Ganglionic type: Autonomic ganglia: increase Na influx: neuronal excitation
CNS type: CNS: increases Na influx: neuronal contraction
Describe the Muscarinic ACh receptor properties according to their locations in the body.
M1: neutral: ANS ganglia, presynaptic, CNS: increases IP3: modulation of central/peripheral
M2: cardiac: Cardiac tissue: decrease cAMP, increase IP3: cardiac slowing
M3: glandular: smooth muscle/glands: increase IP3: smooth muscle/gland
M3: vascular smooth muscle: increase cGMP: vasodilation
describe what a direct acting ACh receptor agonist does.
binds and activates ACh receptors
describe the function of an indirect ACh acting receptor Agonist.
inhibits cholinesterase: decreases ACh breakdown: increases ACh
Augment ACh signal transduction
Name the Choline Esters that are Direct Acting Receptor Agonist of ACh.
Acetylcholine
Bethanechol
Carbachol
Methacholine
Name the direct acting agonist that are plant alkaloids for ACh receptors.
Muscarine
Nicotine
Pilocarpine
where are muscarinic receptors found in the body?
smooth muscle
cardiac tissue
glands at parasympathetic neuroeffector junctions
Presynaptic sympathetic and parasympathetic autonomic nerves
what occurs after a muscarinic receptor has been activated by ACh?
decreased NT release
how are the parasympathetic and sympathetic nervous systems connected?
Muscarinic receptors are present at sympathetic nerve terminal = connection between parasympathetic and sympathetic NS
- release of ACh from parasympathetic NS = decrease NE from sympathetic nerves
describe the Muscarinic receptor.
metabotropic (GPCR)
slow
M1-M5
M1,3,5: increase PLC = increase IP3 and DAG
M2,4: decrease cAMP
A nicotinic ACh receptor have neurotransmission and muscle contraction properties. Where are the three types of receptors found?
Muscle type: NM Junction: increases sodium influx: muscle contraction
Ganglionic type: Autonomic ganglia: increase Na influx: neuronal excitation
CNS type: CNS: increases Na influx: neuronal contraction
Describe the Muscarinic ACh receptor properties according to their locations in the body.
M1: neutral: ANS ganglia, presynaptic, CNS: increases IP3: modulation of central/peripheral
M2: cardiac: Cardiac tissue: decrease cAMP, increase IP3: cardiac slowing
M3: glandular: smooth muscle/glands: increase IP3: smooth muscle/gland
M3: vascular smooth muscle: increase cGMP: vasodilation
describe what a direct acting ACh receptor agonist does.
binds and activates ACh receptors
describe the function of an indirect ACh acting receptor Agonist.
inhibits cholinesterase: decreases ACh breakdown: increases ACh
Augment ACh signal transduction
Name the Choline Esters that are Direct Acting Receptor Agonist of ACh.
Acetylcholine
Bethanechol
Carbachol
Methacholine
Name the direct acting agonist that are plant alkaloids for ACh receptors.
Muscarine
Nicotine
Pilocarpine
what type of drug are:
Cevimeline
Varenicline
Direct acting ACh- receptor antagonist
Acetylcholine
Nicotinic and Muscarinic
- hydrolyzed by choline esterase
- Miosis (ophthalmologic exam)
- Coronary angiography
- Vasodilation
Bethanechol
Direct acting ACh-receptor Agonist
Muscarinic
NOT hydrolyzed by Choline esterase
Oral administration
GI and GU stimulation
Carbachol
Direct Acting ACh receptor agonist
Nicotinic and Muscarinic
NOT hydrolyzed by Choline esterase
Ocular administration
Miosis during ophthalmic surgery
Glaucoma
Methacholine
Direct Acting ACh receptor agonist
Nicotinic and Muscarinic
hydrolyzed by choline esterase
inhalation administration
Asthma challenge
what type of drug is Muscarine?
Muscarinic Plant Alkaloid ACh receptor agonist
- NO medical use
What drug is a nicotinic ACh receptor agonist that is a plant alkaloid, administered orally/transdermally, and used for smoking cessation?
Nicotine
Pilocarpine
Plant Alkaloid ACh receptor Agonist
Muscarinic receptor
Topical ocular/oral administration
Glaucoma
Xerostomia
Cevimeline
ACh receptor Agonist
M3: excitatory
increases IP3
Oral administration
Xerostomia
RX: dry eyes
Varenicline
Acetylcholine receptor Agonist
Nicotinic receptor agonist
Oral administration
Smoking cessation
decreases cravings and withdrawal symptoms
what are the classes of drugs that indirectly act as ACh receptor agonist?
Drugs that inhibit cholinesterase
- Reversible cholinesterase inhibitors
- irreversible cholinesterase inhibitors
Drugs that augment ACh
name the reversible cholinesterase inhibitors.
Donepazil
Edrophonium
Neostigmine
Physostigmine
Pyridostigmine
name the irreversible cholinesterase inhibitors
Echothiophate
Isoflurophate
Malathion
Name the drugs that Augment ACh
Sidenafil
Vardenafil
Tadalafil
Describe Donepazil
Reversible cholinesterase inhibitor
Oral administration
Clinical use: Alzheimers disease
describe Edrophonium
Reversible cholinesterase inhibitor
IV administration
Clinical use: Myasthenia gravis diagnosis
describe Neostigmine
Reversible Cholinesterase inhibitor
Oral, SC, or IM administration
Clinical use: Myasthenia gravis, GI, GU stimulation
describe Physostigmine
Reversible Cholinesterase inhibitor
Topical ocular administration, IM, IV
Clinical use: Glaucoma, Reversal CNS effects of antimuscarinic drugs
describe Pyridostigmine
Reversible Cholinesterase inhibitor
Oral, IM, IV administration
Clinical use: Myasthenia gravis, antidote for curariform drug toxicity
describe Echothiophate
Irreversible cholinesterase inhibitor
Topical ocular administration
Clinical use: Chronic Glaucoma and Accommodation estropia
Isoflurophate
Irreversible Cholinesterase inhibitor
Topical ocular administration
Clinical use: Glaucoma and accommodation estropia
You child plays on a baseball team and they share batting helmets. One of the children on his team has gotten head lice. If you child has it too, what will you use to treat him?
Malathion
- Irreversible Cholinesterase inhibitor
- Topical administration
Clinical use: Pediculosis (lice)
describe the action of Sidenafil.
Drug that augments ACh
- Viagra
- decreases 5-PDE = decrease degradation of cAMP = increase cGMP = increased vasodilation
what would a patient need Vardenafil for? Can the patient eat food with it?
Vardenafil is a drug that augments ACh and is a Sidenafil minor drug for ED.
Patients can eat food with it since it is not affected by food
Which of the drugs that augment ACh receptors has the longest half life?
Tadalafil (Cialis)
absorption not affected by food
what is the most common side effect of Sidenafil?
HEADACHE
What is carbachol most commonly used to treat?
Choline ester ACh receptor agonist.
used to treat Chronic open-angle glaucoma
What is Pilocarpine most commonly used to treat?
Direct acting ACh receptor agonist
Chronic open-angle and acute angle closure glaucoma
Your patient has chronic glaucoma and accommodative estropira. What would you treat them with?
Echothiophate
Isoflurophate
Irreversible cholinesterase inhibitors
It has been determined your patient that has come to the ER has organophosphate poisoning. How do you treat them?
this is cholinergic poisoning
- Echothiophate, Isoflurophate, Malathion are possible causative agents
- Give ACh antagonist (Atropine) and cholinesterase regenerator
what do ACh receptor Antagonist do?
block either Nicotinic or Muscarinic receptors
can affect almost every organ system
Wide range of clinical applications
What do Nicotinic receptor antagonist do?
block neurotransmission at nicotinic receptors
Ganglionic blocking agents and neuromuscular blocking agents used to relax smooth muscle
what do Muscarinic receptor antagonist do?
used to relax smooth muscle
decrease gland secretion
stimulate heart
what is an example of a Belladona alkaloid that is an ACh receptor antagonist?
Atropine
what is an example of a semisynthetic/synthetic muscarinic antagonist?
Ipratropium
what do muscarinic agonist do?
smooth muscle contraction
increase gland secretion
decrease heart rate and conduction
pupil constriction
what do Muscarinic antagonist do?
Opposite effects of parasympathetic NS
- relax smooth muscle
- decrease gland secretion
- stimulate heart (Increase HR & cardiac contraction)
- Pupil dilation
- decrease respiratory secretions
- bronchial smooth muscle relaxation/bronchodilation
- Some can relax GI and slow motility, cause urinary retention, and CNS with sedation or excitement
Can decrease heat loss and lead to hyperthermia and flushing
what are muscarinic antagonist used to treat?
Bradycardia
Obstructive lung disease
Intestinal spasms
Overactive urinary bladder
- increase HR, cardiac contraction, decrease salivary and respiratory secretions, relax GI & GU
Muscarinic Antagonist/Agonist are used to produce mydriasis and cyclopegia in ophthalmologic exams.
Muscarinic Antagonist
- Mydriasis: pupil dilation
- Cyclopegia: decrease accommodation
how do muscarinic antagonist cause mydriasis?
relax iris sphincter muscle
relax ciliary muscle
how do muscarinic antagonist cause cyclopegia?
decrease accommodation
- increase tension of suspensory ligaments attached to the lens: lens flattens: causes focus on distant objects
- decrease lens ability to increase refractory power to focus on near objects
What toxicity is referred to by this mnemonic: drug as a bone, blind as a bat, red as a beet, and mad as a hatter? and why?
Atropine toxicity
Symptoms: dry mouth, decreased sweating, blurred vision, flushing, hyperthermia, delirium, hallucinations, and coma
Urinary retention is also a symptom as well as transient tachycardia and palpitations
why are muscarinic antagonist used in ophthalmologic exams?
muscarinic antagonist aid in the examination of the retina by causing mydriasis
what muscarinic antagonist should be used in children vs. adults in causing mydriasis for an ophthalmologic exam?
Atropine (long-lasting) may be necessary in children, but shorter-acting drugs (tropicamide) are preferred and used in adults and older children
what two muscarinic antagonist are used to prevent increased airway secretions and laryngospasm elicited due to inhalation of anesthetics?
Atropine or Scoplamine
what muscarinic antagonist is used to prevent bronchoconstriction?
Ipratropium is inhaled and used in the treatment of COPD and asthma
Would you administer atropine to a patient with asthma or COPD?
NO
atropine inhibits ciliary activity which would increase thickness of mucus
________ __________ may be used to improve depressed cardiac output resulting from increased vagal tone.
Muscarinic antagonist
- MI
- Hyperactive carotid sinus reflex
- Idiopathic dilated cardiomyopathy
How would a patient become toxic with cholinergic poisoning?
Cholinergic excess resulting from exposure to cholinesterase inhibitors elicits effects resulting from the stimulation of both nicotinic and muscarinic receptors
Lessened by administration of atropine
what is the treatment for Cholinergic poisoning?
Lessend by administration of atropine
The cholinesterase regenerator Pralidoxime may also be administered to patients exposed to organo-phosphate cholinesterase inhibitors
Your patient has been exposed to organophosphate poison. What do you do for them.
Patient was probably exposed to Echothiophate, Isoflurophate, or Malathion which are irreversible cholinesterase inhibitors
Give ACh antagonist: atropine
Give Cholinesterase regenerator: Pralidoxime
List the side effects of Muscarinic antagonist
Dry mouth
blurred vision
hot skin
flushed skin
delirium
tachycardia
agitation
What patients are muscarinic antagonist contraindicated in?
closed angle glaucoma
prostatic hyperplasia
gastric ulcer
USe extreme caution in children
what nicotinic receptor antagonist is a ganglionic blocking agent?
Trimethaphan
- blocks ACh at Nicotinc receptor
- emergency treatment of malignant HTN
- increase hypoTN surgery
Name the depolarizing blocking agent that is an ACh receptor Antagonist.
Succinylcholine
what is Succinylcholine used for?
Depolarizing ACh receptor antagonist
only depolarizing agent
Muscle relaxation during surgery
Causes muscle fasciculations
what is the Duration of Action of Succinylcholine?
short DOA 5-10 minutes
Is succinylcholine hydrolyzed by cholinesterase inhibitors?
NO
what is the method of elimination of succinylcholine?
Plasma cholinesterase
what are the non-depolarizing agents that are ACh receptor Antagonist?
Atracurium
Cisatracurium
Pancuronium
what are the non-depolarizing ACh receptor antagonist clinically used for?
Muscle relaxation during surgery
Atracurium
ACh-receptor antagonist
non-depolarizing
Intermediate DOA 30-60 minutes
route of elimination: plasma esterase
Cisatracurium
ACh-receptor Antagonist
Non-depolarizing
Intermediate DOA
decreased by spontaneous chemical degradation
Pancuronium
ACh-receptor antagonist
Non-depolarizing agent
Long DOA: 60-120 minutes
Elimination by renal excretion
used for muscle relaxation during surgery
name the muscarinic receptor antagonist:
Atropine
Scopolamine
Propantheline
glycopyrrolate
dicyclomine
Tropicamide
Ipratropium
Benzotropine
Oxybutynin
Tolterodine
Homatropine
Cyclopentolate
What muscarinic receptor ACh-antagonist are used in for Ophthalmolgic exams?
Atropine
Tropicamide
Homatropine
cyclopentolate
Describe Atropine
Muscarinic ACh-receptor antagonist
clinical use: Ophthalmologic exam, decreases cholinesterase toxicity, bradycardia
Scopolamine
Muscarinic ACh-receptor antagonist
Rx: decrease motion sicknes s
Propantheline
Muscarinic ACh-receptor antagonist
decrease hypermotility and peptic disease
Glycopyrrolate
decrease hypermotility
peptic disease
Muscarinic ACh-receptor antagonist
Dicyclomine
Muscarinic ACh-receptor antagonist
decrease hypermotility
Peptic disease (IBS)
Tropicamide
Muscarinic ACh-receptor antagonist
Ophthalmologic exams
Ipratroprium
Muscarinic ACh-receptor antagonist
Asthma
Emphysema
Benzotropine
Parkinson's disease
Oxybutynin
Muscarinic ACh-receptor antagonist
Relief of bladder spasm after urological surgery (GU)
Tolterodine
Muscarinic ACh-receptor antagonist
decrease urinary incontinence
Homatropine
Muscarinic ACh-receptor antagonist
Ophthalmologic exam
Cyclopentolate
Muscarinic ACh-receptor antagonist
Ophthalmologic exams
what are the monoamine NT?
Norepinephrine
Dopamine
Serotonin
What do adrenergic receptors release?
Norepinephrine
what adrenergic receptors are excitatory?
a-1
B1-3
what adrenergic receptors are inhibitory?
a-2
where is Dopamine stored?
Concentrated in the VTA and SNc
what dopamine receptors are excitatory?
D1 and D5
what dopamine receptors are inhibitory?
D2, 3, and 4
what does a-1 stimulation cause on a cellular basis?
increased PLC - Increased IP3 - increased Calcium
what actions occur due to a-1 stimulation?
contraction of smooth muscle
vasoconstriction
increased blood pressure
increased gland secretion
what is the mechanism of a-2 adrenergic receptors?
decreased adenylyl cyclase - decreased cAMP
what is the action from stimulation of a-2 receptors?
decreased sympathetic function from CNS (decreased NE)
decreased secretion of aqueous humor
what is the mechanism of all beta-adrenergic receptor stimulation?
increased adenylyl cyclase - increased cAMP
what actions do b-1 receptors cause?
increased HR
increased contractility
increased conduction
increased renin secretion
what does stimulation of b2 receptors cause?
relaxation of smooth muscle
vasodilation
bronchodilation
increased potassium in skeletal muscle
Uterine relaxation
what does stimulation of b3-receptors cause?
Lipolysis
what is the mechanism of action of D1 receptors?
increase adenylyl cyclase - increased cAMP
what is the mechanism of action of D2 receptors?
decreased adenylyl cyclase - decreased cAMP
what does stimulation of D1 receptors cause?
relaxation of smooth muscle
what does stimulation of D2 receptors cause?
modulation of Neurotransmitter in CNS and Sympathetic NS
what does stimulation of Imidazoline receptors cause?
decreased sympathetics from CNS (decreased NE)
Natriuresis
what do muscarinic receptors (ACh) and alpha-1 adrenergic receptors (NE) have in common?
both contract smooth muscle
what do beta-2 adrenergic receptors and D1 receptors have in common?
both relax smooth muscle
what do muscarinic (ACh) and alpha-2 adrenergic receptors have in common?
Treatment of Glaucoma
where do adrenergic receptors receive there NT from?
Adrenergic receptors receive NE from postganglionic neurons b/c adrenoceptors are located on/in target organs
True or False
NE is sympathetic only
True
what is the pharmacological effect of dobutamine?
cardiac stimulation (b1)
Vasodilation (B2)
what is the clinical use of Dobutamine?
Cardiogenic shock
Acute HF
NOT septic shock
what is the pharmacological effect of Dopamine?
Cardiac stimulation (B1)
Renal vasodilation (D1)
increased Blood Pressure (B1, a1)
what is the clinical use of Dopamine?
Cardiogenic shock
Septic shock
Hypovolemic shock
CHF
what is the pharmacological effect of Epinephrine?
vasoconstriction and increase BP (a1)
Cardiac stimulation (B1)
Bronchodilation (B2)
what is the clinical use of Epinephrine?
Anaphylactic shock
Cardiac arrest
V fib
decrease bleeding
what is the pharmacological effect of Isoproterenol?
Cardiac stimulation (B1)
Bronchodilation (B2)
what is the clinical use of Isoproterenol?
Asthma
AV block
Bradycardia
what is the pharmacological effect of Norepinephrine?
vasoconstriction and increase BP (a1)
what is the clinical use of Norepinephrine?
Hypotension
Shock
What is the pharmacological effect of Albuterol?
Bronchodilation (B2)
what is the clinical use of Albuterol?
ASthma
what is the pharmacological effect of Apraclonidine?
decrease aqueous humor formation (a2)
what is the clinical use of Apraclonidine?
control intracranial pressure (short term)
what is the pharmacological effect of Clonidine?
decrease sympathetic stimulation of CNS (a2 & imidazole)
what is the clinical use of Clonidine?
HTN
Opiod dependence
what is the pharmacological effect of Midodrine?
Vasoconstriction (a1)
what is the clinical use of Midodrine?
orthostatic HTN (severe)
what is the pharmacological effect of Oxymetazoline?
Vasoconstriction (a1)
what is the clinical use of Oxymetazoline?
nasal and ocular decongestion
what is the pharmacological effect of Phenylphrine?
Vasoconstriction
increase BP
Mydriasis (a1)
what is the clinical use of Phenylphrine?
Nasal and Ocular decongestion
Mydrias
Maintain BP
RX: Shock via IV administration
what is the pharmacological effect of Ritodrine?
uterine relaxation (b2)
what is the clinical use of Ritodrine?
Premature labor
what is the pharmacological effect of Terbutaline?
Bronchodilation (b2)
Uterine relaxation (B2)
what is the clinical use of Terbutaline?
Asthma
Premature labor
name tow indirect acting adrenergic receptor agonist?
Amphetamine
Cocaine
what is the mechanism of action of amphetamine?
increases NE release
CNS stimulation
what is the clinical use of amphetamine?
narcolepsy
ADD
what is the pharmacological effect of cocaine?
decreased NE reuptake
increased NE
what is the clinical use of Cocaine?
local anesthesia
what are the mixed acting adrenoreceptor agonist?
Ephedrine
Pseudoephedrine
what is the clinical use of Ephedrine?
Nasal decongestant
what is the pharmacological effect of Ephedrine?
Vasoconstriction (a1)
what is the pharmacological effect of Pseudophedrine?
Vasoconstriction (a1)
what is the clinical use of Pseudophedrine?
Nasal decongestant