PNS drugs Flashcards
drugs that directly activate receptors
agonists
drugs that prevent receptor activation
antagonists
drugs can interfere with the termination of transmitter action by two mechanisms
blockage of transmitter uptake
or
inhibition of transmitter degradation
drugs can interfere with the termination of transmitter action by two mechanisms
blockage of transmitter uptake
or
inhibition of transmitter degradation
selectivity is one of the most desirable qualities a drug can have
many neuropharmacologic drugs exhibit high selectivity
to understand any particular PNS drug you need 3 types of information
1- the type or types of receptors through which the drug acts
2-the normal response to activation of those particular receptors
3-what the drug in question does to receptor function (increase or decrease)
What are the three effects that drugs can have on transmitter synthesis?
1- increase transmitter synthesis
2-decrease transmitter synthesis
3- cause the synthesis of transmitter molecules that are more effective than the natural transmitter itself
Functions of the parasympathetic Nervous system
- slow heart rate
- increase gastric secretion
- emptying the bladder
- emptying the bowel
- focusing the ye for near vision
- constricting the pupil
- contracting bronchial smooth muscle
Therapeutic agents that alter the Parasympathetic nervous system are primarily used for their effects on
GI tract
bladder
eye
occasionally used for effects on : heart or lungs
the sympathetic nervous system has three main functions
- regulating the CV system
- regulating body temp
- implementing the acute stress response (fight or flight)
The sympathetic nervous system influences the heart and blood vessels to achieve three homeostatic objectives
- maintenance of blood flow to the brain
- redistribution of blood flow during exercise
- compensation for blood loss, primarily by causing vasoconstriction
The sympathetic nervous system causes
- increased heart rate and BP
- shunting blood away from the skin and viscera and into the skeletal muscles
- dilating the bronchi to improve oxygenation
- dilating the pupils
- mobilize stored energy, providing glucose for the brain and fatty acids for the muscles
Describe feedback regulation
s process that allows a system to adjust itself by responding to incoming information.
What are the main elements of a feedback loop?
1 sensor : monitor the status of the physiological process
2 effector: makes appropriate adjustments in the process
3 neurons connecting the sensor to the effector:
What is the baroreceptor reflex?
feedback loop that helps regulate blood pressure
1) baroreceptors located in the carotid sinus and aortic arch monitor changes in BP and send this info to the brain
2) the brain sends impulses along nerves of ANS including heart and blood vessels to behave in a way to restore BP to normal
What is autonomic tone?
the steady day to day influence exerted by the ANS on a particular organ or organ system
What are the main neurotransmitters of the PNS?
acetylcholine (neurotransmitter employed at each of the junctions of the PNS
norepinephrine (transmitter released by practically all post-ganglionic neurons of sympathetic nervous system
epinephrine (major transmitter released by the adrenal medulla)
What are the two basic receptor categories associated with the PNS?
Cholinergic receptors (mediate responses to ACh)
Adrenergic Receptors (mediate responses to epinephrine and norepinephrine)
What are the three sub-types of cholinergic receptors?
Nicotinic - N
Nicotinic - M
Muscarinic
What are the four sub-types of adrenergic receptors?
alpha 1
alpha 2
beta 1
beta 2
Nicotinic N (neuronal)
name where they are found
name response to activation
found: all autonomic system ganglia and the adrenal medulla
response: STIMULATION of PARASYMPATHETIC and SYMPATHETIC post ganglionic nerves & release of epinephrine from the adrenal medulla
Nicotinic M (muscular)
name where they are found
name response to activation
found: neuromuscular junction
activation: contraction of skeletal muscle
muscarinic
name where they are found
name response to activation
found: all parasympathetic target organs (eye, heart, lung, bladder, GI tract, sweat glands, sex organs, blood vessels)
activation : eye (contraction of ciliary muscle/focus for near vision)
heart: decreased rate
lung: constriction of bronchi, promote secretion
bladder: contraction of detrusor muscle = increased bladder pressure/relaxion of
sphincters = urine leave bladder
GI tract: salivation, increased GI secretions, increased intestinal tone and motility
sweat glands: generalized sweating
sex organs: erection
blood vessels: vasodilation
alpa 1 (adrenergic receptor)
name where they are found
name response to activation
Location: eye, arterioles, skin, viscera, mucous membranes, veins, sex organs (males) , prostatic capsule, bladder
activation: eye (increased pupil size) arterioles (constriction) veins (constriction) sex organs (ejaculation), prostatic capsule (contraction), bladder, contraction of trifgone and sphincter
alpa 2(adrenergic receptor)
name where they are found
name response to activation
location: presynaptic nerve terminals
activation: inhibition of transmitter release
Receptor specificity of adrenergic receptors is
more complex than the receptor specificity of ACh.
ACh can activate all 3 subtypes of cholinergic receptors, not every adrenergic transmitter (epinephrine, norepinephrine, dopamine) can interact with each of the 5 subtypes of adrenerguc receptors
Epinephrine can activate…
all alpha and beta receptors but NOT dopamine receptors
Norepinephrine can activate…
alpha 1, alpha 2 and beta 1 but NOT beta 2 or Dopamine receptors
Dopamine can activate…
alpha, beta and dopamine receptors
dopamine is the only transmitter capable of activating dopamine recptors
the only transmitter that acts on Beta 2 receptors is…
epinephrine
epinephrine is released from the adrenal medulla (not from neurons)
epinephrine prepares body for fight or flight
Cholinergic drugs are
agents that act upon the cholinergic receptors
either mimic or block the actions of ACh
What are the 6 categories of cholinergic drugs?
muscarinic agonists muscarinic antagonists cholinesterase inhibitors ganglionic stimulating agents ganglionic blocking agents neuromuscular blocking agents
Responses to Muscarinic agonists closely resemble responses similar to what
the parasympathetic nervous system
Bethanechol is what type of drug?
a muscarinic agonist
What is the MOA of bethanechol?
direct-acting muscarinic agonist
acts selectively on muscarinic receptors
What are the pharmacologic effects of bethanechol?
act on eyes (constrict pupils and focus for near sight), heart (bradycardia), exocrine glands (increase sweating, salivation and bronchial secretions, secretions of gastric acid), bladder (emptying)
What are the pharmacokinetics of Bethanechol?
PO administration
30-60 mins onset and persist for about 1 hours
only small portion of each dose is absorbed
Therapeutic uses for Bethanechol?
urinary retention (post-op & postpartum) and to treat retention secondary to neurogenic atony of the bladder
GI uses (off label for GI reflux) also can help treat d/o with GI paralysis --* SHOULD NOT be given with GI obstruction
Adverse effects of Bethanechol?
CV- hypotension
GI- excessive salivation and GI secretions, involuntary defecation
Urinary-hazardous for thouse w/ urinary obstruction-increases bladder pressure
Lungs -exacerbation of asthma (bronchoconstriction)
CONTRAINDICATED for pts w/ hyperthyroidism (dysrythmmias r/t barorecptors)
receptor location for muscarinic
sweat glands, blood vessels, all organs regulated by parasympathetic nervous system
receptor location for nicotinic N
all ganglia of aurtonomic nervous system
receptor location for nicotinic M
neuromuscular junctions
effects of receptor activation of muscarinic
decreased heart rate
increased gland secretion
smooth muscle contraction
effects of receptor activation of nicotinic N
promotes ganglionic transmission
effects of receptor activation of nicotinic M
skeletal muscle contraction
example of receptor agonist for muscarinic
Bethanechol
example of receptor agonist for nicotinic N
Nicotine
example of receptor agonist for nicotinic M
Nicotine (much higher dose)
Summary of key prescribing points for Bethanechol therapeutic goal? baseline data? monitoring? identifying high risk pts? evaluating therapeutic effects? minimizing adverse effects?
TG- tx of non obstructed urinary retention
BD- VS, urinary trends (I &O)
Monitoring - I&O, observe s/s of abnormal muscarinic response (over salivation, bradycardia etc)
High risk-contraindicated -obstruction (GI or urinary) asthma, hyperthyroidism, hypotension, coronary insufficienct
eval- no bladder distension
min adv effects- take on empty stomach to decrease n/v
muscarinic (cholinergic) toxicity
DUMBELS
Diaphoresis/diarrhea Urination Miosis Bradycardia/Bronchospasm Emesis Lacrimation Salivation
Pt education for muscarinic agonists
take 1 h b4 food or 2 h after meals
teach about manifestations of muscarinic excess and advise to seek med tx is occur
What is cevemiline?
muscarinic agonist
used to tx dry mouth
What is pilocarpine?
muscarinic agonist
therapy of glaucoma
What are cholinesterase inhibitors?
drugs that prevent the degradation of ACh
increase the amount of ACh available to activate receptors= enhancing cholinergic action
do not bind directly with recptors so they are INDIRECT-acting cholinergic agonists
what are the 2 basic categories of cholinesterase inhibitors?
1- reversible (produce effects of moderate duration)
2-irreversible (produce effects of long duration)
what is Pyridostigmine?
a reversible cholinesterase inhibitor
tx of Myasthenia Gravis
poorly absorbed so minimal effect on brain or fetus
Summary of key prescribing considerations for Pyridostigimine TX goal Baseline Data MonitoringHigh risk pts Eval min Adverse effects
TX goal-tx of myasthenia gravis
Baseline Data: HR, BP, ECG, ability to swallow, muscle strength ptosis
Monitoring:HR, BP, ECG, ability to swallow, muscle strength ptosis
High risk pts- obstruction (urinary or GI) pts w/ poor renal function start low dose
Eval: change in muscle strength and control
min Adverse effects
Irreversible cholinesterase inhibitors
only one indication ; Tx of glaucoma
high lipid solubility
well absorbed
high affinity for toxic - poisoning
what are muscarinic antagonists?
a type of anticholinergic drug
block the actions of ACh
act directly on receptors to block ACh
EX: Atropine
anticholinergic drug in children?
prominent role in management of respiratory conditions
administration via inhalation decrease systemic s/e
no contraindication d/t age but d/t numerous adverse effects benefits should be weighed against risks
anticholinergic drug in pregnant women?
oxybutinin relatively safe
but minimal studies _ caution recommended
anticholinergic drug in breastfeeding women?
may inhibit lactation in some women = decreased breast milk production
due to lack of studies full range of risks unknown
if breastfeeding, infant should be monitored for possible anticholinergic effects
anticholinergic drug in older adults?
potentially inappropriate
blurry vision, confusion, tachycardia, urinary retention and constipation
What is atropine?
the best known muscarinic antagonist
from a plant - like belladona!
MOA of atropine?
competitive blocking of muscarinic receptors
at low dose - decreased secretion of salivary glands, sweat glands and bronchial glands
at high dose- increased HR, urinary-lack of voiding, decreased GI motility, dilation of bronchi, decreased stomach acid secretion
Pharmacologic effects of atropine?
exert influence primarily on heart (increase HR), eyes (relaxation of ciliary muscles and dilation of pupil) , exocrine glands (decreased secretion), and smooth muscles (relaxation of bronchi, decreased motility of GI, decreased tone of bladder)
Pharmacokinetics of atropine?
topically to eye
+
parenterally (IM/IV/SQ)
peak - 30 mins
half-life 3 hours
10-17 hours in older pts
hepatic metabolism and renal excretion
Therapeutic uses of Atropine?
except for eye uses is used short term
-prior to surgery
antidote to anticholinesterase poisoning
tx of sinus bradycardia and AV block
asthma - bronchial dilation
excessive GI motility
disorders of eyes or before eye exa
Adverse effects of atropine?
dry mouth blurred vision elevation of intra ocular pressure urinary retention constipation lack of sweating tachycardia asthma
key prescribing considerations for atropine Tx goal Baseline data Monitoring High risk pts Eval therapy Min adverse effects
Tx goal- bradycardia or AV block, preanesthesia or antidote to anticholinerase poisoning
Baseline data - HR, BP ECG
Monitoring-HR BP recheck ECG
High risk pts- pts w/ no bradycardic dysrhythmias, MIs,
Eval therapy- restroation of normal sinus rhythm, prevention of surgical complications
Min adverse effects-tx dry mouth w/ fluids, manage photophobia w/ redused lighting or sunglasses, void prior to taking meds to avoid urinary retention
What is scopolamine?
an anticholinergic drug with many actions like atropine HOWEVER
therapuetic doses of Scopolamine produces sedation
and this drug suppresses emesis
principle use: motion sickness
Patient education for muscarinic antagonists
- dry mouth relived by sipping fluids
- avoid hazardous activities d/t potential for blurred vision
- void before use
- constipation reduced by increasing dietary fiber and fluids
- avoid exercise in warm environments to prevent hyperthermia
Antimuscarinic toxicity
Hot as a hare (hyperthermia) Dry as a bone (dry eyes, mouth, skin) Red as a beet (flushed face) Blind as a bat (mydriasis) Mad as a hatter (delirium)
What are adrenergic agonists?
drugs that produce their effects by activating adrenergic receptors
sympathetic nervous system acts through these same receptors
adrenergic agonists therefore produce similar effects as the stimulation of sympathetic nervous system
broad spectrum of indications: heart failure, asthma, preterm labor ….
What are the mechanisms of adrenergic receptor activation?
direct receptor binding (most common mechanism) - bind to receptor and mimic actions of natural transmiters
promotion of norepinephrine release-act on the terminal ends of symapthetic nerves to cause NE release (amphetamines and ephedrine)
inhibition of norepinephrine reuptake- block NE reuptake thus causing NE to accumulate and increase receptor activation (cocaine and tricyclic antidepressants)
Inhibition of norepinephrine inactivation (drugs that inhibit MAO can increase the amount of NE available for release)
What are the two major chemical classes of the adrenergic agonists
catecholamines and noncatecholamines
What are catecholamines
contain a catechol group and an amine group
because of their chemistry all catecholamines have three properties in common
1) cannot be used orally (rapid inactivation by MAO and COMT (enzymes)
2) have brief duration of action
3) cannot cross the blood brain barrier
norepinephrine, epinephrine, isoproterenol, dopamine, dobutamine
What are noncatecholemines?
adrenergic agonosts
no not contain a catechol
-ephendrine, albuterol, phenylephrine
less polar than catecholamines so are more able to cross the blood brain barrier
do not degrade quickly by liver metabolism (like catecholemines) so can be given PO
longer half-lives than catecholemines
Which receptors are albuterol selective for?
highly selective for only Beta 2
Which receptors are isoproterenol selective for?
less selective than albuterol
acts on beta 1 & beta 2
Which receptors are epinephrine selective for?
less selective
acts on all four adrenergic receptors
alpha 1, alpha 2, beta 1 , beta 2
what are the therapeutic applications of alpha 1 activation?
** 1) vasoconstriction (blood vessels of the skin, viscera, and mucous membranes)
(stopping bleeding-hemostasis, nasal decongestion, adjunct to local anesthesia -delay systemic absorption of anesthesia, elevation of BP–not primary use)
2)mydriasis
** alpha 1 agonists most often used for vasoconstriction
What are adverse effects of alpha 1 activation?
hypertension (r/t widespread vasoconstriction)
necrosis (IV infusion seeps to surrounding tissue + vasocontriction to site)
bradycardia (vasoconstriction elevates BP -triggers baroreceptor response and BP drops)
what are the clinical consequences of activating alpha 2 receptors?
alpha 2 receptors are primarily located presynaptically
their activation INHIBITS NE release
HOWEVER activating alpha 2 receptors in the periphery has little clinical significance
THOUGH activating alpha 2 receptors in CNS are of great significance
- reduction of sympathetic outflow to heart and blood vessels
- relief of severe pain
What are therapeutic applications of Beta 1 activation?
Heart failure- improve cardiac contractibility and cardiac output
Shock- (characterized by hypotension and reduced tissue perfusion) increase heart rate and force of contraction
AV heart block (impulses from atria to ventricles impeded or blocked entirely) enhance impulse conduction through AV node
Cardiac arrest initiate contractions in asystole or pulseless ventricular rhythms. (not the preferred Tx) —epinephrine IV
What are the adverse effects of activating Beta 1 receptors?
all the adverse effects are r/t activating beta 1 receptors in the heart /activating renal beta 1 receptors not associated w/ adverse outcomes
altered heart rate or rhythm (overstimulation of receptors-tachycardia)
angina pectoris (not enough perfusion and O@ to meet heart demands…beta 2 increase contractibility)
what are clinical consequences of beta 2 activation
related to
lungs
&
uterus
What are therapeutic uses for activating beta 2 receptors?
asthma (activation of receptors promotes vasodilation—use albuterol for its high selectivity)
delay of preterm labor (relaxes uterine smooth muscle- can delay early labor)
What are some adverse effects of activating beta 2 receptors?
hyperglycemia - activation of beta 2 receptors in liver and skeletal muscles promotes breakdown of glycogen
tremor - MOST COMMON SE of beta 2 agonists - activation of beta 2 receptors in skeletal muscles enhances contraction– tremor usually fades with time and ca often be minimized by initiating therapy w/ low doses
What are clinical consequences of activating dopamine receptors?
dilation of renal vasculature
for SHOCK
dilating renal blood vessels improves renal perfusion to reduce risk of renal failure
DOPAMINE is the ONLY drug that can activate dopamine receptors
when dopamine is given for shock it also enhances cardiac performance through activation of beta 1 receptors in the heart
What is the patho of anaphylaxis?
manifestation of a severe allergy
hypotension (widespread vasodilation)
bronchoconstriction
edema of the glottis
histamine contributes - though other mediators (leukotrines ) contribute so antihistamines aren’t particularly useful
What is the treatment for anaphylaxis?
Epinephrine
injected IM or IV
activated alpha 1, beta 1, beta 2 receptors
increases cardiac output, elevates BP, vasoconstriction and activation of b2 receptors can counteract bronchoconstriction
What is the patient education for epinephrine auto-injectors?
- fill Rx immediately and replace if expires
- keep with you at all times
- use immediately if needed (do not wait to see if symptoms will worsen)
- after using call for EMS and take injector with you
What is the receptor sensitivity and chemical classification of Epinephrine?
alpa 1, alpha 2, beta 1 , beta 2
catecholamine
What is the receptor sensitivity and chemical classification of Norepinephrine?
alpha 1, alpha 2, beta 1
catecholamine
What is the receptor sensitivity and chemical classification of Isoproterenol?
beta 1 and beta 2
catecholamine
What is the receptor sensitivity and chemical classification of dopamine?
dopamine, beta 1 and at high does alpha 1
catecholamine
What is the receptor sensitivity and chemical classification of dobutamine?
beta 1
catecholamine
What is the receptor sensitivity and chemical classification of Phenylephrine?
alpha 1
noncatecholamine
What is the receptor sensitivity and chemical classification of albuterol
beta 2
noncatecholamine
What is the receptor sensitivity and chemical classification of Ephedrine?
alpha 1, alpha 2, beta 1, beta 2
noncatecholamine
What are the therapeutic uses for Epinephrine?
can activate all four subtypes of adrenergic receptors therefore can produce a broad spectrum of effects
alpha 1- delay absorption of local anesthetics, elevate BP
beta 1 - overcome AV block, restore cardiac function in pt w/ certain cardiac arrest (v-fib, pulseless v tach, asystole)
beta 2- lungs - bronchodilation- asthma (not first choice for this)
alpha and beta together - choice for SHOCK
What are the pharmacokinetics of epinephrine?
topically or injection
NOT PO d/t catecholamines undergo fast degstruction by enzymes (MAO and COMT)
has short half-life
What are the adverse effects of epinephrine?
because of the activation of all four subtype of receptors it can have MANY adverse reactions
HTN crisis - vasoconstriction secondary to alpha 1 activation
Dysrhythmias-beta 1 receptors in heart
Angina Pectoris- beta 1 receptors in heart
Post-extravasation necrosis-
Hyperglycemia- secondary to b2 receptor actiavtion in skeletal muscles and liver
What are some drug interactions with epinephrine
MOA inhibitors
tricyclic antidepressants - block the uptake of catecholamines (can prolonf effects of epinephrine)
general anesthetics
alpha adrenergic blocking agents
beta adrenergic blocking agents
How is NE different from Epinephrine and what is NE indicated for?
NE doesn’t activate Beta 2 receptors - (no SE of hyperglycemia because this results from B2 activation)
limited clinical applications
indicated for: hypotensive status and cardiac arrest
What are the therapeutic uses for Isoproterenol?
activates Beta 1 receptors in the heart
mange AV block
improve outcomes in cardiac arrest
increase cardiac output during shock
What are the adverse effects from Isoproterenol?
fewer adverse effects than EPi or NE because doesn’t activate alpha receptors
tachydysrhythmias
heart pain
hyperglygcemia
what are the therapeutic uses for Dopamine?
the major indication for dopamine is shock
benefits derive from the effects on the heart and renal blood vessels
dopamine activates B1 receptors and dopamine receptors.
At very high doses activates alpha 1 receptors as well
What are the therapeutic uses for albuterol?
