Pharmacology-Autonomic Nervous system
Beta 2 agonist (specific)
Albuterol, Terbutaline, and ritodrine relieve bronchoconstriction vasodilation
Sympathetic receptors
Alpha and Beta NE binds to Alpha and Beta All have post synaptic receptors (except Alpha 2, which is pre-synaptic)
Dobutamine
B1 agonist, increases heart rate and cardiac output
Beta 1 blockers in general and side efects side effects
Beta blockers inhibit these normal epinephrine and norepinephrine-mediated sympathetic actions ** have minimal effect on resting subjects cause branchoconstriction and decreased heart rate and cardiac output=could be considered side effects
Stimulation of Beta 2 receptors of bronchi, uterus, liver, and skeletal muscles)
Bronchi= causes bronchi dilation=good for ashtma patients Uterus= causes relaxation during pre-labor Liver= glycogenolysis (breakdown of glycogen stores to glucose) Skeletal muscle=enhances contraction
Bethanechol
Choline ester direct acting choline receptor agonist use for treatment of urinary retention but will have side effects of an increase in parasympathetic nervous system: cramping, sweating etc
Carbachol
Choline esters directing acting choline receptor agonist used for treatment of glaucoma
Beta 1 agonist specific
Dobutamine direct inotropic drug, used for severe heart failure increases heart rate and cardiac output
Side effects of Cholinergic antagonist
Dry mouth, reduced sweating, flushing, reduced motility and secretions of GI tract (constipation), increased heart rate, bronchial dilation, urinary retention, drowsiness, hallucinations, coma, blurry vision Important ones: dry eyes, dry mouth, blurred vision, constipation, urinary retention
Myasthenia Gravis
Edrophonium is used to diagnosis this (short-acting cholinesterase inhibitor that is IV administered); if they have this disease the drug will dramatically improve muscle strenth TXN: neostigmine, pyridostigimine and ambenoium; act the same way as edrophonium but are longer acting
Sympathetic nervous system
Fight or flight increase in HR increase in contractility dilates pupil dilates bronchioles constrict blood vessels inhibits digestion increase in renin and ejaculation
Ritordrine
For pre-term labor, causes uterus relaxation
Direct acting choline receptors agonist?
Have direct action on receptor for acetylcholine; some drugs are specific for muscarinic and others for nicotinic receptor Choline esters and Alkaloids But will have side effects of increasing parasympathetic nervous system
Low dose of dopamine
Increased urine output! renal and mesenteric receptor binding=> vasodilation=> better blood supply to kidnies and intestines =>increased urine output
Examples of mixed antagonists
Labetalol, carvedilol
Labetalol
Mostly alpha, with a little beta for pregnancy induced hypotension or postoperative hypertension
Alkaloids
Nicotine Pilocarpine
High dose of dopamine
Overall: BP will go up and vasoconstriction of renal mesenteric vasculoatrorue Increases substrate to make NE and epinhherphine increases effect of Alpha 1/2 and beta 1/2=>vasoconstriction, increased BP-> vasocontriction renal/meseneteric Can cause renal shut down because not enough blood goes to kidneys
Benzatropine
Parkison's disease
Alpha 1 agonists
Phenylephrine= nasal decongestant naphazoline (decreases red eye= vasoconstriction)
Alpha 1 antagonist
Prazosine, terzosin, doxazosin
Cholinesterase inhibitors/indirect-acting cholinomimetics
Reversible and irreversible
Propantheine bromide
Treatment for GI gas or urinary urgency decrease production of gastric acid, used for people with hyperactive bowel/cramping etc
Organosphosphates
accidental poisoning (use anticholinergic agent to relieve symptoms) blocks effect of excess acetylcholine at muscinic receptors Treat with praliosdoxime (helps regenerate cholinesterase) and atropine
Terazosin and Doxazosin
alpha 1 antagonist; used for benign prostatic hypertrophy by impeding urination
Cholinoreceptor blockers (antagonist); anti-cholergenic
antagonize the effects of ACh; mostly directly at the nicotinic or muscarine receptor
metaproterenol
asthma treatment
Carvedilol
beta with some alpha action= for CHF
choline esters
bethanechol carbachol
Problems with Alpha 1 antagonist
can cause hypotension (drop in BP) especially if they stand up quickly; advise them to take it at night Synscope
Metaoprolol
cardioselective (B1) IV; treatment for high blood pressure and pain experienced during agnia
Atenolol
cardioselective (B1) IV; treatment for high blood pressure and pain experienced during agnia (heart attack)
Esmolol
cardioselective, but is short acting, shorter 1/2 life= used in ICU for treatment of arrhtymia or HNT with anesthetic agents
How to increase sympathetic effects? and What are the effects?
cholinoreceptor blockers decreased contraction of smooth muscle, contraction of sphincters, decrease in exocrine gland secretion, relaxation of ciliary muscle in eye
Alpha 2 agonist
clonidine methylodopa
Beta 1 antangoist (blockers) =specific
decrease HR and decreases force of contraction Atenolol Metropolol Esmolol
parasympathethic nervous system
decrease heart rate, nonvascular smooth muscle contracts (increase mobility of digestive muscles, increased bladder motility) sphincters relax eye ciliary muscles contract increase in exocrine gland secretion
Clonidine
decreases BP through central action, Alpha 2 agonist Oral or topical patch if stops suddenly, can get life threatening rebound hypertension (orisis)
Naphazoline
decreases red eye via constriction
Homatoprine
dilation of pupil
Tropicamide
dilation of pupils for exam
Nicotine
direct agonist at nicotinic receptors help patients stop smoking
Beta antagonist (nonspecific) examples
expected to have anti-hypertensive effects proprandolol, nadolol, trimolol particularly used for the management of cardiac arrhythmias, cardioprotection after myocardial infarction (heart attack), and hypertension
trimolol
eye drop for glaucoma
Problem with Beta antagonist
first pass effect (smaller bioavailability if taken orally, liver is a tax man, decreases the systemic effect of the drug when taken orally) = dose given by IV will be much less than if given orally (1/10) diabetes= can cause hypoglycemia (will decrease effects of hypoglyecmia and they will not notice them!) lipids increase cholesterol ashtma (non-specific beta blockers can cause bronchoconstriction)
Nadolol
for HTN
Isoproterenol
for heart transplant patients
Terbutaline
for pre-term labor, causes uterus relaxation
Methyldopa
for pregnancy induced hypotension because it has few side effects (oral and IV)
Pralidoxime
helps regulate cholinesterase (hydrolyze the phosphate band) blocks effect of excess ACh at muscinic receptors
Prolprandolol
immediate and sustained release; IV and orally
positive inotropy
increased contractility
positive chronotropy
increased heart rate
Beta agonist (nonspecific)
isoproterenol, metaproterneol
irreversible cholinesterase inhibitors
lipid soluble; will bind and stay and cross into CNS; organophsophates No therapeutic uses
Beta 2 receptors
located in smooth muscle (arterioles of heart, lungs, and skeletal muscle); located mainly in the lungs, gastrointestinal tract, liver, uterus, vascular smooth muscle, and skeletal muscle Causes: vasodilation when stimulated Relaxation when stimulated Antagonism causes constriction of smooth muscle
Beta 1 receptors (stimulation and antagonism)
located on the heart mostly stimulation=increase in HR, and force of contraction Antagonism= decrease heart rate
Dopamine
metabolism leads to NE, so more dopamine means more substrate to make NE from Causes dilation of renal blood vessels, enhancing renal perfusion
Norpephinephrine
mixed effect, can be Beta and Alpha; Use in patients who have gone septic and gone into shock or a patient who has hypotension
Phenylephrine
nasal decongestant alpha 1 agonist
What should you never give a diabetic patient?
never give them a Beta blocker!
What should you not give a patient with asthma?
non-specific beta blocker =bronchoconstriction Can theortically use Beta 1 specific, but specificity can sometimes become blurred
Pilocarpine
ophthalmic solution used in the treatment of glaucoma
What affect does indirecting acting cholinomimetics have?
parasympathetic action, NMJ for skeletal muscle affects Clinically used for myasthenia gravis (help diagnose and treat) and Glaucoma (for open-angle)
Alpha 1 receptors; stimulation and antagonism
post-synaptic smooth muscle Stimulation results in vasoconstriction (also: located on eyes, blood vessels, male sex organs, prostatic capsule, and bladder)= pupil enlargement, ejaculation, contraction of bladder etc Antagonism results in vasodilation
Glycopyrrolate
pre-anesthesia mediation, muscarinic antagonist, decrease secretions
Atropine
pre-anesthetic to decrease secretions (especially tracheal) prototype of muscarinic antagonist Drug competes with ACh for binding to muscarinic receptor (no intrsinic activity)
Alpha 2
presynaptic terminals; inhibit NE transmitter release by increase NE presynaptic binding (negative feedback loop)= decreases action of Alpha 1 and Beta 1/2
Scopolamine
prevent motion sickness
Belladonna
relieve GI cramps (but cannot have appendicitis)
Dicyclomine
relieve GI cramps, but cannot have appendicitis if something needs to get out or something really causing pain=need to know, like appendicitis
Problems with Alpha 2 agonist
sedation (decreased NE in celft) , depression, sexual dysfunction If drugs suddenly stopped, can get rebound hypertension (life trheatining!
Problems with Beta agonist
tachycardia (heart beat is too fast) anxiety
Albuterol
treatment of asthma and COPD
Ipratropium
used in the treatment of chronic obstructive pulmonary disease (COPD)= produces bronchodilation
How to enhance sympathetic action
using alpha 2 agonist= cause decrease in release of NE from pre-synaptic, no negative feedback loop Beta 1 agonist
Reversible cholinesterase inhibitors
water soluble; compete with with ACh for the active site on cholinesterase enzyme Pyridostigime physostigime neostigmine edrophonium Will cause same side effects as direct cholinergic agonist; but also affect nicotinic receptors (at NMJ)
How to increase parasympathetic activity?
with choline receptor stimulation (choline esters and alkaloids) decrease breakdown of ACh (Reversible and irreversible cholinesterase inhibitors)