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)