Pharmacy Exam 2 Study Material: Focus on Epinephrine, Sensitization, and Local Anesthetics

LC 1 - ANS intro

Main effects of sympathetic nervous system

Fight or flight

Inc HR, vasodilate to muscles (vasoconstrict to stomach), decreased digestion

Main effects of parasympathetic nervous system

Rest and digest

Dec HR, inc digestion, vasodilate to stomach

Thoracolumbar = (sympathetic/parasympathetic)

Craniosacral = (sympathetic/parasympathetic)

Sympathetic

Parasympathetic

What are the pre and post ganglionic neurotransmitters for sympathetic?

What about parasympathetic?

Sympathetic: pre is ach (acetylcholine) and post is NE (noreepinephrine)

Parasympathetic: pre and post is ach (acetylcholine)

T/F: your sympathetic nervous system is only active when you are scared/startled

False, not an on/off balance but both are continuously working (don't want too much or too little)

What are the 6 ANS receptors?

Nicotinic (Nn at ganglia, Nm at neuromuscular junction)

Parasympathetic: muscarinic (M)

Sympathetic: adrenergic (alpha 1&2, beta 1&2)

Dopamine (DA1 and DA2)

Serotonin (5HT)

Histamine (H1 and H2)

What are the 3 ways neurotransmitters can go away? (What is their end fate)

Diffuse away from synapse (NE)

Reuptake by transporters (NE, 5HT)

Metabolize away

Organ: Eye

Symp receptor?

Symp effects?

Parasymp effects? (All at M receptor)

Alpha 1

Mydriasis (to take in environment)

Miosis

Organ: Ciliary muscle in eye

Symp receptor?

Symp effects?

Parasymp effects? (All at M receptor)

Beta 2

Ciliary relaxation (to see farther away)

Ciliary constriction

Organ: Salivary/lacrimal glands

Symp receptor?

Symp effects?

Parasymp effects? (All at M receptor)

Alpha 1

Decrease salivary secretion (dry mouth)

Increase salivary secretion (for digestion)

Organ: Lungs

Symp receptor?

Symp effects?

Parasymp effects? (All at M receptor)

Beta 2

Bronchiole dilation

Bronchiole constriciton

Organ: Heart (SA node, atria, AV node, ventricles)

Symp receptor?

Symp effects?

Parasymp effects? (All at M receptor)

Beta 1 >>> Beta 2

Inc HR, contraction, conduction

Dec HR, contraction, conduction

Organ: Blood vessels

Symp receptor?

Symp effects?

Parasymp effects? (All at M receptor)

Alpha 1, alpha 2, beta 2

Vasoconstriction to non-critical tissues and vasodilation to critical tissues

Dilation (not parasymp, but direct stimulation of M receptors to skeletal muscle or abdominal viscera)

Organ: GI tract

Symp receptor?

Symp effects?

Parasymp effects? (All at M receptor)

Alpha 1, alpha 2, beta 1, beta 2

Dec motility

Inc motility

Organ: GI secretion

Symp receptor?

Symp effects?

Parasymp effects? (All at M receptor)

Alpha 2

Inhibits secretion

Stimulates secretion

Organ: GI sphincters

Symp receptor?

Symp effects?

Parasymp effects? (All at M receptor)

Alpha 1

Increase tone

Decrease tone

Organ: Urinary bladder (detrusor muscle)

Symp receptor?

Symp effects?

Parasymp effects? (All at M receptor)

Beta 3, Beta 2

Relax (store urine)

Contract (eliminate urine)

Organ: Urinary bladder (internal sphincter muscle)

Symp receptor?

Symp effects?

Parasymp effects? (All at M receptor)

Alpha 1

Contract (store urine)

Relax (eliminate urine)

Organ: adrenal medulla

Symp receptor?

Symp effects?

Parasymp effects? (All at M receptor)

Nm

Epinephrine secretion

N/A

Organ: Kidney

Symp receptor?

Symp effects?

Parasymp effects? (All at M receptor)

Beta 1

Renin secretion

N/A

Organ: Liver

Symp receptor?

Symp effects?

Parasymp effects? (All at M receptor)

Alpha 1, beta 2

Glycogenesis, glucogenesis (release glucose for enerfy)

N/A

Organ: Splenic capsule

Symp receptor?

Symp effects?

Parasymp effects? (All at M receptor)

Alpha 1

Contract (so blood goes out, so more O2 in circulation)

N/A

Organ: Sympathetic nerves - Autoreceptor

Symp receptor?

Symp effects?

Parasymp effects? (All at M receptor)

Alpha 2

Inhibits NE release

N/A

Organ: Sympathetic nerves - Heteroreceptor

Symp receptor?

Symp effects?

Parasymp effects? (All at M receptor)

N/A

N/A

Inhibit NE release

Organ: Parasympathetic nerves - Autoreceptor

Symp receptor?

Symp effects?

Parasymp effects? (All at M receptor)

N/A

N/A

Inhibit ach release

Organ: Parasympathetic nerves - Heteroreceptor

Symp receptor?

Symp effects?

Parasymp effects? (All at M receptor)

Alpha 2

Inhibit ach release

N/A

Name the alpha 1 receptor locations/tissues

Vascular smooth muscle, urogenital smooth muscle, spleen

Name the alpha 2 receptor locations/tissues

Presynaptic adrenergic nerve terminals, CNS, brainstem and spinal cord, vascular smooth muscle

Name the beta 1 receptor locations/tissues

Heart, juxtaglomerular cells

Name the beta 2 receptor locations/tissues

Bronchial, vascular, and bladder smooth muscle, skeletal muscle

Name the D1 and D5 receptors locations/tissues

Kidney vascular smooth muscle

Increased MAP and increased BP stimulates the vasomotor center to bring blood pressure down by....

Increases parasympathetic to dec HR

Decreases sympathetic to dec stroke volume and dec vascular tone (vasodilates)

Both of these result in decreased cardiac output

What contributes to blood pressure? What has the biggest effect of blood pressure?

BP = cardiac output (SV x HR) x vascular resistance

Vascular resistance

Decreased MAP and decreased BP stimulates the vasomotor center to bring blood pressure up by....

Decreases parasympathetic to inc HR

Increases sympathetic to inc stroke volume and inc vascular tone (vasoconstricts)

Both of these result in increased cardiac output

What are three ways to activate the renin-angiotensin-aldosterone system?

Via sympathetic nervous system, baroreceptor activation, or via osmoreceptors

The renin-angiotensin-aldosterone system gets activated, walk me through what happens next

Juxtaglomerular cells get activated which secretes renin, causing angiotensinogen to convert to angiotensin 1 then 2, angiotensin 2 causes inc vasoconstriction and inc sympathetic and inc aldosterone (so retain more sodium and water)

When would renin-angiotensin-aldosterone system stimulation be a good thing? When would it be a bad thing?

Good if leg cut off and bleeding out (saves vital organs), bad when chronic stimulation as it progresses heart disease

What do ACE inhibitors do?

Block conversion of angiotensin I to angiotensin II which blocks vasoconstriction, keeps bradykinin around resulting in vasodilation, overall promoting good tissue perfusion

What are ACE inhibitors good for?

Prolongs survival with heart disease (blocks vasoconstriction, enhances vasodilation, decreases aldosterone, promotes good diffusion)

LC 2 - ANS drug classes

Alpha 1 agonist

Effects?

Example drugs? (3)

Vasoconstriction, contract urethral sphincter, mydriasis, glycogenolysis/gluconeogenesis

Phenylpropanolamine, phenylephrine, epinephrine (epi non selective)

Phenylpropanolamine

What is it?

Use?

Clinical effects?

Adverse effects?

Alpha 1 agonist

Urinary incontinence (primarily in spayed dogs)

Contracts internal urethral sphincter, vasoconstricts

Hypertension, tachycardia (bc high doses stimulate beta), seizures, vomiting

Phenylephrine

What is it?

Use?

Clinical effects?

Adverse effects?

Alpha 1 agonist

Nephrosplenic entrapment or colic (horses)

Dec in spleen size (dose dependent)

Hypertension, hemorrhage

Alpha 1 antagonist

Effects?

Example drugs? (4)

Blocks alpha 1 receptor

Prazosin, doxasin, tamsulosin, phenoxybenzamine

Prazosin

What is it?

Use?

Clinical effects?

Adverse effects?

Alpha 1 antagonist

Functional urethral obstruction (nothing obstructed but can't use) and for hypertension

Helps with urination and causes vasodilation

Hypotension, reflex tachycardia, dec cardiac output

Doxazosin

What is it?

Use?

Clinical effects?

Adverse effects?

Alpha 1 antagonist

Functional urethral obstruction (nothing obstructed but can't use) and for hypertension

Helps with urination and causes vasodilation

Hypotension, reflex tachycardia, dec cardiac output

Tamsulosin

What is it?

Use?

Clinical effects?

Issue with this drug?

Alpha 1 antagonist

Greater urethral selectivity (less hypotension than the other alpha 1 antagonists)

Helps with urination

Only available in capsule

Best drug choice for urethral spasms/"functional urethral obstruction"?

Tamsulosin (alpha 1 antagonist with greater urethral selectivity than the others)

T/F: acepromazine is an alpha 1 antagonist that is used for sedation but ALSO can be used to drop blood pressure

True

Alpha 2 agonist

Clinical effects?

Adverse effects?

Example drugs? (4)

Sedative, analgesic, anxiolytic

Initial vasoconstriction/hypertension and bradycardia (PNS) then secondary vasodilation (CNS), dec GI, cardiac and resp depression, hyperglycemia, vomiting, dec sympathetic outflow

Medetomidine, dexmedetomidine, xylazine, detomidine

Alpha 2 antagonist

Effects?

Clinical use?

Example drugs? (3)

Reverse effects of alpha 2 agonists

As reversal or bc of toxins

Atipamazole, tolazoline, vatinoxan (PNS effects only)

Why do alpha 2 agonists cause BP to go up then down? Why does it cause HR to stay low?

PNS causes increase in BP, CNS kicks in later and makes it go down

PNS causes dec in HR bc of baroreceptors, stays low bc of CNS

Are cats or dogs more prone to vomiting from alpha 2 agonists?

Cats

What is the first adverse effect you'll start to see with alpha 2 agonists?

Increase in blood pressure and decrease in heart rate

Medetomidine/vatinoxan (zenalpha)

What is it?

Use?

Clinical effects?

Alpha 2 antagonist that does not penetrate PNS

Sedation (with less cardiovascular effects)

Dec sympathetic outflow, sedation, analgesia (CNS effects) (no PNS vasoconstriction)

Medetomidine

What is it?

Use/clinical effects?

Adverse effects?

Alpha 2 agonist

Sedative, analgesic, anxiolytic

Initial vasoconstriction/hypertension/bradycardia (PNS), secondary vasodilation (CNS), cardiac/resp depression, hypothermia, dec GI motility, vomiting, hyperglycemia (DEC SYMP)

Xylazine

What is it?

Use/clinical effects?

Adverse effects?

Alpha 2 agonist

Sedative, analgesic, anxiolytic

Initial vasoconstriction/hypertension/bradycardia (PNS), secondary vasodilation (CNS), cardiac/resp depression, hypothermia, dec GI motility, vomiting, hyperglycemia (DEC SYMP)

Detomidine

What is it?

Use/clinical effects?

Adverse effects?

Alpha 2 agonist

Sedative, analgesic, anxiolytic

Initial vasoconstriction/hypertension/bradycardia (PNS), secondary vasodilation (CNS), cardiac/resp depression, hypothermia, dec GI motility, vomiting, hyperglycemia (DEC SYMP)

Dexmedetomidine

What is it?

Use/clinical effects?

Adverse effects?

Alpha 2 agonist

Sedative, analgesic, anxiolytic

Initial vasoconstriction/hypertension/bradycardia (PNS), secondary vasodilation (CNS), cardiac/resp depression, hypothermia, dec GI motility, vomiting, hyperglycemia (DEC SYMP)

Atipamezole

What is it?

Use/clinical effects?

Alpha 2 antagonist

Reversal

Tolazoline

What is it?

Use/clinical effects?

Mixed alpha 1/alpha 2 antagonist

Reversal

What is special about the alpha 2 antagonist vatinoxan?

Peripheral effects only

Beta 1 agonist

Clinical effects?

Example drugs? (5)

Inc heart rate, contraction, and conduction, and renin is released (from juxtaglomerular cells)

Dobutamine, dopamine, ephedrine, epinephrine, norepinephrine (last 3 are less selective)

Beta 1 antagonists

Effects?

Uses?

Adverse effects?

Example drugs? (3)

Antagonize beta 1 (dec SA node, HR, conduction and suppress catecholamine induced arrythmias and renin secretion)

Tachyarrhythmias (bc of symp stimulation), controlling ventricular rate, improve hypertrophic cardiomyopathy (dec HR and inc ventricular filling), hypertension (cats), dec intraocular pressure (timolol)

Bradycardia, hypotension, arrhythmias

Atenolol, propranolol, timolol (lol)

Propanolol

What is it?

How is it eliminated?

Clin effects?

Adverse effects?

Beta 1 and 2 blocker (non selective)

Hepatic metabolism

Dec HR, conduction, suppress renin

Bradycardia, hypotension, also blocks beta 2 so may get bronchoconstriction, poor PO so variable effects

Atenolol

What is it?

How is it eliminated?

Clin effects?

Adverse effects?

Beta 1 blocker (selective)

Renal elimination

Dec HR, conduction, suppress renin

High PO so more consistent effects, but hypotension/bradycardia

(Low/high) PO means more consistent effects, not as variable

High

Epinephrine

What is it?

Route?

Use?

Clinical effects?

Adverse effects?

Agonist of all alpha and beta receptors

IV, IM, transtracheal

Short term rescue (cardiac arrest, anaphylactic shock, emergency bronchodilation)

Huge increase in HR and vasoconstriction

Excessive HR/vasconstriction/hypertension, cardiac arrhythmias

Norepinephrine

What is it?

Route?

Use?

Adverse effects?

Alpha 1, alpha 2, beta 1 agonist (like epinephrine but less beta 2)

IV (CRI)

Support arterial blood pressure in sick patients or postoperative cardiac depressed animals

Similar to epinephrine (inc HR) with more hypertension (no beta 2 vasodilation)

Dobutamine

What is it?

Route?

Use?

Clinical effects?

Adverse effects?

Beta 1 agonist

IV (CRI)

Short term HF therapy, inc cardiac output (lost at higher doses, more is not better)

Increase contractility (positive inotropic), less HR inc (chronotropic effcts)

(Related to too high of a dose) tachycardia, arrhythmias, seizures (cats, need lower dose)

T/F: cats require a higher dose of dobutamine (relatively) than dogs and horses

False, cats require a LOWER dose relatively

T/F: more is not better with dobutamine as receptor selectivity is lost a high dosages

True

Define inotropic

Define chronotropic

Define dromotropic

Contractility

HR

Conduction velocity

Dopamine

What is it?

Route?

Clinical effects and use?

DA, Beta 1, alpha agonist (dose dependent)

IV (CRI)

Renal failure (low dose), HF (med dose), CV support (high dose)

Low dose effects: DA agonist - renal, splanchnic vasodilation - use: renal failure (inc renal BF)

Med dose effects: adds beta 1 agonist, inc contracility and HR - use: HF (inc contractility)

High dose effects: add alpha agonist (makes it look like norepi) - use: CV support

Ephedrine

What is it?

Route?

Clinical effects and use?

Alpha and beta agonist (dose dependent)

Intermittent dosing (doesn't require CRI, good for emergencies!)

Beta agonist at low dose-inc CO, SV, little change in HR and SVR

Add alpha agonist at higher dose-inc CO, SV, HR, SVR, O2 delivery to tissues

Beta 2 agonists

Effects?

Adverse effects?

Example drugs? (5)

Smooth muscle relax (vasodilation, bronchodilation), glycogenolysis, hypokalemia (toxic dose)

Tachycardia (b1 >>> b2), sweating, arrhythmias

Albuterol, terbutaline, clenbuterol, zilpaterol, ractopamine

Beta 3 agonist causes....

Lipolysis

Albuterol

What is it?

Route and species used on?

Effects/use?

Adverse effects?

Beta 2 agonist

Inhalation, cats/dogs/horses (rarely PO, too many adverse effects)

Bronchodilation for asthma/bronchitis

Tachycardia, arrhythmia, sweating (horses)

Terbutaline

What is it?

Route and species used on?

Effects/use?

Adverse effects?

Beta 2 agonist

PO, SC in cats/dogs

Bronchodilation emergency (less CV effects than epi)

Tachycardia, arrhythmia

Clenbuterol

What is it?

Route and species used on?

Effects/use?

Adverse effects?

Beta 2 agonist

PO in horses

Bronchodilation for asthma, heaves, bronchitis

Tachycardia, arrhythmia, sweating (horses)

Zilpaterol

What is it?

Species used on?

Effects/use?

Adverse effects?

Beta 2 agonist

Cattle/swine

Enhance weigh gain and muscle mass

Tachycardia, arrhythmias

Ractopamine

What is it?

Species used on?

Effects/use?

Adverse effects?

Beta 1 and 2 agonist

Cattle/swine

Enhance weigh gain and muscle mass

Tachycardia, arrhythmias, hypertension

How does a dog get albuterol toxicity?

Clinical signs?

Treatment?

Prognosis?

By eating an inhaler

Tachycardia, tachypnea (rapid breathing), hyperglycemia, hypokalemia

Fluids, K supplement, non selective beta antagonist

Excellent (resolves quickly)

Muscarinic agonist

Effects?

Example drugs? (3)

SLUD salivation, lacrimation, urination, defecation, dec HR and contractility, vasodilation, bronchiole constriction, miosis

Bethanechol and pilocarprine (direct), pyridostigmine (indirect, acetylcholinesterase inhibitor)

Bethanechole

What is it?

Route and species used on?

Effects/use?

Adverse effects?

Muscarinic agonist

PO in dogs/cats

Primarily used to enhance detrusor contraction (if can't urinate on own)

Not super selective though so can see GI effects, hypotension, bronchiole constriction, miosis

Pilocaprine

What is it?

Effects/use?

Muscarinic agonist

Mitosis (topical use) to diagnose for dysautonomia and glaucoma

Pyridostigmine

What is it?

Effects/use?

Acetylcholinesterase inhibitor (muscarinic agonist indirectly)

Used to treat myasthenia gravis (immune disease against ach receptors)

Muscarinic antagonists (antimuscarinic drugs)

Effects?

Adverse effects?

Example drugs? (3)

Inc HR, dec salivation, dec GI, bronchodilation (meh), mydriasis

Tachycardia, ileus, urine retention

Atropine, glycopyrrolate, N-butylscopolammonium bromide

Atropine

What is it?

Route?

Effects?

Adverse effects?

Muscarinic antagonist

IV, IM, SC

Inc HR, dec salivation, dec GI, bronchodilation (meh), mydriasis

Tachycardia, ileus, urine retention

Glycopyrrolate

What is it?

Route?

Effects?

Adverse effects?

Muscarinic antagonist

IV, IM, SC

Inc HR, dec salivation, dec GI, bronchodilation (meh), mydriasis

Tachycardia, ileus, urine retention

N-butylscopolammonium bromide

What is it?

Route?

Effects?

Adverse effects?

Muscarinic antagonist

IV

Inc HR, dec salivation, dec GI, bronchodilation (meh), mydriasis

Tachycardia, ileus, urine retention

Are nicotinic neural or nicotinic muscle used more often clinically?

Nicotinic muscle, nicotinic neural is not used at all because lack of specificity

Neuromuscular (nicotinic muscle) agonists

Effects?

Example drugs? (1)

Affect endplate depolarization, skeletal muscle contraction

Pyridostigmine

Neuromuscular (nicotinic muscle) antagonists

Effects?

Example drugs? (1)

Skeletal muscle and diaphram paralysis, paralytic

Atracurium

Atracurium

What is it?

Effects?

Use?

What is onset/duration/accumulation like?

Nm antagonist

Skeletal muscle and diaphram paralysis, paralytic

Used for ophthalmic surgery (so eyes no flutter)

Rapid onset, short duration, and doesn't accumulate with multiple doses

LC 3 - ANS dysautonomia

What species is dysautonomia most common in? Where is it mostly found?

Dogs (can happens in cats, horses, cattle too less commonly), found in kansas and missouri mostly

The cause of dysautonomia is unknown. Maybe it's an infection or toxin, we don't know. Why do we not know?

Infection to clinical signs takes a long time so hard to find a cause

Primary pathology with dysautonomia? Which ANS do you see dysfunction with first?

Degeneration of autonomic ganglia

First parasympathetic dysfunction, then symptoms, then way later somatic/motor