Autonomic Drugs

Question 1

onabotulinumtoxinA (botox)

Answer 1

Protein from C. botulinum
Blocks release of ACH (SNAP-25) 
Post-synaptic terminal cannot be stimulated 
= Flaccid paralysis 
Sprouting new nerve may take months

Tx: Blepharospasm, cosmetic, overactive bladder, hyperhydrosis

Question 2

Muscarine

Answer 2

Amanaita muscarina mushroom

Selective agonist of muscarinic receptors

Question 3

Atropine

Answer 3

Atropa belladonna
Competitive antagonist of ALL muscarinic receptors equally
*block all PNS symptoms*
Low affinity for nicotinic
Cross BBB
Dose dependent response

Question 4

Nicotine

Answer 4

Stimulates Nn, Nm (also blocks and stimulate)

Persistent stimulation leads to desensitization

Question 5

d-Tubocurarine (curare)

Answer 5

Competitive agonist of Nm

Does not block Nn

Question 6

Acetylcholinesterase (AChE)

Answer 6

Rapidly terminates cholinergic transmission by hydrolysis in the nerve terminal
Allow for depolarization

Question 7

Butyrylcholinesterase

Answer 7

Pseudocholinesterase
Plasma, glial cells, liver
Drug metabolizing enzyme
Some patients may be deficient

Question 8

Tyrosine hydroxylase

Answer 8

Rate limiting step of catecholamine neurotransmitter formation

Question 9

Mitochondrial monoamine oxidase (MAO)

Answer 9

Degrades catecholamine storage vesicles
Deaminates catecholamines = inactivate!
Clears catecholamines from nerve terminal

MAOIs increase NT in nerve terminal

Question 10

Vesicular membrane monoamine transporter-2 (VMAT-2)

Answer 10

Transports NTs to vesicles and concentrated

Question 11

Reserpine

Answer 11

Antihypertensive, Antipsychotic
IRREVERSIBLE inhibitor of VMAT-2
= NTs are not stored in vesicle, degraded by MAO
Deplete catecholamine
Decrease SNS effects, non-selective side effects

Question 12

Tyramine

Answer 12

Fermentation byproduct of tyrosine in protein rich food
CHEESE, wine, cured meats
Displaces NE from vesicles and causes non-vesicular release from nerve terminals by reverse transport of NET
High concentration of NE in synapse
Problematic with MAO Inhibitors - HTN crisis

Question 13

Methyldopa

Answer 13

Antihypertensive
Can be used safely during pregnancy no birth defects
Can ONLY stimulate A-2 (autoregulator) to decrease NT release of NE

Question 14

Cocaine

Answer 14

Block reuptake of NE everywhere

Block NET from reuptaking NE

Question 15

Catechol-O-methyltransferase (COMT)

Answer 15

Cytosolic (liver, kidney)
Clearance of circulating catecholamines in blood

Inhibitors for Parkinsons

Question 16

Vanillylmandelic acid (VMA)

Answer 16

Metabolite excreted in urine
Measure to determine how active SNS is

High levels - theochromocytoma
Low levels - deficit

Question 17

Synthetic Choline Esters

Answer 17

Selective
Prolonged action to ACH
Do not penetrate BBB
PNS effects

Question 18

Bethanechol (Urecholine)

Answer 18

Resistant to hydrolysis by cholinesterase
Increase bladder detrusor contraction and GI tract
Tx: postpartum urinary retention, GERD, gastric atony

Question 19

Pilocarpine

Answer 19

Prototype Cholinomimetic Alkaloid
Partial agonist of ALL muscarinic subtypes
Eyes miosis, blurred vision, decreased IOP
Tx: dry mouth, wide angle glaucoma

Question 20

Cervimeline

Answer 20

Alkaloid selective agonist of M3
Sjogrens syndrome (stimulate remaining receptors)
Longer duration than pilocarpine w/ less side effects

Question 21

Physostigmine

Answer 21

Antidote to atropine

counteracts both CNS and peripheral effect by elevating synaptic concentration of ACH agonist

Question 22

Scopolamine

Answer 22

Muscarinic antagonist
Better CNS penetration
Sedation at low dose, suppress emesis, motion sickness block M receptor in vestibular
Prophylaxis motion sickness

Question 23

Ipratropium bromide (Atrovent)

Answer 23

Quaternary amine (does not cross membrane)
Bronchodilator (asthma/COPD)
Limited absorption when inhaled, minimal side effects

Question 24

Tropicamide

Answer 24

Mydriatic, cyclopegic
SHORTER DURATION (6 hours)!
Facilitates diagnosis and surgery of ophthalmic disorders
Blurred vision, photophobia common side effects

Question 25

Tolterodine (detrol)

Answer 25

Non-selective muscarinic antagonist Tx: Overactive bladder/urge/incontinence Improved capacity of bladder and decreased urgency sensation

Question 26

Neostigmine

Answer 26

Blocks acetylcholinesterase Blocks ACH degradation (increases ACH effects) Reversible inhibitor, but occupies active site for long time

Question 27

Phyostigmine

Answer 27

Not an agonist of Nicotinic Same as Neostigmine but crosses the BBB Tx: poisoning by atropine

Question 28

Donepezil (Aricept)

Answer 28

More selective inhibition of AChE isoform in CNS | Tx: Alzheimers cognitive decline

Question 29

Malathion

Answer 29

Irreversible Inhibitor of AchE Insecticide Highly lipid soluble Accidental agricultural poisoning, warfare agent

Question 30

Pralidoxime (Protopam)

Answer 30

Reactivates AChE ONLY at NMJ, must be administered before aging occurs Regenerate new enzyme to remove irreversibly bound organophosphate Takes off organophosphate in AChE Tx: Pesticide poisoning, warfare

Question 31

Catecholamines vs. Non-catecholamines

Answer 31

Catecholamine - no oral, short action, no BBB | Noncatecholamine - no catechol fxnl group, oral, long duration, cross BBB (CNS effects)

Question 32

Epinephrine

Answer 32

A1, A2, B1, B2, Non-selective - B1 cardiac effects - A1 vascular/skeletal muscle (high dose) - B2 vascular/skeletal muscle (low dose) - B2 respiratory effects Uses/tx: in combo w/ anesthetics, anaphylactic shock/cardiac arrest, hemostasis

Question 33

Norepinephrine

Answer 33

A1, A2, B1 (lost B2 activity!) B1 Cardio effects Tx: hypotension, septic shock PREFERRED over EPI

Question 34

Isoproterenol

Answer 34

B1, B2 (non-selective B agonist) B1 - cardio, AV block and cardiac arrest B2 - bronchospasm during anesthesia (Rare)

Question 35

Dopamine

Answer 35

D1>B1>A1 Low dose - D1 (renal) - *INCREASE RENAL BF* Medium Dose - B1 (some cardio not a lot increase in HR) Large dose - A1 vasoconstriction Tx: good for shock especially if trying to allow renal BF (NE and Epi constrict renal), maintains bp

Question 36

Dobutamine

Answer 36

B1 agonist B1 cardiac effects - increase contractility, HR, conduction velocity Less reflex tachycardia because no vascular involvement (B2) - but side effect is tachycardia Good for shortterm management of CHF

Question 37

Phenylephrine (Sudafed)

Answer 37

A1 agonist Nose - vasoconstriction, decongestion Vasoconstriction, mydriasis, detmuescent Toxicity in high dose = reflex brady, HTN, arrythmia, vomiting nausea

Question 38

Clonidine

Answer 38

A2 agonist Autoregulators stimulated = decrease NE Any NE effects decreased, reduce SNS outflow Tx: HTN, Severe pain S/E: Bradycardia, dry mouth, sedation Must decrease dose slowly, reflex HTN on withdrawl

Question 39

Terbutaline

Answer 39

B2 agonist Tx: Respiratory - reduces airway resistance in asthmatics Tx: Suppresses premature labor by relaxing uterine smooth muscle contractions SE: tremor, hyperglycemia, tachycardia (high dose), DEATH IN PREGNANT WOMEN

Question 40

Prazosin

Answer 40

``` A1 blocker Dilates arteries/veins, relax SMC of bladder (trigone and sphincter), prostate Tx: HTN, urinary retention S/E: Orthostatic Hypotension Effect depend on activity of SNS ```

Question 41

Tamulosin (Flomax)

Answer 41

Selective A1a antagonist Dilate the prostate arteries, urethra, bladder Tx: BPH, urinary retention S/E: Interacts with erectile dysfunction drugs, can lead to hypotension

Question 42

Propanolol

Answer 42

``` Non-selective B1, B2 antagonist Pure competitive antagonist Inhibit B1 cardio (decrease HR, contractility) B2 respiratory B2 - kidney (no renin), liver (glycogen) S/E: fatigue, lethargy Contraindicated for DM, Cardiac ```

Question 43

Metoprolol

Answer 43

B1 antagonist selective "CARDIOSELECTIVE" No B2 side effects unless high dose Tx: HTN, angina, CHF, MI