SketchyPharm

AUTONOMICS:

[Cholinergic Agonists]
CHOLINOMIMETICS
1. Nicotinic
a. Location:
i. Neuromuscular junction = skeletal muscle motor end plate
ii. Autonomic Ganglia
iii. Adrenal glands (post-ganglion) = produce circulating neurotransmitters
b. Ion Channels = activation leads to opening of ion channels and depolarization of
sk. Muscle cell
2. Muscarinic  mimic parasympathetic nerve discharge at end-organs
a. Location:
i. Heart Smooth Muscle
ii. Sweat Glands
b. G proteins messengers
i. QIQ matches with M1, M2, M3 = Gq, Gi, Gq
ii. Gq = activates IP3-DAG cascade (M1 & M3)   intracellular calcium
iii. Gi = inhibition of cAMP production
c. Effector organs
i. M1 = CNS, enteric nervous system
ii. M2 = heart
1.  activity at SA Node ( HR)
2.  contractility at atria only
3.  conduction velocity at AV node
iii. M3 = glands, smooth muscle of eye, bladder
d. IV injection of muscarinic agonists  marked vasodilation
i. Activation  nitric oxide release from vasc. smooth muscle (M3)  
cGMP and vasodilation
***Atherosclerosis causes endothelial damage  direct activation of
muscarinic receptors  vasoconstriction
3. Muscarinic Agonists:
a. Bethanechol =  secretion and motor activity of gut
i. Non-obstructive GI dysmotility,
1. Post-op ileus, Neurogenic ileus, congenital megacolon
ii. Non-obstructive urinary retention
1. Post-op, post-partum, neurogenic (spinal cord) retention
b. Pilocarpine =  salivation, miosis, lens accommodation
i. Dry mouth
1. Sjogrens, Radiation-induced
ii. Glaucoma
1. Ciliary body contraction  zonular fiber relaxation  spherical
shape of lens
2.  aqueous humor outflow
SketchyPharm

iii. Acute-angle closure glaucoma

1. Sphincter pupillae muscle contraction  pupillary constriction
(miosis)
c. Carbachol (nonspecific – acting on M and N receptors) = miosis and flaccid
paralysis
i. Acute-angle closure glaucoma = pupillary constriction
ii. Muscarinic and nicotinic agonist
d. Methacholine = bronchial smooth muscle contraction
i. Stimulates asthma during asthma testing
ii. Exacerbates copd/asthma
4. Nicotinic Agonist:
a. Varenicline = smoking cessation
5. Adverse Effects:
a. Exacerbate asthma, copd, and peptic ulcers

ACETYLCHOLINESTERASE INHIBITORS
(indirect acting cholinomimetics =  concentrations of endogenous ACH at synapse)
*drug suffix = stigmine

1. Drugs:
a. Quaternary = synthetic, don’t cross BBB
i. Edraphonium = short acting, useful for diagnosis
1. Improvement with administration = Positive Tensilon test
2. Distinguish b/w under or overmedication
ii. Neostigmine = less effective
iii. Pyridostigmine
iv. Poor distribution into CNS
b. Tertiary = naturally derived, infiltrate CNS
i. Physostigmine = treats atropine overdose
ii. Derived from atropine belladonna flower (patients working in gardens,
etc)
iii. Gardner’s Mydriasis = poisoning/overdose of Jimson weed, similar to
atropine overdose and treated by physostigmine
iv. Reverses peripheral and cns effects of atropine/jimson
c. Curare drugs = nondepolarizing neuromuscular blocking agents to inhibit
nicotinic receptors at NMJ endplate
i. Tubocurarine
ii. Pancuronium
iii. Cisatracurium

2. Targets:
a. Eye
b. Resp. tract
c. Urinary tract
SketchyPharm

d. GI tract
3.  Nicotinic receptor activity
a.  sk. muscle strength of contraction
b. Treat urinary retention by muscarinic activation
4. Reverse neuromuscular blockade
a. Muscle blocking agents used with anesthesia for muscle paralysis
b. Two types
i. Nondepolarizing = rocuronium, pancuronium,
1. competitively inhibit nicotinic receptors
2. reversed with cholinesterases (neostigmine)
ii. Depolarizing = succinylcholine
1. Causes depolarizing muscular blockade
2. Overstimulates and depolarizes NMJ for no response to impulses
3.
5. TX = MYASTHENIA GRAVIS
a. Antibodies produced against nicotinic ACH receptors at motor endplates (sk.
Muscle)
b. Clinical presentation = sk muscle weakness
i. Ptosis
ii. diplopia
iii. progressive proximal weakness
c. MOA. = makes more ACH available to outcompete autoantibodies
6. Adverse effects: DUMBBELS
a. Flaccid paralysis from over activation of nicotinic receptors
7. THIOL SPRAY: thiosulfate insecticides
a. organophosphates = parathion, malathion, echothiophate,
b. slow/rapid develop of muscarinic and nicotinic symptoms
c. bradycardic, tearing, dyspnea = acute organophosphate toxicity
i. TX with pralidoxime (peripheral)= reverses nicotinic effects and
peripheral muscarinic
ii. Atropine = reverses both peripheral and central muscarinic but NO
nicotinic effects
8. Galantamine, Rivastigmine, Donepezil = treatment for CNS penetration for alzheimer’s
disease

[Cholinergic Antagonists]

MUSCARINIC ANTAGONISTS
1. Scopalamine = motion sickness, parkinsons, post-op nausea and vomiting
2. Benztropine / Trihexyphendyl (M1 central acting) = parkinson tremor/rigidity
3. Ipratropium / Tiotropium (M3) = bronchodilation for COPD/Asthma
4. Atropine (nonselective) = induces mydriasis and cycloplegia, reverses AV block
5. Oxybutinin / Tolteridone = for post-surgery urinary muscle spasms and urgency
a. Tolteridone is slow dissociating so longer lasting
SketchyPharm

6. Adverse effects:
a.  sweating = hyperthermia
b. Dry mouth and eyes
c. Blurred vision
d. Tachycardia
e.  aqueous humor outflow = acute angle closure glaucoma
f. Neurologic = hallucinations, sedation, agitation, coma  especially elderly

[Adrenergic Agonists]
SYMPATHOMIMETICS:
- Drugs:
o Norepinephrine (NT) (a1&a2 + slight b1) =
 A1 activity
 Reflex bradycardia
  contractility from b1
 Tx for hypovolemic shock (septic shock)
 Tracing:  in both systolic and diastolic but  in PP
o Phenylepinephrine (a1) =
 Tx of nasal congestion = vasoconstriction
 Tx of shock =  systolic pressure and diastolic pressure
 Reflex bradycardia from baroreceptor mechanism
 Tracing =  systolic and  in diastolic and MAP stays same
  in PULSE PRESSURE
o Epinephrine (hormone) (a + b)
 Low doses = beta agonist
 Bronchodilation
  diastolic pressure
  contractility and HR for  blood flow to tissues
 High doses = alpha agonist
  in MAP
  vasoconstriction
o Dobutamine (b1 + slight b2) =
  CO from hr and contractility
 Tx for refractory heart failure
 Tx for cardiogenic shock
  O2 demand
o Isoproterenol (b1 + b2) =
  contractility
 Vasodilation
  diastolic pressure
 Tracing =  in diastolic and no change in systolic leads to  in MAP
  PP
o Brimonidine = a2 agonist for chronic open-angle glaucoma
SketchyPharm

o Terbutaline (b2) and Ritodrine (b2)

 Tx for preventing pre-term labor = uterus relaxation
o Albuterol + other “rol” drugs (b2)
 Tx for asthma = Bronchodilation
- Mechanism: QISS
o a1 = Gq  activate IP3/DAG pathway to  intracellium calcium for sm muscle
contraction
  arterial vasoconstriction =  MAP
  venous constriction =  venous return
 Urinary and genital sm. Muscle contraction
 mydriasis
o a2 = Gi   cAMP
 centrally acting to  sympathetic tone
  insulin release
  lipolysis
  aq humor production
o b1 = Gs   cAMP to  calcium for sm. muscle CONTRACTION
  hr & contractility to  CO
  renin release
o b2 = Gs   cAMP to PKA activation to sm. muscle RELAXATION
 bronchodilation
 vasodilation of coronary and sk. Muscle arteries ( peripheral)
  diastolic pressure
  lipolysis
  gluconeogenesis
  insulin release
 Hypokalemia
  aqueous humor production
 Uterine sm. muscle relaxation
- Catecholamine production:
o Tyrosine transported into nerve terminal
o Tyrosine converted to L-Dopa  dopamine
o Dopamine converted to norepinephrine inside vesicle by dopamine b-
hydroxylase
- Dopamine Receptors:
o D1 = Gs
o D2 = Gi
o Low doses: D1 stimulated in renal vasculature
  GFR, renal blood flow, sodium excretion
 Beta 1 receptors activated for cardiac activation
o High doses:
 Alpha 1 receptors activated for pressor effects
INDIRECT ACTING
SketchyPharm

1. Cocaine = inhibits NET/DAT

a. Hypertension, tachycardia, mydriasis
b. Arousal, addiction, seizures
c. Bloody nose from vasoconstriction
d. Coronary vasospasm, angina, and myocardial ischemia
e. DO NOT give beta blockers because of a1 stimulation causing severe
hypertension
f.
2. Ephedrine
3. Amphetamine = displace catecholamines into synapse
a. Stimulation of CNS
b. Appetite suppression
4. Methylphenidate = amphetamine derivative
a. Tx for ADHD
b. Suppression of appetite
5. Modafinil =
a. Tx for narcolepsy
b. Appetite suppression
6. Atomoxetine = selective inhibitor of NET
a. Tx for ADHD
7. Metyrosine = blocks conversion to L-dopa and  dopamine
8. Mechanisms:
a. NET = norepinephrine transporter
i. Transports NE/E back into presynaptic neuron
b. DAT = dopamine transporter
i. Transports dopamine back into pre neuron
c. VMAT = vesicular monamine transporter
i. Inhibited by reserpine

ALPHA – 2 AGONISTS = inhibit sympathetic tone

1. Effects:  BP, CO, and PVR
2. a-methyldopa = acts on central a2 receptors to  BP
a. side effects = cns depression, lupus-like syndrome
b. tx of gestational hypertension
3. Tizanidine = centrally acting
a. Used as muscle relaxant
4. Clonidine = tx for hypertensive urgency, ADHD, tourette’s syndrome
ALPHA ANTAGONISTS
1. Phentolamine = reversible a1/a2 antagonist
a.  PVR and BP,  vasodilation
b. Tx for cocaine toxicity and associated hypertension
c. Tx for hypertensive crisis from tyramine metabolism + MAO inhibitor interaction
d. Tx for  BP in patients with pheochromocytoma (causes excess catecholamines)
2. Phenoxybenzamine = irreversible a1/a2 antagonist
SketchyPharm

a.
3. Prazosin/terazosin/doxazosin/tamsulosin = a1 antagonist
a. Tx of BPH (terazosin) by inducing smooth muscle relaxation
b. Tx of PTSD (prazosin)
4. Mirtazapine = a2 antagonist
a. Used as atypical antidepressant
5. Side effects:
a. Orthostatic hypotension
b. Reflex tachycardia