Pharmacology Review Sheets: Drugs Affecting the Autonomic Nervous System, p.

1
Note: Under type/receptors receptors bolded are ones that the drug has more activity with; if none are bolded, the drug works equally well on the receptors listed.
Adrenergic Agonists: Catecholamines
General Information
- Common structure: Catechol ring (benzene ring with OH groups at positions 3 and 4)
- Consists of epinephrine, norepinephrine, dopamine (first 3 are naturally occurring), isoproterenol (synthetic)
- Metabolized extensively
- Labile: Sensitive to light (results in unusable colored solutions), O 2 (exposure rapid biotransformation)
Catecholamines are polar and thus have good water solubility and, more importantly, poor membrane solubility
- Therefore, catecholamines are NOT administered orally, because they cant be absorbed from the GI tract
- NO CNS penetration

2
HO
3

HO
5

Catecholamine synthesis & metabolism

- Synthesis: Tyrosine Dopa Dopamine Norepinephrine Epinephrine pathway. Conversion of norepinephrine to epinephrine catalyzed by PNMT in the adrenal medulla
- Metabolism: 2 steps
1. Catechol-o-methyltransferase (COMT)
- Methylates dopamine (to 3-methoxytyramine), norepinephrine (to normetanephrine), epinephrine (to metanephrine) and other catecholamines (i.e. isoproterenol) to
inactive metabolites
- Ubiquitous (found everywhere)
2. Monoamine oxidase (MAO) works on methylated metabolites of dopamine, norepinephrine, epinephrine
- 3-methoxytyramine Homovanillic acid (found in the CSF, small amount is excreted in urine)
- Normetanephrine and metanephrine Vanillyl mandelic acid (VMA); VMA excreted in the urine. VMA seen in pheochromocytoma
Drug
Type/Receptors Pharmacokinetics/Action
Effects and Uses
Adverse Effects
Epinephrine
Direct; , 1, 2
Admin: Inhalation, subcutaneous,
Cardiovascular: + ionotropic, + chronotropic on heart
Cardiac arrhythmias and palpitations
intramuscular
by SA impulses, atrial and vent. muscle refractory
Contraindications with pre-existing cardiac conditions
Duration of action short (20 mins)
period, AV conduction, AV block. Vasoconstriction Epinephrine wont work in acidotic patients correct
Metabolism: COMT/MAO (see above) (esp. skin and mucous membranes) and vasodilation
acid/base imbalance and epinephrine will work
Excretion: Urine (metabolite: VMA)
(esp. skeletal muscle, liver) both occur, resulting in
Patients w/hyperthyroidism ( TH) have adrenergic
pulse pressure, systolic pressure, diastolic pressure; receptors, so dose needs to be adjusted () accordingly
-adrenergic blocker unmasks the vasodilatory effects
Cocaine potentiates epinephrine, so cocaine users
(epi reversal)
receiving epinephrine will have BP
Trachea, bronchioles: Bronchodilation (drug of choice
for emergency Rx of asthma)
Drug of choice for emergency allergic situations
(can also be used for shock)
cutaneous/mucosal oozing of blood (i.e. in dentistry)
Prolongs effects of local anesthetics when injected w/ it
Rx of glaucoma (topical eyedrops ICP)
Eosinopenia (transient)
Norepinephrine
Direct; , 1
Admin: IV
Cardiovascular: Only vasoconstriction (no vasodilation); Vasoconstriction blood flow to the kidney and may
Metabolism: COMT/MAO (see above) of mean BP (which may or may not happen with epi);
cause the kidney to shut down!
Excretion: Urine (metabolite: VMA)
bradycardia, b/c vasoconstriction triggers baroreceptor Breaking of vessels
reflex
Trachea, bronchioles: Nothing (not used for asthma)
Used for emergency Rx of acute hypotensive
episodes (but not shock); ex. spinal anesthesia
leakage to SNS

 Used post-surgery for pheochromocytoma

Pharmacology Review Sheets: Drugs Affecting the Autonomic Nervous System, p.2
Adrenergic Agonists: Catecholamines, continued
Drug
Type/Receptors Pharmacokinetics/Action
Effects and Uses
Adverse Effects
Dopamine
Direct; 1, 2;
Admin: IV
Cardiovascular: + ionotropic agent for heart; no
Sympathetic stim. (nausea, hypertension, arrhythmia), but
Dopaminergic
Metabolism: COMT/MAO (see p.1)
vasoconstriction used to Rx cardiogenic shock
this is short-lived b/c dopamine is metabolized quickly
recept (kidney) Duration of action: Short
(not traumatic shock) by CO and BP
Isoproterenol
Direct; 1, 2,
Admin: Inhalation
Cardiovascular: Vasodilation
Adverse effects are similar to those of epinephrine.
Metabolism: Slower than Epi and NE Trachea/bronchioles: Bronchodilation
Duration of action: > than Epi and NE Used to Rx acute asthmatic attacks (inhalation admin)
Dobutamine
Selective 1
Admin: IV
Used in ER or OR for quick in cardiac contractility
Duration of action: Very short (5 min.) in CHF patients
Adrenergic Agonists: Non-catecholamines (i.e. everything else)
Drug
Type/Receptors Pharmacokinetics/Action
Effects and Uses
Adverse Effects
Ephedrine
Mixed; , 1, 2
Structure: < polar than epinephrine,
Like epinephrine, but less potent. In addition:
Cardiac arrhythmias
so it can be administered orally
- Stimulates CNS
Tachyphylaxis, due to depletion of NE in nerve terminals,
Tachyphylaxis rapid tolerance
- Rarely used in Rx of chronic asthmatics
thus effects; also, there are changes in the actual
( effect w/ mult. administrations)
- Used in Rx of myasthenia gravis, to help stimulate
receptors.
Duration of action: Long (2-4 hrs)
skeletal muscle and improve function
Distribution: Penetrates CSF
- contractility of internal sphincter of bladder, thus
aiding in urinary incontinence
Phenylephrine
Direct; 12
Distribution: Doesnt penetrate CSF Cardiovascular: Vasoconstrictor (used for hypotensive Rebound phenomenon overuse can lead to vasodilation
(Neosenephrine)
Duration of action: 50 mins
states); bradycardia (via baroceptor reflex)
of the vessels affected!
Used as a nasal decongestant (b/c its a vasoconstrictor)
Pseudoephedrine Nonsel. 1, 2
Used as an oral decongestant (via vasoconstriction)
BP
Oxymetazoline
Selective 1
Duration of action: Long (10 hrs)
Long-acting vasoconstrictor used as nasal spray or drops Rebound phenomenon: overuse vasodilation of the
(Afrin)
to nasal mucosa
vessels being treated
Postural (orthostatic) hypotension (not as severe)
Dextramphetamine Indirect, , 1
Distribution: Penetrates CSF
CNS: alertness, fatigue; mild cortical stimulation
Drugs effects can lead to abuse (thus the regulation)
Very federally regulated
w/ low doses; severe cortical stimulation w/high doses Cardiac arrhythmias/death
Action: Displaces NE
may lead to convulsions, cardiac effects. Works to
desire to eat by effects on satiety center (lateral
hypothalamus), but only for about 2 weeks.
Methylphenidate (Ritalin), similar to amphetamine, is
used in the Rx of attention deficit hyperkinetic disorder
(ADHD)
Albuterol
Selective 2
Admin: Inhalation
Trachea/bronchioles: Chronically used Rx for
Fasciculations of skeletal muscle (tremor) in
(Proventil)
Duration of action: 6 hrs
bronchodilation in asthmatics
20% of patients
Terbutaline
Selective 2
Admin: Inhalation
Trachea/bronchioles: Chronically used Rx for
Fasciculations of skeletal muscle (tremor) in
(Brethine)
Duration of action: 4-5 hrs
bronchodilation in asthmatics
20% of patients
Can also be used for uterine relaxation but isn't really
used for it clinically.
Ritodrine
Selective 2
Admin: IV (in hospital); orally outpt. Used in OB for uterine relaxation, prolonging gestation
for up to a month (tocolitic drug)

Pharmacology Review Sheets: Drugs Affecting the Autonomic Nervous System, p.3
-adrenergic BLOCKERS
General comments
- Epinephrine reversal: When an a-adrenergic blocker is given to a subject receiving epinephrine, epinephrine's vasoconstrictory activity is blocked, unmasking the vasodilatory effects of
epinephrine.
- Selective (specific) 1-blockers are good for hypertension and also are used in the Rx of benign prostatic hypertrophy
- -blockers are sometimes used to Rx peripheral vascular disease (i.e. Reynauds, etc.)
Drug
Type/Receptor
Phenoxybenzamine Nonselect. 1, 2

Pharmacokinetics/Action
Metabolism: Requires chemical
transformation for activation
(formation of an immonium ring);
takes 1 hr. to work
Note: Phenoxybenzamine forms
covalent bonds with receptors

Effects and Uses

Used to relax sphincter in the bladder to allow for
complete emptying
Not effective for hypertension

Phentolamine

Nonselect. 1, 2 Duration of action: 4-5 hrs

Used to prevent gangrene from frostbite by blood
Note: Phentolamine forms ionic bonds flow to the extremities
with receptors
Not effective for hypertension

Prazosin
(Minipress)

Selective 1

Note: Dosing has to be gradual due

to side-effect of postural hypertens.

Doxazosin
(Cardura)

Selective 1

Terazosin
(Hytrin)

Selective 1

Tamsulosin
(Flomax)
Yohimbine
(Yocon)

Selective 1a

Admin: Oral
Duration of action: 9 hrs
(> Prazosin)
Note: Dosing has to be gradual due
to side-effect of postural hypertens.
Admin: Oral
Duration of action: 12 hrs
(> Doxazosin > Prazosin)
Note: Dosing has to be gradual due
to side-effect of postural hypertens.
Admin: Oral, qd

Selective 2

Action: Enhances NE secretion at

synapses of SNS neurons, and thus
SNS activity

Adverse Effects
Cardiac tachycardia
Postural (orthostatic) hypotension -- pt. faints when rising
from a resting position. More likely after the first dose
(1st dose effect).
In patients with spinal cord injury -- sympathetic tone
when urinating/defecating (BP , to 200-300 mm Hg)
Blockage of ejaculation, retrograde ejaculation (more
than newer -blockers), [obviously] in males
Cardiac tachycardia
Postural (orthostatic) hypotension -- pt. faints when rising
from a resting position. More likely after the first dose
(1st dose effect)
Postural (orthostatic) hypotension (not as severe)

Used for hypertension

Used for benign prostatic hypertrophy (it relaxes smooth
muscle at bladder outlet, making micturition easier)
Used for hypertension
Postural (orthostatic) hypotension (not as severe)
Used for benign prostatic hypertrophy (it relaxes smooth
muscle at bladder outlet, making micturition easier)

Used for hypertension

Postural (orthostatic) hypotension (not as severe)
Used for benign prostatic hypertrophy (it relaxes smooth
muscle at bladder outlet, making micturition easier)

Used for benign prostatic hypertrophy

Very little effect on BP
Rx of male impotence (stimulation of norepinephrine
may blood flow to penis)

Pharmacology Review Sheets: Drugs Affecting the Autonomic Nervous System, p.4
-adrenergic BLOCKERS
- Effects on -agonist: vasodilation
- Effects on - and -agonist: vasoconstriction, vasodilation (both due to the blocking of vasodilation)

Postural hypotension (least of the -blockers)

Drug
Propranolol
(Inderal)

Type/Receptor
Pharmacokinetics/Action
Non-select. 1, 2

Metoprolol
(Lopressor)
Atenolol
(Tenormin)
Timolol
(Timoptic)
Pindolol
(Visken)

Selective 1

Effects and Uses

Cardiovascular: resting HR by decreasing the height
of the AP, prolonging the depolarization phase of SA
node, AV conduction rate, refractory period of
cardiac muscle; cardiac output, coronary blood flow
(by force of contraction, HR, and contraction
velocity, the O2 requirement of the heart is )
Used in Rx of angina pectoris b/c heart may become
more efficient w/lessO2
Used in Rx of hypertension gradual in BP
Used in Rx of MI to prevent further damage by
exogenous catecholamines (-blockers catecholamine
effects, damage)
Used in Rx of cardiac arrhythmias (atrial arrhythmias,
atrial fibrillation, atrial flutter, paroxysmal tachycardia,
exercise-induced ventricular arrhythmias)
Used in Rx of CHF; -blockers SNS stim. to heart
Used for anxiety by actors/performers by SNS effects
Effects similar to propranolol

Selective 1

Effects similar to propranolol

1, 2

Used to Rx glaucoma; poss. by aqueous humor prod.

by ciliary body
Antagonist effects < other -blockers

Partial agonist

Intrinsic sympathomimetic activity

(ISA): Partial agonist, but
antagonist activity > agonist activity

Adverse Effects
Contraindicated for asthmatics (2-blockage can be
disastrous due to bronchodilation asphyxiation)
Note: For asthmatics, give aminophylline, b/c it
doesnt depend on -receptors for its effects
Diabetics possible disastrous effects if Rx with
propanolol, they need monitoring.
HDL in chronic users of 1-blockers
Blocks sexual activity in some males

Drugs affecting the adrenergic nerve terminal

Drug
Cocaine

Reserpine
reserpine,

Pharmacokinetics/Action
Action: Blocks Na+-activated ATPase, thus blocking
reuptake of NE into adrenergic nerve terminal; NE
stays around longer in the synapse, thus SNS stim.
Note: Imipramine and other tricyclic antidepressants
(TCAs) also block Na+-activated ATPase

Effects and Uses

Adverse Effects
CNS: Stimulation; w/ high doses, tonic-clonic seizures; Potentiates adrenergic agonists
body temp. by affecting reg. in CNS (pyrogenic drug)
Local anesthetic: best one available because it is easily
absorbed through membranes and causes numbing of
all areas. Not used though
Cardiovascular: Cardiac arrhythmias, vasoconstriction
Respiratory: Depression with very high doses
Action: Blocks Mg2+-activated ATPase, thus blocking
PNS: Accentuation of parasymp. activity ( GI motility) Indirect-acting drugs wont work in pts. taking

reuptake of NE from cytosol to vesicle. Because MAO Cardiovascular: BP , and stays low (no tolerance!!)
exists in the adrenergic nerve terminal, this depletes NE CNS: Causes activity by depleting other NTs
in the neuron, but slowly (this takes days).
(i.e. dopamine, 5-HT, etc.) This results in drowsiness
Distribution: Good penetration into CNS
and lethargy; Parkinson-like symptoms w/ high doses
Guanethidine

Action: NE release into synapse (interfering with

adrenergic neuron function); displaces NE long-term
Distribution: NO CNS (guanithinium ion has + charge)

Cardiovascular: BP in anyone, bradycardia

PNS: Initiates parasympathetic activity
(CV: bradycardia; GI: diarrhea; etc.)

or drugs with similar actions

CNS: Drowsiness and lethargy; Parkinson-like
symptoms with high doses; depression also
Males: Gynecomastia
Females: Adverse effects on ovulation, menstruation
Males: Prevents ejaculation (very potent agent for this)
Severe postural (orthostatic) hypotension (most severe!!)

Pharmacology Review Sheets: Drugs Affecting the Autonomic Nervous System, p.5
Choliomimetics (Cholinergic Agonists) Direct-acting
Drug
Acetylcholine
(Choline ester)

Type/Receptor
Nicotinic and
Muscarinic ACh

Pharmacokinetics/Action
Effects and Uses
Duration of action: Very short (mins) Used topically to eye to induce miosis
b/c of rapid hydrolysis by AChE
Admin: topical only (no systemic use)

Carbechol
(Choline ester)

Nicotinic and
Muscarinic ACh

Bethanechol
(Choline ester)

Muscarinic ACh

Pilocarpine
(Alkaloid)

Muscarinic ACh

Duration of action: 1 hr
Used topically to eye to induce miosis and can cause
Admin: topical only (no systemic use) accommodation by causing contraction of the ciliary
Note: Not substrate for cholinesterases muscle
Used in chronic Rx of wide-angle glaucoma because
carbechol can intraocular pressure
Used in acute Rx of narrow-angle glaucoma to
intraocular pressure; chronic Rx is surgery!
Duration of action: Oral (1 hr),
Used to activate muscarinic ACh receptors in ileum
Subcutaneous (slightly > than 1 hr)
(Rx for paralytic ileum) & bladder (Rx for bladder ateny)
Note: Not substrate for cholinesterases
Duration of action: Topical (1 day), Eye: Causes miosis, accommodation (can be used to Rx
Oral (3 hrs), Subcutaneous (> 3 hrs)
glaucoma)
Mouth: Rx for xerostomia (dry mouth)

Adverse Effects
cholinergic activity: salivation, lacrimation, urination,
defecation (SLUD)
Contraindicated in asthmatics b/c of bronchiolar
smooth muscle contraction (precipitates asthma attack)
SLUD (see above)
Contraindicated in asthmatics (see above)

SLUD (see above)

Contraindicated in asthmatics (see above)
Topical use: use cautiously
SLUD (see above)
Contraindicated in asthmatics (see above)

Choliomimetics (Cholinergic Agonists) Indirect-acting (anticholinesterases)

General comments
- Carbamates carbamylation of AChE active site is covalent, but water can remove the inhibitor (this process takes mins-hrs)
- Organophosphates phosphorylate serine oxygen at active site; slowly reversible unless aging occurs (side chain of inhibitor breaks off, disallowing removal of the inhibitor) then, the
inhibition is irreversible
Drug
Edrophonium

Type
Pharmacokinetics
Effects and Uses
Adverse Effects
Rapidly reversible, Duration of action: 10-20 mins
Used for Dx of myasthenia gravis
non-covalent
Tacrine
Rapidly reversible, Duration of action: 8 hrs
Used in Rx Alzheimer Disease (if given early enough)
non-covalent
Admin: Can be given orally
Note: this drug only slows progression it cant stop it
Physostigmine
Rapidly reversible, Admin: Topical; NO systemic admin Used in Rx of glaucoma
(Carbamate)
covalent
Distribution: Penetrates CNS
Neostigmine
Rapidly reversible, Admin: Systemic, often w/ bethanechol Used in Rx of paralytic ileum and bladder ateny
(Carbamate)
covalent
Distribution: Doesnt penetrate CNS
(its more polar than physostigmine)
Carbaryl
Rapidly reversible,
Carbaryl poisoning SLUD effects
(Carbamate)
covalent
- Rx: Atropine ALONE
(insecticide)
- Note: Pralidoxine (2-PAM) makes poisoning worse!!
Echothiophate
Slowly reversible Duration of action: Topical (4 days) Used in topical Rx of glaucoma
(Organophosphate)
Note: NO aging

 Parathion poisoning: SLUD, convulsions, fasciculations

- Rx: Atropine, pralidoxine (2-PAM) rapid reactivator
of AChE (dephosphorylates enzyme in seconds);
diazepam for convulsions
Soman exposure irreversible AChE inhibition
- Rx: Cant use 2-PAM; military has partial reactivators
(which we arent supposed to know about) for Rx

Parathion
Slowly reversible Metabolism: Undergoes activation
(Organophosphate) (insecticide)
by cyt. P-450 in liver

Soman
Irreversible
(Organophosphate) (nerve gas)

Volatile: Airborne exposure possible

Very potent! (Potency >> Insecticides)
Ages immediately within secs/mins

Pharmacology Review Sheets: Drugs Affecting the Autonomic Nervous System, p.6
Cholinergic BLOCKERS
Drug
Atropine
(Alkaloid)

Receptor Blocked Pharmacokinetics/Action

Muscarinic ACh Duration of action: Orally (6-8 hrs),
topically (1 week)

Scopolamine
(Alkaloid)

Muscarinic ACh

Ipratropium
Muscarinic ACh
(Synt. quaternary
amine)
Benztropine
Muscarinic ACh
(Synt. tertiary
amine)

Mecamylamine

Nicotinic ACh
(ganglion blocker)

Hexamethonium

Nicotinic ACh
(ganglion blocker)

Admin: transdermal patch

Effects and Uses

CNS: Hallucinations (mad as a hatter);
body temp (via CNS reg.) leads to vasodilation since
sweating is by atropine (red as a beet)
Eye: Mydriasis, cycloplegia (inability of accommodate)
- Used topically (again, duration = 1 week)
- blind as a bat
Salivary glands: salivation (used in oral surgery)
- dry as a bone
Respiratory: bronchoconstriction, mucus secretion
- Not used clinically though
GI tract: peristalsis (anti-spasmodic drug for ileum)
Bladder: muscle tone; used to Rx urinary urge
incontinence (where bladder tone is very high)
Rx of poisoning by cholinergic agonists
CNS: different effects, at lower conc. than atropine
Used to Rx motion sickness (transdermal patch)

Adverse Effects
Xerostomia (dry mouth)
Contraindicated with glaucoma (or borderline glaucoma)
b/c it may cause it in those w/ high intraocular pressure

CNS: Drowsiness, amnesia

Transdermal patch: xerostomia
Contraindicated with glaucoma (see above)

Distribution: Doesnt enter CNS

Admin: Aerosol (no oral admin!)

Respiratory: bronchoconstriction, mucus secretion

Used to Rx asthma, emphysema (aerosol, 4x/day)

Admin: Oral

Used in Rx of Parkinson Disease. Muscarinic blockers

Parkinson disease symptoms, because dopamine
cholinergic inhibition ( cholinergic activity)
- Note: Benztropine only treats symptoms it wont
help in terms of disease progression.
Used with L-dopa (the primary Rx for Parkinson Disease
at this time) in early stages of the disease
Blocks both sympathetic and parasympathetic ganglion Postural (orthostatic) hypotension: SNS and PNS
(effects vary depending on area)
lead to vascular reflexes
- Note: In general, parasympathetic NS affected more
- Ex) Eye: Iris mydriasis b/c only constrictor (not
dilator) is affected; also, ciliary muscle, which is under
parasympathetic control, is affected
Cardiovascular: BP (vascular smooth muscle is
under SNS control only)