Download Sympathetic NS

Pharmacology of the Autonomic Nervous System
italic = less important agent
Indented = similar action to parent compound
[ ] = questionable therapeutic value
I =drug interactions
S = side effects T = toxicity
CV = cardiovascular system
CNS = central nervous system
Agent (trade name®)
Therapeutic Use
Adrenoceptor Agonists
Notes
E. Ishac
MAOI = Monoamine oxidase inhibitors TCA = Tricyclic antidepressants
Norepinephrine
(Levarterenol)
Hypotension, pressor agent
α / β 1 β 3 (β 2) neuronal, non-circulating, I: MAOI, TCA
Epinephrine
(generic)
Allergic reactions, shock, CPR
Dopamine
(Intropin)
Renal vasodilatation during shock
α / β 1 β 2 (β 3) adrenal medulla, circulating; I: MAOI,
TCA
α1 / β 1 / D, precursor to NE, I: MAOI
Isoproterenol
(Isuprel)
Asthma, cardiac stimulant
β, synthetic, not endogenous; (↓, --) BP HR
Phenylephrine
(Neosynephrine) Nasal decongestant, hypotension
Methoxamine
(Vasoxyl)
Hypotension, pressor agent
not commonly used for hypotension; S: CV, reflex
bradycardia
Metaraminol
(Aramine)
Hypotension, pressor agent
α, orally active; NE or DA better choice
Clonidine
(Catapres)
Hypertension
α2, ↓ cns sympathetic outflow, inhibit NE release,
rebound HT; S: dry mouth, sedation, impotence.
α-methyl-dopa is metabolized to α-methyl-NE (α2agonist)
β 1, iv infusion, tolerance, desensitization
Guanfacine
(Tenex)
α-methyl-dopa
(Aldomet)
Dobutamine
(Dobutrex)
CHF, cardiac stimulant
(Brethaire)
Asthma, premature labor
(Yutopar)
Premature labor
(Alupent)
Asthma - bronchodilator
Prenalterol
Terbutaline
Ritodrine
Metaproterenol
Albuterol
β 2-selective, Oral 1-2 hrs onset ! 4-6 hrs duration,
Inhalation 5-10 min onset ! 3-4 hrs duration;
S: cardiovascular; less via inhalation
(Proventil, Ventolin)
Miscellaneous Adrenoceptor Agonists
L-Dopa
(Dopar, Larodopa) Parkinson’s disease
precursor to DA, cross to CNS! DA
Ephedrine
(Vatronol, Efedron) Nasal decongestant, red eyes
α /β, also indirect to release NE; I: MAOI, TCA
Amphetamine
(Dexedrine)
Tyramine
Adrenoceptor Antagonists
Narcolepsy, hyperactivity, [obesity]
release NE, CNS stimulant, tolerance
None, [high] in red wine & cheese
interaction with MAO inhibitors
HT = Hypertension
PHT = Postural hypotension LA = Local anaesthetic action
α1, irreversible, S: PHT
Phenoxybenzamine
(Dibenzyline)
Pheochromocytoma, acute HT
Phentolamine
(Regitine)
Pheochromocytoma, acute HT, [impotence] α, competitive, S: PHT, reflex tachycardia
Tolazoline
Prazosin
Terazosin
(Priscoline)
(Minipres)
(Hytrin)
Hypertension (HT), benign prostrate
hypertrophy
α1, competitive; no reflex tachycardia S: PHT,
nausea, drowsiness
α2, currently not used as such
Yohimbine
(Yohimex)
[Impotence]
Propranolol
(Inderal)
Hypertension, angina, arrhythmias, tremor, β, non-selective, LA-action, no ISA; A very useful
migraine, hyperthyroidism (propranolol),
group, Contraindications: heart failure (currently
panic stress
under FDA review), asthma, diabetes
Pindolol
(Visken)
Hypertension, angina, arrhythmias
β, LA-action, ISA, angina commonly
Timolol
(Blocadren)
Glaucoma, decrease secretion; (HT)
β, no LA-action, no ISA, glaucoma commonly
(Lopressor)
Hypertension, angina, arrhythmias
β 1, LA-action, no ISA, arrhythmia commonly
(Tenormin)
Hypertension, angina
β 1, no LA-action, no ISA
Metoprolol
Atenolol
β, no LA-action, no ISA, long acting
Nadolol
(Corgard)
Esmolol
(Brevablock)
Arrhythmias, [angina]
β 1, no LA-action, no ISA, very short acting
(Normadyne)
Hypertensive crisis, hypertension, CHF
β / α, some β-agonist action
Labetalol
Miscellaneous Adrenergic Agents
SSRI = Selective serotonin reuptake inhibitors
α-methyl-p-tyrosine
(Metyrosine)
Pheochromocytoma (diffuse)
α-methyl-m-tyrosine
(Metaraminol)
Hypotension, pressor agent
converted to metaraminol (α-agonist)
Drug of abuse, local anaesthetic
inhibit neuronal uptake, cross CNS; I: CA's, amph.
Cocaine (generic)
Imipramine (tricyclic’s)
Amitriptylline
Chlorpromazine
Depression, inhibit neuronal uptake; at toxic S: dry mouth, blurred vision, decrease urination; T:
severe anticholinergic effect, respiratory depression,
(Amitril, Elavil) doses can block muscarinic, alpha, and
histamine receptors
PHT (alpha-block)
(Thorazine)
Schizophrenia, surgery premedication
inhibit extra- & neuronal uptake; sedation
(Janimine)
Pargyline, Phenelzine (MAOAB)
Tranylcypromine
(Parnate)
Clorgiline (MAOA)
Selegiline (MAOB)
inhibit tyrosine hydroxylase (rate limiting step)
(Deprenyl)
Depression: non-selective, accumulation of All MAO inhibitors have important interaction with
NE, TCAs or SSRIs preferred
tyramine → HT crisis, S: agitation, tremor, insomnia,
Depression
found in nerve terminals, liver, kidney, CNS
Parkinson’s Disease
found in platelets, liver, kidney, CNS
Pharmacology of the Autonomic Nervous System
Reserpine
(Sandril, Serpasil) Hypertension
Guanethidine
Bretylium
(Ismelin)
Hypertension, arrhythmias
(Bretylol)
Arrhythmias, surgery premedication
Cholinoceptor Agonists
depletion of NE; S: depression
Inhibit NE release, initial transient HT; I: TCA's
decrease effectiveness; S: PHT
AchE = Acetylcholinesterase
Acetylcholine
(Miochol)
No major use, minor ocular procedures for
brief miosis; muscarine found in certain
mushrooms
Atonic gut, urinary retention
M / N, short acting (AchE); T/S: All M-agonists:
salivation, lacrimation, urination, diarrhea, emesis,
(slude), miosis, bronchoconstriction, ↓HR
M, resistant to AchE
Bethanechol
(Urecholine)
Pilocarpine
(Oscusert-Pilo) Open angle glaucoma
M, resistant to AchE; alkaloid, increase outflow
Carbachol
(Carbacel)
M / some N, resistant to AchE
Methacholine
(Provocholine) Ocular procedures
Glaucoma, if pilocarpine ineffective
M, resistant to AchE
Indirect Cholinoceptor Agents
Edrophonium
(Tensilon)
Diagnostic for myasthenia gravis
Physostigmine
(Eserine)
Reverse atropine toxicity; glaucoma
reversible, CNS action
Neostigmine
(Prostigmin)
Myasthenia gravis, reverse nmj block
reversible, no CNS, some direct agonist action
Myasthenia gravis
AchE inhibitors occupy AchE and prevent Ach
degradation, T/S: same as for high Ach
Ambenonium
(Mytelase)
Pyridostigmine
(Mestinon)
Demecarium
(Humorsol)
Glaucoma
DFP (Isoflurophate) Organophosphate
Echothiophate
(Phospholine)
sarin, soman (nerve gases)
Malathion,
(Chemathion)
Parathion
competitive, short-acting (5-10min)
Military (classified)
Organophosphates, irreversible inhibition of AchE.
Can use 2-PAM before ‘aging’ to regenerate
enzyme, T: same as for high Ach, death due to
respiratory paralysis
Insecticides
(Folidol)
Cholinoceptor Antagonists
Atropine
Homatropine
(Isopto-Atropine) Reverse AChE inhibition; GI-disorders,
ocular (iritis), vagolysis
(generic)
Ipratropium
(Atrovent)
Pirenzepine
Benztropine
Scopolamine
Propantheline
Asthma – bronchodilator
Peptic ulcer
(Cogentin)
Parkinson's disease, esp. drug induced
(Isopto-Hyoscine) Motion sickness, diarrhea, ↓secretions
(Probanthine)
↓GI activity, ↓secretions, relax lung, mydriasis (pupil
dilation), cyclopegia (loss of accommodation),
competitive M-antagonists, pirenzepine (M1selective); T: mad as a hatter (unresponsive), red as
a beet (erythematous), blind as a bat (cycloplegia),
dry as a bone (secretions), hot as hell
(thermoregulation); Reverse toxic effects with AchE
inhibitors eg. physostigmine or neostigmine
GI-disorders ie. mild diarrhea, [peptic ulcer]
Glycopyrolate, Dicyclomine
Cyclopentolate
(Cyclogyl)
Ocular examination
Miscellaneous Cholinergic Agents
Hemicholinium
None
inhibit choline uptake (rate limiting step)
Treat facial muscle spasms, strabismus
prevent release of Ach
Regenerate AchE
need to use before ‘aging’ occurs
Nicotine, Lobeline (Cigarettes)
Insecticide, cigarettes
N-agonist, (blocker) T: convulsions, vomiting, CV
Mecamylamine
↓ BP during surgery, Nn-antagonists
(competitive)
Nn-antagonist, not oral; S: PHT, mydriasis
Botulinus toxin
Pralidoxime, (2-PAM)
(Protopam)
Ganglionic Agents
Trimethapan
(Inversine)
(Arfonad)
Nn-antagonist, active orally; S: PHT, mydriasis
Neuromuscular Junction Agents
Succinylcholine
(Anectine)
NMJ paralysis, depolarizing block
short acting due to plasma AchE; fasciculations
Tubocurarine
(generic)
NMJ paralysis, competitive blockers,
Small/fast nerves first (face, hands), then
trunk, respiratory muscles last. Flaccid
paralysis. Can reverse block with AchE
inhibitors
Nm, some histamine release & ganglia block
Malignant hyperthermia, cerebral palsy
Inhibit calcium release from SR
Glaucoma
Oral, ↓ secretion due to lack of HCO3-
Gallamine
(Flaxedil)
Mivacurium
(Mivacron)
Pancuronium, Vecuronium
Metocurine, Atracurium
Dantrolene
(Dantrium)
Nm, some M-receptor block
short acting 10-20 min, slight histamine release
Atracurium & Mivacurium hydrolysed by AchE, other
competitive agents eliminated:kidney, liver
Diuretics
Acetazolamide, Methazolmide
Dorzollamide, Brinzolamide
Topical, ↓ secretion due to lack of HCO3-