Autonomic Nervous System (ANS) Drugs

Autonomic Nervous System
(ANS) Drugs
Adrenergic Pharmacology
Cholinergic Pharmacology
- Sympathetic Agonists
- Non specific
- Epinephrine is a direct stimulator at all adrenergic
receptors. In addition to local vasoconstriction, it is
indicated for hypotension and shock, allergy, and
bronchoconstriction.
- Epinephrine Indications:
Local Vasoconstriction
Hypotension and Shock
Bronchoconstriction
Allergy
Mechanism:
Direct stimulation of α and β
adrenergic receptors
- The Epi-Pen is used in cases of severe
brochoconstriction either from allergy
(anaphylaxis) or from an asthma exacerbation.
- Image of an EpiPen
- Disease Related Concerns
Cardiac: β1 stimulation increases the work
of the heart and decreases cardiac
efficiency
• Cerebrovascular disease: Use with
caution in patients with cerebrovascular
disease
• Diabetes: Increases in circulating blood
glucose from stimulation of liver glycogenolysis
and glucagon secretion Inhibition of insulin
secretion
• Parkinson's disease: may cause
temporary worsening of
symptoms.
• Thyroid disease: Use with
caution in patients with thyroid
disease
- Antidepressants: Include include the tricyclics and the
serotonin-norepinephrine reuptake inhibitors (the SNRIs). These
block reuptake and degradation of epi, leading to more cardiac
adverse effects
β-Blockers: Non-Selective: Block β receptors in
the peripheral blood vessels, epi acts as a pure
α agonist and blood pressure rises
Selective Block β1 receptors in heart, at high
doses block β 2 receptors in peripheral blood
vessels
- Alpha α
- α Sympathetic Agonists
Methylphenidate (Ritalin), (Concerta)
Amphetamine (Adderall)
Mechanism: Release of Norepi
from synaptic vesicle
Use: ADHD and Narcolepsy
- The FDA asked the Drug Safety and Risk
Management advisory committee to look into
studying the cardiac risk in both adult and children
taking ADHD drugs:
* sudden death in patients who
have heart problems or heart
defects
* stroke and heart attack in adults
* increased blood pressure and
heart rate
Abuse and addiction: Schedule
2 (Ritalin and Adderall)
Dyskinesia, muscle tightness, bruxism
- Provigil (Modafinil)
MOA: α 1 agonist, inhibitor of
dopamine reuptake
Indication: narcolepsy, shift work disorder
Adverse Effects: mania, delusions, hallucinations,
suicidal ideation and aggression, persistent
sleepiness
Provigil is a drug that is similar to Ritalin. It is also indicated for narcolepsy. Its other
indication is shift work disorder. Shift work disorder is a circadian rhythm sleep disorder
characterized by insomnia and excessive sleepiness affecting people whose work hours
overlap with the typical sleep period. Provigil is an alpha 1 agonist and an inhibitor of
dopamine reuptake. It has many adverse effects mainly in the CNS including mania, delusions
and hallucinations.
- Catapres is an inverse agonist. This means that is binds to receptors as an agonist but has the
opposite effects that you would expect from an agonist. Catapres binds to alpha 2 receptors
on the pre-synaptic neuron. This causes a negative feedback signal that inhibits the release of
norepinephrine into the synapse. Less norepinephrine means that blood pressure will
decrease. Catapres is indicated for hypertension and can cause dry mouth and orthostatic
hypertension.
- Alpha Adrenergic Synapse Image
- Beta β
- β2 Sympathetic Agonist
There is only 1 drug in the beta sympathetic agonist drug class that is widely used.
It is Proventil. It binds specifically to beta 2 receptors. It is indicated for asthma
and COPD. It is available in an inhaler. The beta 2 receptors in the lungs will
receive most of the drug. This decreases the chance for adverse effects in the rest
of the body.
- Sympathetic Antagonists
- Alpha α
- When drugs are antagonists in the sympathetic
arm of the ANS, their effects are like that of
acetylcholine.
- Effects of Acetylcholine:
Bradycardia
Vasodilation
Bronchoconstriction
Relaxation of urinary sphincter
Increase GI secretions
Sweating
Contraction of iris
SLUD Response:
Salivation
Lacrimation
Urination
Defecation
- Drugs that are antagonists of adrenergic
receptors are used most commonly in heart
disease and benign prostatic hyperplasia (BPH).
- Therapeutic Uses of Drugs at
Adrenegeric Receptors
(Antagonists)
HTN, Post myocardial infarction, CHF,
Treatment of arrhythmias, Ischemic heart
disease
α blocker: Hytrin
β blockers: Toprol, Propranolol, Coreg
Benign prostatic hyperplasia:
α blocker: Hytrin, Flomax
- Hytrin and Flomax are alpha sympathetic antagonists that are used treat BPH. Hytrin is also
used to treat HTN. Hytrin is the drug of choice when a patient has both BPH and HTN. Both of
these agents block alpha receptors which leads to smooth muscle relaxation. Flomax targets
receptors alpha receptor subtypes that are found only in the prostate gland. As a
consequence, patients on Flomax may experience fewer adverse effects than patients on Hytrin.
- Beta β
- Remember that sympathetic antagonists have the effects of acetylcholine. This
lists the therapeutic effects of beta blockers. The most important one is that
cardiac output decreases. The exact signal transduction steps between the
binding of the beta receptor by a beta blocker and the pharmacological effects
are unknown.
PCOL Effects of Beta Blockers
↓ the force and rate of myocardial contraction
↓ O2 consumption of the heart
↓ of blood pressure in hypertensive patients
CO decreases
HR decreases
Reduction in plasma renin activity
Decrease CNS sympathetic outflow
Alteration in baroreceptor responsiveness
- There are two classes of beta
blockers: selective and
nonselective.
- Selective for β1
Selective beta blockers bind at the beta 1 receptor in the heart. The
mechanism of action is competitive inhibition of epinephrine and
norepinephrine at the beta 1 receptor. Selective beta blockers like
Toprol are almost always used to treat heart disease or hypertension.
- Nonselective
The non-selective beta blockers like Inderal block both beta 1
and beta 2 receptors. Non-selective beta blockers can be used to
treat heart disease and also a number of other conditions, for
instance migraines, stage fright or tremor.
- Beta blockers are well tolerated,
but do have a few adverse effects.
Adverse effects:
Altered taste
Orthostatic hypotension
Non-Selective:
hypertension and bradycardia
- β Antagonists
Carvedilol (Coreg) is a unique beta blocker in that it also blocks
alpha receptors. It decreases heart rate and contractility and also
decreases blood pressure through alpha blockade. It is most
commonly used in heart failure.
- Drugs that act at cholinergic receptors have a mechanism of
action that drugs that act at adrenergic receptors do not have.
Cholinergic drugs are able to inhibit the breakdown of
acetylcholine by inhibiting the action of cholinesterase.
- Diagram of cholinergic synapse
- Parasympathetic Agonists
- Review of pharmacological effects that
cholinergic agonists might produce in the
body:
Effects of Acetylcholine:
Bradycardia
Vasodilation
Bronchoconstriction
Relaxation of urinary sphincter
Increase GI secretions
Sweating
Contraction of iris
SLUD Response:
Salivation
Lacrimation
Urination
Defecation
- Cognex, used for Alzheimer's, is the
most predominant drug in this class.
- Cholinergic drugs have 2 possible mechanisms by which they ace. They can inhibit cholinesterase
to increase the half life of acetylcholine at the receptor site or they can be direct acting by binding
to and stimulating the cholinergic receptors. Cholinergic drugs are not well tolerated. They are
contraindicated in asthma, cardiovascular disease and ulcer. The adverse effects include the
parasympathetic reactions of the SLUD response as well as many more, including nausea, diarrhea,
vomiting, rhinitis, urinary frequency, bronchospasm, hypotension, arrhythmias
- Tacrine (Cognex) is a cholinesterase inhibitor. It
is used in dementia associated with Alzheimer’s
disease or Parkinson’s disease.
Idea: Prolong acetylcholine half life in the brain
- Parasympathetic Antagonists
- Expect these drugs to have the same
pharmacological effects of the sympathetic
agonists.
- Review of the pharmacological effects of
norepinephrine. These are the therapeutic
effects of the parasympathetic antagonists:
Tachycardia
Vasoconstriction
Bronchodilation
Contraction of urinary sphincter
Decreased GI secretions
Glycogenolysis
Gluconeogenesis
Lipolysis
- General therapeutic uses of antimuscarinic drugs:
Bronchodilation: Asthma and COPD
* Ipratropium (Atrovent)
* Tiotropium (Spiriva)
Urinary: antispasmodics
* Tolterodine (Detrol)
* Darifenacin (Enablex)
- Atrovent is a drug that blocks the cholinergic receptors in the lungs. The causes
bronchodilation. It is available on its own in an inhaler or as a combination
product with albuterol in the Combivent inhaler. Spiriva is also a drug that blocks
the cholinergic receptors in the lungs, but it has a much longer half-life then
Atrovent. It is used as once daily dosing in patients that have COPD.
- M3 is the cholinergic receptor found in the
urinary sphincter muscle. Enablex has less
adverse effects than Detrol, less dry mouth and
constipation.
- Anticholinergic drugs can interact with antihistamines. This interaction can
lead to severe dry mouth. Enablex is a CYP2D6 inhibitor. This is the P450
enzyme in the liver that is responsible for the metabolism of codeine. If a
patient is taking Enablex, codeine may not be effective to control dental
pain.
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