- Epinephrine is a direct stimulator at all adrenergicreceptors. In addition to local vasoconstriction, it isindicated for hypotension and shock, allergy, andbronchoconstriction.

- Epinephrine Indications:

Local Vasoconstriction

Hypotension and Shock

Bronchoconstriction

Allergy

Mechanism:

Direct stimulation of α and βadrenergic receptors

- The Epi-Pen is used in cases of severebrochoconstriction either from allergy(anaphylaxis) or from an asthma exacerbation.

- Disease Related Concerns

Cardiac: β1 stimulation increases the workof the heart and decreases cardiacefficiency

• Cerebrovascular disease: Use withcaution in patients with cerebrovasculardisease

• Diabetes: Increases in circulating bloodglucose from stimulation of liver glycogenolysisand glucagon secretion Inhibition of insulinsecretion

• Parkinson's disease: may causetemporary worsening ofsymptoms.

• Thyroid disease: Use withcaution in patients with thyroiddisease

- Antidepressants: Include include the tricyclics and theserotonin-norepinephrine reuptake inhibitors (the SNRIs). Theseblock reuptake and degradation of epi, leading to more cardiacadverse effects

β-Blockers: Non-Selective: Block β receptors inthe peripheral blood vessels, epi acts as a pureα agonist and blood pressure rises

Selective Block β1 receptors in heart, at highdoses block β 2 receptors in peripheral bloodvessels

- α Sympathetic Agonists

Methylphenidate (Ritalin), (Concerta)

Amphetamine (Adderall)

Mechanism: Release of Norepifrom synaptic vesicle

Use: ADHD and Narcolepsy

- The FDA asked the Drug Safety and RiskManagement advisory committee to look intostudying the cardiac risk in both adult and childrentaking ADHD drugs:

* sudden death in patients whohave heart problems or heartdefects

* stroke and heart attack in adults

* increased blood pressure andheart rate

Abuse and addiction: Schedule2 (Ritalin and Adderall)

Dyskinesia, muscle tightness, bruxism

- Provigil (Modafinil)

MOA: α 1 agonist, inhibitor ofdopamine reuptake

Indication: narcolepsy, shift work disorder

Adverse Effects: mania, delusions, hallucinations,suicidal ideation and aggression, persistentsleepiness

Provigil is a drug that is similar to Ritalin. It is also indicated for narcolepsy. Its otherindication is shift work disorder. Shift work disorder is a circadian rhythm sleep disordercharacterized by insomnia and excessive sleepiness affecting people whose work hoursoverlap with the typical sleep period. Provigil is an alpha 1 agonist and an inhibitor ofdopamine reuptake. It has many adverse effects mainly in the CNS including mania, delusionsand hallucinations.

- Catapres is an inverse agonist. This means that is binds to receptors as an agonist but has theopposite effects that you would expect from an agonist. Catapres binds to alpha 2 receptorson the pre-synaptic neuron. This causes a negative feedback signal that inhibits the release ofnorepinephrine into the synapse. Less norepinephrine means that blood pressure willdecrease. Catapres is indicated for hypertension and can cause dry mouth and orthostatichypertension.

- 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 asthmaand COPD. It is available in an inhaler. The beta 2 receptors in the lungs willreceive most of the drug. This decreases the chance for adverse effects in the restof the body.

- When drugs are antagonists in the sympatheticarm of the ANS, their effects are like that ofacetylcholine.

- Drugs that are antagonists of adrenergicreceptors are used most commonly in heartdisease and benign prostatic hyperplasia (BPH).

- Hytrin and Flomax are alpha sympathetic antagonists that are used treat BPH. Hytrin is alsoused to treat HTN. Hytrin is the drug of choice when a patient has both BPH and HTN. Both ofthese agents block alpha receptors which leads to smooth muscle relaxation. Flomax targetsreceptors alpha receptor subtypes that are found only in the prostate gland. As aconsequence, patients on Flomax may experience fewer adverse effects than patients on Hytrin.

- Remember that sympathetic antagonists have the effects of acetylcholine. Thislists the therapeutic effects of beta blockers. The most important one is thatcardiac output decreases. The exact signal transduction steps between thebinding of the beta receptor by a beta blocker and the pharmacological effectsare 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 betablockers: selective andnonselective.

- 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 blocksalpha receptors. It decreases heart rate and contractility and alsodecreases blood pressure through alpha blockade. It is mostcommonly used in heart failure.

- Atrovent is a drug that blocks the cholinergic receptors in the lungs. The causesbronchodilation. It is available on its own in an inhaler or as a combinationproduct with albuterol in the Combivent inhaler. Spiriva is also a drug that blocksthe cholinergic receptors in the lungs, but it has a much longer half-life thenAtrovent. It is used as once daily dosing in patients that have COPD.

- M3 is the cholinergic receptor found in theurinary sphincter muscle. Enablex has lessadverse effects than Detrol, less dry mouth andconstipation.