Pharm Cholinergics And Adrenergics

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1. alpha agonist

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Main Effects Of Adrenergic Receptor Activation "α1-receptors: vasoconstriction

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relaxation of gastrointestinal smooth muscle (except the sphincters)

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α2-receptors: inhibition of transmitter release (including NE and Ach release from autonomic nerves)

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platelet aggregation

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β1-receptors: Increased cardiac rate and force

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Increases renin release

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β2-receptors: Bronchodilation

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Vasodilation

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ISOPROTERENOL (ISO

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IPNE)- β1 β2

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EPI: β2

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β1 > α receptors

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Differential cardiovascular effects of NE

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EPI & IPNE

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High doses: Activates both α1 and β2

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and the alpha effects predominate

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Rapid relief of hypersensitivity reactions including anaphylaxis

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to drugs and allergens

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Epinephrine: Pharmacokinetics "Rapid onset of action (iv

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inhalation routes):

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Rapid inactivation by the liver Monoamine oxidases (MAOs)

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catechol-o- methyl transferases (COMTs)

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" Epinephrine: MOA" Based on its actions on blood vessels

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heart and bronchial smooth muscles

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OXYMETAZOLINE "Common ingredient of many nasal decongestants (Afrin

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Dristan

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OXYMETAZOLINE: MOA "MOA: Non selective (α1

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and α2) agonist

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Constricts the small arterioles supplying the nasal mucosa

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decreasing secretions

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Less potent but longer duration of action than EPI

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NE (not metabolized by COMT)"

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Very useful in treating and preparing addicted subjects for withdrawl from narcotics

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alcohol

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These side effects occur in at least 50% of the patients and may require drug discontinuation. However

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they may diminish after a few weeks of therapy

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Vascular (renal

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mesenteric

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Short-term management of cardiac decompensation that may occur after cardiac surgery

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in CHF

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Essential hypertension

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CHF

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Favorable effects on lipid profile: lowers LDL & triglycerides

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Increases HDL"

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MOA: Specifically blocks α1 receptors on the trigone

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internal sphincter and prostate smooth muscle"

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-Anxiety to control somatic symptoms (e.g. palpitations

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tremor)

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Pseudo-ephedrine (stereoisomer

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OTC cold medications)

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Increases release of DA

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NE

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4. beta2 agonist. "

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Beta1 Agonist

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What is the difference between indirect and direct agonists?

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Main Effects Of Adrenergic Receptor Activation

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"α1-receptors: vasoconstriction, relaxation of gastrointestinal smooth muscle (except the sphincters), thick viscid salivary secretions, and hepatic glycogenolysis, decreases renin release, Ejaculation

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Non-selective Agonists

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"EPINEPHRINE (EPI) - α1 α2 β1 β2

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Affinity of catecholamines for different adrenergic receptors

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"NE: α receptors >β1

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Differential cardiovascular effects of NE, EPI & IPNE

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Vascular Effects Of EPI & NE: Type Of Vascular Bed

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"Cutaneous blood vessels exclusively express α receptors: EPI & NE cause vasoconstriction

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Vascular effects of EPI: Dose dependency

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"EPI potency: β2>α1

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Baroreflex responses to EPI & NE

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"Drugs that activate only alpha receptors on the vasculature elicit a stronger baroreflex response

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Epinephrine: Clinical Uses

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"Reserved for emergency situations

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Epinephrine: Pharmacokinetics

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"Rapid onset of action (iv, inhalation routes):

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"

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Epinephrine: MOA"

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Epinephrine: Side Effects

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"Hypertension

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Non selective alpha agonists

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OXYMETAZOLINE

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"Common ingredient of many nasal decongestants (Afrin, Dristan, Sinex)

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OXYMETAZOLINE: MOA

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"MOA: Non selective (α1,and α2) agonist

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Oxymetazoline: Limitations

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"Loss of efficacy with chronic use

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Selective Alpha Agonists: Alpha1

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"α1 selective agonists

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Selective Alpha Agonists: Alpha 2

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"α2 selective agonists

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PHENYLEPHRINE: Clinical Uses

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"Nasal decongestant

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"

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Phenylephrine: MOA"

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"

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CLONIDINE (Catapres)"

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Clonidine: MOA

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"Partial agonist at α2 receptors

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Clonidine: Pharmacokinetics

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"Crosses the BBB

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Clonidine: Side Effects

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"Dry mouth

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Clonidine: Caution

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Abrupt discontinuation after long-term therapy can cause Rebound hypertension

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APRACLONIDINE (IOPIDINE)

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"Selective α2 agonist

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APRACLONIDINE (IOPIDINE): MOA

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"MOA: α2 receptor mediated reduction in aqueous humor production (Vasoconstriction in the ciliary epithelium)

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Selective Beta Adrenergic Agonists: Beta1

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"β1 selective agonists

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Selective Beta Adrenergic Agonists: Beta2

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"β2 selective agonists

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DOPAMINE

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"Catecholamine

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Dopamine: Clinical Uses

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"To improve cardiac and renal function in critically ill patients with severe congestive heart failure & renal failure

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DOBUTAMINE

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"Resembles dopamine structurally

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DOBUTAMINE (Dobutrex): Clincal Uses

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"CLINICAL USES

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"

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ALBUTEROL (Ventolin)"

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SALMETEROL (Serevent): Clinical use

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"Clinical use:

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SALMETEROL (Serevent): MOA

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"MOA:

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Onset & duration of action of various bronchodilators

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RITODRINE

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"Selective β2 agonist developed specifically for use as uterine relaxant

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β2 Agonists: Side effects

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"Excessive activation of β receptors outside the lungs

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4. Clonidine"

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2. Phenylephrine

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ALPHA ANTAGONISTS

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PHENOXYBENZAMINE (Dibenzylene)

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"Clinical Use:

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Nonselective Alpha Antagonists: Side Effects

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Prazosin (Minipress)

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"Clinical uses:

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Prazosin: Side effects

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"First dose phenomena:

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TAMSULOSIN (Flomax)

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"Clinical Use: Symptomatic relief of urethral obstruction in Benign prostatic hyperplasia (BPH)

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Benign Prostatic Hyperplasia (BPH)

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"Symptoms of urethral obstruction:

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BETA ANTAGONISTS

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Clinical uses of β-adrenoceptor antagonists or beta blockers

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"Cardiovascular:

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Clinical uses of β-adrenoceptor antagonists or beta blockers

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Propranolol: Clinical Uses

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"Treatment of essential hypertension

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Propranolol: MOA

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"Non selective β receptor blocker

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Timolol (Betaoptic)

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"Treatment of open angle glaucoma

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Beta blockers: Side Effects

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"Use non specific beta blockers with caution in patients with asthma

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Third Generation Beta antagonists

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"β blockers with additional effects

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INDIRECT ACTING SYMPATHOMIMETICS

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4. Propranolol"

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1. Phenoxybenzamine

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AMPHETAMINES

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"Amphetamine

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Amphetamines: Actions

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"Increases release of dopamine & other biogenic amines

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Amphetamines: Actions

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"Increases release of dopamine & other biogenic amines

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Amphetamines: Clinical Uses

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"Effective orally & can cross BBB

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MIXED ACTING SYMPATHOMIMETICS

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EPHEDRINE

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"Present in many herbal preparations

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Sympathomimetics: Side effects

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"Arrhythmias

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INDIRECT ACTING SYMPATHOLYTICS

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Drugs that inhibit catecholamine metabolism

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"Monoamine inhibitors (MAOI)