Adrenergics Flashcards
Methoxamine
Adrenergic Agonist
Alpha 1 selective over Alpha 2
Clinical use: Increase blood flow or pressure
Metaraminol
Adrenergic agonist
Alpha 1- Selective
Route: Parenteral, oral, IV, im
Clinical Use: Vasopressor (rev. hypotension NOT shock)
Long Acting Beta1, Alpha1 receptor stim
Mech: Catecholamines usually have a OH attached to benzene ring but loss of this leads to longer duration of action albeit less potent
- Due to COMT inability to metabolize efficiently
- Also has a substitution to the alpha carbon which blocks oxidation by MAO and enhances ability to displace NE in the adrenergic storage vesicles
Phenylephrine
Adrenergic agonist
Alpha selective same for both
Route: nasal, ophthalmic, parenteral
Clinical Use: Nasal decongestant, vasopressor, local vasoconstrictor, mydriatic
Vasoconstriction (alpha 1 agonist) prevents shock,
Substituion on benzene ring to allow longer duration due to inability for COMT to act
Use to increase blood flow or pressure
Also used to decrease blood flow in attempt to reduce diffusion of local anesthetic from injection site
Elicit mydriasis
Alpha-methyldopa
Adrenergic Agonist
Alpha 2 selective
Prejunctional micellaneous
Receptor: alpha 2, DA2
False Transmitter
Action: Stimulate presynaptic on nerve terminals and postsynaptic alpha 2 recetors of nerve terminals,
- Inhibit NE release by terminal
- Elicit hypotension by decreasing total peripheral resistance, heart rate, cardiac output,
- Does not effect baroreceptors and rarely elicits orthostatic hypotension
SIDE EFFECTS: Sedation, Xerostomia, Anorexia, Fluid retention, vivd dreams, and CNS stimulation
- Chronic therapy may: Severe problems, hemolytic anemia, leukopenia, hepatitis, lupus-like problems
Anti-hypertensive agent able to penetrate PNS and CNS, partially replaces DOPA in synthetic pathway leading to alpha methyl NE synthesis being stored (FALSE TRANSMITTER)
Clonidine
Adrenergic Agonist
Alpha 2 selective (receptor agonist binds Gi)
Stimulate presynatpic on sympathetic nerve terminals and post synaptic receptors on nerve terminals in CNS
Elicit hypotension by decreasing total peripheral resistance, lowering heart rate, cardiac output, DOES NOT effect baroreceptor reflexes and rarely elicits orthostatic hypotension
Guanabenz
Adrenergic Agonist
Alpha 2 selective
Stimulates presynpatic on sympathetic nerve terminal and postsynaptic on CNS nerve terminals
Elicit hypotension by lowering TPR, heart rate, cardiac output, DOES NOT effect baroreceptor reflex and rarely elicits orthostatic hypotension
Amphetamine
Adrenergic Agonist
Mixed alpha and beta agonists
Releasing Agent
Enter nerve terminal via Amine I transport (NE displaced from storage vesicles and released into synpase
Taken in via transporter and blocks NE reuptake, reverse trasnport to release intraneuroal NE
VASOPRESSOR: stimulate alpha 1 and beta 1 receptors and act as NE releasing agents
Ephedrine
Adrenergic Agonist
Mixed alpha and Beta agonist
Releasing agent
Administered via: Ophthalmic, oral, parenteral, nasal
Vasopressor, mydriatic, nasal decongestant, relax bronchial smooth muscle, CNS stimulant
Stimulate most adrenoceptors
Substituions to benzene ring may lose some potency but allows drug to last longer due to inability of COMT
Substitution to alpha carbon allows enhanced ability to displace NE from adrenergic storage vesicle, blocks oxidation by MAO
Enter the nerve terminal via Amine I transport (NE gets displaced from storage vesicles and released into synapse)
Directly stimulates alpha 1 and beta 1 receptors and acts as a releasing agent
Elevates cardiac output and arterial pressure, mild stim of CNS, mild Beta 2 activity to dilate bronchial smooth muscle, nasal decongestant.
Clinical use for chronic orthostatic hypotension by achieving increased blood flow or pressure
Reduces congestion of mucous membranes by achieving decreased blood flow
Combats stress incontinence
Epinephrine
Adrenergic Agonist
Mixed alpha and beta agonist
Naturally occurring
Route: IV, parenteral, aerosl
Clinical use: Anaphylatic shock, relax bronchial smooth muscle, local vasoconstriction, mydriatic (glaucoma)
Relax (dilate) bronchial smooth muscle
Stimulate heart (induce heartbeat)
Emergency therapy for, Severe elevated pressure in anterior chamber of eye, anaphylatic shock, severe allergic reactions
Induce vascoconstriction (alpha 1) to restrict diffusion of drug from injection site
Applied to bleeding areas to induce vasoconstriction
Made in Adrenal Medulla
Degraded by COMT (methylation) and MAO(Deamination)
Acts on all alpha and beta receptors
Mimics sympathetic stimulation
Beta receptors more sensitive than alpha receptors to epinephrine
Released directly into venous circulation
Pheochromocytoma: tumor of adrenal medulla, characterized by very elevated release of epinephrine into venous circulation
- Severe tachycardia, hypertension, headaches, increased sweating
Very potent vasoconstrictor and cardiac stimulant, systolic BP increased due to B1 effects on heart and alpha 1 receptor mediated vasoconstriction in vascular beds
- Vasodilation in skeletal muscle due to B2 activity to decrease TPR
Favored method of treatment for anaphylaxis
Norepinephrine
Adrenergic Agonist
Alpha and Beta selective (not much Beta 2 action)
Inhibit Amine I transport increase concentration of this within the synapse and mimic responses of sympathetic nerve stimulation
Administered via IV infusion only
Clinical Use: Vasopressor (shock)
Vasoconstriction (alpha 1) and cardiac output (beta 1)
Primary neurotransmitter of adrenergic nerves
Degraded by methylation from COMT and deamination from MAO
Transported into nerve terminals via vesicular monoamine transporter (VMAT)
Released via exocytosis triggered by Ca2+
Recycled back into the nerve terminal via Amine I transport (NET)
Peripheral resistance and diastolic/systolic BP increased
- Little effect on Beta 2 receptors
Can reduce diffusion of local anesthetics from injection site as well
Dobutamine
Adrenergic Agonist
Beta 1 selective
IV infusion (short acting)
Force cardiac contraction, Increase Cardiac output (congestive heart failure)
Substitutions to amino group to increase Beta activity
Increase lipolysis as well
Receptor agonist binds Gs
Increased blood flow or pressure in case of CARDIOGENIC SHOCK following MI
Rescuing cardiac function from Heart Failure
Isoproterenol
Adrenergic Agonist
B non-selective
Distribution: aerosol, parenteral
Clinical action: relax bronchial smooth muscle, cardiac stimulant (A-V block) (asthma)
Primary use for stimulation of B2 adrenoceptors relaxation of bronhcial smooth muscle,
Can be used for cardiac stimulation (Beta 1)
Substitution to amino group to increase beta activity
Very potent Beta agonist with very little alpha activity
- Potent vasodilator, significant increase in cardiac output with beta 1 receptor activity
- Decreased MAP by vasodilation due to Beta 2 receptor activity
Albuterol
Adrenergic Agonist
Beta 2 selective
Skeletal muscle vasodilation, smooth muscle relaxation, decreased intraocular pressure
Metaproterenol
Adrenergic agonist
Beta 2 selective
Smooth muscle relaxant, vasodilate skeletal muscle
Terbutaline
Adrenergic Agonist
Beta 2 selective
RElax smooth muscle
Routes: parenteral, oral aerosol
Substitute amino group to allow increased Beta activity
Relax Pregnant Uterus
Bromocriptine
Adrenergic Agonist
Dopamine agonist
Autoreceptor: DA2, alpha 2
Primarily used as an anti-parkinson agent w/CNS activities
D2 receptors on post synpatic effector sites in the CNS are not INVOLVED in feedback inhibition
Dopamine
Adrenergic agonist
Dopamine receptor agonist
Administered: IV infusion
Major clinical usage: Vasopressor (shock)
Only used by IV infusion for shock therapy
Vasoconstriction (alpha 1)
Increase cardiac output (beta 1)
Dilate renal blood vessels (DA1)
Released by postganglionic sympathetic nerves of renal and splanchnic vascular smooth muscle
D1 receptor: vasodilation (renal, mesenteric)
D2 receptor: binds Gi, presynpatic nerve terminals (provide negative feedback to decrease NT release from terminals
Fenoldopam
Adrenergic Agonist
Dopamine receptor selective (D1 selective)
- D1: receptor agonist binds Gs, vasodilation (renal, mesenteric)
Doxazosin
Adrenergic Antagonist
Alpha 1 selective
Inhibit constriction/contraction resulting in vasodilation and lower MAP
- Efficaous in relieving urinary symptoms (urinary obstruction, Benign prostatic hyperplasia)
Prazosin
Adrenergic Antagonist
Alpha 1 receptor selective
Antihypertensive
Blocks alpha 1 receptors and results in EPINEPHRINE REVERSAL
Competitive reversible antagonist
Advance for therapeutic application
Exhibit little orno tachycardia due to alpha 1 selectivity
NO inhibition of Beta 1
Good duratino of action 12 hours
Tamsulosin
Adrenergic Antagonist
Alpha 1 selective
Effective at relieving urinary symptoms due to BPH
Terazosin
Adrenergic antagonist
Alpha 1 selective
Inhibit constriction/contraction resulting in vasodilation and lower MAP
Helps relieve urinary obstruction due to BPH
Phenoxybenzamine
Adrenergic antagonist
Alpha non-selective
Amine I Transport (NET=norepinephrine transport) INHIBITOR
Alpha 1 activity greater than Alpha 2
NONCOMPETITIVE antagonist of alpha 1 and alpha 2 receptors and INHIBITS NET by forming cyclic derivative
Duration: 24 hours
Orally or IV
Induces hypotension, tachycardia: DUE to reflex activation of adrenergic nervous system (due to lowered MAP)
- NO inhibition of Beta 1 receptors in heart
Pheochromocytoma: used for management of hypertension preoperatively
- Also in cases where inoperative/metastatic tumors present
- ADJUNCT drug in therapy for SEVERE hypertension
Phentolamine
Adrenergic antagonist
Alpha non-selective
Used in DIAGNOSTIC: Pheochromocytoma (Regitine Test)
Alpha 1= Alpha 2
COMPETITIVE antagonist
Inhibits alpha 1 and alpha 2 with equal efficacy, THERAPEUTIC ABILITY due to alpha 1 inhibition
Antagonism of alpha 1 receptors leads to vasodilation
Alpha 2 antagonism leads to INCREASED NE release (since B1 not blocked get high cardiac output and tachycardia)
-DIRTY DRUG: Reacts with other receptors (muscarinic, histamine)
Pheochromocytoma: Same effects as Phenoxybenzamine
Labetalol
Adrenergic Antagonist
Mixed alpha and beta antagonist
Has more Beta activity than alpha, alpha 1 more than alpha 2
Atenolol
Adrenergic antagonist
Beta 1 selective
Used to treat hypertension (inhibit cardiac output and dilation/relaxation) inhibit cardiac output
Duration: 6-9 hours
Used with great caution for patients with asthma or COPD
Less CNS side effects due to diminished ability to cross BBB
Betaxolol
Adrenergic Antagonist
Beta 1 selective
Used to inhibit cardiac output
Duration of Action: 14-22 hours
Clinical use: Glaucoma
Metoprolol
Adrenergic Antagonist
Beta 1 selective
Antihypertensive
Inhibit cardiac output
Duration of action: 3-4 hours
- Antihypertensive, angina pectoris
EFFECTIVE PROPHYLACTIC agent to prevent recurrence of MYOCARDIAL INFARCTION, help with long term survival
Side Effects: ATAXIA, DIZZINESS, major problems with initial therapy
Nadolol
Adrenergic Antagonist
Beta non-selective
Duration of action 14-24 hours
- Beta 2 activity may inhibit dilation of bronchioles, significant for patients with ASTHMA
ANTIHYPERTENSIVE
Produces fewer CNS effects due to diminished ability to cross BBB
Pindolol
Adrenergic Antagonist
Beta non selective
Antihypertensive
Duration of action: 3-4 hours
Propranolol
Adrenergic Antagonist
Beta non selective
ANTIHYPERTENSIVE, ANTI-ARRHYTHMIC, ANGINA PECTORIS, MIGRAINE HEADACHE
Duration of action: 3-6 hours
May lead to dilation of bronchioles which will be tough on patients with asthma
Adverse Effect: Ataxia and Dizziness
Long term use following myocardial infarction prolongs survival (suppress arrhythmias)
Timolol
Adrenergic Antagonist
Beta non selective
Used for: LOWER INTRAOCULAR PRESSURE, ANTIHYPERTENSIVE, ANGINA PECTORIS
Long term use is effective for prolonged survival in MI patients
Duration of action: 4-5 hours
Guanethidine
Miscellaneous Pre-Junctional
Nerve Terminal Membrane Stabilizer
Depletes NE
Oral Route: Antihypertensive therapy for most severe elevated Arterial Pressures
Hypotensive activity due to eliciting reduced NE release
Agents that inhibit transport (cocaine), tricyclic antidepressants will antagonize (inhibit) desired hypotensive effect
Stabilizes neuronal membranes, interfering with exocytosis
Chronic administration is accompanied by depleting NE within synaptic vesicles
Minimal effects with other biogenic amines (EPI, DA)
Minimal adverse effects in CNS since does not cross BBB
Reserpine
Miscellaneous Pre-Junctional
Norepinephrine Depletion
Depletes EPI, NE, DA, SEROTONIN in both CNS and PNS by blocking transport into storage vesicles
Very Potent, ORALLY EFFECTIVE, Long Duration of Action
Adverse effects are in CNS (sedation, depression, parkinsonian symptoms)K
Increased GI motility leads to ulcers
Cocaine
Inhibit Amine I Transport (NET) (NE rises in synapse)
Achieves decreased blood flow (hemostasis during surgery)
DMI (desmethylimipramine)
Amine I Transport Inhibitor
Tricyclic antidepressant
Tyramine
Phenylethylamine derivative that enters nerve terminal via Amine I transport
Found in cheeses, dangerous for individuals on MAO, combination of lower synaptic NE metabolism with increased NE release from this agent
Elevates arterial pressure
