Adrenergic Pharm Flashcards
List three important aspects of receptor interaction?
- Second messenger amplification
- Effector cell response
- Pre-synaptic receptors
Trace out the formation of and release of NE starting with what amino acid?
- Tyrosine in the circulation
- Tyrosine hydroxylase (convert tyrosine to DOPA)
- Dopa decarboxylase (make dopamine)
- Uptake into vesicle
- Conversion of dopamine to NE by dopamine beta-hydroxylase
- NE in the vesicle can be converted to epi in the adrenal medulla (chromaffin cells with ratio of epi to NE 4:1)
Epi is a ______, whereas norepi is a ______
Neurohormone; neurotransmitter
Adrenergic receptors have how many membrane-spanning helices? Beta1 channels help increase cAMP, but what else do they increase? How does D1 compare to beta 1, 2, 3?
7; activate voltage-sens Ca channels in heart;
uses the same mech of action (increase cAMP)
When NE’s done its job, list the three ways it can leave from the cleft?
- Neuron specific (re-uptake)
- Extraneuronal uptake in effector cells
- Some diffusion back into an e.g. capillary
For extraneuronal uptake in effector cells, what two enzymes will metabolize e.g. NE? Where can this happen?
MAO (mito surface) and catechol-O-methyltransferase (cytoplasm of many cells, NOTABLY LIVER);
this process is VERY PROMINENT in the LIVER
For synthesis of the transmitter, release of transmitter, combining with receptor, and termination step, what can be used to agonize or antagonize each step?
- Trans synthesis: alpha me tyrosine ANTAGONIZES
- Trans release: bretylium antagonizes, amphetamine agonizes
- Combine w/ receptor: isoproterenol agonizes, propranolol antagonizes
- Cocaine agonizes termination step
Beta1 receptor prominent effector organs
Heart: increased HR, force of contraction
Kidney: renin secretion (JGA)
Beta 2 prominent effector organs and response
Arterioles (and arteries in skeletal muscle, coronary): dilation;
Bronchial muscle, pregnant uterus: relaxation
Several sites: increased metabolic effects
Beta 3 prominent effector organs and response
Adipose tissue (lipocytes): lipolysis, thermogenesis (increased)
Alpha1 prominent effector organs and response (skim milk victimizes kids)
Arterioles in skin, mucosa, viscera, kidney (resistant vessels): constriction;
Veins: constriction;
Uterus and Spleen: contraction
Alpha2 prominent effector organs and response
Presyn nerve endings: inhibit NE release and ACh release (gut);
Postsyn in CNS: decreased peripheral symp tone
D1 prominent effector organs and response
Renal, mesenteric, and cerebral arterioles: dilation
Idea of autoreceptors and heteroreceptors?
NE can stim presyn alpha2 receptors and inhibit NE release from the nerve terminal;
NE can control e.g. release of ACh from parasymps and result in relaxation of the gut
For blood vessels in skeletal muscle, which receptor has the dominant tone? What’s activated in low/high NE concentrations?
- alpha1
- At low concentrations of NE, or physiological, you have beta2 receptors activated, promoting relaxation and vasodilation
- At high concentrations of NE, like in shock, alpha1 receptors DOMINATE!!
Difference between norepi, epi and isoproterenol in terms of selectivity?
Norepi: H on N, means alphas and beta ONE
Epi: CH3 on N, means alphas and BOTH BETAS
Isoproterenol: Isopropyl group on N, means BETAS
Some tricks for knowing agonist potencies at adrenergic receptors?
- Epi is always greater than or equal to NE EXCEPT for beta2 receptors, since NE shouldn’t have selectivity for that
- Isoproterenol is best for beta2 and beta1 because of the isopropyl group; but obviously worst at ALPHAS!!
- CLON is best at alpha2 since it’s selective for it
Tyramine is a(n)
indirect agent that causes release of NE to allow it to interact with postsynaptic receptor
Norepinephrine (Levophed)
Class: Non-selective agonist
Mech: Agonist: α1, α2, β1
Thera: Acute Hypotension
Important SE’s: Hypertension; arrythmias; headache
Epinephrine
Class: Non-selective agonist
Mech: Agonist: α1, (α2), β1, β2
Thera: Anaphylactic shock; combined with local anesthetics; glaucoma
Important SE’s: Palpitation; arrhythmias; headache
Amphetamine
Class: Indirect acting
Mech: Increases release of NE
Thera: ADHD, narcolepsy, recreation
Important SE’s: Hypertension, insomnia, anxiety, arrhythmias
Isoproterenol (Isuprel)
Class: Non-selective β agonist
Mech: Agonist: β1, β2
Thera: shock; heart block
Important SE’s: Palpitation; tachyarrhythmia; headache
Dobutamine
Class: β1-selective β agonist
Mech: Agonist: β1
Thera: Cardiac decompensation; shock; heart block
Important SE’s: Tachyarrythmias; hypertension
Albuterol (Proventil)
Class: β2-selective β agonist
Mech: Agonist: β2
Thera: Prevent or reverse exercise-induced bronchospasm; mild asthma; COPD
Important SE’s: Can mask progressively severe inflammation
Other SE’s: Tachycardia, muscle tremor
Misc: 10-15 minutes to take action, 6-12 hours (max) of duration; nebulizer delivers more, but greater side effects; oral is least effective (requires more dose –> side effects); can be used night symptoms, but not ideal
Terbutaline (Brethine)
Class: β2-selective β agonist
Mech: Agonist: β2
Thera: Prevent or reverse exercise-induced bronchospasm; mild asthma; COPD; early labor
Important SE: Can mask progressively severe inflammation
Other SE’s: Tachycardia, muscle tremor
Misc: 10-15 minutes to take action, 6-12 hours (max) of duration; nebulizer delivers more, but greater side effects; oral is least effective (requires more dose –> side effects); can be used night symptoms, but not ideal
Phenylephrine (Neo-Synephrine)
Class: α1-selective α agonist
Mech: Agonist: α1
Thera: Nasal congestion; postural Hypotension
Important SE’s: Hypertension; reflex bradycardia
Clonidine (Catapres)
Class: α2-selective α agonist
Mech: Agonist: CNS α2
Thera: Hypertension; shock; withdrawal from drug dependence
Important SE’s: Sedation
α-methyldopa (Aldomet)
Class: α2-selective α agonist Mech: Metabolite (a-methylnorepinephrine) activates CNS a2 receptors Thera: Hypertension Important SE's: Sedation Misc: Prodrug; crosses BBB
Fenoldopam (Corlopam)
Class: Selective dopamine agonist
Mech: Agonist: D1 only
Thera: Increase blood flow at renal, mesenteric, and cerebral arteries
Misc: ~10 minute half-life
Dopamine
Class: Mixed acting (direct/indirect)
Mech: Agonist: D1, α1, β1
Thera: Shock, renal failure, hypotension
Important SE’s: Vasoconstriction (@ high doses)
Misc: “Low dose = Direct @ D1 Receptors
Medium dose = Direct @ Beta 1, some Indirect
High dose = Direct @ Alpha 1, some Indirect”
Phentolamine (Regitine)
Class: Non-selective α-antagonist
Mech: Antagonist: α1, α2
Thera: Pheochromocytoma, Raynaud’s, frostbite
Important SE’s: Postural hypotension; inhibit ejaculation
Phenoxybenzamine (Dibenzyline)
Class: Non-selective α-antagonist
Mech: Antagonist: α1, α2; non-competitive blocker (covalent bond to receptor)
Thera: Pheochromocytoma, Raynaud’s, frostbite
Important SE’s: Postural hypotension; inhibit ejaculation
Prazosin (Minipress)
Class: α1-selective antagonist
Mech: Antagonist: α1
Thera: Primary HTN, BPH
Important SE’s: Postural hypotension (usually 1st dose)
Terazosin (Hytrin)
Class: α1-selective antagonist
Mech: Antagonist: α1
Thera: Primary HTN, BPH
Important SE’s: Postural hypotension (usually 1st dose)
Propranolol (Inderal)
Class: Non-selective β-antagonist (1st generation)
Mech: Antagonist: β1, β2
Thera: Angina, Hypertension, Arrythmias
Important SE’s: Bradycardia, Bronchoconstriction, Sexual Dysfunction
Misc: Workhorse by which all the rest are judged
Timolol (Betimol)
Class: Non-selective β-antagonist (1st generation)
Mech: Antagonist: β1, β2
Thera: Glaucoma
Important SE’s: Bradycardia, Bronchoconstriction, Sexual Dysfunction
Metoprolol (Lopressor)
Class: β1-selective antagonist (2nd generation)
Mech: Antagonist: β1
Thera: HTN, Angina, Arrythmias, CHF
Important SE’s: Bradycardia, Sexual Dysfunction
Atenolol (Tenormin)
Class: β1-selective antagonist (2nd generation)
Mech: Antagonist: β1
Thera: HTN, Angina, Arrythmias, CHF
Important SE’s: Bradycardia, Sexual Dysfunction
Bisoprolol (Zebeta)
Class: β1-selective antagonist (2nd generation)
Mech: Antagonist: β1
Thera: HTN, Angina, Arrythmias, CHF
Important SE’s: Bradycardia, Sexual Dysfunction
Carvedilol (Coreg)
Class: Non-selective β-antagonist (3rd generation “A”)
mech: Antagonist: β1, β2
Thera: CHF, HTN
Important SE’s: Bradycardia, Fatigue
Labetalol (Trandate)
Class: Non-selective β-antagonist (3rd generation “A”)
Mech: Antagonist: β1, β2
Thera: CHF, HTN
Important SE’s: Bradycardia, Fatigue
Betaxolol (Kerlone)
Class: β1-selective antagonist (3rd generation “B”)
Mech: Antagonist: β1
Thera; CHF, HTN
Important SE’s: Bradycardia
Tyramine
Class: Indirect acting agonist
Mech: Increases cytoplasmic NE release
Misc: Tyramine is involved with an exchange transporter: tyramine goes in, NE comes out
Cocaine
Mech: Prevents NE reuptake
Thera: Local anesthetic, vasoconstrictor
Important SE’s: Insomnia, anxiety, arrhythmias
Guanethidine (Ismelin)
Class: Nerve ending blocker
Mech: False neurotransmitter (vesicles become full of guanethidine rather than NE)
Thera: Antihypertensive
Important SE’s: Many and serious
Misc: Don’t really use this in US; doesn’t cross BBB
Reserpine
Class: Nerve ending blocker
Mech: Release of empty vesicles (NE is not taken into vesicles b/c it binds uptake transporter and stops it)
Thera: Older antihypertensive
Important SE’s: Many and serious (depression and suicide are major ones)
Misc: Cheap! (used abroad, not here)
α-me-tyrosine (Metirosine)
Class: Nerve ending blocker Mech: Inhibit tyrosine hydroxylase (decreases NE synthesis) Thera: Pheochromocytoma Important SE's: Many and serious Misc: Still used for this
Ephedrine (Pretz-D)
Class: Mixed, direct (β2)/indirect agonist
Thera: Nasal decongestion, anorexic
