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262 Cards in this Set
- Front
- Back
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sacral efferents of PANS
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2,3,4
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PANS afferents project to which insular cortex?
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right
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SANS afferents project to which insular cortex?
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left
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small neurotransmitter biotransformed by
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specific enzymes
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large neurotransmitter transformed by
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nonspecific esterases
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VIP MOA
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enhance post-synaptic signaling of ACh on acinar cells
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VIP receptor
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M3>M1
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ACh synthesized by
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Choline acetyl transferase (ChAT)
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What inhibits ChAT?
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methyl mercury
(ChAT synthesizes ACh) |
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What concentrates ACh in the vesicles?
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vesicular ACh transporter (VAT)
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hemicholinium function
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inhibits choline transporter (takes back up to cell) so prolongs ACh activity
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RLS for NE synthesis
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tyrosine hydrolase (BH4 cofactor)
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tyrosine hydrolase product
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Levodopa
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How get levodopa to DA
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aromatic amino acid decarboxylase (AAAD)
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What does carbodopa inhibit?
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inhibits AAAD (prevents Levodopa --> DA)
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cofactor for AAAD?
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B6
(levodopa-->DA) |
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How get DA to NE?
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beta hydroxylase
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How get NE to EPI?
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phenyl-ethanolamine-N-methyltransferase
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Reserpine action
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inhibit vesicular monoamine transported (VMAT)--- so prevent NE concentration in vesicles
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NE biotransformation enzymes and product
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COMT and MAO A and B (catechol-O-methyl transferase and monoamine oxidase)
product= vanilla-mandelic acid (VMA) |
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What inhibits NET (NE reuptake)?
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pressor amine, tyramine, amphetamine, antidepressants, cocaine (allosteric regulation)
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What synthesizes EPI?
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phenyl-ethanolamine-N-methyl transferase
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DA unique function
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vasodilation while enhancing inotropy---inc contraction force
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DA use in clinic
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severe blood loss, some types of shock
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small intensely fluorescent cells
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hold DA, in paravertebral column, modulate SANS
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Nn and Nm MOA
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inotropic, inc Na+ channel conduction
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M1,3,4,5 effect on cell
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enhance intracellular Ca2+, reg IP3 and DAG (like alpha 1)
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M2 MOA
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open K channel, inhib adenylyl cyclase
(myocardium and CNS) |
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alpha 1 effect on cells
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inc Ca2+, reg IP3 and DAG
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alpha 2 effect on cell
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inhibit adenylyl cyclase, reduce future NE release
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Beta 1 effect on cell
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enhance adenylyl cyclase (heart, presynaptic ACh)
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Beta 2 effect on cell
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enhance adenylyl cyclase (smooth mm, some cardiac effect)
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Beta 3 effect on cell
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enhance adenylyl cyclase (lipocytes)
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Bethanecol MOA
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full agonist M1-M3
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Bethanecol effects
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inc secretions, smooth mm contraction, dec HR
(nonspecific cholinomimetic M1,2,3) |
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Pilocarpine effects
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muscarinic --- inc secretions, smooth mm contraction, reduced HR
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Pilocarpine clinical use
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glaucoma
(muscarinic agonist) |
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Pilocarpine toxicity
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bronchospasm
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Iobeline MOA
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full agonist at Nn and Nm
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Iobeline effects
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activate PANS and SANS
activate striated mm (nicotinic agonist) |
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mechanism for nicotine and smoking addiction
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smoke release MAOI = inc DA, NE, 5HT = dependence and euphoria
DA primary mediator of initial addiction Nicotine inc DA by hitting alpha4beta2 Nn receptors on presynaptic DA terminals |
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Varenicline (chantix) MOA
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Partial agonist at alpha4beta2 nicotinic—feeds addiction but don’t get full addictive effects of DA
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Indirect-acting cholinomimetics=?
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mainly AChEI’s
(indirect means stimulate release or inhibit reuptake) |
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Butyrylcholinesterase
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Aka pseudocholinesterase
Break down direct cholinomimetics (bethanechol, carbechol, methacholine) only thing that breaks down succinylcholine |
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3 classes of AChEI’s
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1alcohol –edrophonium
2carbamates- neostigmine 3 organophosphates and nerve gases |
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2 carbamates
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neostigmine (pyridostigmine), physostigmine
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organophosphates and nerve gases
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echothiophate, parathion, malathion
sarin, soman, and VX |
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edrophonium MOA
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(alchohol AChEI)
compete with ACh to bind AChE |
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neostigmine, physostigmine MOA
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carbamate AChEI
processed like ACh but 2nd carbamoylation step is slowed |
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organophosphates MOA
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phosphorylate esteric site of AChE
(echothiophate, parathion, malathion) |
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nerve gases
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sarin, soman, and VX
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pralidoxime action
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treat nerve gas ----regenerate AChE after nerve gas
binds esteric site during aging |
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Why some organophosphate ok for humans but not insects and fish?
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humans rapidly inactivate the dangerous intermediate
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nootropics and AD
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specific AChEI’s--- less peripheral side effects
treat ACh loss in AD list---- tacrine, donepezil, rivastigmine, galantamine |
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Tacrine
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Nootropic AChEI—treat AD
short duration reversible inhibitor at choline site |
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Donepezil
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Nootropic AChEI –treat AD
Noncompetitive, reversible Sleep disturbances Eliminated renally |
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Rivastigmine (exelon)
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Nootropic AChEI- treat AD
Pseudo-irreversible competitive |
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Galantamine (reminyl)
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Nootropic AChEI—treat AD
Reversible Lo potency Noncompetitive Nn agonist |
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What AChE’s do nootropics prefer?
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G1 and G4 (most common in brain)
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SLUDGEM (muscarinic effects)
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Salivation------ M3>M1, VIP
Lacrimation--------- M3 Urination-----detrusor has mostly M2, contraction = M3 Defecation----sacral efferents thru M3 receptors GI upset---------inc peristalsis and secretions, 5HT and other large nt’s reg myenteric plexi Emesis-----------stim cholinergic receptors = vomiting Miosis------M3 activation |
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Brainstem areas involved in emesis
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Area postrema (aka CTZ)
Vagal nuclear complex Reticular formation (at vomiting center) Vestibular complex |
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What receptors in the CTZ?
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CTZ has muscarinic receptors but DA and 5HT receptors predominate
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ACh and vomiting
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Direct and indirect cholingergic agonists inc afferents to CTZ → projections to vomiting center in medulla
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Vestibular apparatus role in vomiting
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R-L mismatch = vomit
(if cholinergics differentially stimulate VA, then vomit) |
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Why cyclosporine treat dry eye?
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Calcineurin inhibitor, block IL2
Reduce inflammation that contribs to dry eye |
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Lymphocytic infiltration in exocrine glands = what disease?
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Sjogren’s
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SICCA symptoms
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Xeropthalmia
Xerostomia Parotid gland enlargement (sjogren’s) |
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Extraglandular symptoms of Sjogrens
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raynauds, pulm disease, GI, leukopenia, anemia, neuropathy, vasculitis
RTA, lymphoma |
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2ary sjogrens assoc with
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SLE, RA, scleroderma
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Miosis receptor
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M3 stim = miosis and accom
M2 stim inhibits counteracting SANS by reducing NE release |
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Chronotropic, inotropic, dromotropic
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HR, strength of contraction, conduction speed of AV node (rhythm)
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Cardiac effects of muscarinics
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neg chronotropic
neg inotropic neg dromotropic ^baroreflex masks these^ |
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ACh on M3 (cardiovascular)
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NO release = vasodilation
-transient reduction in BP (reduced in vascular disease! ☹) |
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ACh on M2 (cardiovascular)
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Inc K current in SA and AV nodes and atrial mm
Reduce slow inward Ca2+ |
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M3 stimulation in asthmatics
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BAD!
Smooth mm contraction-bronchi Inc secretion |
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Body temp up or down w/ muscarinics?
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DOWN
Inc eccrine secretion |
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Edrophonium
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Short-acting AChEI (alcohol)
Use to diagnose Myasthenia Gravis (tensilon test) |
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Pyridostigmine (neostigmine)
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AChEI= indirect-acting agonist
carbamate MG treatment |
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Indirect-acting NE agonist MOA
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Stimulate release of NE or inhibit reuptake
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Succinylcholine
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AChEI
Depolarization blockade for paralysis in surgery |
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AChEIs effect on curare-like drugs
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reverse curare-like drug NMJ blockade in surgery
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Why tolterodine (detrol) and drugs like it used in urinary incontinence?
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M3 antagonist= prevent detrusor contraction
(Oxybutin too) |
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Muscarinic antagonist prototype and MOA
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Atropine
Traps ACh M receptor in inactive state |
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Clinical use for muscarinic antagonist
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GI
COPD Opthalmic exams Urinary incontinence Reverse cholinomimetics (anesthesia) Motion sickness Mushroom poisoning (counteract muscarine) (atropine) |
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Ipratropium and glycopyrrolate for asthma
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M3 antagonist
Quaternary –don’t cross BBB Reduce secretion and dilates bronchi |
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How are nightshade and Jimson Weed toxic?
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contain atropine
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Antimuscarinic overdose
hot as a hare... |
Hot as hare –eccrine glands inhibited
Blind as a stone---block muscarinic-mediated accommodation Mad as a hatter---delusions w/ hallucinations, confusion, worsen AD Dry to the bone---no spit, tear, or sweat, no bowel sounds |
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Why atropine and scopolamine before surgery?
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Musc antag
-Reduce airway secretions -Some amnesia -Urinary retention and GI hypomotility post op |
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Scopolamine patches
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Lipid soluble
(M3 antagonist) Treat motion sickness because vestibular system uses cholinergic fibers in its projections |
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Contraindications for antimuscarinics
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Glaucoma
Obstructive GI Urinary probs Intestinal atony |
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Why need NMJ blockers in surgery?
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Anesthetics are OK mm relaxers, but would up the dose for enough relaxation---cant cuz narrow TI
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2 classes of NMJ blockers
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nicotonic antagonist (d-tubocurarine)
depolarization blockers (succinylcholine) |
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nicotinic antagonists
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(NMJ blockers)
d-tubocurarine atracurium pancuronium rocuronium |
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d-tubocurarine MOA and effects
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competitive antagonist at NMJ w/surmountable affinity
dose dependent weakness →flaccid paralysis |
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d-tubocurarine toxicity
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(nicotinic antagonist)
respiratory compromise hypotension (histamine release) |
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How d-tubocurarine produce hypotension?
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induce histamine release
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d-tubocurarine PK
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poorly lipid soluble = only peripheral effects
(prototypical NMJ blocker- nicotinic antagonist) |
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succinylcholine MOA
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hyperstimulate NMJ
full and specific agonist for Nm receptor phase 1 and 2 ----1= occupy receptor, 2= desensitization |
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succinylcholine toxicity
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minimal
paralysis, hypotension (histamine release), inc intraocular pressure, hyperkalemia |
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succinylcholine contraindications
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glaucoma and burn patients
(intraocular pressure and hyperkalemia) |
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3 NMJ toxins
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alpha-bungarotoxin-------snake venom, inhibits NMJ like curare
alpha-latrotoxin-------widow spiders, depolarization blockade like succinylcholine tick venom---------fusion of synaptic vesicles and inhibit release |
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ganglionic blockers
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mecamylamine, hexamethonium, trimethaphan
blocks all ANS outflow |
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which ganglionic blockers don’t cross the BBB?
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Hexamthonium and trimethaphan
(mercamylamine does) |
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3 NMJ toxins
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alpha-bungarotoxin-------snake venom, inhibits NMJ like curare
alpha-latrotoxin-------widow spiders, depolarization blockade like succinylcholine tick venom---------fusion of synaptic vesicles and inhibit release |
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dibucaine number
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assess genetic of butrylylcholinesterase
normal= 80% inhibition If lower than 80, could have extended desensitization blockade |
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NE vs EPI at various receptors
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NE alpha1=alpha2>beta1>>>>beta 2
EPI alpha1=alpha2<beta1=beta2 |
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ganglionic blockers
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mecamylamine, hexamethonium, trimethaphan
blocks all ANS outflow |
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which ganglionic blockers don’t cross the BBB?
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Hexamthonium and trimethaphan
(mercamylamine does) |
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DA effect on renal and heart
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Vasodilate renal aa
Direct inotropic effects Use in shock bc inc mm contraction and maintain blood flow to kidneys |
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Alpha 1 agonism on eyes
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Mydriasis (pupillary dilator contraction)
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dibucaine number
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assess genetic of butrylylcholinesterase
normal= 80% inhibition If lower than 80, could have extended desensitization blockade with succinylcholine (careful with anesthesia!) |
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NE vs EPI at various receptors
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NE alpha1=alpha2>beta1>>>>beta 2
EPI alpha1=alpha2<beta1=beta2 |
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Alpha 1 agonism on bladder
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Trigone and sphincter contraction = urinary retention
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Alpha1 agonism on apocrine sweat glands
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Inc sweat (stress sweat)
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DA affect on renal and heart
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Vasodilate renal aa
Direct inotropic effects Use in shock bc inc mm contraction and maintain blood flow to kidneys |
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Alpha 1 agonism on penis and seminal gland
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Ejaculation
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Alpha 1 agonism on eyes
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Mydriasis (pupillary dilator contraction)
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Alpha 1 agonism on bladder
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Trigone and sphincter contraction = urinary retention
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Alpha1 agonism on apocrine sweat glands
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Inc sweat (stress sweat)
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Alpha 1 agonism on penis and seminal gland
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Ejaculation
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Pralidoxime regenerates….
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AChE after exposure to nerve gas
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What are Bethanecol, carbechol, and methacholine?
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direct acting cholinomimetics
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Pilocarpine vs muscarine
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Pilocarpine = tertiary, crosses BBB
(both muscarinic agonists) |
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Iobeline= prototypical....
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nicotinic agonist
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Alpha1 agonism on adipose tissue
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Glycogenolysis and gluconeogenesis
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Alpha1 agonism on arrector pili mm
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Contraction
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Alpha 1 action in the cell
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GPCR, inc Ca2+ current regulate IP3 and DAG
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Alpha 2 action in the cell
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Inhibit adenylyl cyclase, dec cAMP via Gi
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Alpha 2 autoreceptors vs heteroreceptors
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Autoreceptors- reduce further NE release
Heteroreceptors- reduce ACh and other nt’s |
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Alpha 2 agonism effects (4)
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(reduce NE release)
Platelet aggregation Mild vasoconstriction urinary urgency reduce aq humor production |
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Alpha1 subtypes
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1A,1B,1D
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Alpha2 subtypes
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2A, 2B, 2C
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How beta receptors affect cells?
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B1,2,3 activate adenylyl cyclase, inc cAMP via Gs
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Beta1 agonism effects on heart
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+inotropy, +chronotropy, +dromotropy
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Beta1 agonism effects on renin secretion
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Inc renin release via effects on juxtaglomerular cells
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Beta2 effects on liver
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Glycogenolysis
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Beta3 agonism
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Fat lipolysis
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How alpha2 stimulation affects beta’s effects?
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Alpha2 reduces NE release
NE attenuates beta effects So alpha2 increase beta effects |
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Low vs High levels of SANS
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Low = release NE = more alpha effects
High= release EPI = full beta 1 and 2 stimulation + alpha effects |
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How do arrestins alter receptor function?
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allow ligation of clathrin and clathrin adaptor proteins
Internalization and downreg receptors |
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Prototypical alpha1 agonist
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phenylephrine
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Phenylephrine MOA
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Prototypical alpha 1 agonist (competitive)
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Phenylephrine clinical use
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-Most widely used decongestant
-Inc BP after anesthesia (HR dec tho bc baroreflex) -Treat wide angle glaucoma |
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Phenylephrine effects
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decongestant
smooth mm contraction htn treat priapism- reverse ED drugs induce mydriasis (alpha 1 agonist) |
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Phenylephrine contraindications
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narrow angle glaucoma
htn aneurysm |
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Phenylephrine toxicity
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htn crises→dissecting aneurysm
high dose = seizure |
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Pseudoephedrine vs phenlyephedrine
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pseudoephedrine =
higher CNS effects used to make meth |
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Drugs to manage hypotension
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phenylephrine, midodrine, methoxamine
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Why alpha2 agonist classified as sympatholytic?
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reduce NE release
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Alpha2 agonists
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clonidine, methyldopa, guanfacine, guanabenz
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Alpha 1 agonists
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phenylephrine
pseudoephedrine midodrine methoxamine |
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Beta nonselective agonist
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isoproterenol
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Beta1 selective agonist
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dobutamine
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Beta 2 selective agonists (6)
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albuterol
terbutaline metaproterenol pirbuterol salmeterol formoterol |
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Clonidine MOA
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alpha2 agonist ---reduce NE release
oral = centrally acting antihypertensive IV or topical= mild vasoconstriction eyedrops = reduce aq humor production |
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Clonidine clinical
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(alpha2 agonist)
-Treat CNS effects of ADHD -treat CNS anxiety of opiate withdrawal -antiHTN -sedation -drops for glaucoma (open and closed) |
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Why alpha 2 agonist produce nasal congestion?
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vasoconstriction →constrict venous sinusoids = nasal congestion
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Isoproterenol MOA
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Direct-acting competitive beta 123 agonist (nonspecific)
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Isoproterenol clinical
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asthma
competitive beta agonist (heart= +ino,dromo,chrono, kidney= inc renin, vasc= dilate, gut=dec tone, detrusor=relax, mm=inc contractility, liver= glucoeno, glycogenolysis |
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isoproterenol toxicity
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initial inc BP→dec HR→arrythmia
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Baroreceptors location and CNS transmission
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Aortic arch→vagus nn
Carotid sinus→glossopharyngeal nn |
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Dobutamine MOA
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Beta 1 agonist
(some alpha effects cuz racemic) |
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S-isomer of beta2 agonists
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Inactive, maybe proinflammatory
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B2 agonist PK
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Max effect w/in 10-15min and lasts 3-4days
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2nd generation beta2 agonists
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salmeterol and formeterol
(last up to 12 hrs) |
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Terbutaline mode of administration
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subQ (use w/ epi pens)
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EPI effects on BP
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Complex bc hits all receptors + reflexes = initial inc in BP
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EPI effects on HR
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Increase in vagal tone, but still inc HR
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EPI effects on pulse pressure
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Inc, followed by reflexive decrease = cancel out to slight inc or normal pulse pressure
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2types of indirect-acting NE agonists
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amphetamine-like and cocaine-like
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Amphetamine-like structure
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Similar structure to catechol
Prevents direct action at adrenergic receptors bc missing hydroxyl group |
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Amphetamine-like effects
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Inc HR and TPR
Readily crosses BBB (complex CNS effects) |
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Amphetamine-like MOA
3 fold NE agonist |
-structure looks like NE and DA
-competitive reuptake inhib (inc synaptic pool of NE, DA>5HT) -substrate for NET (Ca2+ indep release) |
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Amphetamine-like clinical
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ADHD
Sometimes for narcolepsy—improve attn and reaction time, inc motor activity (reduce appetite, inc body temp, inc RR) |
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Amphetamine-like toxicity
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-dependence
-stimulant vasculitis= vasocon→ischemia (esp bowel) -CNS tox -Hyperthermia -Metabolic acidosis |
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Death from amphetamine
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Metabolic acidosis +hyperthermia
(rare cuz of ceiling effect) |
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Amphetamine ceiling effect
|
dose inc→mobile pool competes for access to pump →reduce Ca indep release
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amphetamine vs methamphetamine
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-meth greater CNS effects
-meth becomes amphet in liver -meth has more 5HT effects -meth easier to smoke,snort,inject |
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Ephedrine
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amphetamine-like NE agonist
active ingredient in Ma Huang NE>DA |
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why use pseudoephedrine in cold medicine?
|
because counteract drowsiness of antihistamines
(amphetamine-like NE agonist) restricted cuz use it for meth |
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Why phenylpropanolamine off market?
|
BP shot up = strokes
(amphetamine-like NE agonist) |
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Phenmetrazine
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amphetamine-like NE agonist
less potent than DA |
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Methylphenidate
|
amphetamine-like NE agonist
DA>NE |
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Amphetamine-like NE agonists
|
Ephedrine
Pseudoephedrine Phenylpropanolamine Phenmetrazine Methylphenidate Modafinil Tyramine |
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Cocaine-like drugs MOA
|
NE agonist
Cocaine binds allosteric regulatory site on re-uptake pumps Noncompetitive reuptake inhibition Inhibit NET w/o acting as ligand for transport proteins |
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Amphetamine-like vs cocaine-like
on Ca2+ independent release |
Cocaine --NE not transported in mobile pool -- does NOT facilitate Ca indep release
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Cocaine vs amphetamine effects
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Cocaine –potentiates actions of nt’s that r released (cant induce release alone like amphet)
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Cocaine toxicity
|
‘caine’ properties
NE vasoconstriction limits bioavailbility (alpha effects on nasal mucosa) perf septa= from stimulant vasculitis high dose= arrythmia , seizure, stroke, death |
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Cocaine PK
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short ½ life (~30 min)
cleared by liver extensively |
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Benzoyl Ecgonine
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cocaine metabolite
detectable in urine for several days |
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primary cause of cocaine death
|
arrythmia or seizure
|
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Atomoxetine MOA and clinical use
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selective NE reuptake inhibitor
management of ADHD |
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Calcium independent release
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NET carries transporter into cytosolic side of membrane
‘Mobile pool’ ligands (NE,DA,5HT) bind at cytosolic side Transported out into ‘synaptic pool’ Does not involve release of vesicular pool! (ca dependent) |
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Prazosin MOA and effects
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Alpha 1 selective antagonists
Vascular effects (contraction), orthostatic hypotension |
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How tamsulosin treat BPH?
|
Alpha 1 antagonist
prefers the alpha 1A and 1D alpha1D predominant in prostate |
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Alpha 1 agonists
|
phenylephrine
pseudoephedrine midodrine methoxamine |
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Alpha 1 antagonists
|
prazosin and tamsulosin
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Alpha 2 antagonist
|
yohimbine
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Yohimbine MOA
|
Alpha 2 selective antagonist
Bind alpha autoreceptor →block NE neg feedback Inc SANS activity (^beta and alpha1 tone) |
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Why alpha 2 agonists work with high SANS activity?
|
Alpha 2 agonists reduce NE release, if low NE then don’t see the effect
High SANS in vasculature and urinary bladder—alpha2 agonist = vasodilation and urinary urgency |
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3 nonspecific alpha antagonists
and clinical use |
phenoxybenzamine (covalent)
phentolamine and tolazoline (reversible) ^use to manage pheochromocytoma^ |
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EPI reversal
|
Give EPI after propanolol
Inotropic effects cancel out HR no longer inc BP still elevated tho because vasoconstriction not blocked (alpha1) |
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Propanolol clinical use (5)
|
Dec arrythmia (dromotropy effects)
Migraine prophylaxis Off-label for stage fright Sedation Angina |
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Why pranolol reduce angina?
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Negative inotropy and chronotropy = less O2 demand
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Why propanolol contraindicated for asthma pt’s?
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Block beta2 = lose bronchiole tone = increased airway resistance
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Why have to be careful with T1DM and propanolol?
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1-Beta 2 block= reduces glucagon’s responsiveness to hypoglycemia
(remember beta 2 agonism = ^glucagon →glycogenolysis) 2-And if you do have insulin-induced hypoglycemia, u get tachycardic, a beta blocker will mask this red flag! |
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Why propanolol bad for pt w/ high cholesterol?
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beta 2 block = inc VLDL and cholesterol
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Propanolol effects on TPR and renin release
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inc TPR (lose vasodilation)
reduce renin release (beta1 blockade) |
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2 drugs for migraine prophylaxis
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Propanolol (beta blocker)
Methysergide (5H2 serotonin antagoinst) |
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2 prototypical beta1 selective antagonists
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atenolol
metaprolol |
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phenoxybenzamine
MOA |
alpha antagonist
covalent =nonsurmountable bind alpha1>>>alpha2 |
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Nadolol MOA
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nonselective beta blocker
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Timolol MOA and clinical use
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nonselective beta blocker
no local anesthetic effects treat htn reduce intraocular pressure in glaucoma |
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Pheochromocytoma – site and secretion
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-Adrenal medulla neuroendocrine tumor
-Sympathetic paraganglioma of chromaffin cells - Hypersecretion of catecholamine |
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Pheochromocytoma triad of symptoms
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Episodic headaches
Diaphoresis Tachycardia |
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Esmolol MOA and clinical use
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Beta 1 selective antagonist (but not absolute)
Ultrashort acting – use in ICU for arrythmias |
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Pheochromocytoma treatment
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Nonspecific alpha antagonists—phenoxybenzamine (long), phentolamine and tolazoline (short)
Phentolamine= use for surgery on the tumor Phenoxybenzamine= reduces bp |
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Pindolol= prototypical....?
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Partial agonist at beta 1 and 2
Surmountable with high SANS activity |
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Carvediol= prototypical....?
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mixed antagonist
Block beta and alpha1 receptors |
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Difference in MOA of guanethidine and reserpine
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Guanethidine= NE depletor
Reserpine= peripheral and central depletion of NE, DA, 5HT |
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Reserpine clinical use
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-Depletion of central DA = treat chorea, HD, tardive dyskinesia, (produce parkinsonian symptoms)
-profound hypertensive (lasts for days) |
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Reserpine side effects
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depletion NE and 5HT= depression
deplete DA = parkinsonian symptoms |
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predominant tone in lacrimal glands
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PANS
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action at what receptors increases tears?
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alpha1, M3
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predominant tone in radial/sphincter muscles
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none
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receptors for near and far vision?
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M3 agonism= near vision
beta2 agonism= far vision |
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Pilocarpine and glaucoma
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M3 agonism increases aq humor outflow
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Timolol and glaucoma
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beta blocker, reduces production of aqueous humor
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Dorzolamide
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carbonic anhydrase inhibitor, treat glaucoma cuz reduce aq humor production
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Primary regulator of vascular tone in CNS
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CO2 and other local molecules from neurovascular unit
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Meibomian glands
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produce oil for tears
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PGF2a agonists
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latanoprost and travoprost
facilitate outflow of aq humor through the unconventional pathway |
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rebound congestion
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major problem with alpha1 agonists
desensitization after a few days |
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drugs that make you stuffy
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alpha1 antagonists
alpha 2 agonists (clonidine) trimethaphan |
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Ciclesonide
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aka omnaris
prodrug (to des-ciclesonide) glucocorticoid agonist |
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alpha1 in dayquil or nyquil?
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dayquil!
alpha1 in CNS= promote wakefulness |
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2 reasons antihistamines make you drowsy
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bind muscarinic receptors in CNS and bind H1 receptors (both make you sleepy!)
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predominant tone in salivation
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PANS (M3>>M1 w/ VIP)
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SANS effects on salivation
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alpha1 and beta1 activation = thick secretions, experienced as xerostomia but inc secretions...
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M3 antagonist effects on salivation
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xerostomia
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airways patency and secretion receptors
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caliber = B2 (mediated by circulating EPI)
secretion= M3 |
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predominant tone in bronchiole smooth mm
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SANS mediated by EPI (no direct SANS innervation)
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M3 agonism on heart
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Decreases chronotropy
Less effect on inotropy and dromotropy |
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M3 antagonism on heart
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Markedly increased chronotropy
Less effect on inotropy and dromotropy |
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Primary tone in vessels
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SANS
(5HT and angiotensin etc) |
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alpha1 agonist effect on diastolic pressure
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inc (vasoconstriction)
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what drug class causes orthostatic hypotension?
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alpha1 antagonists
(block NE release, prevent baroreceptor reflexive inc in TPR) |
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beta2 agonist on BP
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reduce (vasodilate skeletal mm pool) mainly drop diastolic pressure (?)
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ANS effects on coronary blood flow
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indirect
Beta 1 agonism inc heart’s work, therefore 2ary inc in coronary blood flow |
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Local control of coronary blood flow via what 2 substances
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NO and adenosine
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predominant tone in sweat glands
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SANS, but ACh effector
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Nn agonists and sweating
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stimulate sweating
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predominant tone in ENS
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PANS
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M3 agonists on GI
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inc motility
inc secretion in stomach/ intestines relax sphincter tone ^deranged motility diarrhea (antagonist = constipation) |
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bladder tone
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PANS = predominant
SANS= trigone |
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beta2 agonism on detrusor
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relaxation
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M3 agonism and tumescence
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stimulate
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How sildenafil citrate treat ED?
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phosphodiesterase 5 inhibitor
PDE5 breaks down cGMP=detumescence (inhibit cGMP break down maintains boners) |
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alpha1 antagonist effect on ejaculation
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inhibits
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Alpha1 agonist on spleen
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inc spleen capsule for more blood
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Beta2 agonism on skeletal mm
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enhance skeletal mm contractility, stim glycogenolysis
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list drugs that cross BBB
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mercamylamine (ganglionic blocker)
pilocarpine (muscarinic agonist) amphetamine-like drugs (NE agonist) nicotine lobeline physostigmine clonidine |
