ANS Flashcards
1
Q
What are the receptor types in the parasympathetic division?
A
Muscarinic (M2, M3, and M) and Nicotinic (Nn and Nm)
2
Q
Where can M2 receptors be found? Cholinergic nerve response at each site?
A
SA node- decrease HR, AV node- decrease conduction velocity, Atria and Ventricles- decrease contractility
3
Q
Where can M3 receptors be found and the cholinergic nerve response at each location?
A
VSM- constriction, Endothelium- NO, dilation, Bronchial muscles- constriction, Bronchial glands- secretion, GI- increase motility/tone, relax sphincters, and increase proton pump secretion, Detrusor- contraction, Trigone & sphincter- relaxation, Penis- erection, Eye sphincter- contraction (miosis), Ciliary muscle- contract (focus near), and Salivary glands- salivation
4
Q
Where can the M receptor be found? cholinergic nerve response?
A
sweat glands, sympathetic response, perspiration
5
Q
Where can Nn receptors be found? Cholinergic nerve stimulation response?
A
autonomic ganglia, EPSP
6
Q
Where can Nm2 receptors be found? Cholinergic nerve stimulation response? What part of nervous system?
A
skeletal muscle contraction, somatic system
7
Q
what are the sympathetic system receptors?
A
M, Nn, Nn2, B1, B2, B3, A1, A2
8
Q
Where can M receptors be found? What is their cholinergic nerve response?
A
sweat glands, perspiration, sympathetic
9
Q
Where can Nn2 receptors be found? Cholinergic nerve stimulation?
A
adrenal medulla, epinephrine release
10
Q
Where can B1 receptors be found? What is the response to adrenergic nerve stimulation?
A
SA node- increased HR, AV node- increased conduction velocity, atria and ventricles- increased contractility, Kidney- increased renin release
11
Q
Where can B2 receptors be found? What is the response to adrenergic nerve stimulation?
A
skeletal muscle BV- dilation, bronchial muscle- dilation, detrusor- relaxation, ciliary muscle- relax (focus far), uterus- relaxation, liver- glycogenolysis
12
Q
Where can B3 receptors be found? What is the response to adrenergic nerve stimulation?
A
detrusor muscle- relaxation
13
Q
Where can A1 receptors be found? What is the response to adrenergic nerve stimulation?
A
BV- constriction, Trigone & sphincter- contraction, penis- ejaculation, radial muscle- constriction (mydriasis), uterus- contraction
14
Q
Where can A2 receptors be found? What is the response to adrenergic nerve stimulation?
A
adrenergic neurons- decreased transmitter release (- feedback)
15
Q
What action on what receptor does mecamylamine have?
A
non-competitive antagonist of Nn, blocks PNS and SNS postganglionic, reveals dominant ANS controlling the tissue
16
Q
What are the tissue responses seen with mecamylamine? which tissues are SNS dominant? PNS dominant?
A
arterioles-dilate (S), veins- dilate (pooling, S), heart tachycardia(PS), iris- mydriasis (PS), ciliary- cycloplegia (blurred vision, PS), GI- constipation (PS), Bladder- urine retention (PS), salivary glands- dry mouth (PS), sweat glands- increased body temp (S)
17
Q
What is the mechanism and site of action of onabotulinum toxin?
A
inhibitor of Ach release, taken into neuron terminal via receptor mediated endocytosis, inactivates SNAP-25 required for docking of vesicle with presynaptic membrane; temporary cholinergic denervation,
18
Q
What is the drug action, therapeutic use and side effects of onabotulinum toxinA?
A
flaccid paralysis of skeletal muscle, softens facial wrinkles, relaxes spasms, inactivates sweat glands; muscle spasms/dystonia (strabismus, blepharospasm, cervical dystonia), cosmetic, axillary hyperhidrosis, overactive bladder; dysphagia and difficulty breathing if spreads beyond injection site, ptosis, pain, allergic rxn rare
19
Q
What type of signaling is utilized by M1 (CNS, ganglia) and M3 (smooth muscles, glands endothelium) receptors? general response?
A
Gq->PLC->inc IP3 + DAG-> inc Ca2+ + PKC; excitation/contraction/secretion
20
Q
What type of signaling is utilized by M2 (heart) receptors? General response?
A
Gi-> dec cAMP; K+ efflux-> hyperpolarization; cell inhibition
21
Q
What is the prototype agonist for M1-M5 receptors? What is the prototype antagonist?
A
muscarine; atropine
22
Q
What is the prototype agonist for Nn receptors? Antagonist?
A
nicotine (high affinity, followed by desensitization), mecamylamine
23
Q
What is the prototype agonist for Nm receptors? Antagonist?
A
nicotine (low affinity, stimulation phase obscured by desense and muscle paralysis), dtubocurarine (non-depolarizing competitive neuromuscular blockade)
24
Q
What is the function and location of BuChE?
A
drug metabolizer of choline esters and AChE inhibitors, plasma, glial cells and liver; if deficient can cause succinylcholine induced apnea
25
Describe the progression of catecholamine synthesis including location. What is the rate-limiting step of all of these? What increases synthesis of EPI? how?
NE formed in adrenergic postganglionic neurons (Tyr->DOPA->DA-> active transport from cytosol to vesicle->NE); DA in basal ganglia of CNS (Tyr->DOPA->DA), EPI in adrenal medulla (Tyr->DOPA->DA-> act trans to vesicle-> NE-> leak to cytosol->EPI) RLS= tyrosine hydroxylase (Tyr->DOPA); glucocorticoids (inc PMNT)
26
Why are catecholamines stored in vesicles? How do they get there?
protect from MAO degradation, VMAT-2 (vesicular monoamine transport-2)
27
What is the mechanism of action of reserpine? Therapeutic use? Side effects?
irreversible inhibitor of VMAT-2, prevents uptake of DA and recycled NE, and reuptake of leaked transmitters, loss of symp transmission-> dec Cardiac output, and TPR lowering BP; antihypertensive and antipsychotic; SE- sedation, unopposed cholinergic (cramping, diarrhea), psychotic depression
28
What is the mechanism of action of the A2 receptor?
Gi-> inhibition of Ca2+ influx; - feedback of NE release
29
What does tyramine do? Mechanism? source? bioavailability?
stimulate NE release; displaces NE from vesicles, non-vesicular release from nerve terminals via reverse transport thru NET;fermentation byproduct of tyrosine, aged cheese, beer/wine, soy/fish, sauerkraut/kimchee, cured meats; low oral bioavil. due to GI/hepatic MAO (except when on MAO inhibitors); high systemic=hypertensive crisis
30
What is the mechanism of action of methyldopa? Therapeutic use? Side effects?
A2 receptor agonist, A2 stimulation in CNS reduces SNS outflow to periphery (dec CO and TPR); gestational hypertension; SE- sedation, dry mouth, edema, hemolytic anemia (Coomb's test positive, rare life threatening, no explanation)
31
What is the mechanism of the receptor A1? A2?
Gq-> inc Ca2+ (SM contract), Gi-> dec cAMP (nerves)
32
What is the mechanism of the receptor B1? B2? B3?
Gs-> inc cAMP->PKA->Ca2+ channels (heart, kidney, excitation/contraction), Gs (relaxation, lung, skeletal muscle, uterus), Gs (lipolysis, relax, adipose, detrusor)
33
What is the mechanism of cocaine?
inhibitor of NE reuptake, CNS and periphery, excess NE in synapse following SNS activation
34
How are catecholamines metabolized? How are they targeted for diseases? Urine metabolite excreted?
MAO (mitochondria) deaminates catacholamines, tyramine, and histamine, clearing in nerve terminals, inhibitors for depression; COMT (cytosol, liver and kidney) o-methylates catechols, clearance of circulating, inhibitors for Parkinson's; VMA
35
What is the mechanism of amphetamines?
promotes NE release/inhibits reuptake (ADHD)
36
What are the pharmacokinetic/dynamic properties of ACh?
poor lipid solubility, short duration of action (BuChE), non-selective cholinergic actions (M + Nn) at multiple sites
37
What are the cardiovascular effects of ACh, receptor, and receptor action?
vasodilation- M3 vascular endothelium, Gq-> PLC-> IP3-> Ca2+/calmodulin induced NO release, diffusing into adjacent smooth muscle->relaxation; (-) chronotrope via M2, (-) ionotrope via decrease Ca2+, decrease AV and SA node CV
38
What happens when ACh is given in the presence of atropine? Why?
ACh-induced stimulation of sympathetic ganglia-> vasoconstriction, inc. HR; Atropine is M antagonist so counteracts all M receptor effects leaving only Nn effects of ACh
39
What is the ophthalmic use for ACh? Adverse effects?
inject into anterior chamber, rapid and complete miosis (drops not lipid soluble enough); cataract surgery, keratoplasty, iridectomy; ciliary muscle contraction opens trabecular meshwork increasing outflow of aqueous humor (reduce intraocular pressure); rarely systemic (bradycardia, hypotension)
40
What are the general properties of Choline esters? Alkaloids?
more selective and prolonged action; esters don't penetrate BBB but alkaloids do; used: bladder disorders, xrostomia and diagnosis of bronchial hyperreactivity, miosis and glaucoma
41
What are the properties and uses of bethanechol? Uses?
choline ester selective for bladder (detrusor) and GI M3, resistant to ChE, postoperative and postpartum urinary retention; orally for 3-4 days can avoid catheterization
42
What are the uses and properties of Methacholine?
inhalation-> diagnosis of hyperreactivity (asthmatics) targets bronchial M3; also used opth. for miosis and glaucoma
43
What are the properties and uses of pilocarpine? Uses?
prototype alkaloid; partial agonist of all M receptors; oral- for xerostomia induced by radiation or sjorgens syndrome (receptor reserve), salivary parenchyma must have residual capacity; topically- 2nd line for wide angle glaucoma, associated with ocular hypertension
44
What are the properties and uses of Cevimeline? Uses?
selective agonist for M1/M3 in lacrimal and salivary glands; sjogrens and xerostomia induced by radiation, longer duration and fewer side effects than pilocarpine
45
What are toxicity and contraindications for ChE and alakaloids? antidotes?
full range muscarinic effects possible, esp. excessive dose; sweating, hypotension, GI effects (cramps, diarrhea); contraindicated in hyperthyroidism (reflex tachycardia), asthma/COPD (M3 more reactive), and peptic ulcers (m3 increase gastric H secretion); AD- atropine (comp. receptor agonist) and epinephrine (physiological antagonist)
46
What is the chemical classification of atropine? mechanism of action? Pharmacokinetics? Tissue response general features?
belladonna alkaloid (henbane, jimson weed, deadly nightshade) very lipid souble; non-selective comp. antagonist of M (unopposed SNS, sufficiently high blocks N); readily cross BBB, blocks recepors in BV, sweat glands and CNS; effects dose dependent
47
What are the CNS effects of atropine?
mild excitation with small dose (differs from scopalmine), Toxic (>10) confusion, hallucinations, delirium resembling psychosis, associated with deceased cognition or dementia in elderly and Alzheimers
48
What are the ocular effects and mechanism of atropine? Dose effects are achieved?
mydriasis- photophobia, blockage of iris sphincter; cycloplegia- paralysis of accommodation, block ciliary muscle; both at 1-3mg dose
49
What are the cardiovascular effects and mechanism of atropine? Dose effects are achieved?
tachycardia- block vagal impulse to SA node M2 receptors (1-3mg), paradoxical and transient slowing of HR with <0.5mg dose (M1 autoreceptors), circulation- flushing effect (mechanism unknown, no indogenous ligand to block)
50
What are the respiratory effects and mechanism of atropine?Dose effects are achieved?
decrease bronchial secretions (0.3-0.8mg), relax bronchial smooth muscle; action most significant in respiratory disease pts. (M3 bronchial glands and smooth muscle)
51
What are the GI effects and mechanism of atropine? Dose effects are achieved?
inhibits salivation (0.3-0.8mg), reduced tone and motility (urinary too, 5mg), partially reduced acid secretion (10mg)
52
What are the therapeutic uses of atropine?
preoperative- reduce salivation and secretion; symptomatic sinus brady or AV block, mydrasis and cycloplegia have long duration of action, prevents muscarinic effects of therapeutic antiChE, antidote for organophosphate/carbamate or nerve gas poisoning
53
What are the adverse effects of atropine? contraindications? drug interactions?
antiCh- dry mouth, blurred vision, photophobia, tachycardia, GI distress, hot and dry skin, urinary retention, confusion; contraindicated in prostatic hyperplasia and narrow angle glaucoma, antidote- physostigmine (Cross BBB) counteract CNS and periphery; interacts w/ antihistamines, phenothiazines tricyclic antidepressants (additive anticholinergic effects but no effect on M receptors)
54
What are the features and uses of scopalmine?
better CNS penetration, sedative in low doses and euphoria in high doses; suppresses postoperative emesis and motion sickness by blocking M receptors in vestibular apparatus (atropine doesn't); prophylactic treatment of motion sickness (transdermal, better than Dramamine)
55
What are the features and uses of ipratropium bromide?
B2 dominant after drug; bronchodilator for COPD; limited absorption when inhaled, QAC (quaternary amine compound) + regardless of pH, direct to site of action
56
What are the features and uses of tropicamide?
mydriatic, cycloplegic- short acting, recovery 6 hours (atropine 7-12 days), facilitates diagnosis and surgery, blurred vision and photophobia common side effects of installation, can increase intraocular pressure
57
What are the features and uses of tolterodine?
non-selective M antagonist, used for OAB (urge incontinence), mechanism unclear, current evidence suggests increase in bladder capacity and decrease sensation of urgency by blocking basal release of ACh during bladder filling; may take 4 wks for full efficacy, less than 30% full continence, not effective for stress incontinence; drowsiness, dizziness, and confusion
58
What are the general features of antiAChE drugs? What are the classes?
decreased ACh breakdown by inhibition of AChE, enhance ACh effects, high enough doses can produce effects at all ACh NT sites (M, ganglia, Nm, or CNS); therapeutic doses usually limited to muscarinic and NMJ; reversible: Type 1 and 2 and irreversible
59
What is the prototype type 1 antiAChE? mechanism? duration?
edrophonium; bound to AChE by weak H bonding and ionic interaction, duration= 5-15min, not metabolized by AChE
60
What is the prototype type 2 antiAChE? mechanism? duration?
neostigmine; bound to AChE by an ionic bond and hydrolysable covalent bond at esteric site; duration 1-2 hours; binds similar to ACh but no action and longer to hydrolyze
61
What is the prototype for irreversible anti AChE? mechanism? duration?
organophosphorous compounds, stable covalent bond w/ AChE, active site serine-OH phosphorylated, ageing of phosphorylated intermediate can occur with loss of one alkyl group, once aged need de novo synthesis to breakdown ACh, duration 50 hours,
62
What are the pharmacologic effects of neostigmine? Metabolized? Use?
reversible type 2 antiAChE, muscarinic responses, NMJ resposnes (direct agonist)- low dose increases force of contraction, high toxic dose reduces force of contraction (desensitization), only inhibitor that is also agonist at NMJ, metabolized by AChE and BuChE; myasthenia gravis, reverse postop competitive NM block, worsen if depolarizing block used, postop bladder retention/distension
63
What are the adverse effects and contraindications of neostigmine?
excessive muscarine stim. (N/V, GI cramp, brady, treat with atropine), paralysis of diaphragm in toxic doses, CI similar to muscarinic (prostatic hyperplasia, narrow angle glaucoma)
64
What are the actions and uses of physostigmine?
similar to neo, cross BBB, not an AChR agonist; treat atropine poisoning and related muscarinic blockade (antihistamines, TCAs, phenothiazine antipsychotics), reverse peripheral and central
65
What are the actions and uses of donepezil? Adverse effects? Drug interactions?
reversible type 1 antiAChE; more selective inhibition of CNS isoform, treat cognitive decline in Alzheimers (dis- reduced cortical ACh synth. and impaired funct., drug improves cognition, not disease altering; mild diarrhea, N/V, bradycardia; DI- anticholinergics (tolterodine) antagonize cognitive effects,
66
What is and what drug is used for Tensilon test?
distinguish myasthenic crisis from cholinergic crisis; edrophonium will improve myasthenic symptoms and worsen cholinergic
67
What are the properties of echothiophate? duration? use? side effects?
prototype organphosphorus, quaternary nitrogen; 1-4wks due to irreversible AChE inhibition; lower intraocular pressure in wide angle glaucoma, associated with development of cataracts and systemic cholinergic effects
68
What are the properties of malathion? source? use?
highly lipid soluble, absorbed all routes including dermal; common source accidental and agricultural cholinergic crisis, chem warfare (sarin, tabun VX); use- head lice and ova; phosphorothioate parent compound inactive, oxidized by insect and mammalian CYPs to active malaoxon (S->O, more rapid in insects than mammals); detoxified in plasma to carboxyl-esterases (more rapid in birds and mammals than insects)
69
How are poisonings distinguished (Muscarinic, Nicotinic, CNS, ChE)?
M- profuse sweating, salivation, miosis, bronchorrhea/bronchospasm, involuntary urination and defecation, N/V; N- muscle weakness, fasciculations, paralysis (apnea, diaphragm); CNS- confusion, ataxia, convulsions, coma, respiratory depression; Apnea +REsp Center depression= Death!!; ChE- depressed activity is diagnostic, bound to agent
70
What are antidotes for anti-AChE?
atropine- counteracts M (antagonist), pralidoxime- reactivates AChE only at NMJ if administered before enzyme aging occurs; O2 and benzodiazepines (treat OP-induced seizures) are adjunctive therapies
71
What are the mechanisms of action of sympathomimetics?
direct acting agonists (not affected by reserpine); indirect acting (abolished by reserpine)- promotion of NE release, inhibition NE reuptake or inactivation by MAO/COMT; mixed acting (agonist plus promotes release, response reduced by reserpine)
72
What are the properties of catecholamines (sympathomimetics)?
not orally effective (give IV, SQ, Inh), short duration of action due to ENT removal from systemic or degradation by COMT; not lipid soluble enough to cross BBB
73
What are the properties of non-catecholamines (sympathomimetics)?
no catechol functional group (2 adjacent hydroxyls on benzene ring, so more lipid soluble and not hydrolized by COMT), oraly effective, long duration of action, CNS effects (lipid solubility)
74
What are some characteristics of receptor selectivity with sympathomimetics?
subtle structure changes produce marked changes in adrenergic receptor subtype selectivity, inversely related to dose and is relative not absolute,
75
What are the clinical applications of alpha 1 stimulation?
BV- vasoconstriction (skin, viscera, mucous membranes): hemostasis, nasal decongestion, prolong action of local anesthetics, and elevation of BP; Mydriasis without cyclopegia unlike anti-muscarinic ( A1 on radial muscle, M on sphincter and ciliary)
76
What are the clinical applications of alpha 2 stimulation?
CNS- antihypertensive via reduced CNS SNS outflow, autoreceptors (methyldopa, chlonidine); Eye- glaucoma, inc outflow of aqueous humor
77
What are the clinical applications of beta 1 stimulation?
heart- cardiac stimulation and treatment of shock- inc CO to maintain organ perfusion
78
What are the clinical applications of beta 2 stimulation?
bronchi- asthma/COPD, uterus- stop premature labor, use is controversial
79
what category is Epinephrine in? what receptors are activated? routes of administration?
prototype catecholamine; A1, A2, B1, B2, relatively non-selective; parenteral- sub Q, intracardiac, inhalation, topical
80
What are the cardiac effects and receptor types corresponding to effect for Epinephrine?
positive ionotropism and chronotropism (B1), increased SA node automaticity
81
What are the vascular effects and receptor types corresponding to effect for Epinephrine?
reduced cutaneous blood flow (A1), decreased (A1) or increased (B2) skeletal muscle blood flow (biggest effect on systemic BP), B2 predominates at low (physio) doses while A1 predominates at high (pharma) doses (higher B2 affinity but A1>B2 receptor density, increased coronary BF (NO), decrease renal BF (A1)
82
What are the respiratory effects and receptor types corresponding to effect for Epinephrine?
relaxation of bronchial smooth muscle (B2), desensitization (down regulation, tachyphylaxis) with repeated doses, B2 selective agents preferred for asthma treatment
83
What are the therapeutic uses of Epinephrine?
prolonged action of anesthetics (A1), treat anaphylactic shock (A1, B1, B2), asthma (B2, only OTC bronchodilator, removed due to CFCs), topical hemostasis (A1), cardiac arrest (B1, pulp fiction!!)
84
What are the adverse effects of Epinephrine and receptor corresponding?
hypertensive crisis- cerebral hemorrhage (A1), dysrhythmias (B1), angina pectoris in patients with atherosclerosis (A1, B1, heart outruns O2 supply), extravasation-induced necrosis (local dermal injections), and hyperglycemia in diabetics (B2)
85
What are the drug interactions with Epinephrine?
MAO inhibitors (phenelzine), tricyclic antidepressants (imipramine), general anesthetics (halothane), alpha and beta blockers (prazosin, propranolol) have to give higher dose of epi to have pharmacologic effects
86
What receptors does Norepinephrine stimulate? Catecholamine or non-catecholamine? route? effects? Use?
A1, A2, B1; C; IV infusion; similar to epi but lacking B2 responses; severe hypotensive states, preferred vasopressor for treatment of septic shock
87
What receptors does Isoproterenol stimulate? Catecholamine or non-catecholamine? route? effects? Use?
B1, B2; C; IM, IV; potent non-selective beta agonist, low affinity for alpha receptors; AV block and cardiac arrest, bronchospasm during anesthesia (rarely)
88
What receptors does Dopamine stimulate? Catecholamine or non-catecholamine? route? effects? Use?
D1>B1>A1 dose dependent receptor response; C: IV; CV- low- renal, mesenteric, coronary vasodilation (D1->Gs), med- inc CO by inc SV (B1), little or no inc HR, high- peripheral vasoconstriction (A1), renal effects- increased urine output, inc RBF dilating afferent and efferent arterioles, GFR mostly unchanged, diuretic- inc Na excretion; shock esp with low CO and compromised renal, maintain BP in hypotensive sepsis
89
What receptors does Dobutamine stimulate? Catecholamine or non-catecholamine? route? effects? Use? adverse effects?
B1; C; IV infusion; cardiac- increase contractility and HR (inc CO), less reflex tachycardia due to lack of vascular B2 stim.; cardiac stimulant approved in short term treatment of severe refractory CHF an cardiac stress (ischemia) testing; effect intensified by MAOIs (90% dose reduction needed), contraindicated in ischemic heart disease (angina or MI, watch closely)
90
What receptors does Phenylephrine stimulate?Catecholamine or non-catecholamine? route? effects? Use? toxicity?
A1 (NC); topical, nasal, oral, ophthalmic; CV- marked vasoconstriction; Nasal deconsgestant, vasopressor, mydriatic, detumescent (Viagra antidote injection); reflex brady (dec CO), excitability, restlessness, hypertension, overdose- vomiting, hypertension, palpitations, arryhtmias
91
What receptors does Clonidine stimulate? Catecholamine or non-catecholamine? route? effects? Use? adverse effects?
A2; NC; oral, transdermal; similar to methyldopa but a direct agonist not pro-drug, red SNS outflow from CNS to heart (brady) vasoconstriction, poss activation peripheral presyn. A2 that suppress NE release; hypertension, relief severe pain (epidural transfusion); brady, dry mouth, sedation, rebound hypertension upon abrupt withdrawal
92
What receptors does Terbutaline stimulate? Catecholamine or non-catecholamine? route? effects? Use? adverse effects?
B2; NC; oral, inhalation; CV- little effect due toB2 selectivity; reduce airway resistance in asthmatics/COPD, off-label- suppresses premature labor by relaxing uterine smooth muscle; tremor, hyperglycemia, tachycardia at high doses, adverse CV events and death in pregnant women
93
What receptors does Mirabegron stimulate? Catecholamine or non-catecholamine? route? effects? Use? adverse effects? Contraindications?
B3; NC; oral; relaxes detrusor, modestly effective and without cholinergic effects; GI (Nausea, diarrhea/ constipation), tachycardia, urinary retention, increased BP; inhibits CYP2D6, muscarinic antagonists
94
What sympathomimetic actions does Ephedrine have? route? effects? Use? adverse effects?
mixed acting- non-selective A/B agonist and release of NE from symp neurons; stimulate HR and CO, variable stimulation of peripheral resistance (inc MAP); bronchodilator and potent CNS stimulant; hypertension, insomnia, herbal meds banned by FDA, regulated (Methamphetamine)
95
What sympathomimetic actions does Methylphenidate or Amphetamine have? route? effects? Use?
indirect acting- NE and DA release, inhibits neuronal vesicular reuptake, CNS stimulant; patch or oral; ADHD- decrease hyperactive behavior due to increased attention span and focus, onset immediate, narcolepsy;
96
adverse effects of methylphenidate?
CV events, peripheral vasculopathy/priapism (rare), insomnia, appetite suppressant; tics, tolerance, physical dependence and withdrawal, abuse potential, schedule II
97
What sympathomimetic actions does Atomexetine have? Use? adverse effects?
indirect acting- selective inhibitor of NE reuptake by NET, no CNS; ADHD (inhibition immediate but efficacy 1-3 weeks, less potential for abuse as methylphenidate); dizziness, insomnia, reduced appetite, priapism (rare), orthostatic tachycardia and elevated BP, suicidal thoughts;
98
Drug interactions and contraindications of Atomoextine?
MAOIs- hypertensive crisis, CYP2D6 inhibitors- paroxetine, fluoxetine, quinidine
99
What are the clinical applications of adrenergic A1 receptor blockade?
vasculature- hypertension, antidote for A1 agonist (Epi) overdose or extravasation, BPH, Pheochromocytoma- catecholamine producing tumor of adrenal medulla, Reynaud's disease (vasospasm)
100
What are the clinical applications of adrenergic B1 receptor blockade?
heart, CNS, eye and kidney; hypertension, angina pectoris and MI (decrease postMI mortality 25%), CHF and arryhtmias, hyperthyroidism (inc sensitivity of heart to NE), glaucoma (decreased prod. of aqueous humor), stage fright, migraine headache prevention
101
What is the mechanism of Prazosin action? receptor effected? Use? Adverse effects?
selective A1 block; improved tolerability, dilation of arteries and veins, relax smooth muscle of bladder neck and prostate capsule, magnitude of effect depends on SNS activity, usually no HR inc. (presynaptic A2 not affected); treat hypertension; first dose effect
(orthostatic hypotension, give HS), inhibits ejaculation, nasal congestion
102
What is the mechanism of Tamsulosin action? receptor effected? Use? Adverse effects? drug interaction?
selective block of A1a over A1b for prostate capsule, urethra and bladder neck, little effect on BP, less likely orthostatic hypotension; BPH in men, often with 5a-reductase inhibitor; abnormal ejaculation (fail, decrease, retrograde); vasodilator for ED can cause dangerous BP drop and MI
103
What is the prototype B blocker? how does it work? Lipid solubility? metabolized where?
Propranolol; pure competitive antagonist; high lipid solubility, CNS penetration, eliminated by liver
104
What are the cardiovascular effects of Propranolol and receptor involved?
B1, decrease HR and contractility (decrease CO), enhanced during exercise or stress, suppress AV node impulse conduction, antagonize vasodilator effects of B2 agonists, initially increase peripheral resistance via reflex activation and B2 block, long term reduce BP
105
What are the renal, pulmonary and metabolic effects of Propranolol and receptor involved?
Kidney (B1)- suppress release of renin; Lung (B2)- promote bronchoconstriction; inhibit glycogenolysis in liver and skeletal muscle (B2)
106
What are the adverse effects of Propranolol?
fatigue, lethargy, coldness of extremities (PVD), exercise intolerance, sexual dysfunction, CV- brady and AV block, rebound tachycardia upon abrupt withdrawal, aggravate asthma/COPD
107
What are the contraindications/precautions of Propranolol?
diabetes (B1/B2)- suppress warning sign (tachycardia) and response (glycogenolysis) to hypoglycemia, HF- exacerbate symptoms acutely, long term beneficial, asthmatics
108
What is the action of Metoprolol and Atenolol? Benefits? Use? Lipid solubility?
prototype B1 selective antagonist; cardioselective at therapeutic doses, less likely to cause bronchoconstriction and suppression glycogenolysis; hypertension, angina pectoris, CHF, and MI; poor lipid solubility poor CN penetration, eliminated via kidney
109
What beta blocker has some alpha 1 receptor blocking activity?
labetalol
110
What is different about pindolol?
beta blocker, has intrinsic sympathomimetic activity, partial B1 agonist, little effect on resting HR and CO
