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  • Naloxone – opioid overdose; override receptor activating by binding to the receptor, blocking hydrocodone from blocking
    Sympathomimetic – mimicking the sympathetic nervous system
    ex: adrenaline rush
    Sympatholytic – blocking/lysing the sympathetic nervous system
    ex: a cholinergic type response
  • Epinephrine is released from the Adrenal Medulla – a presynaptic neurotransmitter.
  • Everything that is released is Acetylcholine.
    Pre-synaptically it’s Acetylcholine for both parasympathetic and sympathetic
    Post-synaptically it’ll be parasympathetic –Nicotinic-n--Acetylcholine---Muscarinic type response
    sympathetic-Nicotinic-n—NE, AcH, Epi, ---Alpha1, Beta1, Beta2 type
  • Alpha2 has no target organ. Only acts as an auto-regulator.
    DON’T worry about the sweat gland.
    Not all muscarinic receptor has the same sensitivity.
  • THEREFORE, if you block the muscarinic receptor---the OPPOSITE of all this happens
  • NE and Epi are SNS responses!!!
  • DOES NOT HAVE A TARGET ORGAN. Autoregulates NE (mainly) and Epi
  • Only Epinephrine activates Beta2
  • Muscarinic agonist – ACTS JUST LIKE ACh, goes to the muscarinic receptor site. – bethanechol
    “ “ antagonist – blocks ParasympatheticNS. Blocking the muscarinic receptor site.
    Cholinesterase inhibitors – prevents breakdown of Ach.
  • Catecholamines is a little bigger—can’t cross BBB
  • Not asked yet.
  • Nursing applications: measure urine output. Stool output. Water intake vs output
  • Atropine given for bethanechol overdose.
  • Nursing applications: dry ice chips? When was the last BM? Urine OP?
  • non-selective means it’ll block both!!!! Be careful to choose!
  • ans uthsc

    1. 1. Brian Tuschl, Pharm D.
    2. 2.    Neurons - are a communication center. Afferent transmission, sensory neurons, impulses toward the spinal cord & brain Efferent transmission, motor neurons, impulses away from the spinal cord, brain & glandular tissue Multipolar – one axon with several dendrites  Bipolar – one axon and one dendrite  Unipolar – one axon and NO dendrites  Axons are an extension of the neuron. they conduct the transmission of information, afferently or efferently, to different parts of the body through the use of AP’s.
    3. 3.  Neuron – Neurons conduct impulses through action potentials (AP). Neurons have a cell body which contain free & fixed ribosomes, Golgi body apparatus & mitochondria which produces ATP for energy. All of these work in conjunction with each other for the ultimate release of sodium. Once an action potential begins and sodium is released it travels down the axon to the ultimately reach the synaptic knob where it there interacts with calcium to release the many NT’s or catecholamines that are stored and are then released into the synapse.
    4. 4.  AP’s are created currents, by reaching threshold, that are propagated at the initial segment of the axon that extends the length of the axon & ends at the synaptic knob. This ultimately causes a large influx of Ca++ which forces the release of NT or catecholamines (ACh, Epi, NE & Dopamine) stored in vesicles at the synaptic knob. This Ca++ dependent process that releases NT’s out of its vesicle and into the synapse to continue the communication process is called “exocytosis.” These NT’s and Catecholamines are used for our senses; such as touch (feeling), motor (movement) they also affect mood, fight or flight
    5. 5.  AP’s are an “all or none” process. AP’s are initiated when a threshold of at least -60 mV to -55 mV is reached. This stimulus is large enough to open the voltage gated Na+ channel. “A graded depolarization is like the pressure on the trigger of a gun and the AP is the firing of the gun.” With no or not enough stimulus there is no AP & the transmembrane potential returns to resting levels. The strength of the AP are independent of the depolarizing stimulus as long as the gradient is strong enough to reach threshold.
    6. 6.     1) Depolarization to threshold “All or None” 2) Opening voltage regulated Na+ channels. Upon depolarization Na+ chan. open. Now more positive ions enter the cytoplasm which cause a shift from a neg. potential at resting state to a positive one upon depolarization. 3) Na+ chan. Inactivation & K+ chan. Activation. As the positive potential reaches +30mV the Na+ gates begin to close & K+ begins moving out of the cytoplasm shifting the potential back to a negative resting state & repolarization begins. 4) The return to normal permeability. As the membrane potential reaches -60mV the Na+ channel become capable of opening again for depolarization. As the K+ channel begin closing as the potential reaches -60mV. The K+ continues to rush out & the potential can reach -90mV causing hyperpolarization. The potential returns to -60mV (resting state) & the AP is over.
    7. 7.   Synaptic Transmission – drugs can affect the firing rate, the release of NT or catecholamines or the crossing of neurotransmitters or catecholamines across the synaptic cleft. If the cell did not have a receptor site the NT or catecholamines could/would not affect the cell so no activation would occur. Many drug interactions occur b/c of drugs competing for the same rec site.
    8. 8.         1) Skeletal muscle 2) Cardiac output 3) Vascular tone 4) Respiration 5) GI function 6) Uterine motility 7) Glandular secretions Also effects pain perception, ideation and mood
    9. 9. Increase ↑ Constriction Increase ↑ Decrease ↓ Constipation Decrease ↓ Xerostomia Mitosis (Mydriasis) Ejaculation Relaxation Contraction Cardiac Output/Heart Rate Vascular Tone Respiration GI GI GI Secretions Secretions Eye Sex Uterine SM Prostate Decrease ↓ Dilate Decrease ↓ Increase ↑ Diarrhea Increase ↑ Salivation Miosis Erection
    10. 10.         Agonist – directly activate receptor (morphine, epi, insulin) Antagonist – prevent receptor activation (naloxone, antihistamines, beta blockers) Direct acting – Stimulate receptor Indirect acting – Stimulate release of NT Sympathomimetic – adrenergic (SNS) Sympatholytic – antiadrenergic Parasympathomimetic – Cholinergic (PSNS) Parasympatholytics – anticholinergic
    11. 11. 1) 2) 3) 4) 5) All PREganglionic neurons of the PSNS & SNS release ACh as their neurotransmitter. All postganglionic neurons of the PSNS release ACh as the neurotransmitter. – all the way to muscarinic receptor Most postganglionic neurons of the SNS release NE as their neurotransmitter. – acts on beta 1 and alpha 1 Epi is the main NT released by the adrenal medulla (which is ONLY a feature of the SNS and is considered prejunctional) All motor neurons to the skeletal muscles directly release ACh as their neurotransmitter. – somatic nervous system 1) Parkinson’s disease pts. Dopamine misbehaves, ACh levels increased  tremors. THEREFORE give dopamine agonists to lower ACh levels.
    12. 12. 1) Epinephrine - released ONLY by adrenal medulla which also releases NE (unlike Epi, NE is also released by neurons). Epi is also the only NT that activates all adrenergic rec (alpha 1 & 2 & beta 1 & 2). 2)  3) Norepinephrine – released by postganglionic neurons of the SNS, except sweat glands (which releases ACh at muscarinic rec at the target organ in the SNS) NE activate adrenergic rec alpha 1 & 2 and beta 1 NOT beta 2 or dopamine rec. NE is not broken down in the synapse but is taken back up through the nerve terminal (alpha 2) to be broken down and restored by monoamine oxidase (MAO.) Dopamine - precursor to NE and epi. Can activate alpha 1, beta 1 and dopamine receptors. 1) Acetylcholine – is the only preganglionic (prejunctional, preneuronal) NT of both the PSNS & the SNS. Postganglionically it is the NT for the PSNS that activates muscarinic and nicotinic M rec. ACh also activates the sweat glands muscarinic rec in the SNS.
    13. 13.           1) ACh Activate cholinergic receptors (muscarinic, nicotinic receptors “m” and “n”) Is broken down by acetyl cholinesterase (AChE) 2) Epi Can activate alpha and beta receptors but NOT dopamine receptors. Only NT that acts on beta 2 receptors Released from adrenal medulla NOT from neuron nerve terminal Dilates blood vessels (lungs, heart & skeletal muscle) Epi counteracts anaphylactic shock Increase glycogenolysis (glycogen to glucose) Relax uterine smooth muscle
    14. 14. PNS regulates, depending on stimulus & the target organ (cholinergic or anticholinergic), an increased or decreased effect on these organs PNS Receptor Activation(NicotinicN rec. activation)  Neurotransmitter is ACh.  NT on all of the ANS ganglia (pre & post) & the adrenal medulla  Stimulation of parasympathetic & sympathetic POSTganglionic nerves release epi from the adrenal medulla  PNS Receptor Activation (NicotinicM rec. activation)  Neurotransmitter is ACh.  NT ACh goes straight to the neuromuscular junction
    15. 15. PNS Receptor Activation (Muscarinic rec activation)  1)Eye - Contraction of ciliary muscle for near vision & Miosis (dec pupil diameter) – pinpoint pupils     2) Heart – Dec heart rate, hypOtension 3) Blood Vessels – Vasodilation (lower BP!) 4) Lung – Contraction of bronchi (difficulty breathing) 5) Bladder - Contraction of detrusor & relaxation of trigone & sphincter muscle (causes urination) (increased urination!!!)  6) GI Tract - Salivation, inc gastric secretions & intestinal tone & motility, defecation  6) Sweat glands - sweating is a SNS response but is through activation of muscarinic rec by ACh  7) Sex organs – Erection (due to dilation of blood vessels) this is only spot where the SNS and PSNS work together (PSNS/erection & SNS/ejaculation)
    16. 16.       Selectively block ACh at muscarinic receptor site Increased heart rate Decreased salivation, bronchial dilation, sweat glands, acid secretion Smooth muscle relaxation of bronchi, decreased GI and bladder motility Mydriasis (dilation) focus lens for far vision NOT all muscarinic receptors have the same sensitivity. Clinical significance is dose dependent.
    17. 17.       Xerostomia (Dry mouth) Blurred vision and photophobia Elevation of intraocular pressure Constipation Anhidrosis (deficiency of sweat) Tachycardia
    18. 18. Drugs function in the PSNS: Notice that the conditions of the PSNS (or drugs that stimulate PSNS conditions) are functions that would normally happen in a resting state NOT in a “fight or flight” condition  1) Slowing of the heart  2) Increased gastric secretion  3) Emptying of the bladder  4) Emptying of the bowel  5) Focusing the eye for near vision  6) Constricting the pupil  7) Contracting bronchial smooth muscle
    19. 19.   3 main functions: 1) Regulating the CV system    2) Regulating body temperature     Increased cardiac output Cause vasoconstriction – increases BP Regulate blood flow to skin Promote secretion of sweat to keep body cool Erection of hair 3) Implementing the “fight or flight” reaction      Increased heart rate & blood pressure Shunt blood away from skin to skeletal muscle (clammy) Dilate bronchi for more oxygen (deeper breaths) Dilate pupils for increased vision Provide glucose for brain, fatty acids for muscles for inc energy
    20. 20. PNS Receptor Activation (Alpha 1 & 2 and Beta 1 & 2 receptor activation) (Adrenergic) Alpha 1 Eye Arterioles Veins Sex organ Prostate Bladder 1) Contraction of radial & sphincter muscle & inc. pupil size 2) Constriction of arterioles (skin, viscera mucous membrane) 3) Venous constriction 4) Male ejaculation 5) Contraction of prostate 6) Contraction of trigone & sphincter muscle in bladder Alpha 2 Presynaptic nerve terminals 1) Inhibition of transmitter release
    21. 21. PNS Receptor Activation (Alpha 1 & 2 and Beta 1 & 2 rec activation) (Adrenergic) Beta 1 Heart 1) Inc HR, force of contraction, AV conduction velocity Kidney 2) Renin release Beta 2 Arterioles 1) Dilation of arterioles in heart, lung & skeletal muscle Lungs Uterus Liver Skeletal muscle 2) Dilation of the bronchi in the lungs 3) Relaxation of the uterus 4) Glycogenolysis in the liver 5) Enhanced contraction of skeletal muscle & glycogenolysis Dopamine Kidney 1) Dilation of kidney vasculature (used for shock)
    22. 22. 4) Beta 2 Bronchial dilation  Relaxation of uterine smooth muscle (Terbutaline – Beta 2 adrenergic agonist) stops premature pregnancy contractions  Dilation of lungs and arterioles, heart contractility, skeletal muscle contraction and glycogenolysis  Liver – Glycogenolysis 5) Dopamine  Is considered adrenergic but does not respond to epi and NE and is primarily found in the CNS.  Receptor located in the vasculature of the kidney. When activated causes dilation and enhances renal perfusion  Used for shock and hypotension. 
    23. 23. NT RECEPTOR ACTIVATION 1. 2. 3. Epi NE Dopamine RECEPTOR ACTIVATION EFFECT 1. 2. 3. 4. Alpha1 Activation Drugs 1. 2. 3. 4. 5. Epi NE Dopamine Phenylephrine Ephedrine 1. 1. 2. Mydriasis (pupil dilation) Vasoconstriction Ejaculation Bladder Contraction  Trigone & Sphincter Bladder Dilation  Detrusor Piloerection (Goosebumps) Prostrate Muscle Contraction
    24. 24. NT RECEPTOR ACTIVATION 1. 2. Epi NE Alpha2 Activation Drugs 1. Epi 2. NE 3. Ephedrine RECEPTOR ACTIVATION EFFECT   Located on nerve terminal NOT on organ tissue & are referred to as Presynaptic or Prejunctional Regulates transmitter release
    25. 25. NT RECEPTOR ACTIVATION 1. 2. 3. Epi NE Dopamine RECEPTOR ACTIVATION EFFECT 1. Beta1 Activation Drugs 1. 2. 3. 4. 5. 6. Epi NE Isoproterenol Dopamine Dobutamine Ephedrine 1. Heart • Increased Heart rate • Increased Force of contraction • Increased Velocity of impulse thru AV node Kidney • Activation of renin
    26. 26. NT RECEPTOR ACTIVATION 1. Epi RECEPTOR ACTIVATION EFFECT 1. 2. Beta2 Activation Drugs 1. Epi 2. Isoproterenol 3. Terbutaline 1. 2. 3. 4. Bronchial dilation Relaxation of uterine smooth muscle  Terbutaline (β2 adrenergic agonist) Stops premature pregnancy contractions Dilation of arterioles Heart contractility Skeletal muscle contraction Liver (glycogenolysis)
    27. 27.       1) Muscarinic agonist (mimic ACh) Bethanechol 2) Muscarinic antagonist (block ACh) Atropine 3) Ganglionic stimulating (blocks ACh at nicotinicn rec. in large doses, reverse in small doses) nicotine 4) Ganglionic blocking agents (mecamylamine) 5) Neuromuscular blocking agents (blocks ACh at nicotinicm rec.) d-Tubocurarine, succinylcholine 6) Cholinesterase inhibitors (prevent breakdown of ACh and ACh inhibitors) neostigmine, physostigmine
    28. 28. Category Agents Endogenous dopamine [Inotropin] norepinephrine [Levophed] epinephrine [Adrenalin] Synthetic dobutamine [Dobutrex] isoproterenol [Isuprel] phenylephrine [Neo-Synephrine]
    29. 29.  Catecholamines :  (epi, NE, dopamine, dobutamine, isoproterenol)  Short duration of action  Cannot give by mouth (PO)  Do not cross blood-brain barrier (bbb) Noncatecholamines: (Phenylephrine, ephedrine, terbutaline)  Longer duration of action  Can give PO  Crosses bbb 
    30. 30.   McHenry (2006), pg 425 Direct Acting
    31. 31. Direct Acting Indirect-Acting acetylcholine ambenonium echothiophate edrophonium bethanechol demecarium isoflurophate neostigmine carbachol physostigmine pyridostigmine methacholine pilocarpine
    32. 32. salivation lacrimation urinary incontinence diarrhea gastrointestinal cramps emesis at recommended doses the cholinergics primarily affect {M} but at high doses {N}
    33. 33.  MOA:       Stimulates cholinergic rec. in the smooth muscle of the urinary bladder & GI tract resulting in 1) Increased peristalsis 2) Increased ureteral peristaltic waves 3) Increased GI & pancreatic secretions 4) Bladder muscle contraction Pharmacotherapeutics: – urinary retention, loss of tone in GI tract – unlabeled use: GERD (has little effect on nicotinic or skeletal muscles)
    34. 34.  Pharmacokinetics and dose: – – – – –  Pharmacodynamics:   PO; 10-50 mg tid or qid (5-10 mg at hourly intervals until desired response) Give on an empty stomach SC ; 2.5-5 mg tid or qid NEVER IM OR IV rapid onset – 30-90 minutes/duration up to 6/hours Same effects as acetylcholine Overdose  Atropine I.V. 0.6 mg every 2 hours per clinical response
    35. 35. Adverse Reactions:       GI – Abdominal cramps, diarrhea, N/V, salivation Genitourinary – Urinary urgency Ocular – Lacrimation, miosis Bronchial constriction/asthma attacks CV - Hypotension/tachycardia/flushed skin Sweating
    36. 36. Contraindications:    Mechanical obstruction of GU or GI tract Peritonitis Parkinson's disease        Low Dopamine levels = high ACh already!!! Bethanechol acts just like ACh which pushes it higher! Hypotension / hypertension Bradycardia Epilepsy Asthma Hyperthyroidism Pregnancy (cat. C)
    37. 37. Drug Interactions:  Cholinesterase inhibitors - > cholinergic      ACh + Bethanechol = TOO MUCH Ganglionic blockers - severe hypotension Quinidine - antagonize cholinergic Pilocarpine - > cholinergic effect Carbachol - > cholinergic effect
    38. 38. Natural Synthetic atropine clidinium dicyclomine glycophyrrolate belladonna hexocyclium homatropine isopropamide mepenzolate methantheline hyscocyamine methscopolamine scopolamine oxyphencyclamine propantheline tridihexethyl
    39. 39. Body System CNS Cholinergic Blocker Effects decreases muscle rigidity & tremors high doses: drowsiness, disorientation, & hallucinations Eye dilates pupils [mydriasis] accommodation: paralyzes ciliary muscles [cycloplegia] CV small doses: decrease heart rate large doses: increase heart rate
    40. 40. Body System RESP GI GU Glandular Cholinergic Blocker Effects decrease bronchial secretions dilate bronchial airways relaxes smooth muscle tone of GIT decreases intestinal & gastric secretions decreases GI motility & peristalsis relaxes detrusor muscle of bladder increases constriction of internal sphincter these two may result in urinary retention decreases bronchial secretions, salivation, & sweating
    41. 41.      Completely block ACh at the receptor site Atropine (belladonna alkaloid) Found naturally in Atropa belladonna (deadly nightshade) and Datura stramonium (jimson weed, stinkweed) At high doses effect nicotinic receptors also. Exerts effect on: heart, exocrine glands, smooth muscles and eye
    42. 42. Dose Low dose High dose Response produced Salivary gland (decreased secretion) Sweat glands (decreased secretion) Bronchial glands (decreased secretion) Heart (increased rate) Eye (Mydriasis, blurred vision) Urinary tract (interference w/ voiding) Intestine (decreased tone and motility) Lung (dilation of bronchi) Stomach (decreased acid secretion)
    43. 43. MOA:  Blocks the action of ACh at parasympathetic receptor sites in smooth muscle, secretory glands and the CNS results in 1) Increased cardiac output 2) Dries secretions 3) Antagonizes histamine and serotonin
    44. 44. Pharmacotherapeutics: PO, SQ, IM, IV, Aerosol, endotracheal instillation Injection 1) Preoperative to inhibit salivation & secretions 2) Tx of symptomatic sinus bradycardia, AV block (nodal level), ventricular asystole, 3) Antidote for organophosphate pesticide poisoning Ophthalmic 1) Produce mydriasis & cycloplegia for examination of the retina and optic disc. PO 1) Inhibit salivation and secretions
    45. 45.  Pharmacokinetics:          Easily absorbed and widely distributed Crosses blood-brain, placental barrier and trace amounts enter breast milk Hepatic metabolism Excreted in the urine IV rapid onset IM onset 5-50 min PO onset 1-2 hours Half life 2-3 hours Dose >5kg 0.01-0.02 mg/kg/dose to a max 0.4 mg/dose 30 to 60 minutes preop.
    46. 46.     Adverse Effects: Dose related and vary greatly and are 1) limited 2) Significant 3) Life-threatening Limited/Common: dry mouth, blurred vision, urinary hesitancy, constipation, palpitations, anhidrosis Significant: tachycardia, photophobia, confusion, insomnia, delirium, hallucinations, rash, allergic reaction, impotence, suppression of lactation, muscular incoordination, hypertension, vomiting, bloating, paralytic ileus, etc.
    47. 47. Atropine Intoxication:       Extreme dry mouth, dry upper respiratory tract, dry skin ("dry as a bone") foul breath Diminished visual acuity due to pupil dilation ("blind as a bat") Elevation of body temperature ("hot as a furnace") hot , dry flushed skin Hallucinations, bizarre behavior, confusion, delirium, < memory ("mad as a hatter") Overdose: Physostigmine (AChE inhibitor) 0.5 mg or 0.02 mg/kg in children. SQ or slow IV
    48. 48. Contraindications:          Narrow-angle glaucoma CAD Urinary/GI obstruction Paralytic ileus Ulcerative colitis Hiatal hernia Hepatic/renal disease Lung disease/asthma Caution   adults over 40 older adults
    49. 49. Drug Interactions: Increased Effect/Toxicity of Atropine  Antihistamines, phenothiazines, TCA’s and other drugs with anticholinergic activity. Decreased Effect/Toxicity of Atropine  Metoclopramide, cisapride, bethanechol Drugs with cholinergic mechanisms
    50. 50. Nursing management: Monitor VS frequently Assess bowel sounds, frequency of bowel movements, voiding patterns Side effects of other drugs Frequent fluids, ice chips, hard candy Frequent sponge baths Assess lung sounds Have suction equipment available Elevate side rails Report changes in LOC
    51. 51. MOA:  Low doses activate nicotinic receptors  High doses block nicotinic receptors  Activates receptors in the CNS which makes it highly addictive.  Activates receptors in the autonomic ganglia to release NE and release of epi from the adrenal medulla  At doses of smoking it has no effect on skeletal muscle nicotinic receptors
    52. 52. Pharmacokinetics:  Widely distributed  90-98% of nicotine that enters the lungs enters the blood stream  Nicotine crosses placenta  Reaches breast milk and can be toxic  Half life 1-2 hours  Excreted by the kidneys
    53. 53. Pharmacotherapeutics :(Low dose effects)  Cardiovascular Releases NE from sympathetic nerves and NE and epi from the adrenals causing blood vessel constriction, accelerate the heart, ventricular contraction which causes increase blood pressure GI  By activation of nicotinic rec. in the parasympathetic system inc. GI motility and secretions.   CNS Stimulates respiration, inc. alertness, cognition and memory and by activating dopamine activates pleasure center.
    54. 54. Acute poisoning :(40 mg and up)  High doses block nicotinic receptors Sx include CNS, GI and CV  N/V, diarrhea, cold sweat, confusion, fainting, pulse is rapid, weak and irregular  Death by respiratory paralysis  Antidote: No real antidote. Give activated charcoal recovery in hours
    55. 55. 2 types: 1) Reversible inhibitors 2) Irreversible inhibitors  Reversible:  1) Neostigmine (Prostigmin) PO, IV, IM, SQ  2) Ambenonium (Mytelase) PO  3) Pyridostigmine (Mestinon) PO, IV  4) Edrophonium (Tensilon, Reversol) IM, IV  5) Physostigmine (Antilirium) IM, IV  6) Donepezil (Aricept) PO  7) Galantamine (Reminyl) PO  8) Rivastigmine (Exelon) PO  9) Tacrine (Cognex) PO  Irreversible: 1) Echothiophate (Phospholine Iodide) topical
    56. 56. MOA:  Prevents the breakdown of ACh into choline and acetic acid(indirect-acting cholinergic agonist)  Has no specificity so it has a broad spectrum response  Same effect and adverse effects as those of direct-acting muscarinic agonist  Mostly used in Myasthenia Gravis
    57. 57. Pharmacokinetics:  Carries Nitrogen with 4 bonds which has a positive charge so does not cross membranes easily (GI, bbb, placenta)  Physostigmine – only 3 bonds so no positive charges so crosses membranes much easier  Once bound to AChE it remains in place for a long time.  PO, IV, IM, SQ  DOA – 2-4 hours Overdose: Atropine
    58. 58. Adrenalin, Bronkaid Mist, Primatene Mist, Epifrin MOA :  Stimulates Alpha 1 & 2 and Beta 1 & 2  Relaxation of smooth muscle in the bronchial tree  Cardiac stimulation  Dilation of skeletal muscle  Direct acting, nonselective Pharmacokinetics:      Crosses placenta IV, SQ, Intratracheal, , Intracardiac injection, IM, Nebulizer, intranasal Metabolism – MAO & COMT & circulating hepatic metabolism Excretion – Urine Short half life
    59. 59. Pharmacotherapeutics:  Anaphylactic shock  Bronchoconstriction  Cardiac arrest  Overcome AV heart block  Elevate blood pressure  Control superficial bleeding  Delay absorption of local anesthetics
    60. 60. Adverse Effects:  CV – Tachycardia, HTN, chest pain, vasoconstriction, arrhythmia, sudden death      CNS – Nervousness, HA, anxiety, insomnia GI – Xerostomia, N/V Genitourinary – Urinary retention Respiratory – Wheezing, dyspnea Necrosis - b/c of vasoconstriction minimized by phentolamine (alpha-adrenergic antagonist)  Hyperglycemia – b/c breakdown of glycogen through activation of beta2 receptors in liver & skeletal muscle (be careful for diabetics!!)
    61. 61. Drug Interactions:  MAO inhibitors – prolongs and intensifies effects  TCA’s – Block re-uptake and prolongs effect  General Anesthetics  Alpha-Adrenergic blockers – block receptor activation  Beta-Blockers – block effects
    62. 62.   Presynaptic alpha2 activation in the ANS has little clinical relevance but has significant relevance in the CNS. Activation inhibits NE release
    63. 63. Therapeutic use of Alpha1 activation: Vasoconstriction (blood vessels on skin, viscera of mucus membrane)  1) epi used to stop topical bleeding (used in boxing)  2) Nasal congestion (nasal phenylepherine, ephedrine orally) 3) used during anesthesia slows absorption of anesthetic  4) Hypotensive pts. Mydriasis Adverse Effects of Alpha1 Activation: 1) HTN 2) Necrosis 3) Bradycardia reflex
    64. 64. All relevant response to beta1 is in the heart Therapeutic Applications: 1) Cardiac arrest – beta1 activation inc. contraction if heart is not beating. 2) Heart failure – beta1 activation cause positive inotropic effect (inc. force of contraction) 3) Shock – inc. force of contraction and heart rate 4) AV block – Enhances impulse conduction through the AV node. Adverse Effects: 1) Altered heart rate/rhythm 2) Angina pectoris (dec of O2 to the heart) 3) Overstimulation produces tachycardia, dysrhythmias 
    65. 65. Therapeutic Applications:  Limited to the lungs and uterus  1) Asthma – bronchodilation  2) Delay of preterm labor/relax uterine smooth muscle. Adverse Effects: 1) Hyperglycemia – Main concern is pt. with diabetes 2) Tremor – b/c of activation of skeletal muscle
    66. 66. Therapeutic Applications:  Dopamine is ONLY NT that can activate dopamine receptors.  Cause dilation of the vasculature of the kidneys which dec. risk of renal failure.  Enhances cardiac performance b/c it acts on beta1 in the heart.
    67. 67. Have a high specificity for their receptors 2 Groups  1) Alpha adrenergic blockers: HTN - Most useful for alpha1 blockade of blood vessels  Alpha1 blockade is also good for benign prostatic hyperplasia  Pheochromocytoma – catecholamine secreting tumor in the adrenal medulla  Reynaud's dz – vasospasm in toes and fingers so prevent vasoconstriction Adverse Effects:  Orthostatic hypotension  Reflex tachycardia  Nasal congestion  Inhibit ejaculation 
    68. 68. 2) Beta Adrenergic blockers:  Biggest therapeutic effects from beta1 blockade in the heart 1) Reduced heart rate 2) Reduced force of contraction 3) Reduced velocity of impulse conduction Therapeutic Application:  Angina pectoris Heart failure  HTN Hyperthyroidism  Headaches Stage fright  Cardiac dysrhythimias Glaucoma Adverse Effects:  Rebound cardiac excitation AV heart block  Reduced cardiac output Bradycardia  Heart failure
    69. 69. Drug Receptor Receptor Phentolamine Alpha1 Alpha2 Phenoxybenzamine Alpha1 Alpha2 Alfuzosin Alpha1 Doxazosin Alpha1 Prazosin Alpha1 Terazosin Alpha1 Tamsulosin Alpha1
    70. 70. Drug Receptor Receptor Carteolol Beta1 Beta2 Carvedilol Beta1 Beta2 Labetalol Beta1 Beta2 Nadolol Beta1 Beta2 Penbutolol Beta1 Beta2 Pindolol Beta1 Beta2 Propranolol Beta1 Beta2 Timolol Beta1 Beta2 Sotalol Beta1 Beta2 Atenolol Beta1 Betaxolol Beta1 Bisoprolol Beta1 Esmolol Beta1 Metoprolol Beta1 Acebutlol Beta1