1. Adrenergic Antagonists
2. Cholinergic Antagonists
3. Adrenergic Agonists
   1. Allergies
   2. Cardiac, vascular conditions
   3. Bronchial asthma
   4. Premature labour
   5. Mydriatic, hypoglycemia
4. Parasympathomimetics
5. B-receptors
6. a-receptors
7. a2
   1. pre-synaptic, inhibits release of NE
   2. decreases cAMP
   3. (post-synaptic on B cells of pancreas)
8. a1
   1. post-synaptic, g-protein activation of phospholipase C
   2. release of calcium into cytosol
9. a-receptors: E > NE >> isproterenol
10. Methoxamine
    1. Direct-acting
       1. Raises BP, arteriolar vasoconstriction
       2. Peripheral resistance, reflex bradycardia
       3. Rapid response to IV admin, 15 mins for IM
       4. Perists 1-1.5 hours
       5. Use: hypotension during surgery
       6. AE: hypertension headache, vomiting
11. Phenylephrine
    1. Direct-acting
       1. Effects similar to methoxamine
       2. Nasal decongestant (1-2%)
       3. Mydraitic: no intraocular tension or loss of light reflex
       4. Vasopressor
    2. To remember: "fennel" (licorice)
    3. smells good: decongestant
    4. black and round: mydraitic
12. Phenylpropanolamine
    1. Urinary incontinence in dogs
    2. To remember:
    3. Stop at gas station to get licorice, propane, and let dog out to pee
13. Mixed-Acting a1 agonists
14. Metaraminol
    1. Treatment of hypotension
    2. To remember: "met a ram" - just one (a1), he was adrenergic!
15. Mephentermine
    1. For hypotension during spinal anaesthesia
    2. To remember:
    3. If a "fender"-bender makes your spine go numb, your BP will go up!
16. Clonidine
    1. Direct-acting in cardiovascular centers of CNS
    2. Suppresses outflow of sympathetic NS activity from brain
    3. Modulates CNS perception of pain, sedation
    4. Oral administration, bioavailability 100%
    5. Renal blood flow, GFR ok
    6. Use: hypertension complicated by renal dz, pre-op sedation, analgesia
    7. AE: sedation, dry mouth, rebound hypertension, sexual dysfunction, bradycardia
    8. To remember: clones are used for kidney transplants, want to keep them sedated, BP down, no sex
17. Apraclonidine
    1. Reduces aqueous humor production
    2. Use: reduction of intraocular pressure
    3. To remember: "apra" = eye aperture of clones. They have little humor.
18. Xylazine
    1. Large animal sedation, muscle relaxant, analgesia
    2. Use: anaesthetic pre-med
    3. AE: bradycardia, conduction disturbances, myocardial depression
    4. To remember: the sedated cows started playing the xylophone before their surgery
19. Methyl Dopa
    1. Similar to clonidine, acts on central a2-receptors: lowers BP
    2. Metabolized to a-methyl norepinephrine in CNS
    3. To remember: dopes are like clones
20. Detomidine
    1. Large animals sedative, mostly horses (IV)
    2. Analgesic properties, pre-med
    3. With Butorphanol: increased effects
    4. With ketamine: short IV anaesthesia
    5. To remember: Tom (the horse)
21. B1
    1. Present in heart, juxtaglomerular apparatus, fat
    2. Equal affinities for E and NE
22. B2
    1. Vasculature of skeletal muscle, liver
    2. smooth mm of bronchus, genitourinary system, uterus
    3. AE: skeletal mm. tremor, pulmonary edema
    4. Down-regulation w/ chronic use
23. Non-Selective B
24. Isoproterenol
    1. synthetic catecholamine, potent B agonist
    2. B1: Most potent inotropic agent:: force, heart rate, and cardiac output
    3. B2: vasodilation of skeletal mm, uterine relaxation
    4. Use: emergency stimulation of heart rate in bradycardia or heart block, asthma
    5. AE: palpitations, tachycardia, headache
    6. AE: cardiac ischemia and arrhythmias in patients with coronary heart dz
    7. To remember: Iso: means equal (effect on both B1 and B2)
25. Dobutamine
    1. Positive inotrpic action through B1-receptors
    2. without increasing hearth rate, cardiac rhythmicity, or BP
    3. Use: Congestive heart failure
       1. Does not significantly increase 02 demand
    4. AE: caution in atrial fibrillation
       1. Increases AV conduction
    5. Tolerance (tachyphylaxis)
    6. To remember: dobut -> a good debut -> start with force! (but keep BP down)
26. Uterine Relaxants
27. Bronchodilators
28. Ritodrine
    1. Administer IV to arrest premature labor
    2. To remember: keep Rita's baby out of the drain (sorry!)
29. Metaproterenol
    1. Orally, by inhalation
    2. Dilation of bronchioles, improves airway fx
    3. Use: long-term treatment of obstructive airway dz
    4. To remember: bronchodilators end in "ol," B-antagonists end in "lol"
    5. Sounds like "metapro-eternal" = can use long-term
30. Salmaterol
    1. slow onset w/ inhalation, prolonged duration ~12 hours
    2. To remember: it takes a long time to make smoked salmon, but then it lasts a long time
31. Albuterol
32. Clenbuterol
33. Salbutamol
34. Both a and b-receptors
35. both a and b-receptors
36. Catecholamines
    1. Not effective orally, SC slow (vasoconstriction)
    2. Epinephrine is metabolized by COMPT and MAO
37. Miscellaneous Adrenergic Agonists
38. Amphetamine
    1. CNS stimulating agent with peripheral a and b action
    2. indirect, peripheral action mediated through release of stored catecholamines
    3. Use: stimulates mood, alertness, reduces appetite (weight loss)
    4. AE: Insomnia, tremor, restlessness, excitement, agitation
    5. AE: dependence, cardiovascular arrhythmyias
    6. AE: dry mouth, anorexia, metallic taste, nausea, diarrhea, abdominal cramps
39. Ephedrine
    1. Ephedra vulgaris - mixed action
    2. Stimulates cardiac rate, output, increases BP
    3. Brochodilation, CNS stimulation
    4. Use: bronchodilator, hypotension (spinal anaesthesia, nasal decongestant
    5. Adjuvant to Myaestehnia gravis
    6. AE: hypertension, cardiac arrhthmias, insomnia, tachyphylaxis
40. Dopamine
    1. metabolic precursor of NE and E, substrate for MAO and COMT
    2. Responsible for regulation of movement
    3. Extravasation can result in ischaemia / tissue necrosis
    4. Avoid in patients on MAO inhibitors or tricyclic depressants
    5. IV use only: treatment of cardiogenic and septic shock
    6. Beneficial for patients with oliguria and low peripheral vascular resistance
    7. Fenoldopam (selective D1-receptor agonist): diuresis in cats
    8. Dopexamine
41. Therapeutic Uses
    1. Respiratory distress due to bronchospasm (asthma)
    2. Use for hypotension, cardiac effects
    3. Rapid relief from allergic reactions
    4. Prolongs action of local anaesthetic drugs (1:100 000)
    5. Topical haemostatic agent on bleeding surfaces
42. Adverse Effects
    1. Fear, anxiety, restlessness, throbbing headache, tremor,
    2. weakness, dizziness, palor, respiratory difficulty, palpitation
    3. Hypertension with headache, cerebral vascular haemorrhage, ruptured aneurysms
    4. cardiac arrhythmias, necrosis of tissue at injections sites
    5. hyperthyroidism / bp / halogenated hydrocarbon anaesthetics -> predispose to myocardial toxicity
43. Low Concentrations
    1. Interacts with D1-Dopaminergic receptors
    2. Causes vasodilation in renal, mesenteric, and coronary beds
    3. Increases GFR, renal blood flow, NA+ secretion
    4. Used in states of low cardiac output associated with compromised renal functino
    5. Use: cardiogenic shock, hypovolumic shock
44. High Concentrations
    1. Acts on B1 receptors
    2. Inotropic effect on heart
    3. Releases NE (affects heart)
45. Max Concentrations
    1. Acts on a1-receptors
    2. Causes vasoconstriction
46. a-receptors
47. B-receptors
48. a1-blockers
49. a2-blockers
50. non-selective a-blockers
51. non-selective B-blockers
52. B1-blockers
    1. Therapeutic Use
       1. Hypertension
       2. Angina Pectoris
       3. Arrythmias
       4. Thyrotoxicosis
       5. Pheochromocytoma
       6. Glycoma
       7. Neuro disorders
       8. Migraines
       9. Sedation and antianxiety
       10. Alcohol withdrawal
53. Neuromuscular Blockers
    1. Target Nm-receptors
54. Choline Esters
55. Cholinomimetic Alkaloids
56. Cholinesterase Inhibitors
    1. Prevents binding of ACh to AChE
    2. Reduces rate of hydrolysis, increases cholinergic effects
    3. Form intermediates with ACE, or act as pure competitive inhibitors
    4. Pharmacological Effects
       1. Digestive Tract
          1. Increase GI motility, peristalsis
          2. Increase frequency and strength of peristalisis: defecation
       2. Ocular Effects
          1. Pupillary constriction, spasm of accomodation
       3. Skeletal Muscle
          1. Anticurare agents
          2. Depolarizing agents - stimulating effect
       4. Ganglionic stimulation, hypotension, bradycardia, arrhythmia
       5. Contraction of bladder, bronchoconstriction
    5. Toxicology
       1. Contraindicated for impaction with obstruction, pregnancy
       2. Pupil constriction, dyspnea, bradycardia, hypotension
       3. Respiratory paralysis + increased bronchiolar secretion (death)
       4. Neostigmine: skeletal muscle weakness, nausea, vomiting, colic, diarrhea
       5. Physostigmine: stimulation followed by CNS depression, convulsions
       6. Treatment: Atropine
57. Ganglionic Blockers
    1. Target Nn-receptors
58. Antimuscarinic Agents
59. Phenoxybenzamine
    1. Irreversible inhibition for 14-48 hours
    2. Non-selective blocker, also inhibits NE reuptake
    3. Cardiovascular Effects
       1. prevents peripheral vasoconstriction
       2. Decreases vascular resistance provokes reflex tachycardia
       3. Blocks cardiac a2-presynaptic receptors: increases cardiac output
       4. Epinephrine reversal
       5. B2-mediated vasodilation of skeletal vasculature
    4. Therapeutic Use
       1. Presurgical treatment of pheochromocytomas, prevents hypertensive crisis
       2. Management of benign prostatic obstruction
    5. Adverse Effects
       1. Postural hypotension, reflex tachycardia, arrhythmias
       2. Nasal stuffiness, nausea, vomiting
       3. Inhibits ejaculation and aspermia
       4. Mutagenic activity - peritoneal sarcomas, lung tumors
    6. To remember: Phe = pheochromocytomas
60. Phentolamine
    1. Non-selective competitive block of a-receptors
    2. Poorly absorbed from GIT
    3. Similar action to phenoxybenzamine
    4. Postural hypotension, reflex tachycardia
    5. Induces diarrhea and GIT secretion due to agonistic action at muscarinic receptors
    6. Therapeutic Use
       1. Treatment of hypertension due to pheochromocytoma
       2. Relief of pseudoobstruction of bowel
       3. Prevention of local dermal necrosis on extravasation of a-agonist
    7. AE: postural hypotension, reflex tachycardia, arrhythmias, anginal pain
61. Prazosin
    1. Less reflex tachycardia than with non-selective a-blockers
    2. Cardiovascular effects: decreases peripheral resistance, lowers BP
    3. Use: treatment of hypertension, benign prostate hypertrophy
    4. AE: dizziness, congestion, headache, drowsiness, orthostatic hypotension
62. Terazosin
63. Yohimbine
    1. Alkaloid from West African tree: easily enters brain
    2. Facilitates release of norephinephrine at synapse
    3. Reversal of xylazine and detomidine, aphrodisiac
    4. Therapeutic Use
       1. Diagnosis of pheochromocytoma
       2. Essential hypertension
       3. Migraine
       4. Benign prostate hyperplasia
64. Atipamezole
65. Acebutolol
66. Esmolol
    1. short-acting ~10 mins
    2. Safest for myocardial infarction
67. Atenelol
68. Metaprolol
69. Propanolol
    1. B-blocker prototype
    2. Negative inotropic and chronotropic
    3. Peripheral vasoconstriction
    4. Increase in Na+ retention
    5. Decrease in glucose metabolism
    6. CNS: anxiety, sedation
    7. Therapeutic Use
       1. Hypertension
       2. Glaucoma
       3. Migraine
       4. Hyperthyroidism
       5. Angina pectoris
       6. Myocardial infarction
    8. Adverse Effects
       1. Bronchoconstriction
       2. Hypoglycemia
       3. Must stop gradually
70. Pindolol
71. Timolol
    1. Wide-angle glaucoma
    2. Decreases secretion of aqueous humour
    3. To remember: Pin and Tim pick up "B"abes at gas (propane) stations, they aren't selective
72. Carbachol
    1. Direct-acting
       1. Very potent nicotinic and muscarinic
          1. Rumen atony and impaction
          2. Colic in horses
          3. Take care to avoid excess peristalsis
       2. Totally resistant to hydrolysis, long-acting
       3. Stimulates autonomic ganglions, releases some ACh
73. Bethanechol
    1. Direct-acting
       1. Pure muscarinic agonist
          1. Rumen atony and impaction
          2. Colic in horses
          3. Take care to avoid excess peristalsis
       2. Totally resistant to hydrolysis: very potent, long-lasting
74. Pilocarpine
    1. Primarily muscainic, derived from Pilocarpus plant
    2. Treatment of intraocular pressure in chronic and acute canine glaucoma
    3. Acts on M3 muscarinic receptor to contract iris and clilary mm
75. Non-depolarizing
76. Depolarizing
77. Succinylcholine
    1. Non-competitive blocker
    2. Interferes with the ability of ACh to depolarize the postsynaptic membrane
78. Miyacurium
79. Pancuronium
80. Atracurium
    1. Non-depolarizing neuromuscular blockers are competitive
    2. They relax and finally paralyze skeletal mm by blocking ACh
    3. ACh can't interact with nicotinic receotors on the motor endplates of skeletal mm
81. d-tubocuraraine
82. Nicotine
83. Trimetaphan
84. Hexamethonium
    1. Prototype
    2. Competitively antagonizes the
    3. nicotinic effect of ACh at all autonomic ganglia
85. Ipratropium
    1. Quaternary derivative of atropine
    2. May be an exception: can produce bronchodilation without affecting mucociliary clearance
86. Homatropine
    1. Mydriasis and cycloplegia
    2. Less toxic than atropine
87. Glyycopyrrolate
    1. Preanaesthetic use in vet med, potent antimuscarinic
    2. Longer-acting than atropine, less lipophillic
88. Telenzepine
    1. Analogue of pirenzepine
89. Pirenzepine
    1. Selective for M1 receptors (ganglia and secretory glands)
    2. Reduces gastric acid secretions at doses that have little effect on salivation or heart rate
    3. Blocks M1 receptors in the intramural ganglia in the stomach and on entero-chromaffin-like cells
90. Scopolamine
    1. Relaxes urinary tract smooth muscles, urinary retention
    2. Light sedation, used for motion sickness (anti-emetic)
91. Atropine
    1. Competitively antagonize ACh or other parasympathomimetics at muscarinic receptors
    2. In dually innervated organs, effect depends on relative dominance of paraympathetic and sympathetic tones
    3. Blocking parasympathetics to an organ can have adrenergic effects, "frees up" sympathetic control
    4. Decreases saliva, sweating (in primates, not horses) at low dose
    5. Bronchodilation (and decrease in secretions), mydriasis, cycloplegia
       1. Higher topical dose needed for cyclopegia than mydriasis - lasts 1-5 days
       2. Use: To inspect retina, treat uveitis, keratitis, adhesins, spasms from eye injuries
       3. Anti-broncho-secretory agent: adjunct to general anaesthesia
    6. Tachycardia (blocks vagal impulses), increased cardiac output, increased BP - at high dose
    7. GI and urinary tract relaxation (at higher dose), inhibition of gastric acid (at even higher dose)
    8. Minimal CNS effects: excess dose leads to hallucinations followed by depression and coma
    9. Herbivores are more sensitive to orally administered atropine, but rabbits are resistant
92. Tolazoline
    1. Treats pulmonary hypertension of newborns
    2. Aid for arteriography
93. Ergot Alkaloids
    1. a-receptor blocking, oxytoxic
    2. partial activity on a-receptors
    3. Stimulates contraction of uterus postpartum
    4. Treatment of migraines
94. Methacholine
    1. Direct-acting
       1. Mild nicotinic, strong muscarinic
       2. hydrolized slowly by AChE: acts longer than ACh
95. Arecoline
    1. Primarily muscarinic, CNS: stimulation and euphoria
96. Reversible Cholinesterase Inhibitors
97. Irreversible Cholinesterase Inhibitors
98. Physostigmine
    1. For Myasthenia gravis, atopine toxicity andtidote
    2. Tertiary amine, well absorbed from GI tract: effective orally
    3. Easily penetrates BB barrier, CNS effects
    4. Miosis of pupil, reduces intraocular pressure, glaucoma
    5. Physostigmine + atropine prevents periodic ophthalmia
    6. Impaction in cattle
99. Neostigmine
    1. Myasthenia gravis, also to reverse neuromusculary blockades
    2. Systemic quaternary amine compound
    3. Effective orally but does not penetrate BB barrier
    4. Selective for nicotinic receptors at neuromuscular jxn and ANS ganglia.
100. Endrophonium
     1. To differentiate Myasethnia gravis and cholinergic crisis
     2. IV injection: improves myscle function
     3. Increased muscle weakness: cholinergic crisis
     4. Quaternary amine, like neostigmine but shorter acting. Anticurare
101. Pyridostigmine
     1. Pharmacologically similar to neostigmine, but longer acting
     2. Myasthenia gravis
     3. Note: effects of cholinesterase inhibitors last 1-3 hours
102. Organophosphorus Compounds
     1. Extremely toxic: see notes
103. Synthesis of Acetylcholine
104. Enzyme choline acetyl transferase
     1. Synthesized in prokarying
     2. Transported to axon terminal
105. Choline
     1. Derived from extra-cellular fluid by energy-requiring axoplasmic uptake process
     2. This process is inhibited by hemicholinium
     3. Choline uptake is rate-limiting step
106. Acetyl Coenzyme A
     1. Synthesixed in mitochondria of axon terminal
107. Storage in Synaptic Vesicles
     1. via vesicular transporter
     2. Transport to vesicles inhibited by vesamicol
108. Synaptic Cleft
     1. Axon potential at axon terminal causes depolarization
     2. Triggered and amplified by influx of calcium into axoplasm
     3. Botulism toxin inhibits this process by irreversibly blocking cholinergic junctions
109. Enzyme Acetyl Cholinesterase
     1. Hydrolyses / degrades ACh at cholinergic junctions
     2. Anticholinesterase drugs inhibit AchE
110. Pharmacological Effects
111. Low doses
     1. 5-10 micrograms/kg, IV
     2. Rapid and brief fall in mean BP, reflex tachycardia
     3. Due to generalized vasodilation caused by activation of noninnervated muscarinic receptors on endothelial cells
     4. BP fall stimulates baroreceptor reflex: heart rate increases
112. High doses
     1. 10-30 micrograms/kg
     2. Generalized parasympathomimetic effect
     3. Effects on heart, bronchioles, GI tract, uterus, urinary tract, eye, exocrine glands
     4. Extensive vasodilation, decrease in peripheral resistance
     5. Vagal stimulation induces pronounced, direct effect on heart
     6. Negative chronotropic and inotropic effects, decreased SA and AV node conduction
     7. Decreased cardiac output, reflex tachycardia
     8. Increased GI motility and secretions, exacerbates nausea
     9. Increased secretions of exocrine glands, bronchoconstriction
     10. Miosis, loss of accommodation, reduced intraocular pressure
     11. Increases release of epinephrine and norepinephrine from adrenal medulla
     12. Depolarization of motor endplates: skeletal mm contraction