class:  parasympathomimetics

type:  endogenous cholinergic

receptor:  nicotinic, muscarinic

effects:  nonspecific, rarely ophthalmic

clinical use:  nonspecific

• class:  parasympathomimetic
• type:  direct-acting synthetic choline ester
• receptor:  muscarinic (M3)
• specific effects:  detrusor contraction, trigone/sphincter relaxation
• clinical use:  empty bladder in the absence of obstruction

• class:  parasympathomimetic
• type:  direct-acting cholinomimetic alkaloid
• receptor:  muscarinic
• specific effects:  nonspecific
• not used clinically
• factor in mushroom toxicity

• class:  parasympathomimetic
• type:  direct-acting cholinomimetic alkaloid
• receptor:  muscarinic
• specific effects:  topical ophthalmic to induce pupil constriction
• clinical use:  induce miosis, reduce intraocular pressure in glaucoma, promote salivation

• class:  AChE inhibitors
• type:  reversible covalent inhibitor
• receptor:  decreases degradation of ACh
• specific effects:  enters the CNS
• clinical use:  counter CNS symptoms of anticholinergic intoxication

• class:  AChE inhibitor
• type:  reversible covalent inhibitor
• receptor:  acts by decreasing degradation of ACh
• specific effects:  stimulate visceral smooth muscle

Organophosphates

(Insecticides)

(Nerve Gases)

• class:  AChE inhibitor
• type:  irreversible covalent inhibitors
• receptor:  inhibits activity of AChE
• symptoms of toxicity:  SLUDGE, DUMBELS
• treatment:  cholinesterase "reactivators" (2-PAM)

• class:  anticholinergic
• type:  natural alkaloid
• receptor:  competitive inhibition of muscarinics
• specific effects:  enters CNS, decreases salivary and airway secretions
• clinical use:  adjunct during anesthesia, relieves AChE inhibitor toxicity
• NOTE:  rabbits have atropinases

• class:  anticholinergic
• type:  natural alkaloid
• receptor:  competitive inhibition of muscarinics
• specific effects:  enters CNS
• clinical use:  low dose causes slight sedation, high dose causes excitement, antiemetic

• class:  anticholinergic
• type:  synthetic alkaloid derivative
• receptor:  competitive inhibition of muscarinics
• specific effects:  decrease salivary and airway secretions, decrease bradycardia (does not enter CNS)
• clinical use:  adjunct during anesthesia

• class:  anticholinergic
• type:  synthetic alkaloid derivative
• receptor:  competitive inhibition of muscarinics
• specific effects:  ophthalmic topical produces mydriasis and cycloplegia
• clinical uses:  ophtho. exams, shorter duration than atropine

• class:  anticholinergic
• type:  synthetic alkaloid derivative
• receptor:  competitive inhibition of muscarinics
• specific effects:  decrease bronchoconstriction and airway secretions
• clinical uses:  asthma in cats, chronic bronchitis in dogs, recurrent airway inflammation in horses
• note:  administer via inhalation to prevent side effects

• class:  anticholinergic
• type:  synthetic alkaloid derivative
• receptor:  competitive inhibition of muscarinics
• specific effects:  detrusor relaxation, trigone, sphincter contraction
• clinical uses:  urine retention (treat incontinence)

• class:  NMJ blocker
• type:  competitive, non-depolarizing
• receptor:  nicotinic receptors at NMJ
• effect:  muscle weakness, then flaccid paralysis
• duration of action:  long (2-3 hours)
• metabolism:  renal elimination (half-like increased with renal dz
• toxicity issues:  little ganglionic blockade, no histamine release, blocks muscarinic receptors-tachycardia

• class:  NMJ blocker
• type:  competitive, non-depolarizing
• receptor:  nicotinic at NMJ
• effect:  muscle weakness, then flaccid paralysis
• duration:  intermediate (0.5-1 hour)
• metabolism:  multiple modes of elimination (half-life not increased with renal disease); degradation reduced with hypothermia and acidosis
• toxicity:  little/no ganglionic blockade, promotes histamine release

• class:  NMJ blocker
• type:  competitive, non-depolarizing
• receptor:  nicotinic at NMJ
• effect:  muscle weakness, then flaccid paralysis
• duration:  short (15 min)
• metabolism:  half-life not increased with renal disease
• toxicity:  little/no ganglionic blockade, promotes histamine release

• class:  NMJ blocker
• type:  non-competitive, depolarizing
• receptor:  nicotinic at NMJ
• effect:  early (phase I) depolarization with muscle fasciculations, late (phase II) with repolarization (receptor desensitization) and flaccid paralysis
• duration:  short (1 min onset, 5 min duration)
• toxicity:  no ganglionic blockade, some histamine release, hyperkalemia

• class:  sympathomimetics
• type:  direct-acting endogenous catecholamine
• receptor:  alpha and beta
• specific effects:
• increases CO (beta-1)
• peripheral vasoconstriction--increased BP at high dose (alpha-1)
• skeletal mm. vasodilation and bronchodilation (beta-2)
• clinical uses:  treat aanaphylaxis and asthma, restore cardiac rhythm, topical hemostasis, adjunct with local anesthetics

• class:  sympathomimetic
• type:  direct-acting endogenous catecholamine
• receptors:  beta-1 EPI=NE; beta-2 EPI>>>NE; alpha-1 EPI>NE
• specific effects:  intense vasoconstriction, increased BP, no bronchodilation
• clinical use:  maintain BP during shock (alpha-1, beta-1 effects)

• class: sympthomimetics
• type:  direct-acting endogenous catacholamine
• receptors:  vascular D1, cardiac beta-1, vascular alpha-1
• specific effects:  low dose increase renal blood flow and Na excretion, positive inotropic effect; high dose vasoconstriction, decreased RBF
• clinical uses:  low dose CRI for CHF with compromised renal function (short-term)

• class:  sympathomimetics
• type:  non-selective beta-adrenergic agonist
• receptor:  beta-1>beta-2 and alpha-1 (closest to beta-1 selective agonist)
• specific effects:  increase cardiac contractility with minimal change in HR and BP, bronchodilation
• clinical uses:  inotrope during heart failure (short-term)
• side effects:  unwanted/excess beta stimulation (increased HR when used as bronchodilator)

• class:  sympathomimetic
• type:  selective beta-2 adrenergic agonist
• receptor:  beta-2
• specific effects:  bronchodilation
• clinical uses:  bronchospasm in dogs, cats, horses
• side effects:  unwanted/excess beta stimulation, cardiac excitation, receptor down-regulation

• class: sympathomimetic
• type:  selective beta-2 adrenergic agonist
• receptor:  beta-2
• specific effects:  bronchodilation
• clinical uses:  recurrent airway obstruction in horses
• side-effects:  minimize with inhalation, proper dose and dosing schedule

• class: sympathomimetic
• type:  selective alpha-1 adrenergic agonist
• receptor:  alpha-1
• specific effects:  vasopressor, decongestant
• clinical uses:  increase BP, treat hypotension and shock
• side-effects:  hypertension

• class:  sympathomimetic
• type:  selective alpha-2 adrenergic agonist
• receptor:  alpha-2
• specific effects:  CNS and presynaptic inhibition (decreases NE release)--sedation, analgesia
• clinical uses:  adjunct for sedation, anesthesia, and analgesia (allows for lower doses of lower-safety agents)
• note:  high safety profile

• class:  sympatholytic
• type: direct-acting non-competitive antagonist
• receptor:  non-selective irreversible alpha antagonist
• specific effects:  vasodilation, CNS excitation
• clinical uses:  treat sympathomimetic-induced hypertension
• note:  cannot be pharmacologically reversed, receptors must be replenished

• class:  sympatholytic
• type:  direct-acting competitive antagonist
• receptor:  non-selective reversible alpha antagonist
• specific effects:  vasodilation, CNS excitation
• clinical uses:  treat sympathomimetic-induced hypertension

• class:  sympatholytic
• type:  aelective alpha-1 adrenergic antagonist
• receptor:  alpha-1
• specific effects:  vasodilation, relax arterial and venous smooth mm.
• clinical uses:  antihypertensive, used for CHF (decreases pre- and afterload)

Atipamezole

• class:  sympatholytic
• type:  selective alpha-2 adrenergic antagonist
• receptor:  alpha-2
• specific effects:  increase sympathetic activity, decrease CNS inhibition (increase NE release)
• clinical uses:  reversal of medetomidine sedation (antisedan)

• class:  sympatholytic
• type:  non-selective beta-adrenergic antagonist
• receptor:  beta-1 and beta-2
• specific effects:  antiarrhythmic, increase bronchoconstriction
• clinical uses:  decrease cardiac arrhythmias
• generally not used due to beta-2 effects (bronchoconstriction)

• class: sympatholytic
• type:  non-selective beta-adrenergic antagonist
• receptor:  beta-1 and beta-2
• specific effects:  ocular use to decrease aqueous humor production
• clinical use:  glaucoma

• class:  sympatholytic
• type:  selective beta-1 adrenergic antagonist
• receptor:  beta-1
• specific effects:  decrease CO, HR, contraactility, BP; antiarrhythmic, decrease cardiac O2 demand
• clinical uses:  feline hypertrophic cardiomyopathy

• class:  Na-channel blockers
• type:  IA
• receptor:  Na channels
• effect:  moderate slowing of conduction velocity, lengthens refractory period
• clinical use:  supraventricular tachycardia (from reentrant arrhythmia)

• class:  Na-channel blocker
• type:  IB
• receptor:  inactivated Na channels
• effect:  little change in conduction velocity, shortens refractory period
• clinical use:  ventricular tachycardia (ectopic pacemaker)

• class: Na-channel blockers
• type:  IC
• receptor:  Na channels
• effect:  large decrease in conduction, little change in refractory period
• use:  use only in life-threatening situations (can be very arrhythmogenic)

•  class: beta blockers (class II)
• receptors:  beta-1 and beta-2
• effect:  decreases sympathetic activity
• clinical uses:  excessive sympathetic activity is arrhythmogenic, manage using beta-blockers

• class:  action potential prolonging (class III)
• receptors:  block K+ channels
• effects:  prolong AP, increase refractory period
• clinical uses:  reentrant supraventricular tachycardia
• side effects:  arrhythmogenic, pulmonary fibrosis, derm problems

• class:  Ca-channel blockers (class IV)
• type:  non-vascular specific Ca-channel blockers
• receptor:  Ca channels
• effects:  slows AV node conduction
• clinical use:  decrease ventricular response to atrial fibrillation
• note:  can decrease cardiac contractility

• class:  miscellaneous antiarrhythmic
• type:  similar action to class IV
• receptors:  Ca channels
• effects:  decrease AV node conduction
• clinical use:  decrease ventricular response to atrial fibrillation
• note:  very arrhythmogenic, AV block (must be tightly regulated)

• class:  miscellaneous antiarrhythmic
• type:  ATP minus the TP
• effects:  blocks AV node conduction
• clinical use:  terminate supraventricular tachycardiacs involving SA node
• note:  half-life=5 sec.

• class:  renin-angiotensin inhibitor
• type:  ACE inhibitor
• receptor:  competitive antagonist of ACE
• mechanism:  prevents conversion of Ang I to Ang II
• effect:  vasodilation

• class:  renin-angiotensin inhibitor
• type:  angiotensin receptor antagonist
• receptor:  competitive antagonist of AT1 receptors
• mechanism:  blocks pro-hypertensive effects of Ang II
• side-effects:  decreases sympathetic activity, tubular water/Na retention (from decreased aldosterone), decreased water reabsorption (from decreased ADH)

• class:  Ca-channel antagonist
• type:  dihydropiridine
• receptor:  vascular-specific Ca channel antagonist (not blocker!)
• effects:  decrease arterial smooth mm Ca channel activity, decrease Ca entry and contraction of smooth mm.
• clinical uses:  vasodilation, decrease TPR, temp increase of CO

• class:  nitrovasodilator
• type:  exogenous NO donor (stable organic nitrate)
• effects:  venous dilation, arterial dilation at high doses
• clinical uses:  cute cardiogenic pulmonary edema, CHF
• note:  tolerance develops over time

• class:  nitrovasodilator
• type:  exogenous NO donor
• effect:  arterial and venous dilation, decrease TPR, decrease BP
• clinical uses:  hypertensive emergencies, acute CHF
• note:  light sensitive--produces cyanide!!!  discard if dark brown, orange, blue

• class:  PDE5 inhibitor
• mechanism:  inhibition of PDE5 increases cGMP, increases PKG-->vasodilation
• clinical uses:  manage pulmonary hypertension, BONERS!!

• class:  K-channel activator
• mechanism:  opens K channels in arterial smooth m.
• effects:  hyperpolarize membranes, decrease Ca entry, decrease TPR, decrease BP
• clinical use:  rarely used

class:  miscellaneous vasodilator

mechanism unclear

effects:  increase NO, increase cGMP, decrease IP3 induced Ca release

clinical uses:  hypertensice crises, reflex tachycardia, fluid retention

note:  use with diuretic in dogs with mitral insufficiency (decrease afterload)

class:  PDE3 inhibitor

receptor:  PDE3 in myocardium

effects:  increase cAMP, increase PKA, increase Ca influx, increase Ca induced Ca release

clinical uses:  mimics effect of beta-1 stimulation, dhort-term use for acute heart failure, can be used with beta blockers

• class:  calcium sensitizer
• mechanism:  enhance contractile process directly by increasing affinity of troponin C for Ca
• clinical use:  CHF in dogs
• note:  only small increase in O2 consumption, not associated with arrhythmias

• class:  diuretic
• type:  osmotic
• mechanism:  overwhelms transporters ability to reabsorb molecule, increased osmotic pressure within lumen pulls water into tubules
• clinical uses:  treat/prevent oliguric renal failure, cerebral edema, acute glaucoma
• notes/side-effects:  do not use if can't establish renal flow or if intrcranial bleeding

• class: diuretic
• type:  carbonic anhydrase inhibitor
• location of action:  proximal tubule
• mechanism:  increases loss of bicarb, increases urine pH
• clinical uses:  treat metabolic alkalosis, glaucoma, altitude sickness
• side effects/notes:  hypokalemia possible, alkalizing effect on urine can cause systemic acidosis

• class:  diuretic
• type:  loop diuretic
• location of action:  thick ascending limb of LOH
• mechanism:  inhibits NaCl reabsorption, water follows urinary loss of NaCl
• clinical uses:  treat oliguric renal failure, CHF, acute pulmonary hypertension, EIPH
• notes/side-effects:  most effective diuretic, hypokalemia possible, may increase Ca loss in urine

• class:  diuretic
• type:  thiazide
• location of action:  distal tubule
• mechanism:  blocks NaCl reabsorption, may indirectly increase Ca reabsorption, reduces kidney stone formation
• clinical uses:  nephrogenic diabetes insipidus, udder edema in cattle, Ca-containing uroliths
• note:  not as effective as loops

• class:  diuretic
• type:  K-sparing
• receptor:  mineralocorticoid receptor antagonist
• mechanism:  competitive aldosterone antagonist; blocks aldosterone-induced expression of multiple genes, delays onset of action and prolongs effect
• clinical uses:  milk diuresis with reduced potential for K loss, used in conjunction with loops

• class:  diuretic
• type:  K-sparing
• location of action:  epithelial Na channels
• mechanism:  principle cell Na channel blocker
• effect:  immediate, mild diuretic
• used in conjunction with loops

• class:  diuretic
• type:  K-sparing
• location of action:  Na channels
• mechanism:  principle cell Na channel blocker
• used in conjunction with loops

What is the primary mode of metabolism for NTs in the parasympathetic system?

What is the primary mode of metabolism for NTs in the sympathetic system?

para:  ACh is degraded by AChE

symp:  NE reuptake by adrenergic neuron (also uptake into effector cell)

Train of Four:  stimulate superficial peripheral nerve four times and evaluate response of target muscle

if response is the same as before the block, need more drug

fade pattern with nondepolarizing block or late depolarizing block

constant but diminished pattern in early depolarizing block

• respiratory paralysis
• prolonged apnea and cardio collapse from histamine release or anaphylaxis
• hypotension from ganglionic blockade
• malignant hyperthermia (rare)--excessive contracture and heat production from skeletal muscle

disorders of impulse formation and/or conduction

pacemaker arrhythmias:

• abnormal slowing of SA firing rate
• abnormal acceleration of extopic firing rate

conduction arrhythmias:

• bradycardia from AV nodal block
• tachycardia from reentrant circuit

reducing workload

increasing performance

sympathomimetics

dobutamine (beta-1, alpha-1)

dopamine (D1, beta-1)

PDE3 inhibitors

milrinone

cardiac glycosides

digoxin

calcium sensitizers

pimobendan