Autonomic Pharmacology

• partial agonist of α4β2 subtype of neuronal nicotinic receptor
• mediates reward effect of nicotine, may help treat nicotine dependence

• competitive antagonist of somatic muscle nicotinic Ach receptors (non-depolarizing)
• can be overcome by high [c] of ACh
• progressive paralysis starting with facial mm, then limbs and respiratory mm
• prolonged paralysis in patients with butyrylcholinesterase

• competitive antagonist of somatic muscle nicotinic Ach receptors (non-depolarizing)
• can be overcome by high [c] of ACh
• progressive paralysis starting with facial mm, then limbs and respiratory mm
• long-acting

• competitive antagonist of somatic muscle nicotinic Ach receptors (non-depolarizing)
• can be overcome by high [c] of ACh
• progressive paralysis starting with facial mm, then limbs and respiratory mm
• intermediate-acting

AChE inhibitor used as a reversal agent for non-depolarizing neuromuscular blockers (vecuronium, pancuronium)

• persistent agonist of muscle-type nicotinic ACh receptor (depolarizing agent)
• leads to flaccid paralysis
• short acting
• not easily reversed
• metabolized by butyrylcholinesterase
• Can cause hyperkalemia and malignant hyperthermia (hyperthermia reversed with dantrolene)
• prolonged paralysis in patients with butyrylcholinesterase

• AChE inhibitor used in the treatment of Myasthenia Gravis
• longer-acting

• AChE inhibitor that penetrates the CNS, used in the treatment of Alzheimer's Disease
• limited effect, improvement seen for less than a year

• Muscarinic ACh receptor agonist
• used to treat glaucoma (topically) and manage urinary retention disorders that impair bladder emptying
• Muscarinic ACh receptor agonists used to treat glaucoma, urinary retention, and xerostomia (dry mouth)

• Muscarinic ACh receptor agonist
• used to treat glaucoma (topically)
• Muscarinic ACh receptor agonists used to treat glaucoma, urinary retention, and xerostomia (dry mouth)

• Muscarinic ACh receptor agonist
• used to treat glaucoma (topically)
• Muscarinic ACh receptor agonists used to treat glaucoma, urinary retention, and xerostomia (dry mouth)

• prevents irreversible inhibition of AChE
• only used in treatment of organophosphate toxicity

• muscarinic ACh receptor antagonist
• reverse AChE inhibitor poisoning
• treat severe bradycardia

muscarinic ACh receptor antagonist

• muscarinic ACh receptor antagonist
• used in ophthalmology to dilate pupils
• short-lived (4-8hrs) via eyedrops

• muscarinic ACh receptor antagonist
• used to treat motion sickness

• muscarinic ACh receptor antagonist
• used to dry secretions

• muscarinic ACh receptor antagonist
• used in Parkinsonism

• muscarinic ACh receptor antagonist
• used to treat asthma and COPD
• ipratropium used in combination with albuterol

• muscarinic ACh receptor antagonist
• used to treat bladder spasm and urinary incontinence

• α1 adrenergic agonist
• treats nasal congestion by limiting blood flow to nasal mucosa or to raise BP (when given IV)
• causes mydriasis, vasoconstriction, urinary retention, and contraction of smooth muscle of the prostate

• α2 adrenergic receptor agonist
• activates presynaptic α2 receptor that has an inhibitory effect on sympathetic nervous system
• used to treat hypertension
• if treatment stopped abruptly, can cause rebound hypertension

• α1-specific antagonist
• used to treat hypertension
• may cause orthostatic hypotension (prazosin especially noted for first dose effect of large drop in blood pressure)

• α1-specific antagonist
• used to treat benign prostatic hyperplasia by relaxing prostatic capsular smooth m
• may cause orthostatic hypotension

• non-specific α antagonist
• phenoxybenzamine acts irreversibly
• used in management of pheochromocytoma (neuroendocrine tumor that produces catecholamines)

• β1 adrenergic receptor agonist
• used to treat cariogenic shock and heart failure

• β2 adrenergic receptor agonist
• short acting used primarily for acute asthma attacks or to prevent symptoms
• can also activate β1 receptors, leading to tachycardia (with repeated use)
• route: inhalation or systemically

• β2 adrenergic receptor agonist
• long acting used for chronic asthma therapy
• use associated with increased risk of asthma death
• usually mixed with corticosteroids

• β2 adrenergic receptor agonist
• can be used as a fast-acting bronchodilator
• causes relaxation of uterine smooth muscle
• used to slow down labor or halt premature labor (now discouraged)

• non-selective β-adrenergic agonist
• lowers peripheral vascular resistance (β2)
• increases heart rate and contractility (β1) - used in symptomatic bradycardia, and as a bridge to pacemaker placement
• blocked by non-selective β-blocker such as propranolol or nadolol

• β3 adrenergic agonist
• used for overactive bladder

• endogenous agonist with most potent actions at α1/2 and β1 receptors, but relatively little β2 action
• used in septic shock to increase BP by increasing vascular resistance and heart rate
• pressor effect triggers compensatory vagal action to slow the heart rate
• CO is unchanged/decreased
• PVR increases

• vasoconstriction of many vascular beds (increase precapillary resistance, α1)
• increase heart rate and contraction (β1)
• vasodilation of large vessels in skeletal muscle (β2)
• dilation of bronchial smooth muscle (β2)
• overall: modest rise in arterial pressure with increase in systolic and decrease in diastolic pressure, inc. pulse rate
• can be combined with α-adrenergic antagonist, making β agonist effects unopposed (AKA epinephrine reversal): strong inc in heart rate, prominent vasodilation, and drop in MAP

• non-selective β-blocker (antagonize β1 and β2)
• used to treat anxiety, muscle tremors, and hyperthyroidism - all work through β2 receptors 
• short half-life
• adverse effects: bradycardia, AV conduction block, hypotension, sexual dysfunction
• can cause problems in asthma patients because of bronchoconstriction, and diabetics by blocking glycogenolysis

• non-selective β-blocker (antagonize β1 and β2)
• treats open-angle glaucoma by reducing aqueous humor secretion
• topical treatment
• adverse effects: bradycardia, AV conduction block, hypotension, sexual dysfunction
• can cause problems in asthma patients because of bronchoconstriction, and diabetics by blocking glycogenolysis

• non-selective β-blocker (antagonize β1 and β2)
• long half-life
• adverse effects: bradycardia, AV conduction block, hypotension, sexual dysfunction
• can cause problems in asthma patients because of bronchoconstriction, and diabetics by blocking glycogenolysis

• selective β1 receptor antagonist
• esomolol: very short half-life (4 min, IV)
• metoprolol and atenolol: intermediate half-life
• adverse effects: bradycardia, AV conduction block, hypotension, sexual dysfunction

• β-adrenergic partial agonists
• intrinsic sympathomimetic activity
• act as antagonists where there is high adrenergic activity
• theoretically should cause less bradycardia and other adverse effects, but not widely prescribed in the US

• β-blocker with α1-adrenergic antagonism
• used for managing certain forms of heart failure

• β-blocker with α1-adrenergic antagonism
• used for hypertension during pregnancy

• blocks NE and dopamine reuptake
• schedule II drug with limited use as local anesthetic in ENT surgeries
• no specific antidote
• high [c] associated with IV use
• complicated metabolism, can vary from 30 min (chronic user) to 11 hrs (newborns
• diagnostic metabolite is benzoylecgonine
• health complications: MI, stroke, brain hemorrhage, seizures, birth defects, placental abruption - constriction of placental vessels

• increase NE release from nerve terminals
• increase release of dopamine
• no specific antidote
• clinical use
• ADHD - amphetamine mixed salts (Adderall), lisdexamfetamine (Vyvanse) lysine linked to dextroamphetamine
• short term weight loss
• narcolepsy

• closely related to amphetamine
• commonly abused as d-methamphetamine
• l isomer marked as Vicks vapor inhaler
• Desoxyn is the only rx form on market: limited use for obesity and ADHD
• smoking and injecting methamphetamine associated with binge use

• misleading name for illicit amphetamine-like drugs
• related to cathinone and the amphetamines: mephedrone, methylenedioxypyrovalerone (MDPV)
• some similarities in pharmacology to amphetamines, with hallucinations and panic attacks reported