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Bethanechol
- A muscarinic receptor stimulant
- Stimulates smooth muscle post-operatively (whe atony of GI tract following surgery, dysfunction with bladder emptying, and promotion of saliva formation)
- Not effectively hydrolyzed by AChE, so has a longer half-life than methacholine
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Methacholine
- A muscarinic receptor stimulant
- Used to test funciton of muscarinic receptors, to slow heart in severe tachycardia (other approaches are tried first), and to test for bronchial hyperactivity
- Effectively hydrolyzed by AChE, so has a short half-life (10 mins)
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Carbachol
- Muscarinic receptor stimulants
- Used for corneal application for therapy of wide-angle glaucoma to constrict ciliary muscle, which opens the meshwork of the canal of Schlemm
- Not effectively hydrolyzed by AChE, so has a longer half-life than methacholine
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Pilocarpine
- Muscarinic receptor stimulants
- Used to increase salivary secretions
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Demecarium
- Reversible inhibitor of AChE
- Topically used for glaucoma
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Edrophonium
- Reversible inhibitor of AChE
- Used to diagnose myasthenia gravis
- Short acting
- Is a simple alcohol with quaternary ammonium group
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Neostigmine
- Reversible inhibitor of AChE
- Increases smooth muscle motility and is useful for paralytic ileus and atony of the bladder from surgery; treatment and diagnosis of myasthenia gravis; and reversal of neuromuscular blockade
- Intermediate acting
- Is a carbamate with quaternary ammonium group
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Physostigmine
- Reversible inhibitor of AChE
- Used topically for therapy of wide-angle glaucoma
- Is a carbamate with tertiary amine group
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Pyridostigmine
- Reversible inhibitor of AChE
- Used in the treatment of myasthenia gravis; pretreatment to reduce mortality after exposure to nerve gases; reversal of neuromuscular blockade
- Is a carbamate
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Echothiophate
- Irreversible inhibitor of AChE
- Used for glaucoma
- Is an organo-phosphate
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Malathion
- Irreversible inhibitor of AChE (is an organo-phosphate)
- Used for treatment of head lice
- Is an insecticide
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Diisopropylfluorophosphate (DFP)
- Irreversible inhibitor of AChE (is an organo-phosphate)
- Used in insecticides
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Parathion
- Irreversible inhibitor of AChE (is an organo-phosphate)
- Used in insecticides and is a common agent of organo-phosphate poisoning
- These O-Ps are highly toxic and cause 25,000 deaths/year worldwide
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Sarin and soman
- Irreversible inhibitor of AChE (is an organo-phosphate)
- These are nerve gases that are highly volatile
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Atropine
- Reversible muscarinic receptor antagonist; has little toxicity at nicotinic receptors
- Used when organo-phosphate intoxication occurs; also useful for making mydriasis and cycloplegia (long-acting); sweat, bronchial, and saliva glands are very sensitive; good treatment for Parkinson disease
- Elicits some tachycardia, because it blocks vagal slowing of the heart
- Can also cause reduced gastric secretions, but only at high doses
- A tertiary amine, capable of crossing the BBB; diffuses quickly
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Pralidoxime
- AChE reactivator
- Used to reverse nerve gas or insecticidal poisoning
- Must be given in a timely manner because it works on the inhibited AChE intermediate, not the "aged" AChE
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Scopolamine
- Reversible muscarinic receptor antagonist
- Used for motion sickness; does cause amnesia
- A tertiary amine, capable of crossing the BBB; diffuses quickly
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Methscopolamine
- Reversible muscarinic receptor antagonist
- Used mainly for GI diseases to inhibit secretions (also inhibits secretion of respiratory tract)
- A quaternary amine, incapable of crossing the BBB
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Homatropine and Tropicamide
- Reversible muscarinic receptor antagonist
- Used to cause mydriasis and cycloplegia [intermediate (2-4 hours) and short-acting (0.5-1.5 hours), respectively]
- Tertiary amines, capable of crossing BBB, but are applied topically to the eye
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Trihexyphenidyl
- Reversible muscarinic receptor antagonist
- Used for Parkinson disease treatment
- A tertiary amine, capable of crossing the BBB
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Oxybutinin
- Reversible muscarinic receptor antagonist
- Used for relaxation of smooth muscle of genitourinary system (urinary urgency, urinary retention, or bladder spasm)
- Some M3 selectivity
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Darifenacin, Solifenacin, Tolterodine
- Reversible muscarinic receptor antagonists
- Used for relaxation of smooth muscle of genitourinary system (urinary urgency, urinary retention, or bladder spasm)
- Very specific for M3 receptor blocking; leads to longer duration of action
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Trimethaphan
- Competitive ganglionic blocking agent (N1 blocker)
- Used to lower arterial pressure to control bleeding
- May cause excessive hypotension and possible brain anoxia
- Is short-acting
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Mecalmylamine
- Competitive ganglionic blocking agent (N1)
- Used to improve absorption from GI tract following oral administration (slows GI movement)
- A secondary amine, capable of crossing the BBB
- Causes CNS sie effects including tremors, confusion, seizures, mania, and depression
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Curare
- Competitive inhibitor of acetylcholine
- Used to cause relaxation of skeletal muscles
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Cisatracurium
- Competitive inhibitor of acetylcholine
- Used to cause relaxation of skeletal muscles
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Vecuronium
- Competitive inhibitor of acetylcholine
- Used to cause relaxation of skeletal muscles
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Succinylcholine
- Noncompetitive inhibitor of acetylcholine
- Causes depolarization of end-plate region (contraction happens first, followed by a persistent relaxation and inhibition)
- Short acting due to degradation by plasma ChE, but plasma ChE inhibitors can augment effect
- Phase I inhibition: Membrane is depolarized
- Phase II inhibition: Membrane repolarizes but is resistant to any other depolarization
- Used to cause relaxation of skeletal muscles
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Ephedrine
- Used to increase transmission at the neuromuscular junction following blocking, but mechanism is unknown
- Adrenergic receptor agonist
- A1 and B1 receptors
- Has a substitution to benzene ring, making it a poor substrate for COMT inactivation and a longer-acting catecholamine
- Also has a substitution to the alpha carbon, making it a poor substrate for MAO inactivation, and can displace NE from adrenergic storage vesicles, making it a norepinephrine releasing agent
- Results in:
High cardiac output and arterial pressure; mild stimulation of CNS; mild B2 activity to dilate bronchial smooth muscle; nasal decongestant - Used clinically for chronic orthostatic hypotension (A1 and B1); hemostasis during surgery, reducing diffusion of local anesthetics from injection site, reducing congestion of mucous membranes (A1 vasoconstriction); rescuing cardiac function (B1); anaphylaxis; stress incontinence (B2)
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Nicotine
- Increased cardiac rate, vasoconstriction, and plasma levels of epinephrine from stimulation of adrenal medulla; decreased mucociliary movement in lungs; and mild CNS stimulation
- Also causes small cell carcinoma of the lung and cardiovascular disease
- Lethal dose: 40mg (same as cigar), but bioavailability is very low
- Keep in mind that nicotine also stimulates N2 receptors in addition to N1
- Acute nicotine toxicity can lead to neuromuscular blockade
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Isoproterenol
- Adrenergic receptor agonist
- Has a substitution to amino group, so has greater B receptor affinity
- B1 = B2 >>>>>> A
- Potent vasodilator (B2) to skeletal muscles, resulting in decreased MAP; significant increase in cardiac output (B1)
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Dobutamine
- Adrenergic receptor agonist
- Has a substitution to amino group, so has greater B receptor affinity
- B1 > B2 >>>>>> A
- Used to treat cardiogenic shock following MI (B1)
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Terbutaline
- Adrenergic receptor agonist
- Has a substitution to amino group, so has greater B receptor affinity
- B2 >> B1 >>>>>> A
- Used for bronchial asthma treatment or to relax a pregnant uterus
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Metaproterenol
- Adrenergic receptor agonist
- B2 >> B1 >>>>>> A
- Used for bronchial asthma treatment
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Albuterol
- Adrenergic receptor agonist
- B2 >> B1 >>>>>> A
- Used for bronchial asthma treatment
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Metaraminol
- Adrenergic receptor agonist
- Has a substitution to benzene ring, making it a poor substrate for COMT inactivation and a longer-acting catecholamine
- Also has a substitution to the alpha carbon, making it a poor substrate for MAO inactivation, and can displace NE from adrenergic storage vesicles
- A1 selective
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Phenylephrine
- Adrenergic receptor agonist
- Has a substitution to benzene ring, making it a poor substrate for COMT inactivation and a longer-acting catecholamine
- A1 > A2 >>>>>> B
- Used to overcome hypotensive crisis to protect cerebral and coronary blood flow (A1); reducing diffusion of local anesthetics (A1); reducing congestion of mucous membranes (A1); eliciting mydriasis to facilitate a retinal exam
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Pseudoephedrine
- Norepinephrine releasing agent
- Used to reduce congestion of mucous membranes
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Methoxamine
- Adrenergic receptor agonist
- A1 > A2 >>>>>> B
- Used to overcome hypotensive crisis to protect cerebral and coronary blood flow
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Clonidine and methyl-NE
- Adrenergic receptor agonists
- A2 > A1 >>>>>> B
- Since they are specific for A2, they inhibit norepinephrine release
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Guanabenz and a-methyldopa
- Adrenergic receptor agonists
- A2
- Since they are specific for A2, they inhibit norepinephrine release
- a-methyldopa: Is a false neurotransmitter, because it is incorporated into biosynthesis by replacing DOPA (enters CNS too); a-methyl norepinephrine (MNE) is made and stored in synaptic vesicles instead of norepinephrine
- MNE is released from terminals, but has little effect on receptors; does also stimulate brainstem to affect the vasomotor center to decrease blood pressure
- Side Effects: Sedation, dizziness, sleep disturbances, impotence, dry mouth, nasal congestion, postural hypotension in some patients
- Severe Problems: Brought on by chronic therapy; hemolytic anemia, leukopenia, heatitis, lupus-like problems
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Fenoldopam
- Adrenergic receptor agonist
- D1 >> D2
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Dopamine
- Adrenergic receptor agonist
- Released by postanglionic sympathetic nerves of renal and splanchnic vasculature smooth muscle
- D1 = D2 >> B >> A
- A1 and B1 are stimulated at HIGHER DOSES
- Also acts as a norepinephrine releasing agent when taken up by amine I transport (NET) into prejunctional sympathetic terminals
- Used as a therapy for shock: Increases vasoconstriction (A1), cardiac rate/contractility (B1), blood flow to kidneys and mesentary (D1)
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Epinephrine
- Adrenergic receptor agonist
- Released from adrenal medulla directly into venous circulation
- A1 = A2
- B1 = B2, but are 10x more sensitive to epinephrine than A1/A2
- In other words, will stimulate B receptors at low doses, resulting in decreased MAP; at higher doses, A1 receptors are stimulated, resulting in vasoconstriction and increased MAP
- Used as a very potent vasoconstrictor (A1) and cardiac stimulant (B1); vasodilation to skeletal muscle also occurs (B2)
- MOST POTENT VASOPRESSOR when given at high doses
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Norepinephrine
- Adrenergic receptor agonist
- Primary neurotransmitter of adrenergic nerves
- A1 = A2 B1 >> B2
- Used as a very potent vasoconstrictor (A1) and cardiac stimulant (B1); elicits MAP due to lack of B2 stimulation
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Cocaine
- Amine I transporter (NET) inhibitor (prejunctional sympathetic stimulator)
- Results in higher synaptic levels of NE, causing sympathetic stimulation
- Causes vasoconstriction, tachycardia, and mydriasis
- Used to prevent hemostasis during surgery
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Tricyclic antidepressants [DMI]
- Amine I transporter (NET) inhibitors (prejunctional sympathetic stimulators)
- Result in higher synaptic levels of NE, causing sympathetic stimulation
- Causes vasoconstriction, tachycardia, and mydriasis
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Haloperidol and chlorpromazine
- D2 receptor blockers
- Block negative feedback of postganglionic sympathetic nerve
- Results in greater dopamine release
- Used as antipsychotic agents
- May have peripheral side effects
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Tyramine
- Norepinephrine releasing agent
- Phenylethylamine derivative that is taken up by NET and displaces NE from storage vesicles, causing greater release in synapse
- Patients on MAO inhibitors (which cause prolonged amounts of norepinephrine in synapse anyway) should avoid eating cheeses, sausage,or smoked/pockled fish because they are high in tyramine
- Excessive release of norepinephrine will raise arterial pressure
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Amphetamines
- Norepinephrine releasing agents
- Taken up by NET and displaces NE from storage vesicles, causing greater release in synapse
- Also reverses amine I transport (NET) to move norepinephrine out of terminal
- Also directly stimulates A1 and B1 receptors
- Results in elevation of arterial pressure
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Apraclonidine and brimonidine
- Adrenergic receptor agonists
- Used for glaucoma treatment (B2 receptors cause decreased intraocular pressure)
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Bromocriptine
- D2 receptor agonist
- Results in decreased amounts of norepinephrine released
- Used as an anti-Parkinson agent for CNS activities
- Side Effects: Postural hypotension durig initial therapy; development of cardiac arrhythmia
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Reserpine
- Norepinephrine depleting agent
- Prevents norepinephrine (and epinephrine, dopamine, and serotonin) transport into storage vesicles by VMAT
- Side Effects: Sedation, depression, Parkinsonian symptoms, increased GI motility & ulcers
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Guanethidine
- Norepinephrine depleting agent via membrane stabilization
- Prevents norepinephrine release by stabilizing the membranes; norepinephrine becomes trapped within synaptic vesicles
- Used to elicit hypotension
- Amine I transport (NET) inhibitors [cocaine, tricyclic antidepressants] antagonize this hypotensive activity by not allowing norepinephrine to be transported back into the cell
- Benefits: Minimal effects with other biogenic amines (epinephrine, dopamine); minimal adverse side effects in CNS because does not cross BBB
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Prazosin
- Competitive A1 adrenergic blocker
- A1 >>>>>> A2
- Used for therapy of hypertension
- Little or no tachycardia due to selectivity for A1 receptors
- Long-acting
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Tamsulosin
- A1 adrenergic blocker
- Likely used for therapy of hypertension
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Terazosin and doxazosin
- A1 adrenergic blockers
- A1 >>>>>> A2
- Used for therapy of hypertension
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Phenoxybenzamine
- Irreversible A1 and A2 adrenergic blocker; also inhibits Amine I of norepinephrine
- Used for treatment of hypertension (as an adjunct) or pheochromocytoma
- Side Effects: Postural hypotension and tachycardia, which results from reflex activation of adrenergic nervous system due to decreased MAP
- Long-acting
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Phentolamine
- Competitive A1 adrenergic blocker
- Inhibits both A1 = A2
- A1 inhibition results in vasodilation
- However, A2 inhibition results in increased levels of norepinephrine, which stimulates the B1 receptors, causing increased cardiac output and tachycardia
- Used for pheochromocytoma preoperative management or for inoperable tumors
- "Dirty" drug because also interacts with muscarinic and histamine receptors
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Labetalol
Blocks A and B adrenergic receptors
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Propranolol
- B1/B2 adrenergic blocker
- Is an effective prophylactic agent to prevent recurrence of myocardial infarction
- Used as an antihypertensive, anti-arrhythmic, chest pain, migraine headache
- Side Effects: Ataxia and dizziness
- 3-6 hour half-life
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Pindolol
- B1/B2 adrenergic blocker
- Used as an antihypertensive
- 3-6 hour half-life
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Timolol
- B1/B2 adrenergic blocker
- Is an effective prophylactic agent to prevent recurrence of myocardial infarctoin
- Used to reduce intraocular pressure in glaucoma patients; as an antihypertensive; and for chest pain
- 4-5 hour half-life
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Nadolol
- B1/B2 adrenergic blocker
- Used as an antihypertensive
- Fewer CNS side effects because cannot cross BBB well
- 14-24 hour half-life
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Betaxolol
- B1 specific adrenergic blocker
- Still use cautiously in asthmatic patients
- Used to treat glaucoma
- Long half-life
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Atenolol
- B1-specific adrenergic blocker
- Still use cautiously in asthmatic patients
- Used to treat hypertension
- Fewer side effects because cannot cross BBB well
- 6-9 hour half-life
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Metoprolol
- B1-specific adrenergic blocker
- Still use cautiously in asthmatic patients
- Is a super effective prophylactic agent to prevent recurrence of myocardial infarction
- Used as an antihypertensive and for chest pain
- Side Effects: Ataxia and dizziness
- 3-4 hour half-life
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Diphenhydramine
- First-generation antihistamine
- Causes sedation
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Dimenhydrinate
- First-generation antihistamine
- Causes sedation
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Cyclizine
- First-generation antihistamine
- Causes sedation
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Promethazine
- First-generation antihistamine
- Causes sedation
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Loratadine
- Second-generation antihistamine
- Low sedation, due to high H1 specificity
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Cetirizine
- Second-generation antihistamine
- Low sedation, due to high H1 specificity
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Fexofenadine
- Second-generation antihistamine
- Low sedation, due to high H1 specificity
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