Cholenergic Agents Flashcards

Question 1

Q

Carbachol (Miostat)

Answer

A

Description

Synthetic carbamoyl ester of choline
Main uses are for obtaining miosis during surgery and for reducing IOP elevation in the initial 24 hr following cataract surgery

Mechanism of action

Agonist at muscarinic receptors; significant N_N activity
Constricts the iris and ciliary body resulting in reduction in IOP

Pharmacokinetics

Supplied as a 0.01% solution that is instilled into the anterior chamber of the eye
Miosis is usually maximal within 2-5 min after administration
Not susceptible to AChE inactivation
Duration of miosis ~ 24 hr

Adverse reactions

Rarely iritis or corneal clouding

Precautions

Acute cardiac failure; bradycardia (M₂)
Asthma (M₃ bronchoconstriction)
Hyperthyroidism (M₃ vasodilation can increase sympathetic outflow to hear further increasing HR)
Peptic ulcer
Urinary tract obstruction
Parkinsonism

Question 2

Q

Methacholine (Provocholine)

Answer

A

Description

Synthetic acetylcholine analog
Indicated for the diagnosis of airway hyperreactivity

Mechanism of action

Agonist at muscarinic receptors; slight nicotinic activity (less than carbachol)

Pharmacokinetics

Supplied as a lyophilized powder that is reconstituted in isotonic saline for inhalation via nebulizer
Three-fold more resistant to AChE than acetylcholine
Most subjects return to baseline pulmonary function after 30-45 min (B2 agonist can reverse effects)

Adverse reactions

Headache
Throat irritation
Lightheadedness
Itching

Precautions

Acute cardiac failure; bradycardia
Asthma
Hyperthyroidism
Peptic ulcer
Urinary tract obstruction

Question 3

Q

Bethanechol (Urecholine)

Answer

A

Description

Synthetic acetylcholine analog
DOC for promoting GI and urinary bladder motility for postop and postpartum nonobstructive urinary retention, neurogenic atony of the urinary bladder, and postop gastric atony or gastroparesis

Mechanism of action

Muscarinic agonist with no nicotinic activity

Pharmacokinetics

Available as tablets for PO dosing, usually 10-50 mg TID-QID
Onset occurs in 60-90 min and duration is usually 60 min
Not susceptible to AChE inactivation

Adverse reactions

Rare, but reflect cholinergic stimulation

Precautions

Acute cardiac failure; bradycardia
Asthma
Hyperthyroidism
Peptic ulcer
Urinary tract obstruction
Parkinsonism

Question 4

Q

Pilocarpine (Piloptic)

Answer

A

Description

Plant alkaloid obtained from Pilocarpus microphyllus
Particularly active on the sweat and salivary glands and eyes; used as TX for xerostomia caused by Sjögren’s syndrome or salivary gland dysfunction and for miosis induction, postop and following ophthalmic examination; second-line TX for chronic open-angle glaucoma

Mechanism of action

Muscarinic agonist
In open-angle glaucoma, pilocarpine contracts the ciliary and circular muscles, producing miosis resulting in increased outflow of aqueous humor; in closed-angle glaucoma, pilocarpine-induced miosis opens the angle of the anterior chamber of the eye through which aqueous humor exits

Pharmacokinetics

0.5-6% ophthalmic solution has a duration of 4-14 hr; PO dose is usually 5-10 mg TID, has a 3-5 hr duration
Ocusert® delivers pilocarpine for 7 days via a contact lens-like system

Adverse reactions

Blurred vision
Exocrine glands: hypersalivation, diaphoresis
Flushing
Headache

Precautions

Asthma
Iritis
Posterior synechiae (adhesion between iris and lens)
Retinal detachment
Heart disease

Question 5

Q

Nicotine (Nicorette)

Answer

A

Description

Plant alkaloid obtained from Nicotiana tabacum
Used to help smokers quit smoking

Mechanism of action

Agonist at NM and NN receptors
Complex action, affects CNS and all branches of peripheral nervous system; stimulates catecholamine release from adrenal medulla

Pharmacokinetics

Dosage forms: gum, lozenge, inhaler, nasal spray, transdermal patch
Widely distributed in body tissues, especially CNS
Mostly metabolized in liver; unchanged nicotine and metabolites are excreted by the kidney
t1/2 = 30-120 min

Adverse reactions

CNS: dizziness, insomnia, irritability
CV: ↑ BP and can have positive inotropic and chronotropic actions
GI: constipation, diarrhea

Precautions

Angina, arrhythmia, myocardial infarction
Caution in patients with hypertension, pheochromocytoma, insulin-dependent diabetes, vasospastic diseases, or thyroid disease resulting in thyrotoxicosis
Pregnancy Risk Category D (transdermal) (other forms are Category C)

Question 6

Q

Varenicline (Chantix)

Answer

A

Description

Smoking cessation aid

Mechanism of action

High-affinity partial agonist at a4b2 nicotinic receptors
reward and carvings from nicotine are diminished
Has moderate affinity at 5-HT3 receptors

Pharmacokinetics

Available as 0.5 mg and 1 mg tablets for PO dosing, usually 1 mg BID after 1 week ramp-up
Peak plasma concentration reached in 3-4 hr; half-life ~ 24 hr
Minimal metabolism; 92% is excreted unchanged in the urine

Adverse reactions

Most common ADRs are GI-related: mild-to-moderate, usually transient, nausea (16-30%), constipation (5-8%), flatulence (6-9%)
CNS: insomnia (18%), vivid dreams (13%)

Precautions

Renal insufficiency; do not exceed 0.5 mg BID if CrCL < 30 mL/min
FDA black box warning of risk of neuropsychiatric symptoms in patients using varenicline. Symptoms include changes in behavior, hostility, agitation, depressed mood, suicidal thoughts and behavior, and attempted suicide.

Question 7

Q

Physostigmine (Antilirium)

Answer

A

Description

Carbamoyl ester-class parenteral and ophthalmic AChE inhibitor
DOC to counteract toxic anticholinergic effects of other drugs; second-line TX of glaucoma

Mechanism of action

Competes with ACh for its binding site on acetylcholinesterase, carbamoylates AChE, inactivating it for extended periods → ↑ ACh
Actions mimic cholinergic stimulation

Pharmacokinetics

Administered as 0.1% solution via IV injection or applied topically to the eye (produces miosis)
Duration of action 1-2 hr when given IV and 12-36 hr after ophthalmic use

Adverse reactions

CNS: restlessness, seizures (penetrates BBB easily)
CV: irregular pulse, palpitations, bradycardia
GI: hypersalivation, cramps, NVD (too much GI motility)
UG: urinary urgency
Lung: bronchospasm, dyspnea, ↑ secretions
Eye: miosis, lacrimation, blurred vision

Precautions

Asthma
GI obstruction, ileus
Urinary tract obstruction
Peptic ulcer
Heart disease
Hyperthyroidism

Question 8

Q

Neostigmine (Prostigmin)

Answer

A

Description

Carbamoyl ester-class peripheral AChE inhibitor (doesn’t cross BBB, no CNS effects)
TX of myasthenia gravis, postop reversal of neuromuscular blockade, ileus

Mechanism of action

Competes with ACh for its binding site on acetylcholinesterase, carbamoylates AChE, inactivating it for extended periods → ↑ ACh
Actions mimic cholinergic stimulation

Pharmacokinetics

Available as 15 mg tablets for PO dosing; average dose is 10 tabs QD with individualized dosing interval
Duration of action 2-4 hr

Adverse reactions

CV: irregular pulse, palpitations, bradycardia
GI: hypersalivation, cramps, NVD
UG: urinary urgency
Lung: bronchospasm, dyspnea, ↑ secretions
Eye: miosis, lacrimation, blurred vision

Precautions

Asthma
GI obstruction, ileus
Urinary tract obstruction
Peptic ulcer
Heart disease
Hyperthyroidism

Question 9

Q

Edrophonium (Tensilon, Enlon)

Answer

A

Description

Rapid-acting, short-duration, parenteral AChE inhibitor
DOC for diagnosing myasthenia gravis; other uses include assessing AChE inhibitor therapy, reversing the effects of nondepolarizing neuromuscular blockers after surgery, ileus
Not useful for the TX of myasthenia gravis due to its short duration of action

Mechanism of action

Competes with ACh for its binding site on AChE, ↑ ACh
In myasthenia gravis, this allows for a greater number of the depleted ACh receptors to bind ACh resulting in an increase in the patient’s muscular strength

Pharmacokinetics

Administered via IV or IM injection
Duration of action ranges from 5-10 min (IV) and from 5-30 min (IM)

Adverse reactions

CNS: dysphonia, seizures
CV: irregular pulse, palpitations, bradycardia
GI: hypersalivation, cramps, NVD
UG: urinary urgency
Lung: bronchospasm, dyspnea, ↑ secretions
Eye: miosis, lacrimation, blurred vision

Precautions

GI obstruction, ileus
Urinary tract obstruction
Asthma
Heart disease

Question 10

Q

Echothiophate (Phospholine)

Answer

A

Description

Second-line TX for chronic open-angle glaucoma (via miosis)

Mechanism of action

Phosphorylates AChE → ↑ ACh

Pharmacokinetics

Usually administered as a 0.03% topical opthalmic solution, 1 gtt QD-BID
Duration of action up to ~ 100 hr

Adverse reactions

Eye: stinging, blurred vision, lacrimation, increased incidence of cataracts with prolonged therapy

Precautions

Uveitis

Question 11

Q

Pralidoxime (Protopam)

Answer

A

Description

Reverses AChE inhibition produced by organophosphates

Mechanism of action

Reactivates AChE by displacing the phosphoryl group from AChE that has been inhibited by organophosphate compounds
Give within 24 hours of exposure

Pharmacokinetics

Dose 1-2 g IV (preferrred), PO, or IM; infuse in 100 mL of saline given over 15-30 min with additional doses PRN
Distributes throughout extracellular water
Metabolized by the liver with a half-life of 74-77 min
Both unchanged drug and metabolite are excreted by the kidneys

Adverse reactions

CNS: dizziness, excitement, agitation, headache
CV: tachycardia, hypertension
GI: NV
Transient elevations in ALT and AST
Eye: diplopia, blurred vision

Precautions

Renal insufficiency
AChE inhibitor TX for myasthenia gravis

Question 12

Q

Atropine (Sal-Tropine)

Answer

A

Description

Plant alkaloid obtained from Atropa belladonna
Most commonly used systemically to treat bradycardia and as a preop agent to reduce secretions; also used as a mydriatic for ophthalmic examinations
Antidote for AChE inhibitor poisoning or muscarinic agonist poisoning

Mechanism of action

Competitive muscarinic receptor antagonist
Main clinical effects are ↓ exocrine gland secretions, mydriasis, cycloplegia, ↑ HR, ↓ tone of bladder detrusor, ↓ tone of GI smooth muscle → ↓ GI motility, bronchodilation

Pharmacokinetics

Supplied as tabs for PO dosing and as a solution for IV, IM, or SC administration
Give 0.5-1 mg as antisialagogue, 2-3 mg for AChE inhibitor or muscarinic agonist poisoning
Well absorbed, widely distributed throughout the body
Metabolized in the liver; t1/2 = 2-4 hr; atropine and metabolites are primarily excreted renally

Adverse reactions

CNS: dizziness, confusion, amnesia, hallucinations, delirium, insomnia
CV: cardiac conduction abnormalities; fibrillation, PVCs, SVT, QT prolongation

Precautions

Acute MI
Bladder obstruction, urinary tract obstruction, prostatic hypertrophy
Glaucoma
GI obstruction or ileus
Hyperthyroidism (sensitive to catecholeamines)
Chronic pulmonary disease; thickens mucous
Conditions that elevate core body temperature (strenuous exercise, fever, dehydration) (because can’t sweat)

Question 13

Q

Oxybutynin (Ditropan)

Answer

A

Description

Bladder muscle relaxant; has antispasmodic effect on smooth muscle
Regularly used for patients with neurogenic bladder to treat urge incontinence

Mechanism of action

Competitive muscarinic receptor antagonist
Antimuscarinic effect is less than atropine but antispasmodic activity is considerably greater than atropine, producing an effect on the detrusor muscle 4-10 times greater than atropine

Pharmacokinetics

Administered topically (transdermal patch) and PO, usually 5 mg BID-TID
Widely distributed to body tissues
Onset within 30-60 min of PO administration, duration 6-10 hr
Extensively metabolized via enteric and hepatic CYP3A4

Adverse reactions

Most adverse reactions associated with oxybutynin stem from the anticholinergic and antispasmolytic activity of the drug
CNS: dizziness, confusion, headache, drowsiness
CV: palpitations, tachycardia
GI: constipation, diarrhea

Precautions

GI obstruction, ileus
Toxic megacolon, ulcerative colitis
Urinary retention or urinary tract obstruction
Uncontrolled narrow-angle glaucoma

Question 14

Q

Ipratropium (Atrovent)

Answer

A

Description

TX for acute asthmatic episode, first-line therapy in COPD once symptoms become persistent
Additive with b2 agonists (like albuterol)
Formulated with albuterol (Combivent®)

Mechanism of action

Muscarinic receptor antagonist, blocks ACh effect on bronchial smooth muscle

Pharmacokinetics

Administered by oral inhalation (metered-dose inhaler) or 0.03% nasal spray; effect persists for 4-6 hr
4° amine, so doesn’t cross membranes or BBB very well

Adverse reactions

Xerostomia
Cough, hoarsness, throat irritation, nasal dryness

Precautions

Glaucoma
Urinary retention, bladder obstruction

Question 15

Q

Tubocurarine

Answer

A

Description

isoquinoline-class paralytic with 4-6 min onset and >45-60 duration
not commonly used (prototype)

Mechanism of action

non-depolarizing competitive antagonist of NMJ nAChR

Pharmacokinetics

60% metabolism by kidney
4° amine, so doesn’t cross membranes or BBB very well

Adverse reactions

weak block of neural nicotinic receptors
moderate histamine release

Question 16

Q

Mivacurium

Answer

A

Description

isoquinoline-class paralytic with 2-4 min onset and 10-20 duration

Mechanism of action

non-depolarizing competitive antagonist of NMJ nAChR

Pharmacokinetics

unique metabolism by plasma cholinesterase
4° amine, so doesn’t cross membranes or BBB very well

Adverse reactions

some histamine release

Question 17

Q

Atracurium

Answer

A

Description

isoquinoline-class paralytic with 2-4 min onset and 20-30 duration

Mechanism of action

non-depolarizing competitive antagonist of NMJ nAChR

Pharmacokinetics

sponataneously Hofmann metabolism (exhaustive methylation)
4° amine, so doesn’t cross membranes or BBB very well

Adverse reactions

some histamine release

Question 18

Q

Cisatracurium

Answer

A

Description

isoquinoline-class paralytic with 2-5 min onset and 30-45 duration

Mechanism of action

non-depolarizing competitive antagonist of NMJ nAChR

Pharmacokinetics

sponataneously Hofmann metabolism (exhaustive methylation)
4° amine, so doesn’t cross membranes or BBB very well

Question 19

Q

Pancuronium

Answer

A

Description

steroid-class paralytic with 4-6 min onset and >45-60 duration
typically not used (prototype)

Mechanism of action

non-depolarizing competitive antagonist of NMJ nAChR

Pharmacokinetics

80% kidney metabolism
4° amine, so doesn’t cross membranes or BBB very well

Adverse reactions

weak block of Nn receptors
some block of muscarinic receptors
patients can get tachycardiac

Question 20

Q

Rocuronium

Answer

A

Description

steroid-class paralytic with 1-2 min onset and 20-30 duration
ideal due to quick onset

Mechanism of action

non-depolarizing competitive antagonist of NMJ nAChR

Pharmacokinetics

80% liver metabolism
4° amine, so doesn’t cross membranes or BBB very well

Adverse reactions

some block of muscarinic receptors
patients can get tachycardiac

Question 21

Q

Vecuronium

Answer

A

Description

steroid-class paralytic with 2-4 min onset and 20-30 duration

Mechanism of action

non-depolarizing competitive antagonist of NMJ nAChR

Pharmacokinetics

80% liver metabolism
4° amine, so doesn’t cross membranes or BBB very well

Question 22

Q

Succinylcholine

Answer

A

Description

paralytic with <1 min onset and <10 min duration
ideal for induction/intubation due quick onset
minimize chances of pulmonary aspiration of gastric contents
used in very short procedures

Mechanism of action

depolarizing agonist of NMJ nAChR
triggers initial muscle contraction but since delivered intravenously contractions are disorganized –> fasciculations

Pharmacokinetics

rapid metabolized by plasma AChE
4° amine, so doesn’t cross membranes or BBB very well

Adverse reactions

Stimulates autonomic ganglia AChRs
HTN, tachycardia
Stimulates cardiac muscarinic receptors
Bradycardia
Histamine release –> bronchospasm in asthmatic pts
Myalgias (due to fasciculations)
Increased intracranial, intraocular pressures
Hyperkalemia
Denervation (e.g. spinal cord injury, stroke cause compensatory proliferation of extra-junctional nicotinic receptors due to previous injury)
Burns, trauma, prolonged immobility
Myopathies (esp. Duchenne muscular dystrophy)
Decreased metabolism by plasma ChE
decreased levels in severe liver disease or inherited (“K-variant”)
decreased activity w/ ChE inhibitors (neostigmine or organophosphates) and inherited (“atypical variant”)

Question 23

Q

Mecamylamine (Inversine)

Answer

A

Description

Classic ganglionic blocker used to treat moderate to severe hypertension
Shows promise in treating Tourette’s syndrome and in nicotine withdrawal

Mechanism of action

Competitive antagonist at nicotinic N_N receptors
Overall effect depends on which division of ANS exerts dominant control on particular organ system and what the existing tone is at various effector sites

Pharmacokinetics

Administered PO as 2.5 mg tablets, usual daily dose is 2.5-25 mg, given as TID or QID
Almost completely absorbed and is excreted unchanged in the urine

Adverse reactions

CNS: choreiform movements, mental changes, paresthesias, seizures, dizziness
CV: postural hypotension (due to lack of normal sympathetic reflex), tachycardia
GI: xerostomia, constipation, ileus
UG: urinary retention, impotence
Eye: blurred vision, mydriasis

Precautions

Cerebral or coronary atherosclerosis or other conditions of deficient blood flow
Recent MI
Glaucoma
Renal insufficiency