PHRM 3310 Test 3

Cholinergic Drugs; Anti-Cholinergic Drugs; Adrenergic Drugs; Anti-Adrenergic Drugs

Cholinomimetics are classified by their mechanism of action into which 2 groups?

acetylcholine receptor stimulants/agonists (cholinoceptor stimulants) & cholinesterase inhibitors

How do cholinesterase inhibitors act?

act indirectly by inhibiting the hydrolysis of endogenous acetylcholine

A 43-year-old man presents with agitation, unsteady gait, difficulty speaking & swallowing, blurred vision, & tearing eyes after working in a field sprayed with a sulfur-odored material. Within 3 hours, he developed chest tightness, difficulty breathing, & disorientation. What is the most likely diagnosis?

organophosphate cholinesterase inhibitor poisoning

Cholinoceptors are members of either…

G protein-coupled (muscarinic) receptors OR ion channel (nicotinic) receptors

The effects of acetylcholine & other cholinomimetic drugs are called parasympathomimetic effects and are mediated by…

muscarinic/nicotinic receptors

The 2 broad categories of cholinergic drugs are…

direct-acting cholinergic agonists & indirect-acting cholinergic drugs

Direct-acting cholinergic agonists work by…

directly binding to & activating muscarinic or nicotinic receptors

Which of the following are choline ester direct-acting cholinergic agonists?

acetylcholine, methacholine, carbachol, & bethanechol

Which of the following are alkaloid direct-acting cholinergic agonists?

muscarine, pilocarpine, cevimeline, nicotine, & lobeline

Which statement about direct-acting cholinergics is correct?

many of these drugs have effects on BOTH receptors; a FEW are HIGHLY selective for muscarinic or nicotinic receptors

Choline esters are poorly absorbed & poorly distributed into the CNS due to their…

hydrophilicity

Compared to acetylcholine, methacholine, carbachol, & bethanechol are…

more resistant to hydrolysis by cholinesterase & have longer durations of action

Compared to methacholine, carbachol, & bethanechol, acetylcholine is…

very rapidly hydrolyzed by cholinesterase

The beta-methyl group, on methacholine & bethanechol, reduces potency at nicotinic receptors while maintaining activity at…

muscarinic receptors

What reduces the potency of methacholine & bethanechol at nicotinic receptors while maintaining activity at muscarinic receptors?

the beta-methyl group

The beta-methyl group reduces the potency of methacholine & bethanechol at…

nicotinic receptors

Is acetylcholine chloride susceptible to cholinesterase?

yes, VERY

The alkaloids (pilocarpine, nicotine, lobeline) are…

WELL absorbed from most sites of administration

Nicotine is sufficiently lipid-soluble to be absorbed across the…

skin

Muscarine is POORLY absorbed from the GI tract; however, it is toxic when ingested, and it can enter the brain.

true

Lobeline is a plant derivative like nicotine and is mainly excreted by the…

kidneys

Lobeline is a…

partial nicotinic antagonist

What is lobeline used for?

smoking cessation

Direct-acting cholinergics work by binding to & activating muscarinic/nicotinic receptors, mimicking the effects of…

acetylcholine

Physiological responses generated by direct-acting cholinergics include…

parasympathetic effects: bradycardia, hypotension, & smooth muscle contractions

Therapeutic uses of direct-acting cholinergics include…

promote urinary excretion & GI motility and relieve increased IOP

Muscarinic agonist binding to M1, M3, & M5 receptors (GPCRs) activates…

the inositol triphosphate (IP3) & diacylglycerol (DAG) cascade

In the IP3/DAG cascade, DAG’s role is…

opening of smooth muscle calcium channels

IP3 releases calcium from…

endoplasmic & sarcoplasmic reticulum

Muscarinic agonist activating M2 & M4 receptors (GPCRs) inhibits…

adenylyl cyclase activity in tissues, leading to inhibition of cAMP synthesis

In the heart, muscarinic agonist activating M2 & M4 receptors inhibits…

cAMP synthesis

Activation of muscarinic receptors in the heart increases…

potassium flux across cardiac cell membranes

Activation of muscarinic receptors in the heart increases potassium flux across cardiac cell membranes, causing…

hyperpolarization

Muscarinic agonists act on…

axonal muscarinic receptors (autoreceptors)

Muscarinic agonists act on axonal muscarinic receptors (autoreceptors) to cause…

inhibition of ACh release (autoinhibition)

Nicotinic agonist binding to the receptor sites causes a…

conformational change in the protein (ion channel)

Nicotinic agonist binding to the receptor sites causes a conformational change in the protein (ion channel) that allows…

sodium Na+ influx

Sodium Na+ influx at the skeletal neuromuscular junction produces…

an excitatory postsynaptic potential

Sodium Na+ influx at the skeletal neuromuscular junction produces an excitatory postsynaptic potential (EPSP), which…

depolarizes the muscle cell membrane, generating an action potential that triggers contraction

Many muscarinic drugs have less effect in the CNS because of their…

limited ability to cross the BBB

The PNS in the eye is…

muscarinic

Cholinomimetics slow down HR & cause…

bronchoconstriction

Cholinomimetics/muscarinics…

increase gland secretion

The brain is richer in which receptor type?

muscarinic receptors

The spinal cord has higher expression of…

nicotinic receptors

Presynaptic nicotinic receptors allow ACh & nicotine to regulate the release of…

glutamate, serotonin, GABA, dopamine, NE

Autonomic ganglia are important sites of nicotinic synaptic action; nicotinic agents cause marked activation of these receptors & initiate…

action potentials in postganglionic neurons

The actions of ACh released from autonomic nerves are terminated by enzymatic hydrolysis by…

acetylcholinesterase (AChE)

Acetylcholinesterase (AChE) is present in high concentrations in…

cholinergic synapses

The indirect-acting cholinomimetics have their primary effect at…

the active site of acetylcholinesterase

Indirect-acting cholinomimetics increase the availability of endogenous ACh at the cholinergic receptor by…

inhibiting acetylcholinesterase (anticholinesterases)

Which of the following is a reversible cholinesterase inhibitor?

neostigmine

Which of the following is an irreversible cholinesterase inhibitor?

echothiopate

Which of the following are irreversible cholinesterase inhibitors?

echothiopate, parathion, malathion, diazinon, sarin, soman, carbaryl, & propoxur

Which of the following are reversible cholinesterase inhibitors?

physostigmine, neostigmine, pyridostigmine, edrophonium, rivastigmine, donepezil, & galantamine

Carbaryl is used as…

an insecticide

Carbaryl has high lipid solubility, allowing…

rapid absorption & distribution to the CNS of the insects

Organophosphates are used in a variety of applications, including…

pesticides, insecticides, herbicides, nerve gas, & solvents

Organophosphates are a class of compounds that…

inhibit cholinesterases, including acetylcholinesterase (AChE)

Organophosphates, except echothiopate, are…

highly lipid-soluble

Which statement about IDAC PK is correct?

the structure of the drug affects its PK properties; absorption depends on the lipophilicity

Drugs with quaternary nitrogen are polar, which makes them…

poorly absorbed orally

Drugs with tertiary substitution are less polar & can be absorbed through multiple routes, including the eyes. Physostigmine & rivastigmine are well absorbed from all sites & can be used topically in the eye.

true

Donepezil is well absorbed when given orally (~100% bioavailability) and is…

metabolized by liver enzymes & excreted in the urine

Organophosphate cholinesterase inhibitors, except echothiopate, are highly lipid-soluble and are…

well absorbed from the skin, lung, gut, & conjunctiva; distributed to all parts of the body including the CNS

Organophosphates are dangerous to humans (CNS toxicity) and are highly effective as insecticides. This statement is…

true

Organophosphate drugs are metabolized by esterases in the…

liver, plasma, & skeletal muscles

Organophosphate metabolites are excreted through the…

kidneys

Cevimeline is a muscarinic, lipid-soluble drug with a duration of action of…

5-8 hours

Myasthenia gravis is an autoimmune disease affecting skeletal muscle neuromuscular junctions, with antibodies against…

nicotinic receptors

The initial 1st-line therapy for most patients with myasthenia gravis is an anticholinesterase medication, usually…

pyridostigmine

Which cholinesterase inhibitors are available for cognition & global functioning in patients with mild to moderate Alzheimer’s disease?

rivastigmine, donepezil, & galantamine

In glaucoma, muscarinic stimulants & cholinesterase inhibitors reduce IOP by causing contraction of the ciliary body and…

increased outflow of aqueous humor

Which of the following can be used in glaucoma as a direct agonist or cholinesterase inhibitor, respectively?

pilocarpine, methacholine, carbachol; physostigmine, echothiopate

To reverse neuromuscular blockade after surgery, neostigmine is preceded by atropine to…

block muscarinic effects

Neostigmine rapidly reverses muscle paralysis induced by neuromuscular blockers.

true

For postoperative urinary retention, neostigmine is a common option, and the indicated pharmaceutical treatment of acute postoperative & postpartum non-obstructive urinary retention is…

bethanechol

For neurogenic bladder, which drug may help complete bladder emptying in those with hypotonic bladder?

bethanechol

Neostigmine is used off-label for…

acute colonic pseudo-obstruction

Cevimeline is FDA-approved for the treatment of symptoms of dry mouth in…

Sjogren’s syndrome

Xerostomia therapy uses muscarinic agonists in patients with an inadequate response to artificial saliva & mechanical stimulation in Sjogren syndrome or patients post-radiation treatment associated with head & neck cancer.

true

Physostigmine is the specific antidote for poisoning with belladonna or other anticholinergics, used only to reverse toxic, life-threatening delirium caused by an anticholinergic agent such as…

atropine, scopolamine, diphenhydramine

Neostigmine is used in patients with neurotoxic snakebite for whom…

antivenom is NOT available or is ineffective

ACh hyperpolarizes the SA nodal cells through M2 receptors of the heart and may cause…

bradycardia or even cardiac arrest

M3 receptors present on the blood vessels mediate dilation, causing…

a fall in BP & flushing

Tone & peristalsis in the GI tract increase & sphincters relax, causing…

abdominal cramps

The detrusor muscle (walls of bladder) contracts while the bladder trigone & sphincter relax, leading to…

the voiding of the bladder

Bronchial muscles constrict, precipitating…

an attack of bronchial asthma

Secretions from glands are increased through the M3 & M2 receptors, resulting in…

salivation, sweating, lacrimation, gastric & tracheobronchial secretions

Pilocarpine eye drops result in contraction of the iris, causing…

miosis & spasms of accommodation

Cholinergic drugs which enter the brain cause a complex pattern of…

stimulation followed by depression

After treatment with an anticholinesterase, ACh released by nerve impulses in skeletal muscles may cause twitching & fasciculations by…

repetitive firing

Physostigmine & organophosphates have more marked muscarinic & CNS effects; stimulate ganglia, but action on skeletal muscle is…

less prominent

Neostigmine & the similar agents produce a more pronounced effect on the skeletal muscles, and stimulate ganglia, but the muscarinic effects are…

less noticeable

The most common etiology of the cholinergic crisis is from inappropriate or elevated doses of medication or accidental exposure to insecticides such as…

malathion, parathion

Other sources of cholinergic crisis include nerve gas such as…

sarin

Anticholinesterases are readily available & extensively used as agricultural & household insecticides, and poisoning can be…

accidental, suicidal, or homicidal

Severe cholinergic toxicity follows ingestion or cutaneous exposure to the substances. The primary toxic effects involve…

the neuromuscular junction, ANS, & CNS

Clinical features of acute cholinergic toxicity include…

miosis, salivation, lacrimation, emesis, bradycardia, bronchospasm, bronchorrhea, urination, & diarrhea

The nicotinic effects of cholinergic toxicity include muscle weakness, fasciculations, & paralysis through ACh stimulation of receptors at…

the neuromuscular junction