cholinergic antagonist

Question 1

answer the following about atropin :
1.high affinity for what receptor?
2.is it competitive or non competitive
3. what is the duration

Answer 1

1. muscarinic receptors
2. competitive
3. about 4 hours, but lasrs for days for the eyes

Question 2

answer the following about atropin effects
1. eyes
2. GIT
3. cardiovascular
4. secretions

Answer 2

1.mydriasis(dilation of the pupil), the eye will become unresponsive to the light, and cycloplegia(inability to focus) and the eye pressure will rise for glaucoma (closed angle)

2.most potent antispasmodic drug,not effective for ulcers, reduce saliva and urination (low compliance)

3. depending on the dose—–at low dose light decrease in heart rate because of the blocking of M1 at the presynaptic neurons thus increasing ach
   ——–at high dose the heart rate will increase due to the blocking of M2

4.low secretion of saliva (xerostomia), inhibition of sweating and lacrimal gland (causes high body temp)

Question 3

what are the therapeutic uses for atropin

Answer 3

1.ophthalmic exerts both mydriatic and cycloplegic
effects, has been replaced by cyclopentolate and tropicamide due to the long duration

2.antispasmodic

3. treatment of bradycardia

4.antisecretory before surgery

Question 4

for what do we use atropine as an antidote for

Answer 4

❖ organophosphate poisoning,
❖of overdoses of anticholinesterases
❖and some types of mushroom poisoning.

Question 5

what are the pharmacokinetics and side effects for atropin

Answer 5

Atropine is readily absorbed, partially metabolized by the liver, and eliminated primarily in the urine.

the side effects might include: dry mouth, blurred vision, sandy eyes, tachycardia, urinary retention and constipation, the toxicity may be overcome by using AcHE inhibitor like physostigmine

Question 6

hoe does scopolamine differ from atropine

Answer 6

it has a greater CNS effects and a longer duration of action

Question 7

what are the unique effects of scopolamine and therapeutic uses

Answer 7

1.short term memory blocking, sedation and euphoria

2. good for prevention of motion sickness, nausea and vomiting

Question 8

what are Aclidinium, glycopyrrolate, ipratropium, and
tiotropium

Answer 8

ipratropium is a SAMA
Aclidinium, glycopyrrolate, and tiotropium
(LAMA)

they are used as brochodilators used for COPD and bronchospasm.

lpratropium and tiotropium are also used in the acute management of asthma

they are postivly charge so the cant enter the CNS and systemic circulation

Question 9

what are tropicamide and cyclopentolate

Answer 9

used as ophthalmic solutions for mydriasis and
cycloplegia. Their duration of action is shorter than that of atropine.

Tropicamide produces mydriasis for 6 hours and cyclopentolate for
24 hours.

Question 10

what are benztropine and trihexyphenidyl

Answer 10

are useful as adjuncts with other
antiparkinson agents to treat Parkinson disease and other types of parkinsonian syndromes, including antipsychotic induced extrapyramidal symptoms

Question 11

name some agents for overactive bladder

Answer 11

Oxybutynin,
darifenacin,
fesoterodine,
solifenacin,
tolterodine, and trospium

Question 12

how does oxybutynin work

Answer 12

by blocking M3 receptors in the bladder——–intravesical pressure is lowered, bladder capacity is increased, and the frequency of bladder contractions is reduced.

Question 13

What other location for that muscarinic receptor that
theses drugs may cause adverse effects for oxybutnin

Answer 13

in the Gl tract, salivary glands, CNS, and eye

Question 14

Which of these drugs is more selective M3 muscarinic
receptor antagonists?

Answer 14

solifenacin

Question 15

What are the therapeutic uses for oxybutnin

Answer 15

These agents are used for management of
overactive bladder and urinary incontinence. Oxybutynin is also used in patients with neurogenic bladder.

Question 16

What are the dosage form, half life,which are patches and gels, and which are not hepaticly metabolized

Answer 16

1.oral dosage forms
2.long half life, so administered once daily
3. Oxybutnin
4. Trospium under go hydrolysis

Question 17

What are the side effects for oxybutnin

Answer 17

include dry mouth, constipation, and
blurred vision, which limit tolerability of these agents. Extended release formulations and the transdermal patch have a lower incidence of adverse effects and may be better tolerated.Trospium is a quaternary compound that minimally crosses the blood-brain barrier and has fewer CNS effects than do other agents, making it a preferred choice in treating overactive bladder in patients with
dementia

Question 18

What are ganglionic blockers

Answer 18

•Act
on
the
nicotinic
receptors
of
both
parasympathetic and sympathetic autonomic ganglia.
• Some also block the ion channels of the autonomic
ganglia.
• The responses of the nondepolarizing blockers are
complex and mostly unpredictable.
•Ganglionic blockers are rarely used therapeutically but

Question 19

What is nicotine

Answer 19

A component of cigarette smoke, nicotine is a poison with many undesirable actions. It is without therapeutic benefit and is deleterious to health. Depending on the dose, nicotine depolarizes autonomic ganglia, resulting first in stimulation and then in paralysis
of all ganglia. The stimulatory effects are complex and result from
increased release of neurotransmitters , due to effects on both sympathetic and parasympathetic ganglia

Question 20

What are some of the nicotine effects

Answer 20

enhanced
release
of
dopamine
and
norepinephrine may be associated with pleasure and
appetite suppression.
• The overall response of a physiological system is a
summation of the stimulatory and inhibitory effects of
nicotine.
•At higher doses, the BP falls because of ganglionic
blockade, and activity in both the GI tract and bladder
musculature cease

Question 21

What are neuromuscular blockers clinicly used for

Answer 21

clinically useful to facilitate rapid intubation when needed due to respiratory failure (rapid sequence intubation). During surgery, they are used to facilitate
endotracheal intubation and provide complete muscle relaxation at lower anesthetic doses. This increases the safety of anesthesia

Question 22

Name some examples for nondepolarizing competitive blockers

Answer 22

• Curare was the first drug that was found to be capable
of blocking the skeletal NMJ.
• Tubocurarine has been largely replaced by other
agents because of its side effects.

Question 23

What is the mechanism of action for nondepolarizing competitive blockers

Answer 23

At low doses: NMBs competitively block ACh at the nicotinic receptors . They compete with ACh at the receptor without stimulating it, thus preventing depolarization of the muscle cell membrane and inhibiting muscular contraction. Their
competitive action can be overcome by administration of cholinesterase inhibitors, such as neostigmine and edrophonium, which increase the concentration of ACh in the NMJ.

At high doses: Nondepolarizing agents can block the ion channels of the motor end plate. This leads to further weakening of neuromuscular transmission, reducing the ability of
cholinesterase inhibitors to reverse the actions of the nonde-polarizing blockers. With complete blockade, the muscle does
not respond to direct electrical stimulation.

Question 24

for nondepolarizing competitive blockers what muscles are paralyzed first and last

Answer 24

Muscles have differing sensitivity to blockade by com-
petitive agents. Small, rapidly contracting muscles of the face and eye are most susceptible and are paralyzed first, followed by the fingers, limbs, neck, and trunk muscles. Next, the intercostal muscles are affected and, lastly, the diaphragm

Question 25

What are the pharmacokinetics of nondepolarizing competitive blockers

Answer 25

All are administered by IV or IM

They can’t go across BBB

They are metabolized by Pancuronium is excreted
unchanged in urine.

Cisatracurium undergoes organ-independent
metabolism (via Hofmann elimination) to laudanosine, which is
further metabolized and renally excreted. The amino steroid drugs

vecuronium and rocuronium are deacetylated in the liver and
excreted unchanged in bile.

Mivacurium is eliminated by plasma cholinesterase.

Question 26

What are the drug interaction for cholinesterase inhibitors with nondepolarizing competitive blockers

Answer 26

Drugs such as neostigmine,
physostigmine, pyridostigmine, and edrophonium can overcome the action of nondepolarizing NMBs. However, with increased dosage, cholinesterase inhibitors can cause a depolarizing block due to elevated ACh concentrations at the end plate membrane. If the NMB has entered the ion channel
(is bound to the receptor), cholinesterase inhibitors are not as
effective in overcoming blockade.

Question 27

What are the drug interaction for halogenated hydrocarbons anesthetic with nondepolarizing competitive blockers

Answer 27

oDrugs such as desflurane,
oThese agents sensitize the NMJ to the effects of
neuromuscular blockers.

Question 28

What are the drug interaction for Aminoglycoside antibiotics with nondepolarizing competitive blockers

Answer 28

Drugs such as gentamicin and
tobramycin inhibit ACh release from cholinergic nerves by
competing with calcium ions. They synergize with competitive blockers, enhancing neuromuscular blockad

Question 29

What are the drug interaction for calcium channel blockers with nondepolarizing competitive blockers

Answer 29

These agents may increase the
neuromuscular blockade of competitive blockers.

Question 30

How do depolarising agents work?

Answer 30

Depolarizing blocking agents work by depolarizing the plasma membrane of the muscle fiber, similar to the action of ACh. However,
these agents are more resistant to degradation by(AChE) thus more persistently depolarize the muscles fibers

Question 31

What is succinylcholine and what’s the mechanism

Answer 31

is the only depolarizing muscle relaxant in use today.

1.Succinylcholine attaches to the nicotinic
receptor and acts like ACh to depolarize the junction

2.Membrane depolarizes, resulting in an initial discharge that produces transient fasciculations followed by flaccid paralysis.

3.this leads to twitching of the muscles

4.Membrane repolarizes, but receptor is desensitized to the effect of acetylcholine.

5.resistenace to depolarizion and flaccid paralysis

Question 32

What does succinylcholine produce initially and for now long does it last (duration)

Answer 32

produces brief muscle fasciculations that cause muscle soreness (prevented by administering a small dose of nondepolarizing NMB)

lasts extremely short due to rapid hydrolysis

Question 33

What are the therapeutic uses and route of administration for succinylcholine

Answer 33

useful when rapid endotracheal intubation is required. It
is also used during electroconvulsive shock treatment.

Administration ——IV

Question 34

What are the side effects for succinylcholine

Answer 34

a. Hyperthermia: Succinylcholine can potentially induce malignant hyperthermia in susceptible patients

b. Apnea: Administration of succinylcholine to a patient who is deficient in plasma cholinesterase or has an atypical form
of the enzyme can lead to prolonged apnea due to paralysis of the diaphragm. The rapid release of potassium may also contribute to prolonged apnea in patients with electrolyte
imbalances. In patients with electrolyte imbalances receiving
digoxin or diuretics {such as heart failure patients) succinylcholine should be used cautiously or not at all.

c. Hyperkalemia: Succinylcholine increases potassium releasefrom intracellular stores. This may be particularly dangerous in burn patients and patients with massive tissue damage in which potassium has been rapidly lost or in patients with renal failure