Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Pharm Exam 1 > Mattingly - Cholinergic Pharmacology I > Flashcards

Mattingly - Cholinergic Pharmacology I Flashcards

1
Q

APPLICATIONS OF CHOLINERGIC PHARMACOLOGY:
• CNS:

o	Alzheimer’s Disease 
o	Parkinson’s Disease and iatrogenic Parkinsonian effects of anti-psychotics 
o	Insomnia
o	Motion sickness 
o	Smoking cessation
A 
o	Alzheimer’s Disease (donepezil)
o	Parkinson’s Disease and iatrogenic Parkinsonian effects of anti-psychotics (benztropine)
o	Insomnia (scopolamine) 
o	Motion sickness (scopolamine)
o	Smoking cessation (varenicline)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

APPLICATIONS OF CHOLINERGIC PHARMACOLOGY:
• CNS:

Abusive:
o Stimulant
o Hallucinogenic

A 
-	Abusive:
o	Stimulant (nicotine)
o	Hallucinogenic (atropine)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

APPLICATIONS OF CHOLINERGIC PHARMACOLOGY:
• Eye:
o Induction of mydriasis and cycloplegia
o Induction of miosis in cataract surgery
o Open-angle glaucoma
o Strabismus

A

o Induction of mydriasis and cycloplegia (tropicamide)
o Induction of miosis in cataract surgery (carbachol)
o Open-angle glaucoma (pilocarpine)
o Strabismus (botulinum toxin)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q
  • Historical cosmetic use:

o Mydriasis

A

atropine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q 
APPLICATIONS OF CHOLINERGIC PHARMACOLOGY:
•	Respiratory Tract:
-	Current:
o	Obstructive lung disease
o	Diagnosis of asthma
A

o Obstructive lung disease (ipratropium)

o Diagnosis of asthma (methacholine)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

APPLICATIONS OF CHOLINERGIC PHARMACOLOGY:
• CV:
- Current:
o Sinus bradycardia
o Diagnosis of vasospastic angina pectoris

A

o Sinus bradycardia (atropine)

o Diagnosis of vasospastic angina pectoris (ACh)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q 
APPLICATIONS OF CHOLINERGIC PHARMACOLOGY:
•	GI:
-	Current:
o	Xerostomia 
o	GI spasm
o	Post-operative ileus without obstruction 
o	Traveller’s diarrhea 
o	Infant colic
A 
o	Xerostomia (cevimeline)
o	GI spasm (propantheline)
o	Post-operative ileus without obstruction (neostigmine)
o	Traveller’s diarrhea (atropine)
o	Infant colic (atropine)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q 
APPLICATIONS OF CHOLINERGIC PHARMACOLOGY:
•	Urinary Tract:
-	Current:
o	Urge continence 
o	Post-operative urinary retention
o	Bladder spasm
A

o Urge continence (tolterodine)
o Post-operative urinary retention (bethanechol)
o Bladder spasm (oxybutynin)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

APPLICATIONS OF CHOLINERGIC PHARMACOLOGY:
• Neuromuscular System:
- Current:
o Skeletal muscle relaxation for surgery
o Skeletal muscle relaxation for intubation
o Skeletal muscle relaxation during electroconvulsive therapy
o Myasthenia Gravis
o Blepharospasm and other spastic disorders
o Malignant hyperthermia

A

o Skeletal muscle relaxation for surgery (cisatracurium)
o Skeletal muscle relaxation for intubation (rocuronium)
o Skeletal muscle relaxation during electroconvulsive therapy (succinylcholine)
o Myasthenia Gravis (edrophonium- diagnosis; pyridostigmine- treatment)
o Blepharospasm and other spastic disorders (botulinum toxin A)
o Malignant hyperthermia (dantrolene)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q 
APPLICATIONS OF CHOLINERGIC PHARMACOLOGY:
•	Skin:
-	Current:
o	Ectoparasites
o	Diaphoretic to aid in diagnosis of CF 
o	Wrinkles
o	Hyperhydrosis
A 
o	Ectoparasites (malathion)
o	Diaphoretic to aid in diagnosis of CF (pilocarpine) 
o	Wrinkles (botuliunum toxin A)
o	Hyperhydrosis (botulinum toxin A now supersedes atropine)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q
  • Ganglionic blocker:

o experimental scenario questions on Step 1

A 
-	Ganglionic blocker:
o	Hexamethonium (experimental scenario questions on Step 1)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Major agonist prototypic drugs:

A

ACh

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Major antagonist prototypic drugs:

A

atropine
d-tubocurarine
mecamylamine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Major anticholinesterase (indirect agonists) prototypic drugs:

A

physostigmine
neostigmine
edrophonium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Drugs that block ACh release:

A

Botulinum toxin A

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Drugs that regenerate AChE:

A

pralidoxime

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Major agonist used as depolarizing blocking agents:

A

succinylcholine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Efferent
Somatic/Voluntary Nerves: control ?

Central control originates:

Where are all of the synapses?

NT =

What happens to skeletal muscles without innervation?

A

Somatic/Voluntary Nerves: control skeletal muscles

o Central control originates in motor cortex via corticospinal tracts

o All synapses are in the CNS (long motor neurons)

o NT is ACh

o Skeletal muscles are entirely dependent on their innervation for activity (will atrophy without it)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Efferent
Autonomic Nervous System: control ?

Central control originates:

Where is there further integration?

NT =

What happens to smooth muscles without innervation?

A

Autonomic Nervous System: operates largely below level of consciousness and controls all other innervated structures in the periphery

o Central control originates in hypothalamus, limbic system and brainstem

o Further integration at peripheral ganglia (between CNS and neuroeffector junction)

o Smooth muscles/glands will exhibit some spontaneous activity even in the absence of functional autonomic innervation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Divisions of the ANS

A

PS and SS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Parasympathetics:

NT =

Effects:

A

Parasympathetics: autonomic output of cranial nerves + sacral portion of spinal cord

NT is ACh: at all ganglionic and neuroeffector junctions

Effects: rest and digest

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Sympathetics:

NT =

Effects:

A

Sympathetics: autonomic output of the thoracic + lumbar portions of spinal cord

NTs: more complicated than PS

ACh: at sympathetic ganglia, adrenal medulla, and a few SS neuroeffector junctions (sweat glands and arterioles to skeletal muscles)
NE: dominant transmitter to most of the SS neuroeffector junctions

Effects: fright, flight or fight

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Cholinergic neuron

A

Cholinergic neuron: any neuron in the CNS or periphery that liberates ACh as its transmitter (release to cholinergic synapse)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What does the enteric system have in addition to chlinergic outputs?

A

“nonadrenergic, noncholinergic (NANC)” Fibers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Locations of cholinergic synapses:

A

o Brain and spinal cord
o All autonomic ganglia (act on nicotinic R)
o Neuroeffector junctions of the PSNS (act on muscarinic R)
o Neuromuscular junction of the somatic nervous system (act on nicotinic R at NMJ)
o Sweat glands (thermal sweating; act on muscarinic R) and some arterioles of skeletal muscles (SS cholinergic neurons with origin in SNS segments T1-L2)
o Nerves termination in the adrenal medulla (innervate chromaffin cells)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Do ACh R on endothelium of vasculature exist? Are they directly innervated?

A

Yes, no (only respond to agents in circulation)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What is the primary signal for transmission through the ganglia outside of the CNS?

A

Nicotinic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Where is ACh synthesized?

A

Cytoplasm of cholinergic nerve terminals

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

ACh substrates:

Where do they come from?

A

Substrates: choline + acetyl CoA

Acetyl CoA derived from glucose metabolism in the mitochondria

Choline (highly charged quaternary amine) is selectively pumped into the nerve from the extracellular space; NOT made in the nerve terminal

30
Q

Enzyme that constructs ACh:

Where does it synthesize ACh?

A

Enzyme: choline acetyltransferase (ChAT)

Synthesized in cell body of the cholinergic neuron

Transported down axon to nerve terminal

31
Q

What is the rate of ACh synthesis dependent on?

A

Rate of Synthesis: dependent on the activity of the choline transport pump (rate-limiting step is availability of choline for ChAT)

32
Q

Where is ACh packaged?
What is the content of a vesicle called?
How many are released at each action potential?

A

Packaging: put in vesicles found in nerve terminal

Content of a single vesicle is called a quantum of ACh

Each action potential releases 100 or more quanta via exocytosis

33
Q

Release of ACh:

General Process: (3 steps)

A
  1. AP travels down axon, reaches nerve terminal, and increases membrane permeability to Na+, K+ and Ca++
  2. Increase in intracellular Ca++ triggers attachment of vesicles to the membrane of the nerve terminal
  3. Vesicles fuse with membrane and contents empty into synapse (exocytosis)
34
Q

In NMJ, what is the function of the background release of random vesicles of ACh occurring during periods of nerve quiescence, independent of APs?

What is produced?

A

Function possibly as trophic influence on the end organ

Produce transient depolarizations of motor end plate called miniature endplate potentials (MEPPs), which do not muscle contraction

35
Q

Sites other than NMJ (heart, visceral organs, glandular tissue)
Do Released vesicles (quanta) of ACh from a single AP promote a maximal response of effector organs?

How must ACh transmitter diffuse through extracellular space?

A

Released vesicles (quanta) of ACh from a single AP do NOT promote a maximal response of effector organ; graded responses are elicited by increasing/decreasing firing frequency

ACh transmitter must also diffuse more widely through extracellular space to reach effect cell receptor sites on cell membranes

No well-organized nerve-to-nerve transmission sites as seen at NMJ, ganglia and in the brain

36
Q

Cholinoreceptors:

A

Cholinoreceptors: ACh R on the post-synaptic membrane, and occasionally, the pre-synaptic membrane

37
Q

What does ACh bind?
How does AChR and ACh orient in respect to each other?
ACh vs analogs:

A

ACh Binding: flexible and will bind ALL cholinoreceptors

AChR have negatively charged area that helps orient positively charged ACh

ACh analogs tend to be more rigid in configuration and therefore more selective for different receptors

38
Q

How are AChRs categorized?

A

Classification: based on selective effects of two agonists (muscarine and nicotine) and two selective antagonists (atropine and d-tubocurarine)

39
Q

Muscarinic receptor:

A

Muscarinic: muscarine agonist and atropine antagonist

40
Q

Muscarine:

Where are M receptors located?

A

Muscarine: alkaloid from a mushroom

Mimics ACh in several organs and tissues (location of M receptors):

Visceral smooth muscles of GI tract, lower urinary tract, uterus and bronchi

Heart and vascular tissue

Secretory glands (salivary, lacrimal, sweat, glands of respiratory tract and stomach, intestine, and pancreas)

CNS (cortex and brain stem)

Autonomic ganglia (but primary AChR here is nicotinic)

41
Q

Atropine:

Subtypes of muscarinic receptors

A

Atropine: alkaloid from plant leaves

M1 (neuronal)
M2 (predominant in the heart)
M3 (predominant in secretory glands)
M4 (less well understood, probably important in CNS)
M5 (less well understood, probably important in CNS)

42
Q

ACh Effects (Parasympathetic) on Eye (2)

A

Eye Iris (circular muscle)

Contracts M3

Ciliary muscle
Contracts M3

43
Q

ACh Effects (Parasympathetic) on heart (2)

A

SA Node Decelerates M2

Contractility Decreases M2

44
Q

ACh Effects (Parasympathetic) on blood vessels

A

Endothelium (not directly innervated by PSNS) EDRF release causes relaxation M3

45
Q

ACh Effects (Parasympathetic) on airway

A

Bronchiolar smooth muscle Contracts M3

46
Q

ACh Effects (Parasympathetic) on GI tract (5)

A 
Walls	Contracts	M3
Esophageal sphincters	Contracts	M
Other sphincters	Relaxes	M3
Gastric secretions	Increases	M1
Other secretions	Increases	M3
47
Q

ACh Effects (Parasympathetic) on GU tract (4)

A

Bladder Contracts M3
Sphincter Relaxes M3
Uterus Contracts M3
Penis Erection (mediated through NO) M

48
Q

Muscarinic Receptors in the Sympathetic Nervous System:

Blood vessels:

Skin/sweat glands:

A

Muscarinic Receptors in the Sympathetic Nervous System:

Blood vessels: skeletal muscle arterioles (activation causes RELAXATION)

Skin/sweat glands: eccrine sweat glands (activation causes INCREASE in sweating)

49
Q

Nicotinic:

Agonist and antagonist:

A

Nicotinic: nicotine agonist and d-tubocurarine antagonist

50
Q

Where does nicotine mimic ACh (location of N receptors)? (4)

A

NMJ of somatic muscle cells on the motor end plate

All autonomic ganglia on the dendrites of post-ganglionic neurons

CNS (some of the cholinergic synapses in the brain; most of the cholinergic synapses in the spinal cord)

Adrenal medulla (on chromaffin cells)

51
Q

Depolarizing blockade

A

In larger doses, response is stimulation followed by depression due to depolarization blockade (sustained depolarization of the receptor membrane- ionic channels left open)

52
Q

Muscarinic Receptors and G Proteins:

Structure of Receptor:

N-terminus:
C-terminus

A

Structure of Receptor: single polypeptide chains that traverse membrane 7 times

N-terminus extracellular

C-terminus intracellular

ACh binds site bounded by transmembrane domains

53
Q

Structure of G Protein:

Alpha subunit binds and hydrolyzes:

Differences in G proteins are based on:

A

Structure of G Protein: heterotrimers of 3 distinct polypeptides (alpha, beta, gamma)

Alpha subunit binds and hydrolyzes GTP to GDP

Differences in G proteins are based on alpha subunit (Gi, Gs, Go, Gq)

54
Q

Signaling After ACh Binds:

5 steps

A
  1. Intracellular portion of receptor activates G protein
  2. G protein releases GDP and binds GTP
  3. GTP + alpha subunit detaches from beta/gamma subunits
    - Both alpha/GTP and beta/gamma act on enzymes or ion channels
  4. GTP hydrolyzed back to GDP by alpha subunit
  5. Alpha subunit reunites with beta/gamma subunit
55
Q

G Proteins are not only signal transducer, but signal amplifiers:

A

G Proteins are not only signal transducer, but signal amplifiers:

Potential for activation of multiple G proteins by a single activated receptor

Potential for GTP-bound state to persist for longer than agonist is bound to receptor

56
Q

Types of G Proteins Associated with Muscarinic Receptors:

A

Gi and Gq

57
Q

Gi: activated by

Affects:

A

Gi: activated by M2 receptors
Heart:
- Increase in K+ conductance (acts on channel), increasing the resting membrane potential (more negative) –> slowed heart rate
- Decrease in cAMP in cytosol due to inhibition of adenylate cyclase

58
Q

Gq: activated by

Affects:

PLC, IPE, and Ca effects

A

Gq: activated by M1 and M3 receptors

Visceral smooth muscle and acinar glands:

Phosphlipase C activation (PIP2 –> IP3 and DAG)

IP3 acts as 2nd messenger in cytosol to release stored Ca++

Ca++ binds calmodulin –> cell-specific effects (MLCK and contraction of smooth muscle, secretion from exocrine glands, NO/EDRF production by endothelial cells)

59
Q

Nicotinic Receptor Mechanisms:

Structure:

Arranged into:

A

Nicotinic Receptor Mechanisms:

Structure: pentameric complexes of polypeptides; each spans the membrane multiple times

Arranged into a bundle that changes conformation to allow Na+, K+ and Ca+ through when agonist binds (causes depolarization of cell membrane)

60
Q

Nicotinic Receptor Mechanisms:

Differences based on location:

A

Nicotinic Receptor Mechanisms:

Differences based on location: nAChRs found in the NMJ have differences in subunit composition when compared to nAChRs in autonomic ganglia

Therefore, possible to selectively block one or the other

Also some differences in nAChRs found in the CNS (selective agents being developed)

61
Q

Varenicline:

A

Varenicline: nicotinic partial agonist is the first agent of this type to be approved

62
Q

Acetylcholinesterases:
Location:

A

Acetylcholinesterases: rapidly hydrolyze ACh (very short half life)
o Location: protein found in membranes of cholinergic nerves, effector cells and RBCs

63
Q

AChE mechanism:

Sites on esterase

How is ACh oriented?

What happens to the ester linkage of ACh?

Acetyle group is transferred where?

What happens to choline? Esterase?

A

Mechanism: cleaves ester linkage of ACh –> choline + acetic acid

Esterase has 2 primary sites that ACh interacts with (anionic site and esteratic site)

Electrostatic attraction between (+) charged quarternary amine of ACh and (-) charged anionic site of esterase (carboxyl side group) orients ACh over esteratic site

Ester linkage of ACh is hydrolyzed

Acetyl group from ACh is transferred to an exposed serine at the esteratic site of the esterase (covalently modifies it)

Choline is released (pumped back into nerve terminal or diffuses away)

Covalently modified esterase is recharged by water (hydrolyzes acetyl group)

64
Q

Pseudocholinesterases (Butyrylcholinesterases):

Location:
Selectivity:
Function:

A

Pseudocholinesterases (Butyrylcholinesterases):

Location: plasma and liver

Selectivity: less selective for ACh, will act on many substrates containing ester linkages

Function: degrade ACh that escapes from transmission sites and that is administered IV (therefore, ACh is an ineffective drug because of rapid metabolism in plasma)

65
Q

Presynaptic Cholinoreceptors:

Location:

Type of Receptor:

A

Presynaptic Cholinoreceptors:

Location: presynaptic nerve terminal membranes of both some muscarinic and nicotinic synapses

Type of Receptor: usually muscarinic (M2)

66
Q

Presynaptic Cholinoreceptors:

Function:

Muscarinic antagonists:

Muscarinic agonists:

A

Function: regulate evoked release of ACh (feedback inhibition); prevent excessive ACh release

Muscarinic antagonists (atropine) promote INCREASE in ACh release in response to nerve stimulation: blocks pre-synaptic receptor, preventing feedback inhibition

Muscarinic agonists REDUCE the evoked release of ACh

67
Q

Presynaptic Receptors at the NMJ:

Function:
Type:

A

Presynaptic Receptors at the NMJ:

Function: stimulatory for the release of ACh; maintain ACh release during periods of intense neuromuscular transmission (ie. tetanic contractions)

Type of Receptor: nicotinic

68
Q

Other Presynaptic Receptors:

o Alpha 2 Receptors:

A

Other Presynaptic Receptors:

o Alpha 2 Receptors: mediate inhibition of ACh release to reduce GI motility in response to SS activity

69
Q

Paradoxical bradycardia:

A

Clinical Correlate: paradoxical bradycardia is sometimes see in response to LOW DOSES of atropine (low doses preferentially act on presynaptic M-receptors to increase ACh release, while having less direct effect on M-receptors on cardiac muscle cells to block ACh action)

70
Q

Use of tiotropium for bronchoconstriction:

A

Clinical Correlate: use of tiotropium for bronchoconstriction (little specificity for M2, therefore little block of ACh feedback inhibition normally seen with antagonists, while at the same time having anticholinergic effects to combat bronchoconstriction)

Pharm Exam 1 (23 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions