Cholinergic Drugs Flashcards
(33 cards)
1
Q
What is a cholinergic drug?
A
-substance that produces the same effect as Acetylcholine
2
Q
Direct acting cholinergic drugs?
A
-stimulate cholinergic receptors
- synthetic- esters of choline (Bethanechol, Carbachol)
- natural- acetylcholine (eyes), alkaloids (nicotine, pilocarpine), marijuana
3
Q
Indirect acting cholinergic drugs?
A
-function to elevate endogenous levels of ACh
- inhibition of acetylcholinesterase
- prevents ACh breakdown
- reversible, competitive, short acting
- irreversible, noncompetitive - enhanced release of ACh
- done via Guanidine
4
Q
Acetylcholine as a drug?
A
Clinical use:
- short duration of action
- non specific cholinergic drug, affects all receptors muscarinic and nicotinic
- highly susceptible to acetylcholinesterase
Miochol:
- ACh for intraocular use
- causes smooth muscle of iris to contract (pupil constriction)
- duration of action 10-20 mins
ADR:
-burning and itching eyes along with headache
-some ACh makes it to systemic circulation when injected into eyes
5
Q
Methacholine?
A
- somewhat susceptible acetylcholinesterase
- acts on muscarinic receptors only
- longer duration of action
6
Q
Carbachol?
A
- synthetic choline ester, direct acting cholinergic
- acts on muscarinic and nicotinic receptors
- not degraded by acetylcholinesterase
Clinical use:
- treat open angle glaucoma (intraocular pressure)
- duration is up to 8 hours
Mechanism:
-pupillary constriction causes opening, allowing aqueous humor to exit via Canal of Schlemm
ADR:
- flushing
- sweating
- cramping
- increased GI activity (urination)
- severe headache
- systemic effects
7
Q
Bethanechol?
A
- synthetic choline ester, direct acting cholinergic
- acts only on muscarinic receptors
- not degrade by acetylcholinesterase
Effects:
- increases GI peristalsis and defecation
- increases detrusor muscle tone
- stimulates urination
Clinical use:
- non obstructive urinary retention
- neurogenic atony of urinary bladder (loss of muscle tone)
- post op abdominal distention
ADR:
- flushing
- sweating
- cramping
- increased GI activity
- urinary urgency
- severe headache
- salivation
When not to use drug (contraindication):
- asthma like attacks (those with asthma are given anticholinergic drugs)
- parksonism (increasing ACh, diminishes the balance between Dopamine)
- usual ANS responses to systemic ACh (ADR above)
8
Q
Pilocarpine?
A
- natural, direct acting cholinergic
- cholinomimetic alkaloid, precursor of ACh
Effects:
- contraction of ciliary muscle, pupil constriction
- decreases intraocular pressure
- systemic salivation, sweating
- bradycardia
Clinical use:
- treat open and narrow angle glaucoma
- reversal of mydriatics (dilation) after eye exam
- ocular therapeutic system- unit inserted into conjunctival sac for continuous release of pilocarpine to open angle glaucoma (for elderly patients, could cause infections)
9
Q
Nicotine?
A
- natural, direct acting cholinergic
- cholinomimetic alkaloid
Effects:
- activates receptors in ANS ganglia, neuromuscular junctions, adrenal medulla, and brain
- causes people to become physically dependent, not carcinogenic
- stimulates cerebral cortex (alertness, cognition increase)
- stimulates limbic system (reward and pleasure)
- Tachycardia
- peripheral vasoconstriction (net effect of sym and parasym)
Clinical use:
-helps someone quit smoking (could OD if smoking still)
ADR:
- hypertension from tachycardia
- Buergers disease- interference of circulation due to vasoconstriction
- diarrhea
- insomnia
- increase cognition
- dysmenorrhea
10
Q
Varenicline (Chantix)?
A
- partial agonist of nicotinic receptors, weaker than nicotine
- increases cholinergic system
- blocks nicotine, releases Dopamine
- could cause schizophrenia, bipolar disorder, depression
11
Q
Cholinergic crisis?
A
-see sawing between cholinergic and anticholinergic drugs
Effects:
- sweating
- increased bronchial and salivary secretions
- bradycardia
- muscle weakness (overstimulation)
12
Q
Physostigmine (Antilirium)?
A
- short acting, reversible, indirect acting cholinergic
- inhibit acetylcholinesterase
- topical, systemic
- highly lipid soluble, tertiary structure, can cross BBB
Clinical use:
- treat open angle glaucoma
- reverse myadriasis from anticholinergic
- antidote to toxic neurological effects caused by having central anticholinergic activity (Scopolamine, antidepressants)
- clinical trials in treatment of alzheimers, short half life, slight increase in memory performance
ADR:
- typical systemic reactions
- bradycardia
- diaphoresis
- bronochospasm
- respiratory paralysis (overstimulation of muscles and too much ACh, can’t get repolarization and relaxation)
13
Q
Edrophonium?
A
- short acting, reversible, indirect acting cholinergic
- inhibit acetylcholinesterase
- given by IV
Clinical use:
- diagnose Myasthenia Gravis (autoimmune disease)
- treat poisoning of non depolarizing skeletal muscle relaxants
- test for cholinergic OD in those with Myasthenia
14
Q
Neostigmine?
A
- short acting, reversible, indirect acting cholinergic
- inhibit acetylcholinesterase
- quaternary compound, does not cross BBB
Clinical use:
- treat Myasthenia Gravis
- treat poisoning of nondepolarizing skeletal muscle relaxants
- reverse neuromuscular blocking agent used for surgeries
15
Q
Pyridostigmine?
A
- short acting, reversible, indirect acting cholinergic
- inhibit acetylcholinestase
Clinical use:
- treat myasthenia gravis
- treat poisoning of non depolarizing skeletal muscle relaxants
- occupies receptors so irreversible nerve gas does not damage
ADR:
- increased salivary secretions
- sweating
- GI and urinary functions increase
- may lose ability to control GI and urinary
16
Q
How do indirect acting irreversible cholinergic drug work?
A
- cause permanent inactivation of acetylcholinesterase via phosphorylation
- remains impaired until new enzymes are synthesized (weeks or months)
- chemical warfare, pesticides
- very lipid soluble, must wear gloves
17
Q
Echothiophate?
A
- irreversible, indirect acting cholinergic
- inactivate acetylcholinesterase
- long duration of action, may persist weeks
Clinical use:
- treat glaucoma
- pupillary constriction, miosis
- angle closure after an iridectomy (remove part of iris)
18
Q
Isoflurophate?
A
- irreversible, indirect acting cholinergic
- inactivate acetylcholinesterase
- similar to echothiophate
- water insoluble, readily absorbed into skin, systemic effects
Clinical use:
-maintenance therapy for glaucoma applied every 8-72 hours
19
Q
Pralidoxine?
A
-cholinesterase inhibitor antidote
Mechanism:
-disrupts bond between phosphorous group of irreversible enzyme inhibitor and binding site of cholinesterase enzyme
Clinical use:
-treat OD of irreversible cholinesterase inhibitor due to insecticide poisoning
20
Q
Guanidine?
A
- indirect acting cholinergic
- stimulates release of endogenous ACh
- relatively high toxicity
Clinical use:
- alleviate muscle weakness in myasthenia gravis
- alleviate symptoms of Eaton Lambert syndrome (muscle cancer)
ADR:
- diarrhea
- abdominal cramping
- tachycardia
- rash and bone marrow depression
- anemia
21
Q
What changes occur to cholinergic neurons as people age?
A
- reduced activity of choline acetylcholine transferase
- reduced synthesis of ACh
- reduced responsiveness of post synaptic M1 receptors in frontal cortex and hippocampus
- loss of cortical neurons
22
Q
How does a person reduce risk of losing memory/alzheimers?
A
-keep brains active and engaged to strengthen synapses
23
Q
Additional neuronal changes seen in patients with alzheimers?
A
- increased deposition of beta amyloid protein
- reduced number of synapses
- reduced activity of acetylcholinesterase
- possible genetic factors
- can also develop due to head trauma - exposure to excessive aluminum
24
Q
Lecithin (phosphatidylcholine)?
A
- drug to try to increase synthesis of ACh
- precursor of ACh
- 26 mg daily PO
Effects:
- increase levels of ACh in central synapses
- reduces tardive dyskinesia
- increase in plasma choline levels
- no improvement in memory or cognition in alzheimers patients, presynaptic uptake of choline may be impaired
- therapeutic only when combined with Physostigmine or Tacrine
25
4-Aminopyridine (4-AP)?
- drug to try to increase release of ACh
- used in clinical trials for treatment of alzheimers
Mechanism:
1. blocks K+ channels
2. reduces K+ exiting the cell
3. longer time to repolarize the cell
4. increased calcium influx, increased vesicle fusion
5. increased release of ACh
Effects:
- could improve memory and cognition
- placebo effect
ADR:
- xerostomia (dry mouth)
- disorientation
- confusion
26
Treatments to reduce alzheimers?
Enhance cholinergic activity
1. increase synthesis of ACh
2. increase release of ACh
3. reduce catabolism of ACh (primary method)
27
Tacrine (tetrahydroaminoacridine, THA, Cognex)?
- centrally acting reversible cholinesterase agent
- inhibits acetylcholinesterase
- short half life (2-4 hours)
- dose 40-120 mg daily PO
Effects:
-increase cognitive performance
ADR:
-HEPATOTOXIC (increase bilirubin)
28
Donepezil (Aricept)?
- centrally acting reversible anti cholinesterase agent
- inhibits acetylcholinesterase
- long half life (70 hours), less frequent dosing, lower rate of ADR
- first product approved by FDA for treatment of dementia and alzheimers
Effects:
- cognitive improvement (disappears when drug therapy is withdrawn)
- NOT HEPATOTOXIC
ADR:
- diarrhea
- anorexia
- muscle cramps
- insomnia
29
Rivastigmine?
Effects:
-inhibits acetylcholinesterase and butyrylcholinesterase
Clinical use:
-treats mild to moderate dementia of alzheimers
30
Galantamine?
Effects:
- inhibits acetylcholinesterase
- stimulates nicotinic receptors at sites different from those of acetylcholine
- enhances action of nicotinic receptors in presence of acetylcholine
- stimulates central cholinergic sites without causing concomitant desensitization
Clinical use:
-treat alzheimers, dementia
31
Memantine?
- Glutamate is excitatory and acts as NMDA receptor
- in some alzheimers, there is over activity of NMDA which may be tearing down receptors
- this promotes excess calcium influx which cause synaptic or dendritic damage, necrosis or apoptosis
Mechanism:
-Memantine binds to NMDA receptor and noncompetitively blocks it
Effects:
- slows progression of alzheimers
- may reduce pain
32
Deferoxamine?
Effects:
- approved as iron chelator to treat acute iron intoxication and chronic iron overload
- may reduce aluminum levels in bones of patients presenting with renal failure, patients with dialysis induced encephalopathy
Clinical use:
- drug to treat alzheimers
- use parenteral form
- could slow rate of cognitive deterioration
ADR:
- hearing loss
- impaired vision
- diarrhea
- leg cramps
- tachycardia
- reversible upon discontinuation
33
1-Deprenyl?
Effects:
- irreversible inhibitor of MAO-B
- stops degradation of ACh in presynaptic membrane
- slows degeneration in patients with Parkinson's
- improves cognition
- additive with cholinesterase inhibitors
Clinical use:
- help treat alzheimer's
- alzheimers may be caused by free radicals
- combine with Tacrine or Physostigmine
- dose 10mg daily PO
