Term
Drug List-Antimuscarinic Agents
(13) |
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Definition
- Atropine
- Tolterodine
- Glycopyrrolate
- Scopolamine
- Solifenacin
- Trihexyphenidyl
- Tropicamide
- Ipratropium
- Dicyclomine
- Oxybutynin
- Tiotroprium
- Hycoscyamine
- Other Pralidoxime
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Term
Antimuscarinic Agents- Mechanism of Action
(7) |
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Definition
-
Antimuscarinic drugs bind to post-synaptic muscarinic receptors, competitively block the binding of ACh
-
blockade can be overcomeby raising the concentration of endogenous ligand (ACh) or cholinergic agonist at the receptors.
-
Antimuscarinic drugs are defined by their mechanism of action
- Competitive inhibitors ACh at muscarinic receptors.
- Are also called antiparasympathetic, parasympatholytic
- Reduce activity of PSNS
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Term
Antimuscarinic Agents
Definition |
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Definition
Decrease stimulation of muscarinic receptors |
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Term
AntimuscarinicAgents;Sitesof
Action, Responses
(5)
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Definition
- Review-ingeneral,act at all muscarinic receptors
- Opposite effects of PSNS- muscarinic stimulation, i.e. cholinomimetics
- Generally non-specific for M1- M5 receptor subtype
- Since mechanism is competitive inhibition- effect depends upon endogenous tone.
- ALSO- conditions where TOTAL muscarinic blockade is clinically important
-
(1) organophosphate poisoning
ii) muscarinic poisoning involving ALL muscarinic receptors
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Term
Organ effects of anti-muscarinics
M1-M5 |
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Definition
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Term
Organ effects of anti-muscarinics
M3,M2
(5) |
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Definition
- Dilation of eye
- Decreased secretion -> salivary gland
- Decreased tone -> small and large intestine
- Sphincter constriction
- decreased urination
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Term
Organ effects of antimuscarinics
M2,M3
(3) |
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Definition
- Lungs -> open airways, decreased secretion
- Heart -> Tachycardia
- stomach ->decreased tone
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Term
Antimuscarinic Agents - Introduction
Prototypes
(2) |
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Definition
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Term
| AntimuscarinicAgents-Introduction |
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Definition
-
Are naturally occurring alkaloids.
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At therapeutic doses are selective for muscarinic vs. nicotinic receptors.
-
d) Generally, agents are Inherently nonselective for muscarinic receptor subtypes.
can produce multiple side effects, due to activation of M receptors in distal organ systems.
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New, relatively subtype-
selective antimuscarinics being designed
-
Selectivity can be obtained by local administration to the eye, lungs, or gut.
- e) Access to CNS
- Atropine crosses blood brain barrier only at high doses, and slowly
- Scopolamine crosses BBB easily; has CNS effects at therapeutic doses
- Scopolamineʼs CNS side effects at therapeutic concentrations (CNS depression, amnesia, excitation, hallucinations) are due to its greater ability to cross the BBB.
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Term
Therapeutic Uses for Antimuscarinics
Excessive Salivation***
Etiology
(7) |
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Definition
-
(1) Increased saliva production
-
(a) pregnancy
-
(b) organophoshpate intoxication
-
(c) oral infections
-
(d) gastroesophogeal reflux
-
(e) heavy metal poisoning
-
(2) Difficulty in swallowing
(a) Parkinsonism,
(b) Post-stroke
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Term
Therapeutic Uses for Antimuscarinics
Excessive Salivation***
Therapeutic goal & Treatment
(5)
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Definition
- Therapeutic goal- reduce saliva production
- Treatment
- Surgical Intervention-ligate salivary ducts
- Pharmacological
- M antagonists
- Atropine (Sal-tropine), glycopyrrolate (Robinul)
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Term
Therapeutic Uses for Antimuscarinics
Ophthalmological Examination***
(7) |
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Definition
- Etiology
- Need for unobstructed view of entire retina and optic disc
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Term
Therapeutic Uses for Antimuscarinics
General Anesthesia
Pre-Surgery*
(5) |
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Definition
- Etiology
- Surgically related risk of PSNS activity
- Therapeutic goal
- Reduce vagally mediated bradycardia in high risk patients (e.g down syndrome)
- Treatment
- Antimuscarinics block parasympathetic impulses to the heart & secretory organs (glycopyrrolate; rubinol)
- Avoids cardiac slowing mediated by PSNS during surgery
- Not routinely in patients at risk for cardiac slowing
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Term
Therapeutic Uses for Antimuscarinics
General Anesthesia
Post-Surgery* |
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Definition
- Post-surgical administration of ChE to overcome neuromuscuar block, increases ACh at all cholinergic synapses, nicotinic and muscarinic.
- Antimuscarinic administered to prevent unwanted side effects of over stimulation at muscarinic synapses to ChE inhibition (Glycopyrrolate; rubinol)
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Term
Cholinesterase inhibitor intoxication
etiology
(3) |
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Definition
- Massive ACh stimulation (organophosphate poisoning)
- Nervegases ( sarin, soman, tabun)
- Insecticides ( diazinon, malathion)
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Term
Cholinesterase inhibitor intoxication
Symptoms
systemic muscarinic
(8) |
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Definition
- miosis
- salivation
- bradycardia
- sweating
- bronchial constriction
- vomiting
- diarrhea
- secretions
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Term
Cholinesterase inhibitor intoxication
Symptoms
systemic nicotinic
(3) |
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Definition
- general weakness
- twitching
- paralysis
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Term
Cholinesterase inhibitor intoxication
Symptoms
CNS
(3) |
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Definition
- Convulsions
- coma
- central respiratory paralysis
- ataxia
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Term
Cholinesterase inhibitor intoxication
Therapeutic goal
(2) |
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Definition
- Block all muscarinic receptors
- reactivates AChE
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Term
Cholinesterase Inhibitor Intoxication***
Organophosphate Poisoning
Treatment 1
High dose
(4) |
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Definition
1) HIGH DOSE .
- Atropine is
the preferred antimuscarinic agent
- readily blocks
peripheral muscarinic
effects.
- although slowly, high
doses penetrate the BBB and block central cholinergic effects
- Does not produce the CNS side effects of scopolamine
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Term
Cholinesterase Inhibitor Intoxication***
Organophosphate Poisoning
Treatment 2
ChE reactivator
(4)
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Definition
ChE reactivator
Pralidoxime (Protopam)
- Cleaves bond between organophosphate and cholinesterase
- Must be applied before “aging”, <24-48 hrs post-exposure, or does no good (c) used with atropine
- only has systemic effects, does not cross BBB
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Term
Cholinesterase Inhibitor Intoxication***
Organophosphate Poisoning
Treatment 3
(2) |
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Definition
- Clinical Management of all symptoms
- Especially respiratory maintenance
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Term
Urinary urgency and frequency***
Etiology
(9) |
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Definition
- Stress Incontinence
- Laughing
- coughing
- sneezing
- exercise
- Urge Incontinence
- Inappropriate urge (i.e. bladder not full)
- Neural
- Inappropriate neural stimulation of detrusor & sphincter muscles
- stroke
- spinalinjury
- Parkinsonʼs
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Term
Urinary urgency and frequency***
Therapeutic Goal |
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Definition
- Reduce detrusor tone
- increase sphincter tone
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Term
Urinary urgency and frequency***
Treatment
Stress and urge incontinence |
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Definition
- Stress and urge incontinence
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Term
Urinary urgency and frequency***
Treatment
Neural Incontinence
Tolterodine
(4) |
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Definition
- Muscarinic antagonist (M3)
- Tolterodine (Detrol) is potent and selective for the bladder, used for urinary incontinence.
- Blockade of M3 receptors- detrusor muscle relaxes and the internal sphincter tightens.
- intherapeutic doses,few side effects andexcellent patient acceptance.
- An extended release preparation (DetrolXL) is available that can betaken once per day.
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Term
Urinary urgency and frequency***
Treatment
Neural Incontinence
Solifenacin
(4) |
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Definition
- Solifenacin (VESIcare) is new (2004)-similar to Detrol.
- Relatively selective M3 antagonist, but has some effect on all muscarinic receptors.
- Differs from Detrol
- less effect on salivary receptors, so dry mouth is less of a problem
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Term
Urinary urgency and frequency***
Treatment
3 drugs |
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Definition
M3 antagonists
- Tolterodine (Detrol)
- Solifenacin (VESIcare)
- Oxybutinin (Ditropan)
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Term
GI spasm, Irritable bowel syndrome***
Etiology
(4) |
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Definition
- food intolerance, e.g. lactose
- GI Infections
- food poisoning
- IBS can produce spasms
-
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Term
GI spasm, Irritable bowel syndrome***
Therapeutic Goal
(5) |
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Definition
- reduce
- GI cramping,
- bloating,
- pain
- Relax GI tract
- decrease secretions
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Term
GI spasm, Irritable bowel syndrome***
Treatment
(3) |
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Definition
Muscarinic antagonist (pharmalogical anti-chlinergics)
- dicyclomine (Bentyl)
- hyoscyamine (A-Spas, ANapraz
- glycopyrrolate (Rubinul)
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Term
Motion Sickness***
Etiology |
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Definition
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Term
Motion Sickness***
Therapeutic Goal |
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Definition
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Term
Motion Sickness***
Treatment
OTC |
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Definition
- Antihistamines
- Therapeuticeffects due to anti muscarinic action
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Term
Motion Sickness***
Treatment
Scopolamine
(Transderm-Scop)
prescription |
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Definition
- Non-specific M1-M5 receptor antagonist
- The single most effective agent known for relief of symptoms of motion sickness
- Effective when given orally, transdermally and parenterally (must be administered prophylactically).
- Transdermal scopolamine patch results in therapeutic blood levels for up to 72 hr.
- Common side effects dry mouth, drowsiness, sometimes blurred vision
- Site of action-unknown
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Term
RespiratoryDistress***
Etiology
(2) |
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Definition
-
Asthma, COPD (chronic bronchitis, emphasema)
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Bronchiolar constriction, inflammation, secretion
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Term
RespiratoryDistress***
Therapeutic Goal |
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Definition
- Increase breathing efficiency
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Term
RespiratoryDistress***
Treatment
Long term
(3) |
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Definition
- Steroids,
- long acting B-agonists
- anti- leukotrienes
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Term
RespiratoryDistress***
Treatment
(5)
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Definition
- Short term bronchodilators (muscarinic M3 anatgonists)
- Ipratropium (Atrovent)
- Tiotropium (Spiriva)
- Beta 2 agonists
- Anto-inflammatory agents
- leukotrienes
- corticosteroids
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Term
RespiratoryDistress***
Treatment
Shorter term bronchodilators
Ipratropium
(Atrovent)
(5)
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Definition
- non-selective muscarinic antagonist for inhalation.
- Fast acting dilator for quick,short term relief
- Bronchodilation and reduced airway secretions--acts on M3 in the lungs.
- Inhalant-produces local effects in the mouth and airways, minimal amounts absorbed systemically. As a result, there are fewer side effects.
- Primary therapeutic use is treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD), also of value in asthma.
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Term
RespiratoryDistress***
Treatment
Shorter term bronchodilators
Tiotropium
(Spiriva)
(4) |
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Definition
- new (2004) receptor antagonist for respiratory use.
- Inhalant
- 24 hr duration longer than Ipratropium- administered once/day,
- Relatively more selective for M1 and M3 receptors
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Term
Parkinsonism Disease
Etiology
(4) |
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Definition
- Loss of inhibitory dopaminergic neurons in the substantia nigra that Normally balance excitatory cholinergic input
- Decreased basal ganglia DA
- Altered balance DA/ACh
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Term
Parkinsonism Disease*
Therapeutic Goal
(2) |
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Definition
- Restore excitatory/inhibitory balance in CNS motor controlcenter-Basal Ganglia
- Restore DA/ACh balance
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Term
Parkinsonism Disease*
Treatment
(5) |
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Definition
- Increase CNS dopamine with levodopa and carbidopa
- Prior to development of these agents, there was no mechanism to restore dopaminergic input.
- Decrease ACh activity
- Primary Pharmacological approach-CNS antimuscarinic agents to reduce excitatory cholinergic tone
- Due to side effects use of antimuscarinic drugs now plays a secondary role in treatment
- Age related cognitive dysfunction
- Still CNS acting antimuscarinic trihexyphenidyl (Artane) can produce modest benefits in tremor predominant (basal ganglia) Parkinsonʼs Disease in patients <65 yrs old
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Term
Antimuscarinics
Common Adverse Effects
(6) |
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Definition
- Symptoms associated with inhibition of peripheral PSNS and/or CNS cholinergic transmission
- Generally predictable
- Result from non-specific inhibition of Muscarinic receptors in organs distal from target sites.
- Depend on bioavailability to distal organs
- Can bereduced by local administration, i.e. lozenges, inhalation
- Cognitive effects with agents which cross the BBB
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Term
Contraindications of Antimuscarinic Agents
(6) |
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Definition
- Glaucoma
- Obstructive GI disease
- Difficulty in urinating
- Dry mouth
- Any condition characterized by impaired parasympathetic nervous system function
- Non-specific M blockade in organs distal to site of pathology can worsen condition
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Term
Summary Antimuscarinic agents
Sites of action |
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Definition
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Term
Summary Antimuscarinic agents
Mechanism of action |
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Definition
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Term
Summary Antimuscarinic agents
Effects |
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Definition
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Term
Summary Antimuscarinic agents
receptor specificity |
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Definition
- Specific for M receptors
- MAJORITY non-specific for muscarinic subtype
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Term
Summary Antimuscarinic agents
Common Clinical Uses
(7) |
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Definition
- Excessive salivation
- Opthamology
- Pre-post surgery
- ChE inhibitor intoxication
- Incontinence
- Motion sickness
- Resporatory distress
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Term
Summary Antimuscarinic agents
contraindications
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Definition
- Pathologies associated with symptoms characterized by PSNS deficits
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Term
Mixed a1/a2
Adrenergic Receptor Antagonists
Drugs |
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Definition
- Phenoxybenzamine
- Covalently binds a receptors
- Irreversible antagonis of a1 and a2 receptors
- Phentolamine
- Competitive, reversible antagonist of a1 & a2 receptors
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Term
Mixed a1 & a2
Adrenergic Receptor Antagonists
Physiologic Effects |
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Definition
- Vascular
- Blockade of a1 and a2 adrenergic receptors leads to vasodilation => decreased peripheral resistance => decrease BP
- Cardiac
- Can indirectly increase heart rate (reflex tachycardia)
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Term
Mixed a1 & a2
Adrenergic Receptor Antagonists
Therapeutic Uses
(4) |
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Definition
- Pheochromocytoma
- Short-term pre-and-peri operative management (Phentolamine)
- Long-term management of pts who are not surgical candidates (Phenoxybenzamine)
- Manage local ischemic necrosis (phentolamine)
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Term
Mixed a1 and a2
Adrenergic Receptor Antagonists
Adverse Effects
(3) |
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Definition
- Orthostatic hypotension with reflex tachycardia and arrhythmias
- nasal stuffiness
- GI irritation, N/V
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Term
Mixed a1 & a2
Adrenergic Receptor Antagonists
Contraindications/Precautions |
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Definition
- Pts with coronary artery disease (eg. MI, atherosclerosis)- contraindication
- Administration of mixed sympathomimetic drugs (eg. Epi)- precaution because B receptor activation will be unopposed (a receptors blocked), which can lead to profound hypotensive peisode with reflex tachycardia.
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