BENZTROPINE
DICYCLOMINE
DARIFENACIN
HYOSCYAMINE
OXYBUTYNIN
PROPANTHELINE
SOLIFENACIN
TOLTERODINE
TROSPIUM
TRIHEXYLPHENIDYL
- Action to be taken: Caution. Monitor cardiovascular function
- Rationale: Benztropine is a selective M1 muscarinic acetylcholine receptor antagonist. It partially blocks cholinergic activity in the CNS, which is responsible for the symptoms of Parkinson's disease. Metabolism of benztropine is unknown however it predominantly undergoes renal excretion. Benztropine can cause tachycardia due to anticholinergic action at the sino-atrial node. Both Sativex and Dronabinol have been associated with averse cardiovascular effects including tachycardia and hypertension. Furthermore exposure marijuana smoke has shown to be a trigger of myocardial infarction. Based on available data medical marijuana should be used in caution with Benztropine due to increased risk of cardiovascular diseases and heart attack.
DICYCLOMINE
- Action to be taken: Caution with close monitoring for anticholinergic side effects. Possible dosage adjustment.
- Rationale: Dicyclomine relieves smooth muscle spasms of the gastrointestinal tract. Animal studies indicate that this action is achieved via a dual mechanism: which includes antimuscarinic and musculotropic actions. Agents with anticholinergic activities may increase certain actions or side effects of dicyclomine. Cannabinoids have cardiovascular effects that include tachycardia, and transient changes in blood pressure, including episodes of postural hypotension. Furthermore some of the common side effects of sativex include dizziness, disorientation, amnesia, balance disorder,dysarthria,lethargy, somnolence,blurred vision,vertigo,constipation and dry mouth. Caution is advised with co-administration with anti-spasticity agents since reduction in muscle tone and power may occur, with greater risk of falls.
DARIFENACIN
- Cytochrome P450 enzyme substrate: CYP2D6 and CYP3A4
- Action to be taken: Caution with close monitoring for anticholinergic side effects. Possible dosage adjustment.
- Rationale: Darifenacin is extensively metabolized by the liver following oral dosing. Metabolism is mediated by cytochrome P450 enzymes CYP2D6 and CYP3A4.Therefore, inducers of CYP3A4 or inhibitors of either of these enzymes may alter darifenacin pharmacokinetics. In vitro studies have shown that marijuana has minimal inhibitory impact on CYP3A4 and CYP2D6.Nonetheless, given the lack of inhibition data at several CYP-450 isoforms, clinically significant inhibitory effects cannot be ruled out entirely. Delavirdine is an inhibitor of both CYP2D6 and CYP3A4.Concomitant use with darifenacin requires patient monitoring for increased anticholinergic effects. Dosage adjustment may be necessary.
HYOSCYAMINE
- Action to be taken: Caution with close monitoring for anticholinergic side effects. Possible dosage adjustment.
- Rationale: Hyoscyamine inhibits gastrointestinal propulsive motility and decreases gastric acid secretions.Once absorbed, this product disappears rapidly from the blood and is distributed throughout the entire body. The majority of hyoscyamine sulfate is excreted in the urine unchanged. Absorption of other oral medications may be decreased during concurrent use with anticholinergics due to decreased gastrointestinal motility and delayed gastric emptying. Agents with anticholinergic activities may increase certain actions or side effects of hyoscyamine. Cannabinoids have cardiovascular effects that include tachycardia, and transient changes in blood pressure, including episodes of postural hypotension. Furthermore some of the common side effects of sativex include dizziness, disorientation, amnesia, balance disorder,dysarthria,lethargy, somnolence,blurred vision,vertigo,constipation and dry mouth. Caution is advised with co-administration of cannabis with hyoscyamine due to increased risk of anticholinergic effects.
OXYBUTYNIN
- Cytochrome P450 enzyme substrate: CYP3A4
- Action to be taken: Caution with close monitoring
- Rationale: In vitro studies show that marijuana is a CYP3A4 inhibitor. Systemic azole antifungals are CYP3A4 inhibitors and can reduce the metabolism of oxybutynin. Serum concentrations of oxybutynin were approximately 2-fold higher when administered with ketoconazole or itraconazole. Oxybutynin should be used cautiously in patients receiving these drugs.
PROPANTHELINE
- Action to be taken: Caution with close monitoring for anticholinergic side effects. Possible dosage adjustment.
- Rationale: It is a non-specific acetylcholine antagonist at the muscarinic M1–3 receptors, but it also has a direct musculotropic effect causing relaxation of smooth muscle. Propantheline undergoes extensive first pass metabolism mainly via hydrolysis reducing bioavailability significantly to between 10–25%. bsorption of other oral medications may be decreased during concurrent use with anticholinergics due to decreased gastrointestinal motility and delayed gastric emptying. Agents with anticholinergic activities may increase certain actions or side effects of propantheline. Cannabinoids have cardiovascular effects that include tachycardia, and transient changes in blood pressure, including episodes of postural hypotension. Furthermore some of the common side effects of sativex include dizziness, disorientation, amnesia, balance disorder,dysarthria,lethargy, somnolence,blurred vision,vertigo,constipation and dry mouth. Caution is advised with co-administration of cannabis with propantheline due to increased risk of anticholinergic effects.
SOLIFENACIN
- Cytochrome P450 enzyme substrate: CYP3A4
- Action to be taken: Potential dose reduction
- Rationale: Solifenacin is significantly metabolized via CYP3A4 pathway. At therapeutic concentrations, solifenacin does not inhibit CYP1A1/2, 2C9, 2C19, 2D6, or 3A4 derived from human liver microsomes. In vitro studies have shown that marijuana has minimal inhibitory impact on CYP3A4 and CYP2D6. Patients receiving CYP3A4 inhibitors should not receive solifenacin doses greater than 5mg per day.
TOLTERODINE
- Cytochrome P450 enzyme substrate: CYP2D6 and CYP3A4
- Action to be taken: Potential dose reduction
- Rationale: Pharmacokinetic studies of use of tolterodine concomitantly with CYP3A4 inhibitors have not been performed. Systemically administered azole antifungals are considered CYP3A4 inhibitors. Because of difficulty to assess which patients are poor metabolizers of tolterodine via CYP2D6, patients receiving strong CYP3A4 inhibitors should not receive >2 mg/day of tolterodine. In addition, tolterodine is associated dose-dependent QT prolongation, especially in poor CYP2D6 metabolizers.
TROSPIUM
- Action to be taken: Caution, Monitor anticholinergic effects
- Rationale: The concomitant use of SANCTURA with other antimuscarinic agents that produce dry mouth, constipation,
and other anticholinergic pharmacological effects may increase the frequency and/or severity of such effects. SANCTURA may potentially alter the absorption of some concomitantly administered drugs due to anticholinergic effects on gastrointestinal motility. Cytochrome P450 (CYP) is not expected to contribute significantly to the elimination of trospium. Data taken fromin vitro human liver microsomes investigating the inhibitory effect of trospium on seven CYP isoenzyme substrates (CYP1A2, 2A6, 2C9, 2C19, 2D6, 2E1, and 3A4) suggest a lack of inhibition at clinically relevant concentrations.
TRIHEXYLPHENIDYL
- Action to be taken:Caution. Monitor cardiovascular function
- Rationale: Trihexylphenidyl is a selective M1 muscarinic acetylcholine receptor antagonist. It partially blocks cholinergic activity in the CNS, which is responsible for the symptoms of Parkinson's disease. It is rapidly absorbed by the GI tract and excreted by the kidneys however metabolism of trihexylphenidyl is unknown. can cause tachycardia due to anticholinergic action at the sino-atrial node. Both Sativex and Dronabinol have been associated with averse cardiovascular effects including tachycardia and hypertension. Furthermore exposure marijuana smoke has shown to be a trigger of myocardial infarction. Study by Benovitz et al, showed that during THC ingestion, heart rates were significantly greater after parasympathetic (atropine) blockade . During THC ingestion, atropine had a pronounced pressor effect, which might represent a clinically significant drug interaction Based on available data Cannabinoids may have additive effects with Artane. Medical marijuana should be used in caution with Trihexylphenidyl due to increased risk of cardiovascular diseases and heart attack.
References
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