cannabinoids/antiparkinsons Flashcards
Cannabinoids
Marijuana; others: Hashish, K-2, Spice, etc.
plant: Cannabis sativa (hemp plant)
active ingredient: -9-tetra-hydrocanacinol (THC)
K-2 and spice sold as “legal weed” over internet and in head shops
weed and hashish duration of action
Although the duration of action is only 2-3 hours, low levels of the drug and its metabolites may be present for several weeks
cannabinoid effects part 1
- Relaxation and increased sense of well being, giddiness.
- Sedation and drowsiness.
- Memory and cognitive impairment, confusion.
- Psychomotor slowing, loss of coordination, decreased ability to perform complex tasks.
- High doses can cause hallucinations, paranoia, psychotic reactions.
cannabinoid effects part 2
- Increase in appetite.
- Tachycardia, postural hypotension.
- Reddening of conjunctiva - tell-tale sign.
- Decrease intraocular pressure - THC is being tried for treatment of
glaucoma. - Inhibition of vomiting reflex - THC is available for use in patients undergoing
cancer chemotherapy (Dronabinol, Marinol)
cannabinoid MOA
pecific canabinoid receptors in the CNS
-analog of arachidonic acid, arachidonylethanolamide. New drugs that modulate “endcanabinoids” and canabinoid receptors are under development
cannabinoid toxic effects
immunosuppresion
lower testosterone levels in males–>dec. libido, gynecomastia
terotogen: decreased birthweight; increased incidence of birth
defects; learning disabilities
“Amotivational Syndrome”
Damage to lungs similar to that seen in tobacco smokers. esp. severe w. paraquat
-sev. poisoning is rare; may have unpleasant effects: paranoia, fear, panic, hallucinations, and psychotic reactions
how to tx unpleasant psych effects
symptomatic, calming, reduce sensory input; if severe: anxiolytics/antipsychs
marijuana tolerance
may occur, or may be paradoxical: become MORE sensitized to effects (i.e. they get high more easily) via situational and psychological cues, body fat deposition
marijuana physical dependence
may occur
withdrawal syndrome: irritability, insomnia, tremors, nausea and vomiting (almost never seen w. typical use)
Medical Uses of Cannabinoids
- prevention of N/V during chemo (Dronabinal)
- prevention of “wasting” in AIDs patients
- tx of glaucoma and asthma (have been proposed but not yet proven or approved uses). There is actually a lot of data that marijuana does not work in conditions like glaucoma.
Salvia
Salvia divinorum hallucinogenic effects (diff. than LSD) Active agent is salvinorin A: agonist at kappa opioid and D2 dopamine receptor smoking, available via internet, criminalized -varied drug responses: dysphoric effects and “bad trip” symptoms
Kratom
Thailand
- stimulant and pain reliever; opioid-like effects
- mitragynine and 7- hydroxyragynine have agonist activity at mu-opioid receptors
- varied drug responses: euphoria to dysphoria to no effect
- available via internet and head shops; also used in US for self-dig. management of pain/opioid w.drawal (and abused)- currently legal
drugs for Alzheimer’s Disease
AChE inhibitors (want to increase ACh, does not alter progression of disease)
NMDA receptor antagonist
antioxidantes
alternative txs
AD NT changes
decreased ACh
^ glutamate
loss of acetylcholine producing neurons in the nucleus basalis of Meynert and areas of the frontal cortex
AChE inhibitors for AD
*rivastigmine (Exelon),
*donepezil (Aricept)-least SEs
galantamine (Reminyl)
tacrine (Cognex)-liver damage
also tx for other types of dementia
AChE inhibitor SEs
(cholinergic)
salivation, sweating, nausea, diarrhea, intestinal cramping, urinary incontinence, bradycardia, bronchoconstriction
FA: Nausea, dizziness, insomnia
Memantine (Namenda)
NMDA receptor antagonist for tx of AD
block the excitatory actions of glutamate at NMDA receptors in the hippocampus and frontal cortex (mediated by Ca2+)
-can improve cognitive function; may prevent some of the excitoneurotoxic effects of glutamate (which are thought to contribute to the neurodegenerative changes seen in AD)
Memantine (Namenda) SEs
^blood pressure, dizziness, GI distress and cough
FA: also confusion, hallucinations
vitamin E (AKA alpha-tocophenol) and seligiline/deprenyl (Eldepryl)
antioxidants
-reduce some of the degenerative changes and slow the progression of AD?
Alternative/Non-traditional AD Therapies
Ginko biloba NSAIDS Antimicrobial agents Estrogen new targets: tau and B-amyloid
ALS mechanism
astrocytic glial cells replacing the neurons
degenerative process appears to involve a combination of oxidative stress and glutamate excitotoxicity
UMN and LMN
ALS tx
Riluzole (Rilutek): slows progression; inhibits the release of glutamate from nerve endings and reducing the so called “excitotoxicity”, “orphan drug”, start early
other drugs used for symp. support: muscle relaxants, antidepressants, anti-convulsants, also antimicrobials, antivirals and immunomodulators in the future
ADHD tx
Stimulants
non-stimulants: Atomoxatine (Straterra)
alternative tx
stimulant action
affect locus ceruleus; act by causing the release and/or inhibiting the reuptake of DA and NE from synaptic nerve endings
methylphenidate (Ritalin)
mainstay stimulant, relative mild (less than amphet.), short duration
d-amphetamine, d,l-amphetamine and their salts
powerful stimulants generally reserved for pts who don’t show an adequate response to methylphenidate.
- *Adderall is a brand name product that contains a complex mixture of amphetamine salts.
- Schedule II drugs: complicates prescribing.
Atomoxatine (Straterra)
non stimulating agent; for ADHD in kids and adults
-inhibits the synaptic reuptake of NE
-good for pts who cannot tolerate/don’t respond to stims.
CONS: may not be as effective as stims, may cause hepatotox
Nontraditional/alternative agents for ADHD?
- Antidepressants especially TCAs and bupropion (Wellbutrin)
- Alpha-2 receptor agonists – clonidine (Catapres) and guanfacine (Tenex)
- Carbamazepine (Tegretol)
- Fish oil and Omega-3 fatty acids
