week 10: CNS Drugs Flashcards
What are “adaptive changes” and how does this contribute to tolerance and physical dependence?
Adaptive changes occur when the body physiologically adapts to adjust to the drug in the body.
What happens when drugs that elicit adaptive changes are abruptly discontinued?
When the drug is taken away abruptly, your body can go into a state of withdrawal but it’s known as abstinence syndrome due to the adaptive changes.
With Parkinson’s disease - what two NT do we manipulate with pharmacologic interventions?
Dopamine = decreases and this decrease acts as a inhibitory factor in the disease ACH = increases in this disease and acts as an excitatory
what neurotransmitter do you want to manipulate specifically for Parkinson’s through medication usually
we want to increase our dopamine and to do this we use dopamine agonists
3 groups of dopaminergic agents in the context of PD
- Levadopa
- MAO B
- Amantadine
- Dopamine agonist
what is the MOA of levodopa
- directly activates DA receptors
- SO this is a prodrug that needs to be converted to DA in the CNS BUT in order to do this we need to avoid three things (see below)
What MAO B
- we use this in mild to moderate cases
- prevents dopamine breakdown → which usually MAO B breaks down
- this is the 1st line drug because it is selective and reversible
- Selegiline
- Rasagline
what type of drug is a -giline (selegiline)
- prevents dopamine breakdown → which usually MAO B breaks down
- this is the 1st line drug because it is selective and reversible
what is the MOA amantadine
*promotes DA release and inhibits reuptake
what is the MOA Dopamine agonist
*ergot alkaloid = no selective DA receptors
*NON ergot alkaloid = SELECTIVE DA receptor
Act like dopamine
Less effective then L-Dopa BUT less risk of dyskinesia
what drugs are combined with levodopa
COMT inhibitors = carbidopa
Decarboxylase inhibitors = entacapone
what type of drug is carbidopa
COMT inhibitors
what type of drug is entacapone
Decarboxylase inhibitors
what else do you want to avoid with levodopa
Avoid high protein meals
why does levodopa need to be combine with other drugs in order to have an effect
SO this is a prodrug that needs to be converted to DA in the CNS BUT in order to do this we need to avoid three things
What is the difference between MAO-B & MAO-A?
MAO A breaks down serotonin and norepi = there is larger risk of HTN with these patients
MAO B breaks down dopamine = MORE SELECTIVE = so there is less risk of HTN when using a more selective drug
For cognitive impairment what drugs related to NT do we manipulate
AChE = INHIBIT NMDA = Antagonize
three AChE inhibitors commonly used in Alzheimer’s Disease
Donepezil = a reversible drug that is highly protein bound and CNS selective Galantamine = leads to reversible inhibition Rivastigmine = this drug is irreversible and has PNS effects
what class of drug is donepezil and what makes it special
an AChE inhibitor and is a reversible drug that is highly protein bound and CNS sensitive
what type of drug is galatamine
an ACHe inhibitor
this drug leads to reversible inhibition
what AChE inhibitor leads to reversible inhibition
Galantamine
what drug for alziehers leads irreversible and has PNS effects
Rivastigmine
what drug is associated with NMDA
Memantine
what AChE inhibitors is highly protein bound and CNS selective
Donepezil
Understanding the pathophysiology of MS, it makes sense that we would want to inhibit immune responses. What are the two types of drug classes used for this purpose?
- Immunosuppresants
2. Immunomodulators
how does a immunosuppressant work for MS
*inhibits DNA synthesis and repair
*decreased immune cell proliferation
Decreased myelin sheath destructions
how does a immunomodulator work for MS
*preferred choice when looking at these two options to stop the progression of the autoimmune
*can stimulate antibody production against drug itself
*special handling
Beta 1a drugs
Beta 1b drugs
what drug can be used for treating distressing or harmful symptoms of MS
Dalfampdine = will help with the gait issues
When giving any medications that suppress immune responses, what are points of patient education?
Avoid live vaccines when using Want to start treatment right away Concurrent use of immunomodulators High risk of infection Can have flu like adverse effect
what type of drug is mitoxantrone
used for MS
List the three MAJOR adverse effects of mitoxantrone
Myelosuppression
Cardiotoxicity irreversible and leads to HF that can occur years after use
Fetal injury (even in low doses)
what is a traditional anti seizure drug
Well established Less well tolerated More cplex pK Drug interactions due to CYP450 Less safe in pregnancy but remember some of these benefits outweigh the risks
what is a new generation antiseiure drug
Not as well established Well tolerated Simpler PK NO cyp450 interaction Safer in pregnacy
what is the prototype for traditional anti seizure drugs
Phenytoin
what is the MOA of Phenytoin
- Selectively inhibits Na+
- Slows recovery from inactive
- Metabolizing enzymes in liver quickly become maxed out → narrow the dosing for this reason
what antiseizure drug has the same MOA as phenytoin?
Carbamazepine
which antiseizure drug should be avoided in pregnancy
Valproate
what traditional antiseizure drug can lead to live threatening pancreatitis
Valproate
what is the MOA of Valproate
Enhances GABA transmission and blocks Na+ like phenytoin
what is the MOA of Ethosuximide
Suppression of Ca++ channel in the thalamus
Absence of seizure usage
what are the A/E of phenytoin
HIGH TOXICITY RISK CNS sedation Insomnia, nystamias Gingival hyperplasia Measle like rash Necrosis with the IV
what is Phenobarbital
traditional antiseizure drug
Potentiates effects of GABA used in anesthesia!!
what is special about Phenobarbital
long half life
Acute intermittent porphyria
VitD metabolism
what is the prototype of the new generation antiseizure medication
Oxcarbazepine
what is Oxcarbazepine
Is a derivative of Carbamazepine which is a Na+ channel inactivation
what do we want to avoid taking Oxcarbazepine with
Can induce CYP450
Avoid with other drugs that reduce Na+
Avoid alcohol
what is Lamotrigine
new generation antiseizure medication
what is the MOA of Lamotrigine
Na++ channel inactivation and Ca++ channel block
what does Lamotrigine adversely lead to
Unusual AE
Hypo NA+
Hypothyroidism
what two new generation antiseizure drugs have unknown MOA
Gabapentin
Levetiracetam
what is known about pregabalin
Binds Ca++ and inhibits glutamate, NE, sub P
Skin rxn
Euphoria
Decreased fertility
what new generation antiseizure medication can lead to euphoria and decreased fertility
Pregabalin
what new generation antiseizure medications have minimal adverse effects
Gabapentin
Levetiracetam
what drug decreases GABA reuptake in relation to new generation seizure medications
Tiagabine
Topiramate
GABA potentiation
Na++ channel and Ca++ channel block
Metabolic acidosis
Possibly high SI
what two drugs are used for spasticity disorders
Dantrolene
Baclofen
how does dantrolene work
- decreases CA++ efflux from the sarcoplasmic reticulum
* peripherally acting so reduces strength can make you weak, drowsy
how does beclofen work
- micics GABA @ hyperreactive motor neurons in spinal cord
* centrally acting
when would you not take baclofen
Leads to GI issues as AE and recommended not to take if having urination isuses
what is serotonin syndrome
Serotonin syndrome is when several disorders happen from CNS drugs. SS is one of them. It’s when disoders look similar but are treated inversely. It is when there is wayyy too much serotonin.
what drug can put you at risk of serotonin syndrome
MAO B inhibitors can put you at risk of serotonin syndrome (this is because at high doses they aren’t selective )
what is a controlled substance
a drug that has high potential for abuse
what should you avoid when taking 1. Selegiline, a MAO-B inhibitor
- SSRIs (selective serotonin reuptake inhibitors)
* tyramine containing foods
how does Carbidopa work
prevents deactivation of levodopa before it gets to the CNS
how does donepezil work
prevents ACh degradation in CNS
how does donepezil work
prevents ACh degradation in CNS
w does varenicline work?
partially agonize nicotine receptors with stronger affinity than nicotine
when thinking about muscle spasms and treatment which may you use in order to avoid muscle weakness
baclofen
for traditional antiseizure medications, why in phenytoin do you want to avoid taking drugs that are impacted. by CYP450 (indices or inhibitors)
because phenytoin quickly maxes out metabolizing enzymes
this means that if CYP450 being altered by another drug can cause high toxicity risk more readily
