Drugs Final Flashcards by Stephen Barna

AEDs can antagonize excitation aka they inhibit it… This occurs via 2 ways

1) Voltage gated ____ ion channels
2) Low-threshold (T type) ___ channels

Hopes are to inhibit glutamate transmission or enhance GABA transmission

1) Na+ (Nav)

2) Ca2+

How well did you know this?

Not at all

Perfectly

****** WILL BE TESTED ON

Voltage gated Na+ ion channels (Nav) can have FAST inactivation or SLOW inactivation

The drugs that can prolong FAST inactivation are ____

The drugs that can prolong SLOW inactivation are _____

Note if a patient is not responding to any of the Fast inactivation drugs, one might think of switching to ____

Phenytoin, Carbamazepine, Lamotrigine, Oxcarbazepine, and Zonisamide

Lacosamide

How well did you know this?

Not at all

Perfectly

During Na + depolarization, there are three states

1) Resting state
2) Open state
3) Fast-inactivated state

In the resting state, the activation gate is ___ and the inactivation gate is ___

In the open state, both are open

In the fast-inactivated state, the activation gate is ___ and the inactivation gate is ____

For repolarization there are 3 states as well

1) Fast-inactivated state
2) Inactivated, closed state (slow)
3) Resting state

In the fast-inactivated state, just like at the end of depolarization, the activation gate is ___ and the inactivation gate is ____

In the inactivated, closed state, the activation gate is ___ and in inactivation gate is ____

^*** This is a fast inactivation, and realize that at this point it must first have the activation gate close before anything can happen, and once that activation gates closes, it can open the inactivation gate and return to resting state

In the resting state, just like the original resting state, the activation gate is ____ and the inactivation gate is ____

Closed, Open

Open, Closed

Closed, Closed

Closed, Open

How well did you know this?

Not at all

Perfectly

The fact that NAv channels undergo ___ changes during the action potential is what allows the epileptic drugs to be selective for channels that are overactive, versus normal channels

^** Aka since the epileptic drugs are opening and closing more frequently, and since the drugs act by entering the channels and binding to pores inside them, by chance alone those that open more often will have a greater chance of being acted upon by drugs, aka this is why drugs usually are selective for ONLY epileptic channels rather than normal channels too

**^^^^ One more time, the probability of a Nav blockade is proportional to the frequency of Nav channels opening and the dose given

If the ___ gate is open, than AEDs can access the “pore” and if closed, they can not

So since the activation gate is only opened in the ___ state or ____ state, those are when the drug will be able to come in and perform its action

conformational

Activation

Open state and Fast-Inactivated state

How well did you know this?

Not at all

Perfectly

____ and ____ are state-dependent agents that slow the recovery of NAv ion channels from inactivation aka they lock it into the ___-inactivated state (to slow down the actviation potential)

Phenytoin is ____ effective than Carbamazepine at depolarized membrane potentials and high frequency action potential firing (with minimal effects on low frequency firing)

Carbamazepine is less effetive than Phenytoin, but acts ____ and therefore it is better at blocking high frequency firing due to the fact that it binds much faster

Similar to the above 2 drugs is ___, however, this drug acts on OTHER molecular targets as well including N and P type voltage-gated ____ channels in cortical neurons and neocortical potassium currents

Phenytoin and Carbamazepine, FAST

Faster

Lamotrigine, Ca2+

How well did you know this?

Not at all

Perfectly

****** WILL BE TESTED ON

Unlike Phenytoin, Carbamazepine, and Lamotrigine, _____ stabilizes the ____-inactivated state (aka the inactivated CLOSED state) and is more effective at reducing the amplitudes and frequency of sustained repetitive firing spikes when the stimulus is prolonged for tens of seconds

^** Compared to the other drugs which exert their action over shorter time scales aka the FAST-inactivated state

AKA if stimulus causing APs is prolonged (tens of seconds), use Lacosmide and if they are short (less than 1 second), use the FAST-inaction blocking drugs

Lacosamide, SLOW

How well did you know this?

Not at all

Perfectly

AEDs can also antagonize post-synaptic Low-threshold (T type) Ca2+ channels (CAv3.1)

^** T type Ca2+ channels mediate a ___Hz spike and wave activity in the thalamus, which is the hallmark of _____ seizures (aka Petit mal) and therefore AEDs of this type are great at controlling absence seizures

^** So AEDs of this type target ___-____ oscillations

The drug of choice for this is ____

***** One good side effect of this is that Ethosuximide is a ____ drug

3Hz (AKA 3Hz = ABSENCE SEIZURE)

Absence

Cortex-Thalamus

Ethosuximide

Non-Sedative

How well did you know this?

Not at all

Perfectly

If Ethosuximide does not work, another drug you could use instead would be the Broad Spectrum drug ____ or ____

Valproate or Lamotrigine (also Zonisamide, but less common)

How well did you know this?

Not at all

Perfectly

The drug ____ can be used to treat absence seizures, but it has “Intolerable” adverse effects like weight gain, tremor, hair loss, etc… So often the patients might not comply and take it

Also remember we already talked about Lamotrigine and the fact that its main action is to block Nav ion channels, but also can affect N and P type voltage gated Ca2+ channels

_____ is another drug, a sulfonamide derivative, that is structurally unrelated to other anticonvulsants and can be used to block T-type Ca2+ channels, even though it is mainly used for blocking voltage-dependent Na+ channels

Valproate

Zonisamide

How well did you know this?

Not at all

Perfectly

AEDs antagonize excitation, but they can also augment inhibition via 2 ways

1) Block pre-synaptic ____ re-uptake or metabolism

^** Work at the neurons AND glial cells

2) Potentiate GABAa receptor ___ currents aka enhance post synaptic GABA neuronal transmission

1) GABA

2) Cl-

How well did you know this?

Not at all

Perfectly

There are 2 drugs that block pre-synaptic GABA re-uptake or metabolism and include ____ or _____

Also realize these 2 drugs are usually used in conjunction with other drugs

Tiagabine inhibits GABA ____ (aka the transporters), whereas Vigabatrin inhibits GABA ____ (aka GABA-T)

^** So if you inhibit the re-uptake transporters, more GABA available leading to more inhibition leading to decreased excitation

If you inhibit GABA metabolism, no GABA will be turned into somthing else… And normally it is turned into Glutamate which causes excitation. So not only do you get less excitation, but you get more GABA since it was never metabolized leading to decreased excitation due to increased inhibition

Tiagabine or Vigabatrin

Re-uptake, Metabolism

How well did you know this?

Not at all

Perfectly

Post-synaptic modulation of GABAa receptors include _____ and related barbiturates and ____ with the two most important being ___ and ____

Phenobarbital, Benzodiazapines, Diazepam and Lorazepam

How well did you know this?

Not at all

Perfectly

Phenobarbital is very good at causing CNS depression, however the problem is that it’s so non-specific that it is over-powerful leading to significant sedation, lethal respiratory depression and abuse/addiction potential and this is why ____ are a better choice for treating seizures

Benzodiasepines

How well did you know this?

Not at all

Perfectly

So remember, when GABA is released, it binds to its receptor on the post-synaptic cell, causing the Cl- channel to open and when the Cl- channel opens, ____polarization occurs which blunts the action-potential propagation

Benzodiasepines (BZDs) bind to distinctive subunits on the GABA channels, causing an allosteric change which POTENTIATES the GABA binding aka BZD = Increased GABA binding and this all leads to increased Cl- channel opening with greater frequency

^** So realize BZD is GABA dependent aka you can give someone a shit load of BZD and that itself won’t open the channel…. GABA must be present as well for it to have any affect

Hyperpolarization

How well did you know this?

Not at all

Perfectly

The barbiturates (like Phenobarbital aka PB) have a similar MOA at the post-stynaptic GABAa Cl- channel, except it increased the ____of the Cl- channel opening (compared to the increased ____ that occurs when BZD binds)

**** ^^WILL BE TESTED ON

At high concentrations, PBs become GABA independent and therefore at high doses, the channel can be opened even if no GABA is present and therefore this makes it VERY lethal causing ____ depression

^** BZD wont cause lethal respiratory depression

Duration, Frequency

Respiratory

How well did you know this?

Not at all

Perfectly

_____s can be used to treat Status Epilepticus

So one would use the BZDs (Diazepam or Lorazepam) to treat it, which is when epileptic seizures occur one after another without recovery of consciousness between them

^** Can occur from abrupt withdrawal of AEDs, sedatives, etc…

Benzodiazepines

How well did you know this?

Not at all

Perfectly

So lets say a patient is in status epilepticus…

First you obviously want to stop the seizure, so you would give the patient ____ or ___ for 5 minutes

If the seizure stops, great, but if not you can give the patient ___ which is Na+ channel antagonist so the combination of the BZD and Fosphenytoin should do the trick

****____ is another drug that can be used for myoclonic seizures and its advantage to other BZDs is that is can be given via IV (like Diazapam or Lorazepam) AND also it can be given ____**

Diazepam or Lorazepam

Fosphenytoin

Clonazepam, Rectally

How well did you know this?

Not at all

Perfectly

Topirimate is a drug that works everywhere, but one unique feature is that it acts as a receptor ____onist for ____

^ So the Topiramte binds and causes no glutamate binding and therefore no depolarization via Na+ or Ca2+

Antagonist, Glutamate (AMPA)

How well did you know this?

Not at all

Perfectly

Gabapentin has its MOA via binding to ____ channels and it is unique because it has ____

Leviteracetam has its MOA via binding to ____ (a synaptic vesicle protein) that blunts ___ release (via preventing fusion of the vesicles with the membrane) and is unique because it is well-tolerated and no ____ interaction

____ is a drug with multiple MOAs and has 100% renal clearance

Ezogabine has its MOA via binding and opening ____ channels and is unique because it causes ___ retention

Ca2+, No drug interactions

SV2A, Glutamate, CYP

Pregabalin

K+, Urinary

How well did you know this?

Not at all

Perfectly

Remember, Carbamazepine and Phenytoin are 2 drugs that commonly are used to treat both Generalized or Partial seizures

However both of these can have various drug-drug interactions with other drugs

First off, phenytoin is one of the few drugs that has ____ order pharmacokinetics and ****therefore if you double the dose, it does NOT double the serum level and therfore dose adjustments are VERY difficult****

^*** WILL BE TESTED ON

Phenytoin also induced ___ enzymes so if other drugs are being used, and are cleared by P450, you also would have to worry about that

Distinct toxicities include ____ hyperplasia, Hirsutism (hair growth), hyp___, and osteoporosis

Zero

CYP-450

Gingival, Hypocalcemia

How well did you know this?

Not at all

Perfectly

Remember, Carbamazepine and Phenytoin are 2 drugs that commonly are used to treat both Generalized or Partial seizures

However both of these can have various drug-drug interactions with other drugs

****Carbamazepine is also an inducer of hepatic CYP 450 enzymes, just like Phenytoin**

^** Carbamazepine is a more common TEST question about a drug inducer……*******

2 complications include an _____ which is rare, but fatal and the other is WBC count problems such as Leukopenia, Neutropenia, or Thrombocytopenia leading to ____ or bruising

^** So if you get a question about a patient that was treated for seizures and now has infections or petechia (bruising), the drug most likely causing these effects are ____

Also like phenytoin, it can cause hypocalcemia and osteoporosis

Idiosyncratic Aplastic anemia, infections

Carbamazepine

How well did you know this?

Not at all

Perfectly

******* THIS STUFF WILL BE ON THE TEST

Along with Carbamazepine and Phenytoin, 2 other drugs that are associated with Hepatic CYP450 include ____ and ____

These drugs induce CYP450-dependent vitamin D ____ and therefore reduce circulating vitamin D levels… So now you lose the vitamin D dependent affects on ____ uptake in the intestines and the resultant decreased absorption of intestinal Ca2+ can trigger compensatory PTH-mediated responses that break up bone (demineralize bone) in order to increase the Ca2+…. So this all leads to HYPOCALCEMIA leading to Osteoporosis

*** Realize when we say induce, we mean increases… So CYP is increased due to the drugs

So this is also why it is hard to adjust a dose for Carbamazepine, because it induces its own metabolism due to the fact that it induces CYP450, which metabolizes the drug, so if you give Carbamazepine a few days later it will have induced so much CYP450, that the drug itself will be reduced from the CYP450 metabolizing it aka you have lose _____ and seizures might come back

Phenobarbital and Valproate

Catabolism (breakdown), Ca2+

Efficacy

How well did you know this?

Not at all

Perfectly

Since Carbamazepine induced CYP450, if a patient is taking oral contraceptives (estrogen)… Since those are also cleared by the liver and it’s CYP isoenzymes, there is a huge ___ risk for unplanned pregnancy due to increased clearance of oral contraceptives

It can also increase the clearance of ____ (an oral anti-coagualant) and then you might be at an increased risk for arterial/venous thrombosis since normally warfarin is suppose to break down the clots

New AEDs can have less drug interactions due to CYP450 induction due to the fact that they have ____ clearance (renal-hepatic) and the drugs include ___ (the most common substitute for patients who have drug interactions as a problem), ____, ____, and ____

^** Along with these interactions, Oxcarbazepine can cause ____ and rash, Topiramate can cause _____ and open angle glaucoma, and Zonisamide can cause rash and renal calcui

So realize that Oxcarbazepine has less side effects and since it has mixed clearance, if a patient is taking lots of drugs it might be a better option than carbamazepine

Increased

Warfarin

Mixed

Levetiracetam, Topiramate, Oxcarbazepine, and Zonisamide

Hyponatremia, Nephrolithiasis

How well did you know this?

Not at all

Perfectly

____ and ____ have 100% renal clearance and therefore if one has a renal insufficiency, the dose must be adjusted

Gabapentin and Pregabalin

How well did you know this?

Not at all

Perfectly

****************** ____ (which is also a CYP450 enzyme inducer) and ____ together inhibits conjugation of drugs by ____ enzymes, causing the accumulation of parent drugs

Valproate, Lamotrigine, UGT

Which 3 drugs are associated with SIGNIFICANTLY increased risk for birth defects due to the fact that they are Class D teratogens

Valproate, Carbamazepine, and Phenytoin

THE INABILITY TO FEEL PAIN IS CALLED ANALGESIA... And this is what opioid drugs accomplish If you see the words "Raphe nuclei" or "periaqueductal gray" in a question stem, then the question will be asking about ____ or their receptors aka something about pain transmission

Opioids

There are 3 types of opioid receptors which include Mu, Kappa, and Delta ^** All are GPCRs and subtypes, splice variants, confer diversity The ligands for these 3 receptors are 1) ____ for MOR 2) ____ for KOR 3) ____ for DOR

1) Peptides - Endorphins 2) Peptides - Dynorphins 3) Peptides - Enkephalins and Endorphins

Opioids can affect the 1) Cortex and limbic system, specifically the Thalamas and Hypothalamus 2) The midbrain, specifically the ____ 3) The medulla, specifically the reticular formation, Locus caeruleus, and the ____ 4) The spinal cord, specifically the spino-thalamic tract

2) Periaqueductal gray | 3) Raphe nuclei

The way a normal pain impulse works is that an afferent sensory signal occurs, ____ influx leads to increased ____ release at the presynaptic terminal and then ____ receptors become activated on the postsynaptic axon, allowing ____ influx leading to a EPSP When opioids are present, the agonist binds to its receptor on the presynaptic axon, leading to no influx of ____ and since no Ca2+ influx occurs, no glutamate is released, which causes downstream signaling to be blunted The opioid agonists also work on the post-synaptic axon by binding to their opioid receptors and causing ____ to be driven out of the post-synaptic cell into the synaptic cleft and this hyper-polarizes the cell and makes the AP harder to achieve ^** Don't be confused, in this case an agonist inhibits a signal

Ca2+, Glutamate, NMDA, Na+ Ca2+ K+

Potency is the amount of drug needed to produce a specific effect and therefore a lower Kd means a ___ potent drug Efficacy is how much of a drug is needed to produce a maximal effect (aka Bmax) and is related to how many receptors are available to bind the drug and therefore, a higher Bmax means ____ efficacy

More Higher

For mild pain, treat the patient with ____ or Acetaminophen For Moderate pain OR Persisting/uncontrolled Mild pain, you can treat the patient with ____-related drugs with or without the addition of Acetaminophen or Tramadol If Severe pain or Persisting/uncontrolled Moderate pain, you can treat the patient with the prototype ____, Fentanyl, or other drugs with extended release forms

NSAIDs Codine Morphine

Morphine is a ____ receptor Mu receptors have their clinical effects as analgesia (supre-spinal aka above the spine like in the thalamus and portions of the brain)... Even though we say Mus are supra-spinal, realize there are Mu receptors that have effects in the spinal cord ^** However, other clinical effects include euphoria, CNS and ___ depression, Miosis, and GI/Uterine motility ^*** Do NOT give morphine to patients with a ___ injury or ____ since they already have problems with CO2 and respirations *********** If you see a question saying which drug constricts the SPHNICTER OF ODI, the answer is OPIOIDS and the Mu receptor Morphine also has some K receptors that have analgesic effects in the Spinal area along with sedation, miosis, GI and uterine motility Realize that patients can build tolerance to Morphine for Mu agonist receptors, however ____ and ____ don't build tolerance ******************* So if you see a patient in the ER with constricted pupils, decreased respirations confirmed by a ABG (Ph, HCO3-, and PaCO2)... Start thinking OPIOID OVERDOSE

Mu Respiratory Brain, emphysema Miosis, Constipation

Morphine can be used for post-op pain, cancer pain such as primary metastatic malignancies, and ___ crisis

Sickle cell

Morphine, Methadone, Meperidine, Hydromorphone, Oxymorphone, and Levorphanol all are ____ agonists with ____ receptor binding (Morphine is an exception with mostly Mu receptor binding, but some ___ receptor binding) All of these drugs can be give via parenteral (straight into the blood via IV, IM, SC, Patch, or Buccal aka 100% bioavailability) and oral routes One thing that is important to take into account is the Oral/Parenteral potency ratio aka how much drug is metabolized via first pass metabolism Name if the oral/parenteral potency ratio is high (aka oral drug dose almost fully gets into blood), medium or low (aka most is metabolized so you get much less in oral form versus parenteral form) JUSt remember, Methadone/Levorphanol is ____ and Morphine and the others are ___ 1) Morphine****** 2) Methadone 3) Meperidine - Medium 4) Hydromorphone 5) Oxymorphone 6) Levorphanol ^** So if something is low, that means high first pass and therefore you must ____ the drug dose for when you switch to an oral form One more kind of confusing topic is that even though Morphine has a high first pass rate, most of the metabolites that are formed from the breakdown of morphine are active (M3 and M6 glucuronide or hydromorphone) so you can get completely different responses from the same dose in two different people Also Equivalent dose refers to efficacy aka can you give someone the same amount of drug if you switch? ____ is 6 times LESS efficacious than Morphine aka if you switch someone from Morphine -> Meperidine you would need to increase the dose by 6x would be 6 times more efficacious ____ has the same efficacy as morphine and the others are about 5 times MORE Morphine and Methadone are 10 mg, Meperidine is 60 mg, and Hydromorphone/Oxymorphone/Levorphanol are around 2 mg

Full agonists, Mu, K High, Low 1) Low 2) High 4) Low 5) Low 6) High Increase

One reason to switch from Morphine to Methadone is due to the fact that methadone has a longer ____ and therefore only needs to be taken half a day Also it has a higher absorption (lower first pass) ^** These pharmacokinetic properties are what makes it useful And this is good for withdrawal/maintenance and detoxification ************** Methadone's bad side affect is that it can create problems in patients with prolonged ____ in acute overdose or long term treatment and this is unrelated to the Mu receptor interaction... Instead it just blocks the flow of K+ channels causing delayed cardiac repolarization

Half life QT-interval

Meperidine can be distinguished due to the fact that it causes ____ rather than miosis and therefore it is hard to tell if someone has overdosed Also, Normeperidine is a toxic metabolite by-product from this drug that can accumulate and cause ____

Mydriasis Seizures

The short acting Full agonist drug is ____ that occurs very quickly but lasts very little... Compared to morphine and meperidine that lasts MUCH longer Fentanyl also uses ___ receptors, but is 100x more ____ than morphine and methadone (0.1 vs 10 mg) and is equally efficacious It has ____ first pass metabolism because it can pretty much only be given paretnterally ^** Often give as a lollipop for children to lick aka it works via transmucosal and it is often given for breakthrough pain aka if a patient is on morphine, and they have breakthrough pain, fentanyl will be given There is a strong abuse potential via heating up patches of fentanyl (transdermal delivery) Sufentanil, Alfentanil, and Remifentanil are 3 other drugs similar to fentanyl ____ is gaining popularity for use as a analgesic for child birth and occurs extremely fast (after 1 minute) and has a low risk for neonatal depression

Fentnyl Mu, potent Low Remifentanil

Codeine is a ___ agonist at ___ receptors and often used in combination with ____ and has a smaller potential for drug dependence and respiratory depression Most commonly used for MODERATE pain and often patients use codeine for cough relief (anti-___ agents) but realize that this relief is Mu-INDEPENDENT aka has nothing to due with Mu receptors ^***** Cough and respiration are 2 different things***** Codeine has a ____ first pass rate aka HIGH oral/parenteral potency ratio which means most of it goes straight into the blood and is not metabolized.... Codeine also has a low maximum efficacy compared to oxycodone which has a high maximum efficacy Another drug used for Anti-tussive agents aka cough supression is ____, which also relieves cough independent of opioid receptors, is not analgeic, and not addictive

Partial, Mu, Acetaminophen Tussive Low Dextromethophan

Codeine is usually a safe drug, however it can be harmful in children with obstructive sleep apnea who receive it after a tonsillectomy or adenoidectomy due to its metabolism Codeine gets converted to Norcodeine (the inactive form), and it also gets converted to morphine via ____************************* which is active ^**** WILL BE TESTED ON It is important to realize that patients can be ULTRA-FAST metabolizers, Intermediate metabolizers, or Poor metabolizers of the CYP2D6 and if a patient has a gene ____ and ultrafast allele, they are ULTRA-FAST, if the gene is Heterozygous, they are intermediate, and if the gene is ____ and a slow allele, they are poor metabolizers So if you are a fast metabolizer, a lot of the codeine coming in gets converted quickly to morphine, and in some settings that unusual excessive exposure to morphine can lead to respiratory depression and death ^*** So one more time.... A fat patient with sleep apnea who is an ____ metabolizer of codeine to morphine due to a DUPLICATION and ultrafast allele could possibly die from the codeine drug ********************************

CYP2D6 Duplicated, Deleted Ultrafast

So morphines active metabolites, like we already talked about, are M6G/M3G/Hydromorphone Codeine's is Morphine Meperidine is ____, which remember we said is toxic ____ and ____ have NO active metabolites, so if you see morphine in a patients urine who is on one of those two drugs, you know they must be abusing some other drug like codeine or morphine itself ^** Also Fenanyl has NO active metabolites

Normeperidine Hydromorphone and Oxymorphone

____ and ___ are anti-diarrheals that interact with ___ opioid receptors in the gut and have poor solubility so it is ******hard to abuse them***** ^**** This concept is important, because one could use other opioids to treat anti-diarrheal problems, but since these have low parenteral abuse potential, they are available over the counter and a good drug for those with diarrhea

Loperamide, Diphenoxylate, Mu

Tramadol is a moderate Mu agonist used to treat ___ pain and the 2 important features are that 1) It inhibits ___ re-uptake 2) Associated with ___

Moderate 1) Catecholamine 2) Seizures

Buprenorphine is a partial mixed agonist aka ___ partial agonist plus ____ antagonist It is a great drug of choice for office-based detox since it is a partial agonist, you can't get a very big high... So patients can be put on this to only get a mild euphoria and then gradually work them off of it This drug is also used in combination with ____ often _____ is another mixed agonist/antagonist with being a K agonist, Mu partial agonist, and Delta antagonist

Mu, K and D Naloxone Pentazocine

____ is an acetylated form of morphine that penetrates the BBB very rapidly leading to exaggerated euphoria and great addiction liability The most common addiction programs use ____ maintenance or Buprenorphine-Naloxone

Heroin Methadone

********* 100% WILL BE ON THE TEST*********** Like we already talked about, if a patient shows up with pin-point pupils, low respiratory rate, and sedation... They are obviously overdosed on opioids and in order to cure them, you MUST give them an opioid ANTAGONIST, which could be ____ via IV or ____ via PO in order to displace the overdosed drugs from the receptor ^** So if you need an instantaneous effect, use ___ since it is IV and also realize that Nalozone is NOT ABSORBED BY THE GUT aka it must be given via IV Once the patient revives, you can give them Naltrexone via PO

Naloxone, Naltrexone Naloxone

************* Remember, opioids increase smooth muscle tone and inhibit the coordinated peristalsis required for propulsion, which contributes to nausea and vomiting as well as constipation so in order to help constipation, one could use _____ which is GI specific in order to prevent the constipation in the GI tract, but not affect the opioid analgesic actions for the rest of the body ********************

Methyl-Naltrexone

If one were to perform monitored anesthesia care, used for diagnostic or minor therapeutic surgical procedures, they could provide ____ for premedication causing anxiolysis, amnesia, and mild sedation.... Followed by a titrated ____ infusion to provide moderate to deep levels of sedation ____s and _____s can be used for conscious sedation like a dentist for wisdom teeth and can be reversed via specific receptor antagonist drugs such as ____ for Benzodiazepines and ____ for Opioids

Midazolam, Propofol Benzodiazepines, Opioids, Flumazenil, Naloxone

____ and ___ channels are the primary inhibitory ion channels considered for anesthetic action Excitatory channels that are targeted include those that respond to ___ (nAChRs or mAChRs), those that respond to excitatory amino acids (AMPA, Kainite, NMDA), or those that respond to ____ (5HT2 and 5HT3 receptors)

Cl- and K+ ACh, Serotonin

There are 2 types of general anesthetics 1) Inhaled 2) Intravenous The inhaled anesthetics can be either volatile, which has a ____ vapor pressure and thus high boiling point (aka liquid at room temp) or gaseous, which has a ___ vapor pressure and low boiling point (aka gas at room temp) ^** The ONLY gaseous general anesthetic is ____, all the rest are volatile

Low, High Nitrous Oxide

Both volatile and gaseous inhaled anesthetics are taken up via gas exchange in the alveoli The driving force for the uptake is the alveolar concentration determined by the 1) Inspired concentration aka partial pressure aka how much is inside the alveoli 2) Alveolar ventilation aka how much can diffuse into the blood ^** If either 1 or 2 are increased, the rate of rise in the alveoli will also increase, leading to accelerated induction Partial pressure = ___ (alveolar concentration) / ___ (Inspired concentration) ^** The faster Fa/Fi approaches 1, the faster the anesthesia will occur during inhaled induction... **Discussed more on next card

Partial pressure = Fa/ Fi

The solubility of a chemical is based upon its blood:gas partition coefficient, so a chemical with a blood:gas partition coefficient of 0.5 will reach a higher concentration in the brain ____ than one with a partition coefficient of 1.5 ^** AKA an INVERSE relationship between blood:gas coefficient values and a the rate of anesthesia onset aka those with a LOW blood solubility will reach high arterial pressures faster since they aren't dissolved in the blood *** NO and Desflurane have ____ blood solubility leading to rapid onset and recover, and Halothane has ____ leading to medium rate of onset and recovery This is due to the fact that those that can dissolve in the blood are able to be distributed throughout the body and essentially that means the blood compartment for which the drug circulates in is HUGE.... Compared to insoluble drugs that have a much smaller blood compartment for it to be circulated in So now going back to FA/FI, the FA approaches the FI fastest for the ___ soluble agents aka NO or Desflurane versus Halothane

Faster Low, high Least

An increased in cardiac output causes a ____ rise in partial pressure due to the fact that more blood is circulated, leading to a greater volume of distribution and remember when that occurs the anesthetic takes longer Also increased rate and depth of ventilation causes an ____ concentration in the blood and vice-versa, so if you give someone opioids (which decreases ventilation) you would get a ___ onset of anesthesia Also realize that the heart, liver, kidneys, and brain have 75% of cardiac output and therefore a higher immediate concentration and onset of anesthetic compared to the skin and muscle which only have 1/5th cardiac output

Decreased (aka slower) Increased, slower

Anesthetic potency is described as _____ required to prevent a response to a surgical incision ____ is the concentration where 50% of patients have no response to surgical stimulation ^** A dose of 1 MAC of any anesthetic prevents movement in response to surgical incisions in 50% of patients aka 1 MAC of isoflurane is 1.4% volume but 1 MAC of halothane is 0.75% volume and this means that the concentration needed to cause anesthesia would be higher in ____ than ____ since Isoflurane has a larger % of volume needed to achieve the same effect as Halothane AKA HALOTHANE is the MOST potent ^** If MAC is more than 100%, then a supplement drug MUST be used to achieve full surgical anesthesia (one example is NO not being able to produce surgical anesthesia alone) So just to clarify, if ALL of the air was pure NO (aka 100%), than STILL less than 50% of the patients would be anesthetized since the MAC is greater than 100%

MAC (Minimal alveolar concentration) ED50 Isoflurane, Halothane

4 stages for CNS depression 1) Stage 1 (Analgesia) - Analgesia and amnesia produced at the end 2) Stage 2 (Excitement) - Patient is delirious, irregular respirations, and vomiting can occur Once regular ___ is established and the loss of responsiveness to ___ stimuli has occurred, you know you are in stage 3 3) Stage 3 (Surgical anesthesia) - Regular breathing and complete cessation of spontaneous respirations (apnea) 4) Stage 4 (Medullary depression) - Depression of vasomotor centers in the medulla and respiratory centers. Circulatory and respiratory support are needed to avoid death ___ can cause bradycardia and ____ or ____ increases heart rate All volatile anesthetics are respiratory depressants Also not all inhaled anesthetics decrease metabolic rate of the brain and increase cerebral blood flow

Breathing, Painful Halothane, Desflurane or Isoflurane

Toxicity of the inhaled anesthetics include Halothane can cause _____ (symptoms are anorexia, nausea, myalgia, arthralgia, rash, eosinophilia, hepatomegaly, and *****jaundice****) ____ and ____ can cause renal toxicity via metabolizing products including fluoride ions ***************************************If a patient is given an inhaled volatile anesthetic with succinycholine, it can cause ____ leading to tachycardia, hypertension, muscle rigidity, hyperthermia, hyperkalemia, acidosis, etc... And the only way to cure this is via ____ ********************* KNOW THIS^********

Hepatitis ^**(Think HHHHEpatitis for HHHHHalothane) Enflurane and Sevoflurane Malignant hyperthermia, dantrolene

General IV anesthetics are a much faster way to induce anesthesia and is the preferred method over inhalation (except in ___ populations) These are HIGHLY lipophilic and perfuse into lipophilic tissues like the brain and spinal cord very quickly

Pediatric

********************************* Propofol has ____ onset and recovery, and is used in induction and for maintenance, hypotension, and useful as an ____ agent (aka effective against vomiting and nausea) ^** So once again, if you want to maintain anesthesia, you can use THIS DRUG Since the major component of it is ____ phsophatide fraction, allergic reactions are possible MOA is via ____ receptors as an agonist that potentiates Cl- current Rapidly metabolized in the liver, has a high plasma clearance leading to low "hangover" effect, patients can ambulate (walk around) quickly after use Has a ___ context sensitive half-life which means the amount eliminated in one half-life after a continuous infusion, does not change much.... Compared to Thiopental or Diazepam, which has a large context-sensitive half life means that as a continuous infusion occurs, the drug's elimination increases rapidly and therefore those with a high sensitivity are not very sustainable for a maintenance drug Finally, Propofol causes ___ cerebral blood flow and ICP, a HUGE ___ in systemic blood pressure due to profound vasodilation in arterial and venous circulation, and respiratory ___ Fospropofol is a prodrug that has similar effects, but recovery and onset are prolonged

Rapid, antimetic Egg yolk GABAa Short Decreased, decreased, depression

Etomidate has rapid onset and moderately fast revocery and provides CV and respiratory ___ (Aka minimal cardiovascular and respiratory depression) and therefore is useful in patients with impaired CV and respiratory systems It also causes decreased ____ and involuntary ___ movements MOA is via increased ____ on GABAa receptors Causes ___ cerebral blood flow and ICP, stable CV, stable respiration, and ____ suppression and therefore these endocrine adverse effects limit its use for continuous infusion

Stability Steroidogenesis, muscle GABA Decreased, Endocrine

Ketamine has moderately rapid onset and recovery and causes CV ____, ____ cerebral blood flow, and emergence reactions that impair recovery ^** Emergence reactions aka ___ (bad dreams) MOA is via an ____ receptor ____onist Patients eyes remain open with a slow nystagmic gaze, lacrimation and salivation increased, ___ cerebral blood flow and ICP (THIS IS BAD if you have a patient with already increased ICP), unpleasant emergence reactions, increase systemic blood pressure but also is a direct myocardial depressant (which is often masked by the fact that it stimulates blood pressure via activating sympathetics Ketamine is the ONLY IV anesthetic to cause analgesia (loss of pain), stimulation of the ___ nervous system, broncho____, and minimal respiratory depression

Stimulation, increased Hallucinations NMDA receptor antagonist Increased Sympathetic, bronchodilation

____ Is mainly used for short-term sedation of intubated and ventilated patients in an ICU It has its MOA via ____ ___onist that causes hypnosis and analgesia

Dexmedetomidine Alpha-2 adrenergic agonists

Thiopental is a ____ aka a drug that acts as a CNS depressant has a rapid onset and recovery in the bolus dose and a slow recovery following infusion It is the standard ____ agent and causes CV ___ and you want to AVOID it in ____ *** So remember, ____ causes CV stability, ____ causes CV stimulation, and ___ causes CV depression ___, another barbiturate, has rapid onset and recovery and is preffered over Thiopental for ambulatory procedures (aka same day procedures) Both Methohexital and Thiopental cause CNS depression, respiratory depression, ***NO analgesia***, and the MOA is via acting on ___ receptors to increase the duration of channel opening (agonists) along with enhancing inhibitory neurotransmission

Barbiturate Induction, depression, prophyrias Etomidate, Ketamine, Thiopental Methohexital GABAa

____ is a benzodiazepine most commonly used to calm patients down prior to surgery and has a slow onset and recovery and ___ can be used to reverse its affects Unlike the other BDZs (Diazepam and Lorazepam), Midazolam is water-soluble and therefore the drug of choice for parenteral administration Used in balanced anesthesia and conscious sedation (like Fentanyl aka the Opioid) and provides CV stability and marked retrograde ____ (Aka like if you are doing a surgery where you need the patient to be awake a little, but not remember anything) It also has potent anticonvulsant properties to treat status epilepticus

Midazolam, Flumazenil Amnesia

Anesthetic adjuncts are used to increase the specific components of anesthesia, while allowing lower doses of general anesthetics and fewer side effects to be used Opioids and ____s (Diazepam, Lorazepam, and Midazolam) are often used together to achieve a general anesthetic state Fentanyl, Sugentanil, Remifentanil, and Morphine are examples of Opioids used with BZDs The MOA of opioids is that they act as agonists their opiate receptors The MOA of BZDs is that they act on ___ receptors to increase receptor sensitivity to GABA (agonist) and enhance ____ neurotransmission ^** BZDs actions can be terminated by the antagonist ____

Benzodiazepines GABAa, Inhibitory Flumazenil

Local anesthetics bind reversibly to, ___-gated ___ channels to inhibit them in nerves at the inner vestibule of the channel, and block ion movement through the channel pore, which blocks the APs responsible for nerve conduction If the drug has 2 "i"s in it, then its chemical class is an ____ If not, then its chemical class is an ____ ************Esters are more prone to hydrolysis and therefore have a ____ duration of action compared to Amides ^** ____ is one example of a ester local anesthetic with a very short duration of action Amide is used commonly after IV bolus administration Allergic reactions are commonly seen in ____-type local anesthetics due to metabolism of allergy causing compounds

Voltage, Na+ Amide Ester Shorter Procaine Ester

The use of a vasoconstrictor substance like ____ will reduce systemic absorptions of agents and are useful for drugs with intermediate or short durations of action ^** This is because it decreases the rate of absorption into circulation, reducing the rate at which the drug is metabolized, reducing systemic toxicity Epinephrine-containing solutions should NOT be injected into the tissues supplied by the end arteries due to the fact that the resulting vasoconstriction can cause ischemia ____ ___ is unique due to its intrinsic sympathomimetic vasoconstrictive properties so in other words, it can potentiate the effects of ____ on Alpha-adrenergic receptors since it blocks NE, causing more NE to be around, leading to excess sympathetic stimulation and localized vasoconstriction without the need for combining the drug with epinephrine

Epinephrine Gangrene Cocaine, NE

Esters are metabolized in the plasma via circulating butyrylcholinesterase enzymes (plasma cholinesterase) and amides are metabolized in the ____ via ____ and therefore if a patient has a liver disease, they are more likely to get toxicity form amide drugs The smaller and more lipophilic the local anesthetic, the faster the rate of interaction with the NA+ channel and the more potent the agents actions Which 3 drugs are the most potent aka most lipohilic? ^** Tetracaine/Bupivacaein/Ropivacaine are more lipophilic than Lidocaine/Procaine/Mepivacaine and therefore more potent and longer durations Also realize that ____ (large or small?) ____ (Myelinated or Un-myelinated?), ____ (higher or lower?) firing frequency fibers are blocked preferentially Also, motor nerve blocks occur before sensory With the above info in mind, Type A delta fibers are ___ sensitive than Type A alpha fibers due to the fact that Alpha fibers are large and Delta fibers are smaller (both are myelinated) Furthermore, Type C fibers are the MOST sensitive to blocks due to the fact that they are so small (So type As are the largest, then Bs, then Cs)

Liver, CYP450 BuRT Small and Myelinated, higher More

2 major effects of local anesthetics 1) Systemic effects after absorption of the local anesthetic 2) Direct neurotoxicity due to the close proximity of the spinal cord or other never trunks ************LOW doses lead to sleepiness, light-headedness, visual and auditory disturbances, restlessness, and drowsiness *****************HIGH doses of anesthetic (usually via IV) can lead to nystagmus, muscular twitching, and convulsions ^** If large doses are needed, you can give the patient ____ (diazepam or midazolam) to provide prophylaxis (prevention) against CNS toxicity since it raises the seizure threshold It also blocks cardiac Na+ channels leading to systemic hypotension (this is NOT the case with ____, instead that causes hyPERtension and cardiac arrhythmias) ^** The MOST cardiotoxic drug due to its long duration of action is ____

Benzodiazepine Cocaine Bupivacaine

The therapeutic drugs (which are to halt a migraine, not prevent it) are _____ which are 5HT1B/1D (a serotonin) receptor _____onists and should be given at the START of the ___ phase (such as an Aura or something distinctive or common that usually occurs at the start of the migraine) ^** Ergot alkaloids can also be given After the prodrome phase, during the actual Headache phase, one can prescribe ____ like ____

Triptans, Agonists, Prodrome NSAIDs, Acetaminophen

Like we said, there is therapeutic agents (which are to rescue/halt a migraine attack as it occurs) and there are preventive agents to PREVENT the migraines from occurring in the first place (aka limit the frequency and severity of the attacks) ^** These include ____ blockers like ___ and ____ OR ___ channel blockers like ___ and other examples not so much discussed are Tricyclic antidepressants and Anticonvulsants These are taken daily and given during the ____ PHASE, which is before the prodrome phase ___ is a good first choice since side effects are not very large and the idea behind these Ca2+ channel blocker drugs is to cause vasodilation, in order to prevent vasoconstriction and therefore secondary vasodilation (A little counter-intuitive) ^** They also lessen Ca2+ dependent vesicle fusion The idea behind Beta blockers is that it ___ sympathetic activity and blunt the spread of the initial electrical wave expression (aka central inhibitory activity)

Beta blockers, propranolol, or timolol Ca2+ channel blockers, verapamil ASYMPTOMATIC Verapamil Decrease

Migraines are thought to occurs via the release of neuropeptides ____ and ____, and the inflammatory mediators ___, histamine, and prostaglandins that dilate cranial blood vessels and sensitive nerves to pain (like the ____ nerve) The pathway first starts with a wave of electrical activity passes through neurons with H+, K+, and NO being discharged and traveling through the cortex causes CEREBRAL _____ causing the blood to be shunted into the CRANIAL vasculature causing DILATION in these vessles ^***** DON'T CONFUSE THIS CONCEPT Once the Cranial arteries have been dilated the Trigeminal nerve depolarizes and releases its neuropeptides (NO and CGRP) causing neurogenic inflammation ^** Realize if someone has coronary artery disease and treated with NO to open up the arteries, the NO will also cause vasodilation in the cerebral arteries just like as mentioned above leading to possible migraines

CGRP and Substance P, NO, Trigeminal nerve Vasoconstriction

Cranial vessels and pre-synaptic TG nerve terminals express a unique receptor The cranial vessels have ____ receptors and the peripheral neuron has ___ receptors and the Central neuron has ___ receptors ^** These receptors act as a balance for normal functioning to bring the dilation to levels that don't hurt someone on a daily basis *******So these drugs work because they are selective serotonin receptor _____nists ************* aka cause vasoCONstriction

5HT-1B, 5HT-1D, both Agonists

So giving someone a 5HT-1B agonist like ____ will lower the cAMP leading to vasoconstriction of the cranial vessel aka OPPOSE vasodilation and same Triptan binding to 5HT-1D on the neurons will also lower cAMP and inhibit pre-synaptic release of ___ leading to decreased vasoDilation

Triptan, CGRP

The prototype for Triptans is ____ (aka ____) These drugs are metabolized by ____ Sumatriptan is an indoleamine ^**However, this drug has bad bioavaiability so new drugs like Naratriptan (Amerge) has a 70% bioavailability Delivery routes include Oral, Nasal, and Injection ___ route wont be good for a patient vomiting, but ___ would ____ is available as Injectable ____, Nasal, and Tablets ____ is another triptan with lots of delivery options if a patient needs a different nasal spray than sumatriptan

Sumatriptan, Imitrex MAOs Oral, Nasal Sumatriptan, subcutaneous Zolmitriptan

Sub-cutaneous sumatriptan is the fastest working method but ____ delivery works fast as well ***************************************Remember, these drugs like Imitrex are metabolized by MAOs so if the patient is taking other medications that also are metabolized by MAOs, they can get a ____ syndrome***************************************** So if mutliple drugs alter serotonin you can get MAJOR problems If you have a patient with Angina (Heart does not get enough blood) or uncontrolled HT, it could be a contraindication to give a patient a triptan since they can also have some effects on other 5-HT1 receptors like those located in renal vessels... Also look out for patients taking MAO inhibitors since these drugs need to be broken down by MAOs Depression + Migraine = look out Coronary artery disease + Migraine = look out

Nasal Spray Serotonin

If triptans DO NOT work, and you need something to help a severe or refractory migraine, you can prescribe ____ including ____, Ergotamine and Caffeine, etc... These drugs still constrict the vasculature, but are less specific than Triptans since they also interact with alpha, DOPA, and various other 5-HT receptors and therefore you get a VERY profound vasoconstriction in beds outside the cranial bed ******* DO NOT USE DHE AND TRIPTAN TOGETHER ***** Triptans work faster, but DHEs work longer ************* Side effects of Ergot Alkaloids include a strong ____ response and ____ is MUCH worse than with triptans, which is called _____, aka a dry gangrene You can use Triptan in pregnant women cautiously, but NOT DHE or Ergot alkaloids Remember, you can also use ____ when NOTHING ELSE WORKS

Ergot Alkaloids, Dihydroergotamine (DHE) Vomiting (aka Emesis), vasoconstriction, St Anthony's Fire BOTOX

Beta blockers are contra-indicated in ___ patients since they cause bronchoconstriction

Asthmatic

The tremor seen in PD is referred to as ____ tremor So if you have the patient keep their arms in a resting position it starts to tremor There is also ___ tremor, aka Benign Familial tremor aka a postural tremor.... So if you have the patient hold their arms out it starts to tremor aka movement induced tremor Chorea is defined as involuntary continuous, rapid, jerky dyskinetic movements Tics are involuntary, compulsive, rapid, repetitive, stereotyped movements or vocalizations and classified as either simple or complex

Resting Essential

____ is characterized by Bradykinesia, muscle rigidity, resting tremor, and impairment of postural balance with disturbances in gait and falling ^**Lewy bodies are seen The pathway goes 1) Nigrostriatal fibers from the Substantia nigra Pars compacta send DOPA to the _____ 2) DOPA in the striatum binds to D2 receptors, causing an ____PSP which inhibits those GABAergic output from the striatum ^** At the same time, ACh is exerting an EPSP onto the GABAergic output from the striatum 3) The IPSPs and EPSPs on the GABAergic output balances the actions of GABA released onto the Globus Pallidus and therefore controls movement down the pathway line HOWEVER, in PD, the DOPA fibers are gone, leading to only ACh stimulating at the striatum, leading to the excess GABA released and therefore disturbed movements So one could treat a patient with DOPA agonists, of ACh antagonists

Parkinsons disease 1) Striatum (Caudate and Putamen) 2) IPSP 3) GABA

____ is the immediate metabolic precursor to dopamine and acts as an agonist at D___ receptors It is quickly absorbed by the small intestine and enters the CNS via ___ (L-amino acid transporter), but only 1-3% make it to the brain since most is metabolized via decarboxylation from L-dopa -> Dopamine (and Dopamine does NOT cross the BBB) If you give someone L-Dopa + ____, which inhibits ____ aka L-Dopa does not get metabolized as fast, then it increases the amount to the brain from 1-3% to 10% aka you can have the patient take less L-Dopa daily ******The BEST results are seen during the first few years of treatment, and then an _____ phenomenon can occur during long-term treatment where mobility is improved, but rigidity and akinesia return rapidly at the end of dosing intervals aka they respond well still, but symptoms come back right away

Levodopa (L-Dopa), D2 LAT Carbidopa, decarboxylases Wearing-off

Side effects of L-Dopa include GI: If L-Dopa is combined with ___, very little GI side effects usually occur aka you decrease anorexia, nausea, and vomiting ^** If L-Dopa given alone, 80% of patients have these problems 80% of patients have impaired voluntary movement aka ____ with ____ being the most common presentation Mental status changes On-off phenomenons where off-periods characterized by akinesia (loss of voluntary movement) and then on-periods of improved mobility but dyskinesia (impaired involuntary movements) and this can be treated with subcutaneous injections of _____ to provide relief to the patients off-periods (also can be used for end-of dose akinesia) ^**** Aka multiple episodes of immobility per day and often occurs over LONG PERIODS OF TREATMENT*********** ********* DON'T CONFUSE WEARING OFF WITH ON-OFF PHENOMENON so wearing off is due to DOSE TIMING and on-off is NOT RELATED to drug ****** Also note On-offs occur randomly

Carbidopa Dyskinesias, Choreoathetosis Apomorphine

Contraindications include patients taking _____ which can cause hypertension Patients with angle-____ glaucoma, ____ or undiagnosed skin lesion, or peptic ulcers due to a GI bleed

MOA inhibitors Closure, melanoma

Dopamine receptor agonists are associated with a lower incidence of the response fluctuations and dyskinesias that occur with long term L-Dopa therapy They include: 1) ____, and Ergot Alkaloid derivative that acts as a D2 agonist ^** Has a high first pass-metabolism (CYP3A4) 2) ____, which has preferential affinity for D3 receptors and can treat Restless Leg Syndrome (RLS) ^** 90% is excreted uncharged in the urine 3) ____ has affinity for D2 and can also treat RLS and metabolized via hepatic CYP450 (specifically, CYP1A2) ^** If you give this with another drug that is metabolized by CYP1A2, it'll ___ the clearance since the enzyme is busy dealing with the other drugs 4) ____ (which remember, can be used to treat patients with on-off phenomenon) stimulates POST-synaptic D2 receptors in the Caudate and Putamen ^** Adverse effects include neausea (which can be pre-treated with the antiemetic ____), sweating, hypotension, etc.... Apomorphine is the ONLY injectable agent here

1) Bromocriptine 2) Pramipexole Decrease 3) Ropinirole Reduce 4) Apomorphine Trimethobenzamide (TMB) So remember, Pramipexole and ropinirole can treat RLS

Adverse effects of dopamine receptor agonists include GI and CV problems, Dyskinesias, ____ changes (which are more severe that with L-Dopa) Contraindications include a patient with a history of ____ illnesses, recent MI, or active peptic ulcer ____ is contraindicated in patients with Peripheral Vascular Disease due to the fact that it has Vasoconstricting properties

Mental changes (confusion, hallucinations, delusions, etc) Psychotic Bromocriptine

MAO-A and MAO-B metabolizes dopamine and tryptamine If you inhibit it, your DOPA levels will increase 2 MAO inhibitors are ____ and _____ 1) Selegiline (aka deprenyl) is a ____ MAO-___ inhibitor (at high concentrations it can inhibit MAO-A also) that can prolong the effects of ____ (so can be used if patients have declining responses to L-Dopa) ^** Only 10% bioavailability and contraindicated in patients taking ____ re-uptake inhibitors due to risk of serotonin syndrome 2) Rasagiline is an ____ MAO-___ inhibitor and used as a neuroprotective agent or early onset of PD Which one is more potent? DO NOT USE L-DOPA AND A NON-SELECTIVE MAO INHIBITOR because it can lead to ___ crisis due to the peripheral accumulation of NE****************

Selegiline and Rasagiline 1) Irreversible, MAO-B, L-DOPA Serotonin 2) Irreversible, MAO-B Rasagiline Hypertensive

____s metabolizes L-Dopa to 3-)-methyldopa, which competes with L-Dopa for transport across the intestines and BBB causing it to have less of an effect Therefore, COMT inhibitors can help PD patients with the two most common being ____ and ____ that decreases clearance and increases bioavailability of L-Dopa ___ has CNS and PNS effects and ___ has PNS effects only Tolcapone can cause ____ ** Orange discoloration of urine might be seen and also Tolcapone can increase ____ enzymes and lead to acute hepatic failures and therefore Entacpone is not as dangerous

COMT Tolcapone and Entacapone Tolcapone, Entacapone Liver failure Liver

_____ is a agent with no known MOA and can cause Livedo reticularis which is a vascular condition characterized by purplish mottled discoloration on the skin (usually legs) and therefore one should be cautious when using in patients with a history of heart failure or seizures

Amantadine

Anticholinergic drugs aka ___arinic AChR antagonists can improve tremor and rigidity, but have LITTLE effect on ____ Drugs include Benztropine, Biperiden, Orphenadrine, Procyclidine, and Trihexyohenidyl Adverse effects are constipation, urinary retention, blurred vision, etc

Muscarinic, bradykinesia

Other movement disorders like Tremor can be treated via ____ and ____ due to the interactions with B1 receptors The anti-epileptic drug ____ to treat symptomatic tremor ____, a serotonin receptor agonist can also treat tremor Intramuscular injections of ____ Or _____, a benzodiazepine

Metoprolol and propranolol Primidone Topirimate Botulinum Toxin A, Alprazolam

Huntingonts disease can result from the OVERACTIVITY of ____ nigrostriatal pathways and therefore ____ (which is irreversible) and ____ (which is reversible) can be used to impair dopaminergic neurotransmission alleviating the chorea *** Also realize HD has no dementia ^** Impairment occurs via blocking the vesicular ____ and depleteing the cerebral dopamine stores ** Most therapy is for patients who are depressed, irritable, paranoid, anxious, or psychotic

Dopaminergic, Reserpine or Tetrabenazine MT (Monoamine transporters)

Tics can be treated with ____, but often have bad side effects like weight gain, irratbility etc.... In that case you could use an ALpha-adrenergic agent ____ or _____

Pimozide Clonidine or Guanfacine

____ is the only drug to have been shown to prolong survival of ALS and acts by inhibiting ___ release and blocking NMDA and Kainite-type glutamate receptors and inhibiting voltage-dependent ___ channels

Riluzole, Glutamate, Ca2+

A recessively inherited disorder of copper metabolism is ___ disease characterized by reduced Ceruloplasmin and increased concentrations of copper in the brain and viscera Patients often present with liver disease neurological symptoms, and psychiatric symptoms Treatments include ____ which has its MOA via a chelating agent that forms a stable complex with copper ____ which reduces the intestinal absorption of copper ____ which is also a chelating agent Zinc ___, and Zinc ____ which increase fecal excretion of copper by decreasing GI absorption

Wilsons Penicillamine Postassium disulfide Trientine Zinc acetate and Zinc Sulfate

When deciding to use L-Dopa/Carbidopa vs Dopa receptor agonists, just realize you can use the agonsits when you need something with a LONGER half life, few motor complications, *******____-stage disease aka patients less than 65***********

Early