Pharmacology Exam 3 Content

the change in electrical potential associated with the passage of an impulse along the membrane of a muscle cell or nerve cell - the way neurons communicate with each other - efficiently conveys info over long distances - also called: spike, nerve impulse, discharge - all or nothing phenomenon - typical length: ~ 2 millisec

AP (action potential)

Which of the following *is* a TCA (antidepressant) drug? a. Amitriptyline b. Sertraline c. Alprazolam d. Duloxetine

A (amitriptyline)

___________ have been used for a long time as sedative-hypnotic drugs. Due to their increased risk of serious adverse effects they have largely been replaced by other drugs for clinical use. - believed to bind at the junction of alpha and beta subunits on GABA A receptors - *MoA: Facilitate the action of GABA on GABA A receptors* (can increase the frequency or duration of GABA-mediated channel opening) - at high doses, *directly* activate GABA A receptors - used to treat insomnia, seizures, HA, & may also be used in a hospital setting for pre-operative sedation (*anesthesia*) - Drugs from this class we need to know: Thiopental & Phenobarbital

Barbiturates (Thiopental - anesthesia; ultra short acting Phenobarbital - epilepsy; long acting)

This anti-epileptic drug functions by altering conductance through several channels, especially Na+ channels. It is only administered orally and is a strong inducer of a number of liver enzymes - SEs: diplopia (double vision), ataxia, memory loss with prolonged use

Carbamazepine

What 3 NTs "fine-tune" the CNS?

DA (dopamine), NE (norepinephrine), Epi (These 3 NTs = monoamines)

This pharmacologic treatment method involves a drug directly stimulating CNS post-synaptic dopamine receptors in the striatum. These drugs have a longer duration of action and are less likely to cause the fluctuations in response and dyskinesia as occurs with L-DOPA. - can be used as monotherapy, but this is somewhat less effective in PD treatment compared with L-DOPA - Ergotic (derived from fungi) or non-ergotic - better for younger patients - e.g. Pramipexole, Ropinirole

DA agonists (DA agonists act directly on striatal neurons [enter brain via BBB and stimulate neurons directly]) (Drugs we need to know: Bromocriptine, Pramipexole, Ropinirole, Rotigotine, Injectable Apomorphine)

What are the 4 types of drugs (classes) used to treat Parkinson's disease?

DA replacement (provide precursor to dopamine), DA agonists (stimulate dopamine receptors in striatum), DA degradation inhibitors (inhibit enzymatic breakdown of dopamine), Cholinergic receptor antagonists

This type of anti-depressant drug class functions by increasing *both* dopamine (DA) and norepinephrine (NE) levels in the brain by inhibiting their reuptake - *Mostly a DA reuptake inhibitor* (DA >>> NE) - Drug we need to know: Bupropion - SE's: Insomnia/excitation

DNRI (dopamine norepinephrine reuptake inhibitor)

This OTC opioid is less potent than codeine and is used as an *antitussive* (cough suppressant) - minimal abuse potential

Dextromethorphan

What are the two over-the-counter (OTC) opioid drugs we need to know for this class

Dextromethorphan, Loperamide

What drug is the only *NMDA receptor antagonist* that is specifically used for patients with suicidal depression. It is administered via nasal spray and relieves depression *rapidly* (min/hr) by increasing BDNF (neuropeptide) activity which makes neurons "happy" - also functions as a dopamine transporter (DAT) inhibitor, leading to increased levels of DA in the brain - SE's: higher doses can exacerbate psychosis

Esketamine

This anti-epileptic drug functions as a *Ca2+ channel blocker*. It is the drug of choice in treating absence seizures and has lower interactions with other drugs compared to other anti-epileptic agents. - Administered orally - SE's: GI distress, wt loss, lethargy, blood dyscrasias (rare)

Ethosuximide

T/F: if the NT GABA is *not* present, benzodiazepines can directly activate GABA A receptors if given at high doses

FALSE (if NT GABA is not present then Benzodiazepines will *not* be able to activate the GABA A receptors; at *high doses* Barbiturates *can* directly activate GABA A receptors)

__________ is an antagonist to Benzodiazepines and acts by binding to the same site on GABA A receptors, preventing the Benzodiazepines from binding

Flumazenil

The NT GABA is *inhibitory* and acts on _________ receptors which are *ionotropic* and permeable to Chloride (Cl-). - this receptor has 5 subunits: 2 alpha, 2 beta, and 1 gamma or delta subunit - GABA binds at intersection of alpha and beta subunits which causes receptor to change shape and open ionic pore (allowing Cl- to *influx* into cell leading to *hyperpolarization* of the cell, inhibiting the cell to fire an action potential)

GABA A (receptor)

What are the two major *inhibitory* NTs in the CNS?

GABA, glycine

Opioid receptors belong to a super family of __________ receptors. Activation of these receptors affects the ion channel gating, modulates intracellular Ca2+ and K+, and alters the down-stream signaling events. Opioids have 2 well-established actions on neurons which are: 1) they *(open/close)* voltage-gated Ca2+ channels on presynaptic nerve terminals 2) they *(depolarize/hyperpolarize)* postsynaptic neurons by *(opening/closing)* K+ channels

GPCR, close (close Ca2+ channels, reducing transmitter release, prevents influx/depolarziation), hyperpolarize (inhibit firing), opening

*___________* is the first and main drug used for *dopamine replacement* in treating Parkinson's. This drug enters the systemic circulation and crosses the BBB to access the brain. Once in the brain, it can be converted to dopamine in the substantia nigra. Unfortunately, this drug can be metabolized in the periphery as well so it is usually taken with *__________* which prevents enzymes in the periphery from doing this, leaving more to be converted to dopamine in the brain. - Associated with "On-Off" episodes - Begins to lose effectiveness in 5-7 yrs - Alleviates some bradykinesia and rigidity - Adverse effects: nausea, vomiting, psychiatric toxicity (hallucinations), cardiac arrhythmia, orthostatic hypotension

L DOPA (Levodopa), Carbadopa (On-Off episodes: periods of the drug working and the drug not working; off periods characterized by sudden pt freezing or fluctuations in motor performance)

___________ dementia is a unique from Parkinson's dementia and is the second most common type of progressive dementia after Alzheimer's disease dementia. Protein deposits develop in neurons in the brain regions involved in thinking, memory and motor control, specifically in the cerebral cortex and substantia nigra. - Increased risk of this dementia with *contact sports* (repeated concussions) - will see cognitive impairments *before* you see motor deficits - No specific Tx for this Dx, focus on alleviating Sx - Music therapy works pretty well with this Dx (music provides constant, steady cueing while doing a task)

Lewy Body (LBD) (people with classic PD would have motor abnormalities before showing cognitive impairments) (Being active is very important for these pts Tx [ADLs, high reps, keep them moving])

This is the drug of choice for treating *bipolar disorder*. It is an *ion* that decreases overactivity of NTs and signaling proteins thought to contribute to mania. - SE's: dizziness, lethargy, HA, memory loss, NV&D, dry mouth, *metallic taste*, hand tremors, muscle weakness, reversible leukocytosis - Interacts with NSAIDs leading to *decreased clearance* and increased risk of toxicity - Interacts with diurectis leading to *increased clearance* - Eliminated through the kidneys

Lithium

This OTC opioid alters GI motility patterns and possesses anti-secretory activity, which is why it is used as an *anti-diarrheal* medication. - unlikely to be abused (due to limited ability of the drug to access CNS)

Loperamide

_______ and _______ *inhibitors* are drugs used in Parkinson's treatment. They both act by preventing the breakdown of dopamine (DA) in the presynaptic terminal following reuptake, which allows for more DA to be available for re-release into synaptic cleft. - Adverse effects: nausea, vomiting, postural hypotension

MAO-B (monoamine oxidase) COMT (Catechol-O-Methyl transferase) (COMT inhibitors: Tolcapone [Tasmar] and Entacapone [Comtan]. Tolcapone can cause concern of liver toxicity and should only be used with pts whose Sx are not adequately controlled by other medications)

This opioid receptor subtype functions in pain relief (analgesia), sedation, inhibition of respiration, slowed GI transit, physical dependence and euphoria

Mu (μ) (Effects when activated: respiratory depression, miosis [constrict], antitussive [cough], sedation, euphoria/dysphoria, addiction, and/or altering GI motility pattern)

What are the 3 opioid receptor subtypes - *all of these provide analgesic effects when stimulated*

Mu (μ), Delta (δ), Kappa (κ)

Moderate opioid analgesic agonists are often formulated in a combined pill/tablet with an ____________ or acetaminophen, like Vicodin (hydrocodone + acetaminophen) and Percodan (oxycodone + aspirin)

NSAID (acetaminophen = pain reliever, fever reducer Aspirin is in a group of drugs called salicylates. It works by reducing substances in the body that cause pain, fever, and inflammation.)

What are the 5 basic steps in autonomic neurotransmission: (a drug can target any of these 5 processes)

NT synthesis, NT storage (in vesicles), NT release (from presynaptic terminal into synaptic cleft), NT reception (postsynaptic response), termination of signal(Neurotransmission = transmission of signals between neurons and their targets - can be other neurons in the NS, or peripheral targets like glands or muscles.)

__________ is an opioid receptor *antagonist* that is *peripherally selective* (does not cross BBB) - *Use*: Tx for opioid-induced constipation

Naloxegol

________ is a pure opioid receptor *antagonist*. It blocks *all 3 receptor types* with some preference for Mu (μ) receptors. It binds to the receptors *without activating* them. - *Not* orally effective; given by IV - short duration of action - *Use*: reversal of opioid overdose and diagnosis of opioid abuse (*ambulance drug*)

Naloxone

This progressive BG disorder is characterized by having trouble initiating willed movements due to increased inhibition of the thalamus by the BG; the condition leads to shaking, stiffness, and difficulty with walking, balance, and coordination. - pts with this *lose Dopaminergic* neurons (from the *substantia nigra* in the midbrain; which then don't have input on the striatum and also results in an imbalance between dopamine and ACh in the BG) - Sx: hypokinesia, bradykinesia, akinesia, rigidity, tremors of hand and jaw - Avg Onset: ~60 y/o (incidence increases with age) - not hereditary - L-dopa treatment: facilitates production of dopamine to alleviate some symptoms

Parkinson's (PD)

This anti-epileptic drug functions by *blocking Na+ channels* and, to a lesser extent, Ca2+ channels. It is a nightmare pharmacokinetically due to it being a *potent inducer of many liver enzymes*, and has a lot of side effects. It is still used / on the market because of its efficacy in epilepsy treatment. - can be administered orally (variable results) or by IV - non-linear metabolism - SE's: drowsiness, dizziness, gingival hyperplasia, nystagmus, hirsuitism (hair growth), skin rash and fever (may indicate hypersensitivity), lympadenopathy (can be fatal and may look like leukemia)

Phenytoin

This type of anti-depressant drug class functions by increasing *both* serotonin (5-HT) and norepinephrine (NE) levels in the brain by inhibiting their reuptake - Drugs we need to know: Venlafaxine, Duloxetine - SE's: nausea, vomiting, dry mouth, insomnia, drowsiness, sexual dysfunction (decreased libido)

SNRIs (Serotonin Norepinephrine Reuptake Inhibitors)

This type of anti-depressant drug class functions by *specifically* increasing *serotonin* (5-HT) levels in the brain by inhibiting its reuptake - *Drugs we need to know*: Fluoxetine, Paroxetine, Citalopram, Escitalopram, Sertraline - Metabolized by P450s - May take 2-3 weeks to see any effect with these agents - SE's: nausea, vomiting, dry mouth, insomnia, drowsiness, sexual dysfunction (decreased libido)

SSRIs (selective serotonin reuptake inhibitor)

This type of anti-depressant drug class functions by *non-specifically* inhibiting the storage or reuptake of serotonin (5-HT) and norepinephrine (NE) in the CNS leading to increased 5-HT and NE levels in the brain - *Drugs we need to know*: Amitriptyline, Imipramine - Metabolized in the liver rapidly - Clinical benefits may take 2-3 weeks to be seen - SE's: hypotension, impaired ejaculation, drowsiness, anti-SLUD - Uses: good for pts who have previously responded to another drug from this class, medically healthy pts, non-suicidal pts

TCAs (tricyclic antidepressants) (SLUD: salivation, lacrimation, urination, defecation)

This anti-epileptic drug (AED) functions by blocking Na+ channels and increasing GABA availability. It is the broadest spectrum AED, and may also be used for migraines or bipolar disorder. - SE's: GI upset, rare but potentially fatal hypersensitivity (hepatotoxicity and thrombocytopenia)

Valproate

Which of the following *is* a *therapeutic* effect of opioids: a. Antitussive b. Increased GI motility c. Tachypnea d. Mydriasis

a (antitussive = cough suppression) (Therapeutic effects of opioids: analgesia, antitussive, antidiarrheal, acute pulmonary edema, sedation/mood elevation, anesthesia Adverse/unwanted effects: CNS euphoria/depression, respiratory *depression*, *constipation*, physical and psychological dependence, *miosis* [pupil constrict])

___________ and __________ are two drugs used to treat spasticity a. diazepam, baclofen b. baclofen, phenobarbital c. Thiopental, Zolpidem d. none of the above

a (diazepam, baclofen) (Diazepam = benzodiazepine drug class Baclofen = GABA B receptor agonist)

Which of the following is *not* a MAO-B inhibitor? a. Entacapone b. Selegiline c. Rasagiline d. Safinamide

a (entacapone = COMT inhibitor)

Sedative-hypnotic drugs with *shorter* half-lives are better suited for patients who: a. have sleep-onset insomnia b. have daytime anxiety c. are younger d. all of the above are correct

a (have sleep-onset insomnia) (Drugs with shorter 1/2 life are better for pts with sleep-onset insomnia [have difficulty falling asleep] and *no* daytime anxiety; as well as good for elderly patients - if effect of drug persists during daytime, elderly pts have tendency to fall) (Drugs with longer 1/2 life are better for pts who have difficulty *maintaining sleep*, & pts with significant daytime anxiety - residual effects of drug lasting in daytime can help with daytime anxiety)

Besides Facial masking, bradykinesia, decreased arm swing during gait, and stooped posture or scoliosis, patients with Parkinson's may also show impairments in their written and verbal communication including: a. micrographia, hypophonic voice b. macrographia, hyperphonic voice c. dysgraphia, aphasia d. Parkinson's does not effect handwriting or a person's voice

a (micrographia, hypophonic voice) (micrographia = tiny handwriting Hypophonic voice = low / quiet talking) (Other PD impairments: loss of motor planning, visuoperceptive problems, & postural instability)

Synthesis of Dopamine (DA) begins with ___________, an amino acid that is the precursor for the entire synthesis process. This amino acid is converted by an enzyme to become ___________ which is the precursor molecule for Dopamine. The molecule is acted on by dopamine decarboxylase (DD) to produce Dopamine. a. tyrosine, L-Dopa b. lysine, COMT c. valine, L-Dopa d. tryptophan, COMT

a (tyrosine, L-DOPA) (synthesis of DA takes place in *substantia nigra*, released into striatum) (DA then packaged into NT vesicles that migrate down axon into terminal, released into synaptic cleft, then stimulate post-synaptic ganglion)

As the drug schedule changes-- Schedule II, Schedule III, etc., so does the *__________ _________*- - Schedule I drugs have a high potential for abuse and currently have no accepted medical use. They are the only schedule of drug that cannot be prescribed. Examples include heroin and lysergic acid diethylamide (LSD). - Schedule II drugs may lead to severe psychological or physical dependence - Schedule V drugs represents the least potential for abuse

abuse potential

Opioid ________ are drugs that act at some or all of the opioid receptors to produce a biological effect. - Common *strong* examples: Morphine, methadone - Common *moderate* examples: codeine, oxycodone

agonists

Benzodiazepines rarely produce toxic adverse effects (e.g. medullary depression, coma, death), but the risk for this *increases* when these drugs are taken with ____________ - Tx for Benzodiazepine toxicity = Flumazenil

alcohol (*or any other CNS depressants*)

Opioid _________ are drugs that bind to all or some opioid receptors, but do *not* produce a physiological effect - Examples: naloxone, Naloxegol

antagonists

Traditional __________ agents, such as Chlorpromazine and Haloperidol, are used in treatment of Schizophrenia. They act by *non-specifically* inhibiting dopamine (DA) at the level of its D2 receptor - used in pts not responding to other agents - SE's: dystonia, akinesia, akithesia (restless), pseudoparkinsonism (bradykinesia, instability), tardive dyskinesia

antipsychotic (tardive = delayed onset / shows up later)

Which of the following *is* a pharmacological option for PD treatment: a. Beta Blockers b. COMT and MAO-B inhibitors c. Beta Lactam antibiotics d. Z-agents

b (COMT and MAO-B inhibitors) (PD Pharm Tx includes: Anti-cholinergic drugs, COMT inhibitors, MAO-B inhibitors, DA receptor agonist, DA replacement) (Beta blockers = decrease HR and BP COMT inhibitor = blocks enzyme that breaks down dopamine MAO-B inhibitor = blocks enzyme that breaks down dopamine Beta Lactam antibiotics = inhibit cell wall synthesis in bacteria Z-agents = drugs used in treatment of insomnia / sedative-hypnotic drug that work by facilitating the action of GABA)

Which of the following is *not* a Z-agent drug: a. Zaleplon b. Flumazenil c. Eszopiclone d. Zolpidem

b (Flumazenil) (Flumazenil is an antagonist drug to Benzodiazepine drugs) (Z agents bind at the junction of the alpha and gamma subunits on GABA A receptors - *MoA: Facilitate the action of GABA on GABA A receptors* [can increase the frequency or duration of GABA-mediated channel opening])

Which of the following has been linked to a *decrease* in risk of developing Parkinson's disease? a. exposure to pesticides b. caffeine intake c. chronic use of sedative-hypnotic drugs d. exposure to herbicides

b (caffeine intake) (according to Progressive neuro lecture 1-2 cups of coffee/day is associated with a *decreased* risk in developing PD, but 5+ cups of coffee will actually have the reverse effect and *increase* a person's risk of developing PD)

Which of the following is *not* a contraindication for the use of opioid drugs: a. Impaired pulmonary function b. inability to ambulate c. Head injury and trauma d. pregnancy

b (inability to ambulate)

Taking the drug Carbidopa in PD treatment is associated with higher mortality rates because this drug has been linked to the depletion of __________ in the body: a. Vitamin A b. Vitamin B c. Vitamin C d. Vitamin D

b (vitamin B - specifically B6)

___________ work to calm or sedate a person, by raising the level of the inhibitory NT GABA in the brain. Common drugs from this class include diazepam (Valium), alprazolam (Xanax), and clonazepam (Klonopin), among others. - used for treating anxiety, insomnia, seizures, muscle disorders - Bind at the junction of alpha and gamma subunits on GABA A receptors - *MoA: Facilitate the action of GABA on GABA A receptors* (can increase the frequency or duration of GABA-mediated channel opening) - can be short, intermediate, or long acting - relatively *safe* to use

benzodiazepines (Drugs from this class we need to know: Midazolam [short acting], Alprazolam [intermediate], Diazepam [long acting], Lorazepam Diazepam is effective at sedative doses and is useful for treating specific spasticity states, including CP) (Benzodiazepines don't directly activate GABA A receptor, they just promote the activity of NT GABA; effect plateaus even with higher doses [if NT GABA is not present then Benzodiazepines will not be able to activate the GABA A receptors]; much better safety profile than Barbiturates)

The (Barbiturates/Benzodiazepines) drug class of sedative drugs tend to saturate off *even with increased dosage* leading to less severe adverse effects, whereas (Barbiturates/Benzodiazepines) do no and will cause serious adverse effects if given at high doses

benzodiazepines (safer), barbiturates (dangerous bois)

The in thalamus and limbic system, opioids _________ the perception of pain at the level of the *thalamus* and ___________ the reaction to pain in the *limbic system*

block, depress

Cholinergic interneurons are autonomously active in the striatum and Dopamine (enhances/blocks) their activity

blocks (therefore, a cholinergic receptor antagonist would provide the same type of effect as increased dopamine)

What are the 4 cardinal symptoms of Parkinson's disease?

bradykinesia (slow movements), resting tremor, rigidity, postural instability (lack of muscle control)

Which of the following drugs works by increasing dopamine (DA) and norepinephrine (NE) in the CNS by blocking their reuptake? a. Fluoxetine (Prozac) b. Esketamine (Spravato) c. Bupropion (Wellbutrin) d. Venlafaxine (Effexor) e. Amitriptyline (Elavil)

c (Bupropion) (Fluoxetine - SSRI - serotonin only Esketamine - NMDA antagonist [glutamate receptor] - leads to upregulation of that BDNF peptide Bupropion - YEP! Dopamine and NE! Venlafaxine - SNRI - Serotonin and NE Amitriptyline - Serotonin, NE, dopamine and lots of other stuff too [pretty nonspecific])

Most sedative-hypnotic drugs act on ________ receptors. a. AMPA b. Kainate c. GABA A d. NMJ

c (GABA A) (AMPA and Kainate receptors are excitatory post-synaptic glutamate receptors; excite CNS GABA A = inhibitory post-synaptic GABA receptors; depress CNS)

Which of the following is a major inhibitory NT in the CNS? a. Glutamate b. Glutamine c. GABA d. Dopamine e. Norepinephrine f. Epinephrine g. Serotonin

c (GABA)

patients with Parkinson's lose this type of neurons: a. glutamatergic b. GABAergic c. Dopaminergic d. Cholinergic

c (dopaminergic)

Which of the following is *not* a family of endogenous opioid peptides: a. endorphins b. enkephalins c. glasgophalins d. dynorphins

c (glasgophalins) (idk just made that word up)

All of the following are SSRI antidepressant agents *except*: a. Sertraline b. Citalopram c. Imipramine d. Paroxetine e. Fluoxetine

c (imipramine)

Which of the following NTs is/are *majorly* effected by antidepressant drugs (more than one choice may be correct)? a. Glutamate b. GABA c. Serotonin d. Norepinephrine e. Acetylcholine

c, d (serotonin and NE)

Which sedative-hypnotic drug class is *most commonly* used for seizure disorders (e.g. epilepsy)? a. Z-agents b. Barbiturates c. Tetracylines d. Benzodiazepines

d (benzodiazepines) (benzodiazepines are used, Z compounds are less effective as anticonvulsants. A barbiturate [Phenobarbital] is used in status epilepticus [severe condition, continuously having seizures]) (Z agents mainly used for insomnia Tx)

At lower doses, the therapeutic effects of sedative-hypnotic drugs include all of the following *except*: a. anti-convulsant action b. anxiolysis c. sedation d. mania e. hypnosis

d (mania) (these drugs are CNS depressants that cause sedation & sleep anxiolysis = anti-anxiety, person becomes more calm/relaxed hypnosis = sleep Full list of adverse effects: cognitive and motor impairment - light headed, motor incoordination, confusion, anterograde amnesia; daytime drowsiness, rebound anxiety, paradoxical effects, toxicity - medullary depression, coma, death)

Majority of pain killers (analgesics) derive from: a. Spotted mushroom fungi b. Sassafras roots c. Blue agave plant d. Opium poppy seeds

d (opium poppy seeds) (morphine and codeine are derived from opium poppy seeds sassafras roots are the origin of the drug ecstasy blue agave plant is what tequila is made from)

Dopaminergic neurons are found in the: a. subthalamic nucleus b. striatum c. globus pallidus d. substantia nigra

d (substantia nigra)

Inhibiting cholinergic activity (increases/decreases) parasympathetic activity

decreases (leading to decreased secretions, gut motility, etc.)

This opioid receptor subtype functions in pain relief (analgesia), has antidepressant effects, and modulates the Mu (μ) receptor

delta (δ)

___________ on sedative-hypnotic drugs can be psychological and/or physical - Psychological: compulsive use of the drug to reduce anxiety - Physical: development of withdrawal symptoms when the drug is discontinued (including tremors, sweating, unpleasant dreams, dizziness, seizures, etc.)

dependence

Na+ and Ca2+ cause (depolarization/hyperpolarization) of neuron leading to APs Chloride (Cl-) causes (depolarization/hyperpolarization) of neuron preventing APs In epilepsy treatment you are trying to *downregulate* the (depolarization/hyperpolarization) of the wonky firing neurons

depolarization, hyperpolarization, hyperpolarization

In the brainstem, opioids activate (ascending/descending) inhibitory systems in order to modulate pain transmission at the level of the spinal cord

descending

This family of endogenous opioid peptides is composed of 17 amino acid residues. They likely function as NTs and function in pain relief - high affinity for Kappa (κ) receptors

dynorphins

This family of endogenous opioid peptides is composed of 31 amino acid residues. They function as neurohormones and are believed to mediate the psychological* responses to pain and stress*. They may also be involved in memory, mood states, and the *regulation of appetite drives* (e.g. thirst, sex, hunger, etc.) - high affinity for Mu (μ) receptors

endorphins

This family of endogenous opioid peptides is composed of 5 amino acid residues. They have be localized throughout the brain and spinal cord and likely function as NTs. They bind to opioid receptors and reduce pain sensation. - high affinity for Delta (δ) receptors

enkephalins

The COMT inhibitor (Tolcapone/Entacapone) acts only in the periphery of the body, whereas (Tolcapone/Entacapone) can also be centrally-acting

entacapone, tolcapone

T/F: sedative-hypnotic drugs are ideal pharmacological treatment for chronic anxiety

false (being replaced with other drugs such as SSRI antidepressants for *chronic* anxiety Benzodiazepines are used in *acute* anxiety - panic disorder, situational anxiety, and generalized anxiety)

T/F: Dopamine can cross the BBB

false (can't just give a pt dopamine for PD treatment because it won't be able to cross BBB and get into brain)

What is the major *stimulatory*/excitatory NT in the CNS?

glutamate (AMPA or Kainate receptors permeable to Na+)

In the spinal cord, opioids (enhance/inhibit) release of NTs from primary afferents and directly (enhance/inhibit) dorsal horn neuronal activity

inhibit, inhibit

this type of NT receptor is linked directly to ion channels. These receptors contain two functional domains: an extracellular site that binds NTs, and a membrane-spanning domain that forms an ion channel.

ionotropic

What are the 2 major classes of NT receptors

ionotropic, metabotropic

This opioid receptor functions in pain relief (analgesia), sedation, and has effects of dysphoria and miosis (pupil constriction)

kappa (κ)

This type of NT receptor does not use ion channels. Instead, NTs bind to these receptors activating G-proteins, which then dissociate from the receptor and interact directly with ion channels or bind to other effector proteins, such as enzymes, that make intracellular messengers that open or close ion channels

metabotropic

__________ symptoms refer to a decrease or dampening of normal perceptions/emotions - e.g.: apathy, lack of motivation, anhedonia (lack of pleasure from normal pleasurable experiences), asocial behavior

negative

Pharmacologic treatment for PD can be divided into 2 different categories: ___________ therapy (e.g. caffeine and nicotine) and ____________ treatment (e.g. pro-dopamine, anti-cholinergic)

neuroprotective (preventative), symptomatic (once someone gets PD)

__________ effects of a drug = pt given a drug and within the first few days on the drug it *produces what the pt is trying to avoid* - e.g. taking anxiety meds and getting more anxiety initially - only some drugs in benzodiazepine class do this - can affect pt's compliance with the drug

paradoxical

When a neuron is resting it is said to be ____________. If membrane potential moves more *towards zero* it is ______________ = *more excitable* if membrane potential moves *more negative* it is ______________ = *less excitable*

polarized, depolarized (inward current of Na+), hyperpolarized (outward current of K+)

____________ symptoms refer to an exaggeration of normal perceptions/emotions - e.g.: hallucinations, delusion, thought disorders, insomnia, bizarre behavior

positive

The area __________ is a chemoreceptive trigger area for vomiting when toxins enter the body. It is open to the BBB. This area contains Dopamine receptors and, when stimulated, can induce nausea and vomiting

postrema

Newer generation anti-psychotic agents function by inihibiting _________ at the level of its *receptors*. Most of these drugs also inhibit D2 receptors. They are used as first-line agent for the treatment of schizophrenia. - Drugs we need to know: Risperidone, Quetiapine, Olanzipine, Aripiprazole - SE's: similar to, but way *less severe* compared to typical anti-psychotic agents - dystonia, akinesia, akithesia (restless), pseudoparkinsonism (bradykinesia, instability), tardive dyskinesia

serotonin (5-HT)

What are the 3 primary sites of action in the CNA for Opioid analgesic drugs:

spinal cord, thalamus (+limbic system), brainstem

______________, a decreased responsiveness to a drug following repeated exposure, commonly occurs with continued use of sedative-hypnotic drugs.

tolerance (a great amount of medication is needed to maintain therapeutic effect)

T/F: All conventional antidepressants raise the risk of suicide in the first 1-2 months of therapy/use

true

T/F: Tricyclic antidepressants have less specific inhibition of NT reuptake compared to other antidepressant drug classes

true

T/F: Benzodiazepines exert anterograde amnesia effects (i.e. the inability to remember events occurring during the drug's action) at sedative doses. This action is a primary reason some benzodiazepines are commonly used for short duration invasive procedures. These drugs *DO NOT* provide pain relief

true (Benzodiazepines are used as anesthetic adjuncts [prior to anesthesia induction or during procedures not requiring general anesthesia])

T/F: PD is a disease of exclusion meaning it it diagnosed by eliminating majority of other possible diagnoses. If a CT/MRI, spinal fluid, urine, and blood work are all negative and the pt presents with *bradykinesia* + one more physical sign (rigidity, tremor, and/or gait & balance disorders) then the *final definitive test* would be putting them on dopamine medication to see if it decreases their symptoms

true (Hallmark 3 Sx for Dx of PD: Bradykinesia [*must have*], + either rigidity, tremor, and/or gait and balance disorder, & pt reaction to dopamine drugs) (by the time you can Dx PD via MRI the condition will be pretty far along / advanced)

T/F: opioid analgesics can act on peripheral nociceptors to inhibit pain transduction/conduction

true (pain can be prevented by interrupting transmission at any step on the ascending pathway, or by modulating the feedback circuits in the descending pathways)

T/F: as the dosage of sedative-hypnotic drugs *increases* the adverse effects can include anesthesia, medullary depression, coma, and potentially death

true (anesthesia - LOC Medullary depression: hypofunction of CV and respiratory systems)

T/F: The adverse effects of sedative-hypnotic drugs most of the time is just an exaggeration of the therapeutic effects or having the therapeutic effects occurring during an undesired time

true (increased CNS depression, confusion, daytime sleepiness)

CV: Opioids cause a release of histamine leading to *(vasoconstriction/vasodilation)* GI: Opioids *(increase/decrease)* secretions and propulsive activity Sphincters: Opioids *(increase/decrease)* tone

vasodilation, decrease, increase (= relaxation of smooth muscle in GI, urinary and CV system)