Neuro Pharm 2 Flashcards by Lori Shenep

Neurons in the hypothalamus that mediate very rapid transition between the sleep and awake cycles
Input from the suprachiasmatic nucleus, amygdala, dorsomedial hypothalamis
these neurons also act on the NPY neurons of the arcuate nucleus of the hypothalamus to increase food intake
These are significantly decreased in narcolepsy

Orexin

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Rx works by increasing the length of time that the Cl-channel GABA-A neurons stay open (still need GABA)

Barbituates

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Rx that has an allosteric leftward shift on the GABA-A neurons
Category X, CI: Liver dz, COPD, depression, glaucoma, other CNS Rx
3 kinds:
1-
2-
3-

Benzodiazepines
1- Sedation/ Amnesia

2- Anxiolysis

3- Myorelaxation/ Anti-convulsant

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IV rapid acting Benz antagonist

Flumazenil

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Benz Agonist

Most widely prescribed hypnotic, reduced dose for women, withdraw Rx slowly

Zolpidem

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Benz agonist

Ald. Dehydrogenase, variability in Asians

Zaleplon

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Melatonin Receptor Agonist
MT-1: attenuates Suprachiasmatic nucleus activity
MT-2: circadian rhythms
MT-3: not involved in sleep

Ramelteon

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1st gen anti-hist AEs

xerostomia, blurred vision, urinary retention, increased occular pressure, rapid tolerance

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Only antidepressant approved to tx insomnia
anti-H1 at low dose
SNRI

Doxepin

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Antidepressant off-label for insomnia

a2 antagonism

Mirtazapine

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Antidepressant off-label for insomnia

5-HTRI

Trazodone

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TOC for migraines during pregnancy

Acetominophen

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produce selective carotid vasoconstriction (via 5HT1B) and pre-synaptic inhibition of the trigeminovascular inflammatory responses of migraines (via 5HT1D/5HT1F – calcium entry)

Triptans

Sumatriptan

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Routes and AE of triptans

Nasal route – faster

SC- fastest & most effective but w/ most AEs: CNS – dizziness, drowsiness, fatigue

May cause coronary or peripheral vasospasm, contraindicated w/ heart disease, uncontrolled HTN, ischemic bowel disease

Do not use w/ MAOIs or Ergots

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Long Acting Triptan

Frovatriptan

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Intermediate Acting Triptan

Naratriptan

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Alkaloids derived from a mold

In moderate doses: causes contraction of smooth muscle fibers (used to control hemorrhage & promote uterine contractions (also used to treat migraine headaches)

In large doses, ergotamine paralyzes motor nerve endings of the SNS

Acute/Chronic AE: mental disorientation, convulsions, muscle cramps, dry gangrene

Generally less effective, may work in pts unresponsive to first-line drugs

Contraindicated in pts with vasospastic predisposing conditions
Hepatic metabolism, renal elimination

Complex agonist on multiple receptors (5HT), peripheral alpha, decreased amine uptake

Beta blockers, DA can potentiate vasoconstrictive effect
Strong CYP3A4 can increase ergot persistence
Triptans, 24 h rule
Teratogenic

Ergotamine

Duhydroergotamine

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May be given for migraines in later trimesters
Last resort, respiratory depression, bradycardia, histamine, QT prolongation, constipation, N/V
*high AUS

Opiates: hydrocodone, oxycodone, codeine

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Antiemetic for migraines

D2, cholinergic, and alpha adrenergic blockade

Prochlorperzine

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Antiemetic for migraines

D2 central blockade & prokinetic

Metoclopromide

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Antiemetic for migraines

anticholinergic

Chlorpromazine

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Prophylaxis of migraines

Decreases reuptake of 5HT and NE + strong anti-cholinergic effect

Amitriptyline

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Prophylaxis of migraines

Sodium channel blocker, increases GABA, Cat X, hepatotoxic, sedation, nausea, increase weight, highly protein bound

Valproic acid

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Decreases arterial dilation and decreases NE induced lipolysis, fatigue, exercise intolerance, problems with asthma & diabetes, AV block
Only drug approved for migraines in children

propanolol

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Blocks sodium, glutamate | Increases GABA

Topiramate

No vascular or systemic effects, decreases the incidence of headache, high placebo rate, not recommended for episodic headaches

Botox

Non-enzymatically activated pro-drug (DNA methylating agent) Resistance via upregulation of MGMT activity

Temozolimide

alkylating agents; cross-resistance w/ other alkylating agents is uncommon -lipophilic, non-ionized at physiologic pH AE: myelosuppression, pulmonary fibrosis, endocrine problems (increase prolactin, hypothyroidism), encephalopathy/seizures

Carmustine and Lomustine

theory: Myer-Overton?

the more lipid-soluble the drug, the more potent it is (but in reality, making a drug more lipid soluble will not always enhance its potency)

minimum alveolar concentration: vol % of the atmosphere that is the anesthetic needed to anesthetize 50% pts Increasing the oil:gas partition can lower the drug's MAC

minimum alveolar concentration

allows you to lower how much of the anesthetic to add to the mixture Incomplete anesthetic – useful as an additive Not as lipid soluble so it rapidly reaches saturation in the blood Does not block reflex response to increasing N2O No significant CV effects alone but causes depression w/ an opiod agent Produces analgesia Reflexes are maintained if this is used alone Teratogen in animal models Increased risk of spontaneous abortion; sporadic neuro px in infants due to myelin sheath degredation upon chronic exposure (N2O is an inhibitor of B12 synthestase) All medical facilities now have expensive N2O scavenging air-handling systems Special Problems: 1- Second gas effect: High volume of N2O and relative insolubility, rapid uptake of anesthetic accompanying agent 2- Diffusional hypoxia – administer O2 immediately post-anesthetic phase 3- N2O solubility: can accumulate in other airspaces of body: middle ear, pneumothorax, bowel surgery

Nitrous Oxide

Potentiate GABA and glycine inhibitory signaling, reinforce 2 pore potassium channel activity & inhibit glutamatergic signaling * Do not produce analgesia * Produce a lack of reflexes

Volatile Gases

Older volatile gas with hepatic and heart toxicity

Halothane

Volatile Gases A/w seizures

Halothane, Enflurane

Newer Volatile Gases: Newer agent, equilibrates much faster to reach the brain more quickly

Desflurane and Sevoflurane

Increase in cardiac output and HR of an anesthetized patient Also act on NMDA receptors for glutamate Inhibits glutamate by occluding the channel Increases cerebral blood flow and intracranial pressure Also cardio stimulatory (increase HR, MAP, CO) no effect on RR Produces analgesia Preserves protective reflexes Bronchodilatory actions Selective neuronal depression Dissociative anesthetic

Ketamine

Barbituate | Increases heart rate; depresses RR, CBF

Thiopental

Short Acting Hypnotic depresses RR, CBF increases heart rate Reinforce GABA and inhibit Glutamate by blocking binding to receptor Also act on NMDA receptors for glutamate Anti-emetic Propofol Infusion syndrome: fatal CV and organ systems failure – bad press

Propofol

Short Acting Hypnotic Reinforce GABA No effect on heart or vasculature (good for cardiac pt) depresses RR, CBF Inhibition of steroidgenesis (not used in the ICU) drop in cortisol seen with one dose

Etomidate

Systemic Toxicity of local agents

Minor toxicity: ringing in ears, metallic taste, numbness of lips and tongue Seizures: administer diazepam, protect airway, succinylcholine in severe rxn

*Separate into long and short-acting

lower pkA will have a faster onset

Recall agents producing methemoglobulinemia:

prilocaine & benzocaine

= lidocaine and prilocaine, advance of skin graft collection, onset within 1 hour

EMLA

= Lidocaine and oxymetazoline – analgesia and vasoconstriction for suturing lacerations

LET

Local anesthetic Metabolism mostly in the liver but affected by CV, pregnancy, liver, BBs Urinary metabolite elimination

Amide

Local anethetic Can be metabolized in any structure except CSF by non-specific esterase enzymes (can have genetically low capacity) Urinary metabolite

Ester

Amide | More potent, cardio toxic, prolonged activity; inadvertent trauma to tongue/mouth

Bupivacaine

Amide | Reduced CV activity; greater margin of safety

Ropivacaine

: first line tx for glaucoma; mechanism is unclear, thought to increase aqueous outflow via uveoscleral outflow pathway; undergo in situ hydrolysis after penetrating the cornea (blurred vision, burning/stinging, itching, chronically slow & permanent brown pigmentation of iris, eyelid skin, eye lashes, also increases growth & length Brand name, very expensive

Prostaglandin: Latanoprost

tx for glaucoma : decrease aqueous humor production, decrease cAMP, can be detected in systemic circulation (don’t use in pt w/ low heart rate or asthma)

Timolol maleate

reduces fluid transport to decrease IOP; blurred vision, lacrimation, photophobia, xerophthalmia; sulfonamides : allergic rxns (will inhibit aqueous production?)

Carbonic Anhydrase Inhibitors Dorzolamide Brinzolamide

intravitreal use of VEGF inhibitors a/w atertial thromboembolic events

Aflibercept Pegaptanib Ranibizumab Bevacizumab

IV nonthermal laser activator; free radicals damage vessles

Verteporfin

ACheE Inhibitors: more potent, longer acting miotics + adverse effects more common; not used w/ closed angle glaucoma

Echothiophate

Partial vs. generalized | Partial: simple vs. complex

simple - no loss of consciousness complex: loss of consciousness

Promote inactivated sodium channel state (partial and secondary generalized) Binds proteins One of the few zero order drugs; metabolism varies based on the dose CNS effects: nystagmus, headache, ataxia, drowsiness not common at tx levels Gingival hyperplasia, hirsutism, derm

Phenytoin

Promote inactivated sodium channel state (partial and secondary generalized) Inhibition of voltage gated calcium channels for T-type calcium currents (absence seizures) Increases GABA, decreases sodium Binds proteins CNS related to the infusion rate; heme: thrombocytopenia Greatest risk of teratogenicity DOC: tonic/clonic, absence/ myoclonic/ atonic

Valproate

Promote inactivated sodium channel state (partial and secondary generalized) CNS effects especially during initial tx: sedation, dizziness/ drowsiness Heme: risk of agranulocytosis/ anaplastic anemia Xerostomia, N/V Needs to get increased over time to maintain serum concentrations due to CYP induction DOC: partial/ secondary generalized seizures

Carbamezepine

2 anti-convulsants that act on the sodium channel and are weak carbonic anhydrase inhibitors (can cause lactic acidosis)

Topiramate & Zonisamide

First response for a pt w/ an acute prolonged epileptic crisis

Lorazepam (benzodiazepines) – instant effect that you follow up by loading in IV at a slower rate: Diazepam (giving it rectally, it does avoid first pass metabolism, but not as rapid as IV push)

Inhibition of voltage gated calcium channels for T-type calcium currents (absence seizures)

Ethosuximide

Decreases NMDA, increases GABA Decreases alpha-2 delta-1 subunit of calcium SOB on exertion and weakness? Tachycardic w/ pale skin  anemia

Felbamate