Neuro Pharm 2 Flashcards
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
Rx works by increasing the length of time that the Cl-channel GABA-A neurons stay open (still need GABA)
Barbituates
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
IV rapid acting Benz antagonist
Flumazenil
Benz Agonist
Most widely prescribed hypnotic, reduced dose for women, withdraw Rx slowly
Zolpidem
Benz agonist
Ald. Dehydrogenase, variability in Asians
Zaleplon
Melatonin Receptor Agonist
MT-1: attenuates Suprachiasmatic nucleus activity
MT-2: circadian rhythms
MT-3: not involved in sleep
Ramelteon
1st gen anti-hist AEs
xerostomia, blurred vision, urinary retention, increased occular pressure, rapid tolerance
Only antidepressant approved to tx insomnia
anti-H1 at low dose
SNRI
Doxepin
Antidepressant off-label for insomnia
a2 antagonism
Mirtazapine
Antidepressant off-label for insomnia
5-HTRI
Trazodone
TOC for migraines during pregnancy
Acetominophen
produce selective carotid vasoconstriction (via 5HT1B) and pre-synaptic inhibition of the trigeminovascular inflammatory responses of migraines (via 5HT1D/5HT1F – calcium entry)
Triptans
Sumatriptan
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
Long Acting Triptan
Frovatriptan
Intermediate Acting Triptan
Naratriptan
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
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
Antiemetic for migraines
D2, cholinergic, and alpha adrenergic blockade
Prochlorperzine
Antiemetic for migraines
D2 central blockade & prokinetic
Metoclopromide
Antiemetic for migraines
anticholinergic
Chlorpromazine
Prophylaxis of migraines
Decreases reuptake of 5HT and NE + strong anti-cholinergic effect
Amitriptyline
Prophylaxis of migraines
Sodium channel blocker, increases GABA, Cat X, hepatotoxic, sedation, nausea, increase weight, highly protein bound
Valproic acid
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
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
