Pharm 2 - Insomnia, Migraine, Brain Tumors, Anesthetics, Ocular, Epilepsy, Vertigo Flashcards
1
Q
Mediator of sleep and awake states
A
Orexin
2
Q
Drug classes for insomnia
A
Benzodiazepines (BNZ), BNZ receptor agonists (BRAs), Melatonin receptor agonists, tricyclic antidepressants, 1st gen anti-histamines
3
Q
MOA of BNZ and BRAs
A
Binding to GABA-A receptor (but at different locations) - GABA channel open longer - more inhibitory action - more CNS depression; BRAs have ceiling effect at high doses
4
Q
Goals of insomnia drug pharmacokinetics
A
Rapid onset time and sufficient durability as to not wake up in the middle of the night but not too long as to have “morning after” symptoms
5
Q
Benzodiazepine drugs
A
Estazolam, flurazepam, quazepam, temazepam, triazolam
6
Q
Pregnancy category for BNZ
A
Category X!
7
Q
Side effects of BNZs
A
Contraindicated with COPD, driving, depression, other CNS drugs, and glaucoma
8
Q
BNZ with least CYP interaction
A
Temazepam
9
Q
BNZ receptor agonists
A
Zolpidem, zaleplon, eszopiclone
10
Q
Zolpidem
A
Most widely prescribed hynotic, only drug approved for “middle of the night” awakening (short acting/less durable)
11
Q
Role of melatonin on sleep
A
Works on suprachiasmatic nucleus and sleep-wake switch
12
Q
Antidepressants for insomnia
A
Doxepin, mirtazapine, trazodone
13
Q
Side effect of antidepressants
A
Suicidal ideations
14
Q
First generation anti-histamines
A
Diphenhydramine and doxylamine; cross the BBB
15
Q
Drug offenders of insomnia
A
TCA, MAOI, SSRIs, Venlafaxine, Bupriopion, Levodopa, Felbamate, Beta-Blockers, Decongestants, Antibiotics, Asthma meds, Stimulants
16
Q
NSAIDS MOA for migraine Tx
A
Inhibiting inflammatory stimuli, thus decreasing MAPK and decreasing CGRP synthesis
17
Q
Triptans MOA for migraine Tx
A
Selective carotid vasoconstriction and presynaptic inhibition of trigeminovascular inflammatory response
18
Q
NSAIDS for migraine
A
Ketoprofen, fenoprofen, nabumetone, ibuprofen, naproxen
19
Q
NSAIDS in pregnancy
A
Cat C; but avoid in late pregnancy bc of PDA and prolonged labor
20
Q
NSAID combinations
A
Combined with butalbital (for sedative effects via GABA) and caffeine (for caffeine withdrawal headaches)
21
Q
Serotonin agonists “triptans”
A
Almotriptan, Eletriptan, Frovatriptan, Naratriptan, Rizatriptan, Sumatriptan, Zolmitriptan
22
Q
Triptans with fastest onset
A
Sumatriptan - given sub-Q
23
Q
Triptans most durable (also long onset)
A
Naratriptan and frovatriptan
24
Q
Contraindications of triptans
A
Don’t take with other vasoconstricting drugs or ergots; don’t combine with SSRIs or SNRIs (serotonin syndrome)
25
Ergots
Dihydroergotamine, ergotamine
26
Location of ergot receptors
CNS and periphery (unlike triptans)
27
Ergot use in pregnancy
NO!...Cat X
28
Migraine drug to use during pregnancy
Acetaminophen; opioids maybe in later trimesters
29
Tx of menstrual migraine
NSAIDS 2-3 days before period until it ends
30
Migraine and oral contraceptives
Multiplicative risk when taking OC and having migraine w/ aura
31
Antiemetics used in migraine
Metoclopramide, prochlorperazine, promethazine, chlorpromazine
32
MOA of antiemetics
All block D2 centrally except promethazine (cholinergic blockade)
33
Management of brain metastases
Antitumoral agents (chemo generally not indicated) and steroids (for brain edema) and anticonvulsants (for seizures). Definitive Tx with surgery or radiation
34
Mechanisms of resistance in brain tumors
Inability to pass BBB, overexpression of P-gp, and gene-related effects from astrocytes (don't forget also the usual mechanisms from regular tumors too)
35
Uses for Temozolomide
Astrocytoma, GBM, malignant glioma, malignant melanoma
36
MOA of Temozolomide
Pro-drug yielding DNA methylator
37
Mechanism of resistance to TMZ
Repair with methyl guanine methyl transferase
38
Nitrosourea drugs
Carmustine (BCNU) and lomustine (CCNU)
39
MOA of nitrosoureas
Alkylating agents; CARmustine also CARbamylates proteins
40
Side effects of nitrosoureas
Myelosuppression, pulmonary toxicity, endocrine dysfunction
41
Inhaled Anesthetics
Gases: nitrous oxide, Liquids: halothane, enflurane, isoflurane, desflurane, sevoflurane
42
Conscious sedation
Maintain protective reflexes, airway maintained, response to external stimuli
43
Levels of sedation
Analgesia, anxiolysis, conscious sedation, deep sedation, general anesthesia
44
Advantage of inhalation and IV route
Immediate control over dose and duration of action
45
Minimum Alveolar Concentration
Minimum amount of drug required to render half of the patients unconscious
46
Correlation of MAC and lipid solubility
Higher partition coefficient (more lipid soluble) means lower MAC (more potent)
47
Agents containing halogens
Isoflurane, desflurane, sevoflurane (fluorine makes it less volatile)
48
Incomplete anesthetic
Nitrous oxide; MAC 105% - does not work completely, so don't use alone!
49
Inhalation agents with faster equilibrium in blood
Sevoflurane and desflurane
50
Ventilation rate and arterial tension
More delivery to blood with greater ventilation; more pronounced for nitrous oxide
51
Respiratory effect of inhaled agents
Increased respiration rate and decreased tidal volume
52
CV effects of inhaled agents
Decreased blood pressure and cardiac output
53
Inhaled agent with no CV effects
Nitrous oxide
54
Inhaled agent with analgesic effects
Nitrous oxide
55
Inhaled agents with muscle relaxant properties
Enflurane and isoflurane
56
Inhaled agents causing hepatic toxicity and arrhythmias
Halothane
57
Inhaled agent that causes seizures
Enflurane
58
Toxicity of nitrous oxide
Teratogen, myelin sheath degeneration, B12 deficiency
59
Problems with nitrous oxide
Second gas effect, diffusional hypoxia, solubility
60
Targets of IV agents
Mostly reinforces GABA and glycine inhibitory effects; propofol and ketamine work on NMDA receptors for glutamate
61
MOA of propofol
Acts like GABA itself and also blocks binding of glutamate
62
MOA of ketamine
Physically blocks ion channel
63
Drug distribution of IV agents
Instant effect - goes to high flow organs first (brain, heart, liver, kidneys) then to skeletal muscle/skin and then accumulates in adipose tissue
64
Redistribution of IV agents
Drug passes BBB by going down concentration gradient into the brain and then leaves BBB when gradient inverts
65
IV agent with longest half life....shortest?
Longest - diazepam; shortest - etomidate
66
IV agent with increased cerebral blood flow
Ketamine
67
IV agent with increased ICP
Ketamine again
68
IV agent without respiratory depression
Ketamine a third time
69
IV agent with cardiostimulatory effect
Thiopental, propofol, but mainly ketamine
70
Best drug to use during surgery if there is nausea and vomiting as an adverse effect
Propofol (anti-emetic)
71
IV agent that inhibits steroidogensis
Etomidate
72
More special properties of ketamine
Preserves reflexes, bronchodilatory action, analgesia, hallucinations (like angel-dust)
73
Propofol Infusion Syndrome
Metabolic acidosis, rhabdomyolysis, arrhythmias, MI, renal failure, heptaomegaly
74
BNZ used for anesthesia
Diazepam, lorazepam, midazolam
75
Properties of BNZ in anesthesia
No analgesic properties, but functions as an anticonvulsant and amnesic
76
CV effects of opioids
Bradycardia, hypotension, reflex HTN
77
Anesthetics and response to CO2
Decreased responsiveness (less ventilation to increased CO2)
78
Neurolept-analgesia
State of indifference and pain relief but still responsive; can be transitioned into anesthesia with nitrous oxide
79
Neurolept-analgesia combination
Droperidol and fentanyl
80
Ultrafast acting opioid
Remifentanil (need analgesia coverage when finished)
81
Long vs short acting opioid
Morphine good for long-lasting relief; fentanyl is short acting (less nausea and vomiting unlike morphine)
82
Mechanism of malignant hyperthemia
Release of calcium from sarcoplasmic reticulum; succinylcholine thought to be involved
83
Antidote for malignant hyperthemia
Dantrolene - repackages calcium back into SR; don't take with calcium channel blockers
84
Naturally occurring toxins
Erythroxylum coca, gymnodinium breve, puffer fish, snake/spider venom
85
The ideal local anesthetic
Lipophilic AND hydrophilic; low toxicity, short onset, reversible
86
MOA of local anesthetics
Passes through neuronal membrane and blocks voltage-gated sodium channels
87
Differential blockade
Certain nerves are more susceptible to blockade than others; this depends on fiber diameter, myelination, position, and nerve activity
88
Fiber sensitivity to anesthetic
Small myelinated and non myelinated most sensitive; large myelinated A alpha fibers least sensitive
89
When are local agents most effective
When nerve is more spontaneously active
90
Ideal pH in extraneural and neural spaces
Extraneural pH should be basic (relative to pKa); neural pH should be acidic (relative to pKa). You want uncharged molecule to cross membrane but you want a charged molecule to bind to Na channel
91
Local anesthetic in area of inflammation
IT WAS SUPER INEFFECTIVE
92
Anatomical aspects of nerve block
Block begins proximal to distal and outside to inside; recover also proximal to distal
93
Nomenclature of amides and esters
____i____caine = amide; _____caine = ester; just remember amIde has the I in it; exception is articaine which is considered an ester despite it's spelling
94
Metabolism of amide agents
Hepatic
95
Metabolism of ester agents
Any other tissue - shorter duration of action because of this
96
Systemic toxicities of local agents
Ringing in ears, metallic taste, numbness in lips and tongue (stop drug immediately); can also have seizures
97
Role of vasoconstrictors in nerve blockade
Vasoconstrictor will increase the duration and intensity of the blockade; phentolamine will vasodilate and promote removal of the anesthetic
98
Additives to local anesthetics
Epinephrine or levonordrefin - can lead to situational anxiety
99
Sulfite allergy
Allergic to esters give amides
100
How many mg/mL in a 2% solution?
Let's arbitrarily say there's 100 mL; so 2% = 2 g/100 mL = 2000 mg / 100 mL = 20 mg/mL at a density of 1 g/mL
101
How many ug/mL epinephrine at 1:100,000 solution?
1:100,000 = 1 g / 100,000 mL = 10 ug/mL
102
Local anesthetics that cause methemoglobinemia
Prilocaine and benzocaine (a lesser extent)
103
Prolonged drug action in bupivacaine
Good for postoperative analgesia, more cardiotoxic
104
Articaine
Penetration into bone; good for dental work
105
Topical anesthetic for mouth, pharynx, larynx, trachea, esophagus, and urethra
Benzocaine, dyclonine
106
Topical anesthetic for skin ONLY
Dibucaine, pramoxine
107
Epidural/spinal anesthesia
Distribution depends on baricity and pt orientation; works on nerve fibers exiting the cord not the spinal cord itself
108
Drug sequence regimen
BNZ night before surgery for anxiety; shortly before surgery - sedative/amnesic, drugs to neutralize acidity/dry secretions
109
Other drugs for anxiety
Phenothiazines, 1st gen antihistamines
110
Benefits of H1 antagonists
Sedation, cholinergic antagonism, and anti-emetic effect
111
Prophylaxis for allergic reaction
Treat with H1 and H2 blockers
112
Problem with delayed awakening
Residual anesthetics and ancillary drugs - give opiate or BNZ antagonists; physostigmine can reverse anticholinergic effects
113
Postoperative nausea and vomiting
Propofol rarely causes it but nitrous oxide is associated with it
114
Glycemic control for surgery
Stop oral hypoglycemics and cut down on insulin
115
Anaphylaxis support
Stop drug, discontinue anesthesia, give O2, give epi, expand intravascular volume
116
Effect of opiates on the eye
Pinpoint pupils
117
Use of esterases for the eye
Good for local activation of prodrugs - dipevefrin and latanoprost
118
Effects of muscarinic antagonists
Loss of accomodation (cycloplegia) and adaptation (mydraisis) - pupils enlarge and can worsen glaucoma
119
Muscarinic antagonists
Atropine, homotropine, tropicamide, cyclopentolate, scopolamine
120
Adverse effects of muscarinic antagonists
Increased intraocular pressure, transient stings
121
Two mechanisms to treat glaucoma
Decreased production of aqueous humor; increased outflow of humor
122
Firstline Rx for glaucoma
Prostaglandin analogs - Latanoprost, Travoprost, Bimatoprost ("Bi, Lata, Travo" = "Bye, Later Trevor (Sweatman)"
123
Beta blockers for glaucoma
Timolol maleate, levobunolol, metipranolol, carteolol
124
Carbonic anhydrase inhibitors to treat glaucoma
Dorzolamide, Brinzolamide, Acetazolamide (zolamides)
125
Effects of PGF2a analogs
Acutely - blurred vision, stinging, itching
| Chronically - brown pigmentation of iris, eyelid, eyelashes
126
Drug that produces eye lash thickening
Bimatoprost
127
MOA of beta blockers in glaucoma
Inhibits production of aqueous humor
128
MOA of CA inhibitors in glaucoma
Less bicarb = less fluid transport = decreased IOP
129
Adverse effects of CA inhibitors
Allergic reaction to sulfonamides, agranulocytosis, aplastic anemia, SJS/TEN, fulminant hepatic necrosis, taste disturbances (early)
130
MOA of muscarinic agonists and AchE inhibitors for glaucoma
Increased aqueous humor flow
131
Contraindication of muscarinic agonists/AchE inhibitors
Not used when constriction not wanted
132
Contraindication of AchE inhibitors
Not used in closed angle glaucoma (increased IOP)
133
Muscarinic agonists/AChE inhibitors
Carbachol, pilocarpine, acetylcholine, achothiophate
134
MOA of sympathomimetics
Work on alpha receptors to increase outflow of aqueous humor
135
Sympathomimetic drugs
Dipivefrin, phenylephrine, apraclonidine, brimonidine, naphazoline, tetrahydrozoline
136
Rx for macular degeneration
Aflibercept, pegaptanib, ranibizumab, bevacizumab, verteporfin
137
VEGF inhibitors
Ranibizumab, bevacizumab (the mAbs), aflibercept (intercepts), pegaptanib (antagonist)...it kinda rhymes
138
Generates free radicals when activated by a laser
Verteporfin - obviously avoid direct sunlight
139
3 MOA of anti-epileptics
Inhibition of voltage gated sodium channels, activation of GABA-mediated inhibition, inhibition of voltage gated calcium channels
140
GABA enhancement
Vigabatrin and valproate will stall the metabolism of GABA; gabapentin works presynaptically to promote GABA release; BNZ and barbituates bind to GABA receptors itself promoting Cl- influx
141
Calcium channel blocker AEDs
Ethosuximide and zonisamideq
142
Problem with AEDs
Suicidal ideation
143
AEDs that inactivate Na channels (still depolarized/open but stabilizes inactive conformation)
Carbamazepine, phenytoin, topiramate, lamotrigine, valproate, zonisamide
144
Hepatically eliminated AEDs
Half-life decreases as there is more hepatic metabolism so upward adjustment of drugs necessary; all are hepatically eliminated except for Gabapentin and Pregabalin
145
Issues with topiramate and zonisamide
Weak CA inhibitors - decreased bicarb, formation of renal stones
146
Abrupt termination of AEDs
Don't do it - can cause status epilepticus
147
Pharmacokinetics of phenytoin
Zero ordered metabolism - half life varies with dose
148
Prodrug of phenytoin
Fosphenytoin
149
Adverse effects of phenytoin
CNS EFFECTS (Nystagmus, headaches, ataxia), GINGIVAL HYPERPLASIA, SJS/TEN/DRESS, HYPERTRICHOSIS/HIRSUTISM
150
Adverse effects of carbamazepine
Agranulocytosis/aplastic anemia, dizziness, drowsiness, ataxia, DERM EFFECTS RARE (but also has SJS/TEN), n/v, dry mouth
151
HLA-B 1502 screening
Worry about with Asians using carbamazepine, phenytoin, fosphenytoin, lamotrigine - can cause SJS/TEN
152
Adverse effects of valproic acid
Thrombocytopenia, derm effects rare, n/d
153
Other black box warnings
Felbamate - aplastic anemia, myelosuppression, hepatic dz; lamotrigine - serious rash (TEN/SJS)
154
AED most associated with teratogenicity
Valproate
155
Birth defects seen with phenytoin and carbamazepine
Fetal hydantoin syndrome - upturned nose, mild midfacial hypoplasia, long upper lip w/ thin vermilion border, distal digital hypoplasia
156
Regimen for partial seizures
Lamotrigine, carbamazepine, levetiracetam, oxcarbazepine
157
Regimen for primary generalized tonic-clonic seizures
Valproate, lamotrigine, levetiracetam
158
Regimen for absence seizures
Ethosuximide, valproate
159
Regimen for atypical absence, myoclonic, atonic seizures
Valproate, lamotrigine, levetiracetam (same as for primary generalized tonic-clonic)
160
Rx for status epilepticus
BNZ initially and followed with AED
161
Use of phenobarbital/benzodiazepine in seizures
Issues with dependence/withdrawal/tolerance, dose-related sedation, but good for rapid IV administration
162
Drug causes of irreversible hearing loss
Aminoglycosides, loop diuretics, chemo drugs
163
MOA of toxicity of aminoglycosides and cisplatin
AG - both caspase-dependent and independent; CP - only caspase dependent
164
MOA of diuretic toxicity
Same - block Na/K/2Cl transporter and upsets fluid balance in endolymph
165
Rx for vertigo
Meclizine, diphenhydramine, scopolamine, promethazine, diazepam (except for dizepam all work to block H1 and M1 receptors)
166
Adverse effects of H1 and M1 blockers
Produce dizziness/drowsiness; diphenhydramine and promethazine are CYP2D6 inhibitors
167
Centers involved in emesis
Lateral reticular formation, chemoreceptor trigger zone (in area postrema), solitary tract nucleus, cerebral cortex, vestibular center
168
Receptors in chemoreceptor trigger zone
5-HT, dopamine, opioids
169
Receptors in solitary tract nucleus
5-HT, enkephalin, histamine, Ach
170
Serotonin antagonists for antiemesis
Dolasetron, granisetron, ondansetron, palonosetron ("setrons")
171
Adverse effect of serotonin antagonists
CYP interactions, QT prolongation
172
D2 receptor antagonists for antiemesis
Prochlorperazine, chlorpromazine
173
Adverse effect of D2 receptor antagonists
Don't give with antipsychotics (CNS effects), QT prolongation, Torsades
174
Substance P/Neurokinin-1 receptor antagonist
Aprepitant, fosaprepitant (works on solitary tract)
175
Metabolism of Sub P/NK1 receptor antagonists
Hepatic - CYP3A4 inhibitors
176
Cannabinoid receptor agonists
Dronabinol, THC
177
Adverse effects of cannabinoid receptor agonists
Gets you HIGH, Schedule III (weakly reinforcing and slow onset - not too addictive)
178
Antiemetic regimen for chemotherapy
Serotonin antagonist, NK-1 antagonist, corticosteroid
