Pharm Flashcards
1
Q
MOA of Benzodiazepines
end in -lam or -pam
A
- binds the BZD receptor site on the alpha subunit of the GABA receptor
- there are 3 receptor subgroups: BZ1, 2, 3; BZDs act at all 3 and each results in a different depressive effect:
BZ 1 - sedation, amnesia
BZ 2 - anxiolysis
BZ 3 - myorelaxation, anticonvulsant
2
Q
MOA of Zolpidem [Ambien], Zaleplon, and Eszopiclone
A
Benzodiazepine receptor agonists; only bind the BZ-1 receptor subgroup
3
Q
MOA of Ramelteon
A
Melatonin receptor agonist; MT is a GPCR and stimulation induces sleep
4
Q
MOA of Doxepin, Mitazapine, Trazodone
A
- Antidepressants (doxepin is a TCA)
- sedation is a side effect when used for depression but for insomnia it achieves clinical utility
- caution with SI and psychosis
5
Q
Suvorexant
A
- Dual orexin receptor antagonist
- orexin mediates transition between sleep and wake
- CI’d in narcolepsy
- beware SI
6
Q
Major drug classes commonly used to treat insomnia
A
On-label for insomnia: - Benzodiazepines - BZD receptor agonists Most are used off-label: - melatonin agonist - Antidepressants - TCA - 1st gen antihistamines (diphenhydramine and doxylamine)
7
Q
MOA of barbiturates
A
binds/stimulates GABA receptor in the middle of the transmembrane portion
8
Q
Which is allowed in pregnancy: BZDs or BzRAs?
A
BzRAs - these are Category C
BZDs are Cat X
9
Q
Flumazenil
A
BZD and BzRA antagonist; given IV, can be antidote for OD but may cause withdrawal symptoms and/or seizures
10
Q
Sedative MOA of antihistamines
A
- cross BBB, act on histamine receptors in tuberomammillary nucleus; removing histaminergic tone reduces wakeful state
- don’t use in elderly
11
Q
Treatment of tension HA
A
NSAIDs
12
Q
Treatment of cluster HA
A
- triptans, or
- ergots plus “burst-and-taper” steroids
13
Q
Prophylaxis of migraine
A
Involves 1/more different drug classes: antiepileptic, antidepressants, beta-blockers. 1st line drugs: - amitriptyline - divalproex or valproic acid - propanolol or timolol - topiramate
14
Q
Acute treatment of migraine
A
- aimed at mitigating action of “inflammatory” mediators, which are NTs/NPs released that cause a sterile inflammatory response
- tx includes NSAIDs, ergots, triptans
15
Q
MOA of triptans
A
serotonin agonists:
- produce selective vasoconstriction via 5-HT1 B receptors,
and
- presynaptic inhibition of the trigeminovascular inflammatory response via 5-HT1 D/F receptors
Nasal spray for fast onset: sumatriptan and zolmitriptan.
More effective than ergots.
16
Q
MOA of NSAIDs for treating migraine
A
COX inhibition, decreased synthesis of inflammatory mediators
17
Q
MOA of ergots
A
- sm muscle contractions, like muscular arteries –> vasoconstriction
- too much (as in mold in middle ages) would constriction distal arteries and lead to a painful gangrenous death
- less effective than triptans; DON’T take within 24hrs of triptans because they both do vasoconstriction
18
Q
What to do for a pregnant woman with migraines?
A
Acetaminophen in 1st trimester.
If persists - opioids.
DON’T USE ERGOTS (also avoid during lactation).
19
Q
MOA of Amitriptyline
A
decreases reuptake of NE and 5HT; strong anticholinergic action
*off-label for migraine
20
Q
MOA of Divalproex or Valproic acid
A
Na channel blocker; increases GABA activity
21
Q
MOA of Topiramate
A
blocks Na and Glutamate; increases GABA activity
22
Q
MOA of Propranolol and Timolol
A
decreases arterial dilation, decreases NE-induced lipolysis
23
Q
Only FDA approved drug for migraine prophylaxis in kids
A
propranolol
24
Q
Why are brain tumors hard to treat?
A
- BBB
- astrocytes help protect tumor cells
- traditional resistance mechanisms
- brain tumors overexpress P-gp
25
Carmustine (BCNU): MOA
- DNA alkylator PLUS its breakdown product carbamylate proteins which inhibits DNA repair ("carmustine carbamylates")
- indicated for astro, medulloblastoma, brain mets, and malignant glioma
- parenteral; wafer for high grade gliomas
- lipophylic, non-ionized
26
Lamustine (CCNU): MOA
- DNA alkylator
- only indicated for malignant glioma
- oral
- lipophylic, non-ionized
27
Temozolamide: MOA
- oral pro-drug that is non-enzymatically activated to DNA methylating agent
- MGMT can undo the methylation, tumor cells can upregulate MGMT
- causes myelosuppression, N/V; teratogen
28
Local delivery techniques for chemo to brain tumors
- carmustine wafer
| - convection enhanced delivery (infusion catheter)
29
Chemo-fog: what is it and how is it produced
- chemo-related cognitive impairment: verbal/visual memory, attention, concentration, motor skills, multitasking
- may be 2/2 direct neurotoxic effects of the chemo, or mediated via cytokines (TNF ab is protective in animal models)
30
What treatments are there for brain tumors?
- steroids (edema)
- anticonvulsants (seizures)
- surgery, WBRT, radiosurgery; alone or in combination
31
Bacterial Meningitis treatment for a patient 1mo-50yo
Vancomycin + cefotaxime or ceftriaxone + ampicillin if listeria suspected
32
MOA, AEs of cephalosporins
MOA: inhibits cell wall synthesis (transpeptidation)
AEs: GI upset, diarrhea, vomiting, injection site pain/phlebitis, rash
33
MOA, AEs of vancomycin
MOA: inhibits cell was synthesis (transpeptidation and transglycosylation)
AEs: nephro-/oto-toxicity
34
Aspergillosis
Voriconazole IV
| Alt: Lipid AmpB
35
Blastomycosis, mild
Itraconazole PO
| Alt: Fluconazole
36
Blastomycosis, severe
Amp B IV then Itraconazole PO
37
Candidiasis
Fluconazole PO
| Alt: Azole, or AmpB, or fungin agent
38
Coccidiodiomycosis
Fluconazole IV/PO or Itraconazole PO
| Alt: AmpB
39
Cryptococcus
AmpB IV plus Flucytosine PO, then Fluconazole PO
40
Histoplasmosis
AmpB IV plus Itraconazole PO
| Alt: Fluconazole
41
Mucormycosis
AmpB
| Alt: Posaconazole
42
Sporotrichosis
AmpB IV and/or Itraconazole PO
| Alt: Itraconazole PO
43
What antifungals penetrate CSF?
Fluconazole, Voriconazole, and Flucytosine
44
Flucytosine - MOA, indication, AE
- converted to 5-FU by fungus, block thymidylate synthase, disrupts DNA synthesis
- cryptococcus
- not used alone b/c resistance develops rapidly
- AEs: bone marrow toxicity, derangement of liver enzymes (sometimes)
45
Nitrous oxide
Enhances inhibition:
1. potentiates 2-pore K channels
2. also potentiates GABAa, inwardly rectifying K channels, and glycine
3. inhibits NMDA, nAChR, 5HT, and KAR
- maintains CO2 reflex drive to breathe (no effect on protective reflexes)
- questionable damages; animal teratogen, spont. abortions?, neuronal damage in babies?; unclear
- second gas effect means this plus another inhaled agent is additive
- analgesic effects
- must administer O2 upon awakening 2/2 diffusional hypoxia
46
Halothane
- highest blood:gas partition coefficient, so it takes the longest time and most volume to build up in the blood
- highest % metabolized (hepatically), so it takes the longest to leave the body
- highest lipophilicity, so it gets bound by blood very well
- lowest MAC
- can cause halothane hepatitis
* rarely used anymore
47
Enflurane
- effects on muscle relaxation
| - pro-epileptic
48
Isoflurane
1. potentiates GABAa, 2-pore K channels, glycine, serotonin, and kainate
2. inhibits inwardly rectifying K channels and AMPAR's
- effects on muscle relaxation
49
Desflurane
1. potentiates GABAa
2. sorta potentiates muscarinic ACh
3. inhibits voltage-gated K channels and KARs
* much lower BGPC than halothane therefore go air-->blood-->brain (and back) much faster
50
Sevoflurane
1. potentiates GABAa and glycine
| * much lower BGPC than halothane therefore go air-->blood-->brain (and back) much faster
51
Meyer-Overton hypothesis
states that anesthetic activity is directly linked to lipid solubility - the more soluble, the greater anesthetic activity
(not entirely true)
52
Inhalational anesthetic agents basically have what 2 MOAs?
1. enhance inhibitory signaling (GABA, glycine)
| 2. inhibit excitatory signaling (glutamate, ACh, NMDARs, AMPARs)
53
Guedel stages of anesthesia
1. analgesia
2. delerium: inc. BP, mydriasis, inc. muscle tone; likely removing inhibitory paths
3. Plane 1: BP normal, miosis, muscle tone trending down
4. Plane 2: dec. BP, dec. muscle tone
5. Plane 3: HOTN, mydriasis again
6. Plane 4: HOTN, mydriasis
7. medullary paralysis/death
* with depth of unconsciousness comes depression of both CV (BP, HR, CO) and pulm (RR, TV) systems
54
Different anesthesia concentrations are required to produce
- action on different neuronal pathways (dose-dependent)
| - degree of absorption (higher concentration)
55
Blood-gas partition coefficient
- there's a difference in concentration of a gas in going from gas (air) to liquid (blood)
- partial pressure/tension will be maintained but absolute mass/volume of the anesthetic agent will change
56
MAC
- minimum alveolar concentration (volume %): measure of potency
- NO is highest, Halothane is lowest
57
Agents used for anesthesia induction
- thiopental, propofol, etomidate
| - enhance GABA/glycine, inhibit excitation
58
Propofol
- enhances GABA and glycine
- inhibit NMDARs (not as much as ketamine; blocks Glut binding) and nACh/mACh/AMPA
- anti-emetic; propofol infusion syndrome (met acidosis, rhabdomyolysis, arrhythmia, CF, RF)
59
Ketamine
- potentiates GABA and 5-HT
- inhibits NMDARs (physically occlude the channel) and mACHRs
- the only IV anesthetic that increases (instead of depresses) CBF O2 and ICP; is also cardiostimulatory
60
Benzodiazepines for anesthesia
- diazepam, lorazepam, and midazolam
- they potentiate GABAa by binding and altering the conformation, which increases potency of whatever GABA is present
- have the longest onset of action and half-lives
- very hard to OD (compared to barbs) since they have a ceiling of CNS depression (exception is in combo with alcohol/other drugs)
- no analgesia; anticonvulsant/amnesic
- antidote: flumazenil
61
Opioids for anesthesia
- morphine, meperidine, fentanyl (20min drug), remifentanil (ultra short-acting)
- controversial because they can cause bradycardia (vagus or direct on SA/AV nodes) and HOTN/HTN; also dose-dependent respiratory depression
62
4 goals of balanced anesthesia
1. relax muscles
2. relieve anxiety
3. prevent secretions
4. induce unconsciousness
63
Etomidate
- used for anesthesia induction
64
Barbiturates for anesthesia
- thiopental
- they potentiate GABAa by binding within the channel (on the left in the picture) and prolonging GABA binding, which increases efficacy
- quintessential CYP inducers -- can exacerbate porphyria
65
Neurolept-Analgesia
the use of a drug combination that produces pain relief and provides a state of indifference
66
Malignant hyperthermia
- MOA: IC Ca release from SR which stimulates metabolism and generates heat; muscle rigidity and tachycardia/tachypnea
Culprits:
- Succinylcholine (NM blocker)
- all volatile anesthetic agents (desflurane, isoflurane)
Treatment: Dantrolene (returns Ca to SR), hyperventilate with O2, cool core temp, correct hyperK and acidosis
67
MOA of Local anesthetics
- block neuronal V-gated Na channels from the INSIDE
- must be lipophilic to pass into membrane
- differential blockade of nerve fibers in a bundle
68
Nerve type order of sensitivity to local anesthetic application
small > large; non-myelin > myelinated
1. B fibers
2. C fibers (SNS and dorsal root) and Adelta fibers
3. Agamma fibers
4. Abeta fibers
5. Aalpha fibers
69
What conditions do local anesthetics prefer?
1. When the nerve is firing: the agent can only reach the internal binding site when the channel is open or when it's inactivated
2. Basic: most are weak bases (pKa~8), so more of the agent will be non-ionized in an environment with pH>8; within the nerve the pH is 7, so the agent is recharged which also happens to be better for binding; if the pH is lower (like in area of inflammation) it'd be a weaker, less durable nerve block because not as much gets into the cell
70
How is the LA structure represented in the name?
- if word leading up to “-caine” contains an i, it's an amide (which also contains an i)
- if it does not contain an i, it's an ester
*Exception: articaine contains both
Amide vs. ester is the linker btw the amine and aromatic appendage comprising the local anesthetic
71
Phentolamine
- alpha adrenergic blocker
| - applied following local anesthetic to reverse VC and increase blood flow to the region, hasten removal of anesthetic
72
Local Anesthetics with these duration of action:
- short-acting
- intermediate-acting
- long-acting
```
- short-acting (least potent):
procaine
chloroprocaine
- intermediate-acting: PALM
prilocaine, articaine,
lidocaine, mepivacaine
- long-acting (more potent): BRT
bupivacaine
ropivacaine
tetracaine
```
73
Acquired methemoglobinemia
- excess accumulation of ferric form of Hgb that can't release O2
- associated with prilocaine, and to a lesser extent benzocaine
- will see blue skin, HA, SOB, lack of energy
- treat with ascorbic acid or methylene blue
74
Topical local anesthetics
- benzocaine
- dyclonine
- dibucaine (ONLY skin)
- pramoxine (ONLY skin)
75
EMLA and LET
```
EMLA = "eutectic mixture of local anesthetics"; lidocaine + prilocaine used before cannulation or skin graft harvesting
LET = lidocaine-epi-tetracaine; liquid application for stitches that provides both analgesia and VC
Lidocaine-oxymetazoline = used for reducing vessels, used by otolaryngologists
```
76
What's the typical pre-operative drug sequence, and what's the role of each drug?
1. Psych prep - relieve anxiety (BZD*, phenothiazines, antihistamines 1st gen), sedation, amnesia, +/- analgesia (NSAID/opiate)
2. Reduce ANS - dry secretions, dec. gastric volume, inc. gastric pH; all to prevent aspiration
3. Prophylaxis - against allergic rxn
Then off to surgery.
*which BZD chosen depends on desired duration of action.
77
H1 vs. H2 antagonist CNS effects
H1 - Diphenhydramine; Promethazine; Hydroxyxine
- sedative, cholinergic antagonism (drying secretions), anti-emetic
H2 - Cimetidine; Ranitidine
- only cimetidine has some sedative effect
- no other CNS effects
78
Drugs (and MOA) for anti-emesis
- they inhibit the chemo trigger zone (operates with ACh, 5HT, DA, Hist, SP, opioids), or suppress emetic signals from GI tract (via vagus n.)
1. Ondansetron - 5HT3 receptor antagonist
2. Scopolamine - muscarinic antagonist
3. Metoclopramide - D2 receptor antagonist
79
Roles of drugs employed in rapid sequence intubation
1. oxygenation
2. avoid inc. ICP: lidocaine, fentanyl, vecuronium
3. sedative + short-acting NMB (usually succinylcholine)
80
Post-op drugs used in respiratory and CV support
Dopamine, Phenylephrine, Nitroprusside, Trimethaphan
81
What are the pharmacologic reasons for delayed awakening from anesthesia?
- MCC is residual anesthetics and ancillary drugs
| - reversal aimed at most likely agent: usually narcotic or BZD
82
Gastrokinetic agent
- Metoclopramide to accelerate gastric emptying (compromised by antagonism from anti-ACh and narcotics)
- can also use water to stimulate the gastric stretch receptors
83
Atropine, Scopolamine, and Glycopyrrolate
These are anticholinergics that block muscarinic stimulation arising from Anti-AChE's; used to mitigate reflex bradycardia, block vagal activity, and dry secretions:
- glycopyrrolate has the most anti-sialogogue effect
- atropine has the strongest vagolytic effect
- scopolamine has the strongest sedative effect
- atropine and scopolamine can cause delirium and cognitive decline
84
Drugs used for sedation
BZDs and 1st gen H1 antagonists:
- diazepam, lorazepam
- promethazine, hydroxyzine, diphenhydramine
85
Drugs used for amnesia
- BZDs (also used for sedation and anxiety)
86
Drugs used for anxiolysis
- BZDs (also used for sedation and amnesia)
- phenothiazines (anti-DA/ACh/Hist effects)
- 1st gen antihistamines
87
Anaphylactic reaction - precipitating drugs?
epinephrine, aminophylline, hydrocortisone, methylprednisolone, barbiturates, etomidate, local anesthetics, NMBs, and narcotics
88
What are the symptoms of an anaphylactic reaction, and what to do about it? (prevention and treatment)
- Sx: respiratory depression and bronchospasm, CV issues, and cutaneous urticaria/flushing/edema
- Prevention: H1/H2 receptor blockers (won't prevent histamine release)
- Acute Tx: stop drug/anesthesia, give O2, give epi, expand intravascular volume for CV support
89
Potential errors of Drug Administration
- wrong drug, wrong dose, wrong solution
- incompatible combination
- wrong site
- wrong rate of administration
90
Muscarinic antagonists for ocular administration: Mnemonic
```
ACH anTagonistS
A = atropine
C = cyclopentolate
H = homotropine
T = tropicamide
S = scopolamine
*These drugs produce cycloplegia and mydriasis; used to treat inflammation and for eye exam; CI'd in glaucoma/sulfa allergy
```
91
Sympathomimetics for ocular administration (suffixes)
- Ephrine: dipivefrin and phenylephrine
- onidine: Apraclonidine, brimonidine
- zoline: Naphazoline, Tetrahydrozoline
--> stimulate the alpha-2 receptors in the ciliary body to reduce aqueous production; stimulate a1s in vessels to vasoconstriction and reduce diffusion
92
Muscarinic agonists for ocular administration: Mnemonic
```
CAP:
Carbachol
ACh
Pilocarpine
--> constrict pupil, open TM for outflow
```
93
Timolol
Beta-adrenergic antagonist; blocks the production of aqueous humor by ciliary body
94
Levobunolol
Beta-adrenergic antagonist; blocks the production of aqueous humor by ciliary body
95
Metipranolol
Beta-adrenergic antagonist; blocks the production of aqueous humor by ciliary body
96
Carteolol
Beta-adrenergic antagonist; blocks the production of aqueous humor by ciliary body
97
Carbachol
Muscarinic agonist; constricts the pupil to open the TM for aqueous outflow
98
Pilocarpine
Muscarinic agonist; constricts the pupil to open the TM for aqueous outflow
99
Dipivefrin
Sympathomimetic; stimulates alpha 2 in ciliary body to reduce aqueous production, vasoconstricts (a1) vessels to ciliary body to reduce diffusion
100
Phenylephrine
Sympathomimetic; stimulates alpha 2 in ciliary body to reduce aqueous production, vasoconstricts (a1) to reduce diffusion
101
Apraclonidine
Sympathomimetic; stimulates alpha 2 in ciliary body to reduce aqueous production
*This is pretty selective for a2
102
Brimonidine
Sympathomimetic; stimulates alpha 2 in ciliary body to reduce aqueous production, vasoconstricts (a1) to reduce diffusion
103
Naphazoline
Sympathomimetic; stimulates alpha 2 in ciliary body to reduce aqueous production, vasoconstricts (a1) to reduce diffusion
104
Tetrahydrozoline
Sympathomimetic; stimulates alpha 2 in ciliary body to reduce aqueous production, vasoconstricts (a1) to reduce diffusion
105
Aflibercept
decoy receptor for VEGF in the tx of macular degeneration
106
Pegaptanib
VEGF antagonist; tx for macular degeneration
107
Ranibizumab
mab for VEGF for macular degeneration
108
Bevacizumab
mab for VEGF for macular degeneration
109
Verteporfin
- IV agent that (when activated by laser) generates free radicals which cause vessel damage and occlusion of choroidal neovascularization
- tx for macular degeneration
- AEs: temp photosensitization
110
Where are SNS receptors in the eye?
- -> a1: dilator smooth (aka iris radial) muscle, oriented radially, contracts to cause mydriasis
- -> a1: lacrimal gland secretions
- -> a2: SNS autoreceptor in ciliary epithelium; stimulation is sympatholytic
- -> B2: stimulate ciliary epithelium to produce aq. humor
- -> B2: ciliary muscle relaxation
111
Where are PSNS receptors in the eye?
- -> M3: pupillary sphincter smooth muscle, oriented circularly, contracts to cause miosis
- -> M2/3: stimulate lacrimal secretions
- -> M3: ciliary muscle accommodation
112
Ciliary body
2 functions:
1. secretes aqueous humor by epithelial bilayer (stimulated by B2, inhibited by a2 SNS)
2. change shape of the lens by ciliary muscle (accom. by M3 PSNS; relaxation by B2 SNS)
113
How do eyedrops cause systemic toxicity?
- absorbed via conjunctiva, sclera in the eye
- absorbed via ocular blood vessels
- after draining from the eye to the nasopharynx they can be absorbed through mucosa, or drip down to GI tract
114
What drug classes produce miosis/loss of accommodation?
| Produce mydriasis?
- miosis: PSNS mimics and opioids*
- mydriasis: SNS mimics
* opioids remove the inhibition of EW nucleus and allow it to dominate tone
115
How to treat open and closed angle glaucoma?
Open: decrease aq. humor production; inc. outflow; use PGs, sympathomimetics, or miotics
Closed: surgical iridectomy; short-term meds to dec. IOP prior to surgery
116
What drugs are used to treat glaucoma?
1st line: PG(F2) analogs (thought to facilitate outflow; can cause iris hyperpigmentation and hypotrichosis)
Then:
- beta-blockers (recall B2 stimulate aq humor prod)
- carbonic anhydrase inhibitors: -zolamides
- sympathomimetics: stimulation of a2 auto-receptors inhibits SNS action, a1 stimulation vasoconstricts
117
Carbonic anhydrase inhibitors
"-zolamide"
- reduce bicarb secretion and fluid transport, thereby dec. IOP
- taste disturbance
- sulfa drug - allergies
118
Macular degeneration treatment
- they all have to interrupt VEGF-mediated vascular growth
- injected into vitreous humor
- beware of arterial thromboembolic events (ATEs)
119
Carbamazepine
- inhibits Na channels (from intracellular side)
- AEs: CNS sx like dizziness, drowsy, ataxia, blurred vision; routine monitoring for agranulocytosis or aplastic anemia; rare derm effects (rash/DRESS; SJS/TEN in asians)
- teratogen
120
Ethosuximide
- inhibits T-type Ca channels to reduce pacemaker currents
121
Gabapentin
- acts presynaptically to enhance GABA release
| - inhibits Ca channel subunit
122
Lamotrigine
- inhibits Na channels (from intracellular side)
- serious rash - SJS/TEN
- teratogen
123
Phenytoin
- inhibits Na channels (from intracellular side)
- zero-order kinetics, so half-life varies with dose
- gingival hyperplasia (>15%)
- hypertrichosis, hirsutism, SJS/TEN are rare
- CNS effect MC are nystagmus, HA, ataxia, incoordination
- teratogen
124
Valproate
- inhibits Na channels (from intracellular side)
- inhibit Ca channels to reduce pacemaker currents
- enhances GABA activity (pre-synaptically? vs. in the cleft?)
- CNS effects, thrombocytopenia, rare derm effects (SJS/TEN/DRESS)
- worst teratogen
125
Clonazepam
GABA agonist (BZD)
126
Felbamate
- enhances GABA
- dec. NMDA activity
- **Aplastic anemia, myelosuppression, hepatic disease
127
Pregabalin
- inhibits Ca channels
128
Topiramate
- inhibits Na channels (from intracellular side)
- decreases Glut activity
- inc. GABA; inc. K current
- weak CA inh, so monitor serum bicarb and beware of kidney stones
129
Zonisamide
- inhibits Na channels (from intracellular side)
- inhibits T-type Ca channels
- accumulates in RBCs
- weak CA inh, so monitor serum bicarb and beware of kidney stones
130
Lacosamide
- inhibits Na channels (from intracellular side)
131
Oxcarbazepine
- inhibits Na channels (from intracellular side)
| - possibly inc. K current and inhibits Ca channels
132
ADME of AEDs
- most are PO, may be slow-release
- limited protein binding - except phenytoin and valproate
- hepatic metabolism - exception: Gabapentin (no metabolism)
- may interact with CYPs: esp. Carbamazepine and Phenytoin, so dose adjustment is needed over time (monitor serum with Carb, Ethosux, Gabapentin, Pheny, Valp)
- urinary elimination
- long half-lives
133
First line drugs for primary generalized tonic-clonic seizures
Valproate
Lamotrigine
Keppra
134
First line drugs for Absence seizures
Ethosuximide
| Valproate
135
First line drugs for atypical Absence, Myoclonic, Atonic seizures
Valproate
Lamotrigine
Keppra
136
First line drugs for Status Epilepticus
```
BZDs (IV lorazepam, IM midazolam, PR diazepam) - can rapidly terminate SE, but the have short half life so must be followed by IV AED:
Valproate
Phenytoin
Keppra
Phenobarbital
```
137
Ototoxic drugs
Aminoglycosides - usually permanent
Cisplatin - irreversible
Loop diuretics - can be irreversible
138
What is the etiology of drug-induced vertigo?
- direct: affect hair cells
| - indirect: changes BP (pre-syncope dizziness)
139
What is the mechanism of ototoxicity for those drugs acting through caspase-dependent mechanisms?
- AG enters outer hair cell, forms AG-Fe complex, makes ROS which activate JNK
- Cisplatin enters outer hair cell and forms monohydrate complex, activates NOX3, ROS which activate JNK
JNK transcribes genes which trigger cytC release; apoptosis
140
What is the mechanism of ototoxicity for loop diuretics?
- inhibit Na/K/2Cl transporter
| - upsets endolymph which results in edema and loss of function
141
MOA of short-term tx of vertigo
- act primarily on the H1 and M1 receptors; block them
- meclizine hydrochloride
- diphenhydramine
- scopolamine (TD patch) - lasts 72hr
- promethazine - BBW for injection
- diazepam - for nausea from higher cortical centers (fear, emotion, anticipation, etc)
142
Drugs to treat emesis
1. Setrons: Serotonin antagonists; act in CTZ and NTS
2. -axines: D2R antagonists
3. -prepitants: SP/NK1 receptor antagonists
4. Cannabinoid agonist
143
Prochlorperazine
- D2R at CTZ for anti-emesis
- also have anti-hist/ACh activities
- all-purpose, but NOT for CINV
144
Chlorpromazine
- D2R at CTZ for anti-emesis
- also have anti-hist/ACh activities
- all-purpose, but NOT for CINV
145
MOA of Aprepitant and Fosaprepitant
- substance P (SP) and neurokinin-1 (NK1) receptor antagonists
- action at Nucleus Tractus Solitarius
- fosaprepitant is a pro-drug
- CYP3A4
146
Dronabinol
- agonist at the cannabinoid receptor
- GPCR dec. activity in medullary vomiting center and NTS; opposes 5HT mediated vagal stimulation
- stimulates appetite in lateral hypothalamus
147
Prophylaxis of chemo-induced N/V (CINV)
MC: 5HT antagonist + NK1 antagonist + corticosteroid
148
CYP activators among the anti-emesis drugs?
3A4: SP/NK1 antagonist
2D6: H1/M1 blockers
CYPs (in general): 5HT
