Pharm Flashcards
(100 cards)
1
Q
Levodopa (L-DOPA) (Dopar)
A
- class: dopamine precursor
- crosses BBB→DA; improves nigrostriatal functioning
- +carbidopa= first-line treatment for Parkinson’s (unless patient is young; delay use as long as possible)
- side effects: dyskinesias; hypotension, nausea, anxiety, fatigue; psychoses if dosed too high
- MAO-A inhibitors contraindicated (MAO-Bonly hits DA)
2
Q
Carbidopa (Lodosyn)
A
- class: aromatic AA decarboxylase inhibitor
- inhibits peripheral conversion of L-DOPA to dopamine; does not cross BBB
- given with Levadopa to lower side effects
- treats parkinson’s
- side effects: dyskinesias, on-off phenomenon
- MAO-A inhibitors contraindicated (MAO-B only hits DA)
3
Q
Buproprion (Wellbutrin)
A
- class: norepi-dopamine reuptake inhibitor (NDRI)
- blocks DAT→ increased DA synthesis
- treats: parkinson’s, SAD, good for patients with addictive behavior (maintain nicotine abstinence in quitting smokers);
- side effects due to increased NE: insomnia, anxiety, agitation, nausea, dry mouth, sweating, palpitations; mild increase in BP
- less pronounced DA side effects because it’s less aggressive in CNS and not 100% agonist
- lowers seizure threshold
4
Q
Modafinil
Armodafinil
A
- class: stimulants
- increases histamine activity in tuberomammilary nucleus; may block DAT
- wake promoting; treats narcolepsy, apnea
- side effects: similar to but less severe than amphetamines; less addictive than the phetamines
5
Q
Selegiline (Eldepryl)
Rasagiline (Azilect)
A
- class: MAO-B inhibitor (more relevant for DA)
- prevents breakdown of DA
- treats: early Parkinson’s
- side effects: hypotension (due to NE→ a1), dizziness, insomnia, weight gain; N/V
- selegiline: patch for depression too (EMSAM)
6
Q
Tranylcypromine (Parnate)
Isocarboxazid (Marplan)
Phenelzine (Nardil)
A
- class: MAOI
- irreversibly inhibits MAO-A and MAO-B
- treats depression
- side effects: hypotension, dizziness, insomnia, weight gain
- HTN crisis with tyramine rich foods
- serotonin syndrome (MAOI + SSRI)
7
Q
Entacapone (Comtan)
Tolcapone (Tasmar)
A
- class: COMT inhibitor
- prevents breakdown of DA
- treats parkinson’s (good add on for other drugs)
- side effects: nausea, fatigue; dopamine side effects
- entacapone: short acting (2 hours)
- tolcapone: use only if entacapone fails, risk of liver failure
8
Q
Bromocriptine (Parlodel)
Pramipexole (Mirapex)
Ropinerole (Requip)
Apomorphine (Apokyn)
A
- class: D2 receptor agonist
- increases DA activity (phasic)
- treats: mild/early parkinson’s, restless leg syndrome
- side effects: mania, nausea, dizziness, fatigue; peripheral DA-like effects
- less effective with motor symptoms of PD
- bromocriptine: treats hyperprolactinemia; must be titrated slowly due to hypotension
9
Q
Aripiprazole (Abilify)
A
- class: D2 & D3 receptor (partial) agonist
- increases DA activity (tonic)
- treats: schizophrenia; depression
- side effects: less side effects than other DA
10
Q
Amantadine (Symmetrel)
A
- class: antiviral
- ? stimulates D2 receptors, blocks DAT; leads to DA release from terminal vesicles
- treats: mild parkinson’s (2nd-line; not used much); influenza
- side effects: nausea, dizziness, psychosis, insomnia, seizures
- contraindicated in elderly with dementia (anticholinergic effects)
11
Q
Reserpine
Tetrabenazine
A
- class: synapse depleter
- blocks VMAT (no release of monoamines into synapses)
- reserpine: treats HTN
- tetrabenazine: treats huntington’s
- side effects: depression (lowers NA and DA)
12
Q
Benztropine (Cogentin)
Trihexiphenidyl (Artane)
Diphenhydramine
A
- benztropine, trihexiphenidyl: anticholinergics; contraindicated in parkinson’s dementia; abrupt discontinuation exacerbates symptoms
- diphenhydramine: antihistamine
- muscarinic receptor antagonist (inhibiting cholinergic tone in basal ganglia improves DA tone in nigrostriatal pathway)
- treats: early parkinson’s, reduces EPS
- side effects: dry mouth, blurred vision, racing heart, constipation, confusion, delirium, hallucinations
13
Q
First-generation antipsychotics (Low Potency)
A
- Chlorpromazine, thioridazine
- non-selective D2 receptor antagonism (also H1, anticholinergic, and a1 antagonism)
- treats psychosis (schizophrenia)
- side effects: EPS; fatigue and weight gain (H1 antagonism); anticholinergic effects; orthostasis (alpha1 antagonism)
- tardive dyskinesia with chronic use
- little effect on negative symptoms
14
Q
First-generation antipsychotics (High Potency)
A
- Fluphenazine, thiothixine, haloperidol
- non-selective D2 receptor antagonism
- treats: psychosis (schizophrenia); movement disorder in Huntingtons
- side effects: EPS; NMS (skeletal muscles microcontract→hyperthermia, muscle rigidity)
- tardive dyskinesia with chronic use
- little effect on negative symptoms
15
Q
Second-Generation Antipsychotic (Low potency)
A
- ‘pines: olanzapine, quetiapine, asenapine
- D2 receptor antagonist, 5HT2a receptor antagonist
- less EPS but more sedating
- treats: psychosis, mania, agression
- side effects: suicide risk in ages <25; metabolic syndrome; TD/EPS; stroke in dementia patients
16
Q
Clozapine (Clozaril)
A
- class: second generation antipsychotic (low potency)
- D2 (& D1, D4) receptor antagonist; 5HT2a receptor antagonist
- treats refractory shizophrenia (use if all else fails)
- side effects: similar to other “pines”; agranulocytosis, most metabolic risk of all antipsychotics, but little EPS/TD; must monitor WBC
17
Q
Second-Generation Antipsychotics (High Potency)
A
- ‘dones: risperidone, ziprazidone, paliperidone, iloperidone, lurasidone
- D2 receptor antagonist; but various other receptor agonism/antagonism
- higher potency, more EPS
- treats: psychosis, mania, agression
- side effects: suicide risk in ages <25; metabolic syndrome; TD/EPS; stroke in dementia patient, fewer metabolic complications than ‘pines
18
Q
Pilocarpine HCl (Salagen)
A
- class: direct muscarinic agonist
- pupillary constriction, increased aqueous outflow
- treats: glaucoma (open angle and acute closed angle); cataract surgery
- used infrequently due to side effects (decreased vision when patient has cataracts due to miosis, headache; SLUDGE)
19
Q
AChEI
A
- Edrophonium: short-acting, fast onset; used to diagnose myasthenia gravis
- Echothiophate: irreversible, long acting; treats glaucoma
- Neostigmine: MC used for reversal of NMB; more complete antagonism than edrophonium
- Pyridostigmine: Longer acting than neostigmine, edrophonium
- side effects: SLUDGE
20
Q
Atropine
Scopolamine
A
- class: antimuscarinic
- pupillary dilatation; paralysis of ciliary body
- treats: improve discomfort during active eye inflammation (ueveitis)
- side effects: ataxia, nystagmus, restlessness, mental confusion, hallucination, violent and aggressive behavior, insomnia, photophobia, urinary retention
- atropine: v. long acting so not used unless inflammation is severe
21
Q
Tropicamide (Mydriacyl)
A
- class: antimuscarinic
- pupillary dilatation; paralysis of ciliary body
- treats: MC used cycloplegia for eye exams
- side effects: ataxia, nystagmus, restlessness, mental confusion, hallucination, violent and aggressive behavior, insomnia, photophobia, urinary retention
22
Q
Epinephrine (Epinal)
A
- class: direct adrenergic agonist
- dilation of episcleral vessels→ increased aqueous outflow and a1 pupillary dilation
- side effects: extrasystoles, palpitation, hypertension, myocardial infarction, trembling, paleness, sweating
23
Q
Hydroxyamphetamine (Paredrine)
A
- class: indirect adrenergic agonist
- mechanism: release NE
- separates 1st and 2nd from 3rd order neuron dysfunction in Horner’s syndrome (positive dilation means 1st or 2nd order)
24
Q
Cocaine
A
- class: indirect adrenergic agonist
- blocks reuptake of DA, NE, 5HT
- use to confirm diagnosis of Horner’s
- topical anesthetic, combined vasoconstrictor and local anesthetic
- side effects: sympathetic effects; paranoia, aggression
- rapidly hydrolyzed by plasma cholinesterase
25
Phenylephrine (Neo-Synephrine)
* class: direct α1-agonist
* dilate pupil for eye exam and cataract surgery
* side effects: extrasystoles, palpitation, HTN, myocardial infarction, trembling, paleness, sweating
* caution in elderly patients: at 10% can cause cardiac side effects
26
Brimondine tartrate (Alphagan)
* class: direct α2-agonist
* suppresses aqueous humor production through cAMP in non-pigmented ciliary epithelium
* **primary agent for treatment of glaucoma**
* side effects: may cause follicular conjunctivitis; use with MAOi can cause fatigue/drowsiness
27
β-blockers used for treatment of glaucoma
* **Timolol:** β-blocker; contraindicated in CHF, asthma
* **Levobunolol:** β2-blocker
* **Betaxolol:** β1-blocker; few side effects
* mechanism: reduce intraocular pressure by reducing aqueous production at ciliary process
* **2nd line treatment of glaucoma**
* side effects: bradycardia, hypotension, syncope, CHF, bronchospasm, sexual dysfunction, hyperkalemia
28
Nifedipine (Procardia)
* class: Ca-channel blocker
* mechanism: increases ocular perfusion at nervehead
* treat low-tension glaucoma
* not widely used
29
carbonic anhydrase inhibitors
* interferes with active transport of Na through Na-K-ATPase pump→reduced aqueous production
* **dorzolamide, brinzolamide:** 2nd line glaucoma therapy
* side effects: red eyes, lid allergies
* **acetazolamide:** oral agent for advanced glaucoma and with cataract surgery (only if topical therapy fails)
* side effects: paresthesia, fatigue, drowsiness, depression, diarrhea, met. acidosis, electrolyte changes
30
MAOIs
* **tranylcypromine, p****henelzine**
* irreversibly inhibit MAOa,b
* treats: **depression,** anxiety, PTSD, chronic pain, enuresis, bulimia, alcoholism
* important side effects: agitation (rare), delerium→ seizures; **HTN crisis with tyramine-rich foods; serotonin syndrome (MAOI + SSRI)**
* other side effects: anticholinergic, orthostatic hypotension, sexual dysfunction, weight gain, sedation
31
Tricyclics
* **Desipramine**
* **Imipramine:** active metabolite desipramine
* **Amitriptyline (Elavil):** active metabolite nortriptyline; high side effects
* **Nortriptyline**
* **block reuptake of NE or 5-HT at varying potencies/ selectivity; also variably block muscarinic, a-adrenergic, DA, and histamine receptors**
* treats: depression, anxiety, PTSD, chronic pain, enuresis, bulimia, alcoholism
* **not very safe; rarely used**
* side effects: sympathomimetic (cardiac arrhythmias and conduction defects, especially at OD), antimuscarinic, orthostatic hypotension, sedation (additive with alcohol), seizures
32
SSRIs
* **Fluoxetine (Prozac):** model drug; potent P450 inhibitor
* **Paroxetine:** more selective for 5HT than fluoxetine; potent P450 inhibitor
* **Sertraline, escitalopram, citalopram**
* mechanism: inhibit reuptake of 5-HT (and NE to lesser extent)
* treats: depression, anxiety, PTSD, chronic pain, enuresis, bulimia, alcoholism; pre-menstrual dystrophic disorder
* fewer side effects than tricylics, mostly nausea, decreased sexual function
* **Serotonin syndrome (with MAOIs)**
33
SNRIs
* **Duloxetine (Cymbalta)**
* **Venlafaxine (Effexor):** low risk of side effects
* mechanism: inhibits reuptake of 5-HT and NE
* treats: depression, anxiety, PTSD, chronic pain, enuresis, bulimia, alcoholism
34
Mirtazapine
* 5HT2a antagonist; also inhibit 5HT reuptake
* treats: depression, anxiety, PTSD, chronic pain, enuresis, bulimia, alcoholism
35
Lithium
* mechanism unknown; **Li depletes 2nd messengers** IP3 and DAG, important in a-adrenergic and muscarinic-cholinergic transmission
* treats: **anti-manic/mood-stabilizing (bipolar); LT cluster headache prevention**
* side effects: drowsiness, weight gain, tremor, polydipsia, polyuria; high levels→neurotoxicity, cardiac toxicity, renal dysfunction
36
Nalmefene (Revex)
* class: opiod antagonist
* may produce a prolonged withdrawal state (N/V, piloerection, yawning)
37
N-acetylcysteine (Mucomyst)
* class: antioxidant
* mechanism: supplies sulfhydryl groups to glutathione; improves microcirculation, anti-inflammatory effect
* treats: acetaminophen overdose
38
Fomepizole (Antizol)
* mechanism: blocks alcohol dehydrogenase
* treats: methanol & ethylene glycol poisoning
* $$$$
39
Schedule I Hallucinogens
* 5HT2A receptor agonist on Raphe cell body→ inhibition of Raphe Nuclei firing→ increased sensory input; partial dopamine agonist
* **LSD:** model hallucinogen; limited studies in psychoanalysis, alcoholism, autistic children, and terminal cancer patients; oxidized in liver
* bad trips (anxiety and panic attacks), flashbacks; no overdoses, birth defects, or chronic psychoses linked to LSD
* **Mescaline**
* **Psilocybin**
40
Phencyclidine (PCP)
* class: dissociative anesthetic
* mechanism: antagonist of ion channel associated with NDMA receptor; agonist at mu opioid receptors
* side effects: violent behavior, coma, seizures, arrest; inexplicable psychoses; dissociation, confusion, ataxia, marked nystagmus
* Long half-life due to being highly lipid soluble and having active metabolites
41
Amphetamines (Benzadrine)
Dextroamphetamine (Dexedrine)
Methamphetamine (Desoxyn)
Methylphenidate (Ritalin)
* class: stimulants
* mechanism: Blocks DAT, also increases VMAT2 (indirect sympathomimetic→ release biologic amines from nerve terminals in periphery and in CNS, esp. dopamine most important)
* treats: narcolepsy, ADHD
* side effects: vasospasm leading to possible stroke or MI, arrhythmia, weight loss (anorectic effect); tremor, anxiety, irritability, confusion, possible paranoia
42
THC
* mechanism: hits cannabinoid receptors (CB1, CB2: GPCRs)
* **Marijuana:** cannabinoid, schedule I drug; antiemetic, antinausea, appetite stimulate for chemotherapy and AIDS; analgesic for neuropathic pain
* potential use for glaucoma, asthma, anxiolytic, migraine, and MS
* side effects: vasodilation→ tachycardia, dilation of conjunctival vessels, bronchodilation, decreased intraocular pressure, hunger; may impair reproductive function in adolescents; heavy use may impair development of very young users; possible respiratory damage due to tar
* Active ingredient is delta-9-THC (metabolized by P450); highly lipid soluble
* **Anandamide:** endogenous cannabinoid
* **Dronabinol:** synthetic THC; schedule III drug; antiemetic, antinausea, appetite stimulate for chemotherapy and AIDS patients
* **Nabilone:** synthetic THC; schedule II drug; treatment-resistant N/V weight loss and anorexia in AIDS patients; less psychoactive side effects than marijuana
43
Morphine
* class: opioid; mu-opioid receptor agonist
* treats: **severe analgesia (step 3)**
* side effects: miosis, constipation, respiratory depression; dry mouth, N/V, sedation, sweating; dreams, dysphoria, delerium, myoclonus, seizures, pruritis, urticaria, urinary incontinence
* 2 major active metabolites: M6 (more potent/active), M3 (little affinity); intraspinal administration possible
44
Codeine
* class: opioid; mu-opioid receptor agonist (low receptor affinity)
* CYP2D6 polymorphisms: 10% of caucasians can't convert to morphine (can still experience side effects)
* treats: **moderate analgesia (step 2), antitussive**
* side effects: miosis, constipation, respiratory depression; dry mouth, N/V
45
Tramadol (Ultram)
* class: opioid; mu-opioid receptor agonist (weak); some NE/5HT uptake inhibition (leading to analgesia)
* treats: **moderate analgesia (step 2)**
* side effects: miosis, constipation, respiratory depression; dry mouth, N/V
46
Fentanyl (Duragesic)
* class: opioid; mu-opioid receptor agonist (strong); highly lipid-soluble
* treats: **severe analgesia (step 3) after identification of dose level via other opiod (e.g., morphine)**
* **IV, transdermal;** do not change dose more than 1/week (long half-life); intraspinal administration possible
* side effects: miosis, constipation, respiratory depression; dry mouth, N/V
47
opioids
* Codeine: step 2
* Tramadol: step 2
* Oxycodone: step 3 (+acetominophen=2)Morphine: step 3
* Fentanyl: step 3
* Methadone: step 3
* Diphenoxylate
* Loperamide
48
Methadone (Methadose)
* class: opioid
* mu-opioid receptor agonist
* treats: chronic, severe pain; **treatment of heroin and opiod addicts**
* **90% bound to plasma protein,** accumulates in tissues (extended duration of action); do not change dose more than 1/week **(long half-life)**
* side effects: miosis, constipation, respiratory depression; dry mouth, N/V sedation, sweating; dreams, dysphoria, delerium, myoclonus, seizures, pruritis, urticaria, urinary incontinence
49
Oxycodone
* class: opioid
* mu-opioid receptor agonist
* treats: moderate to severe analgesia
* oxycontin is extended release
* side effects: miosis, constipation, respiratory depression; dry mouth, N/V sedation, sweating; dreams, dysphoria, delerium, myoclonus, seizures, pruritis, urticaria, urinary incontinence
50
Loperamide (Imodium)
Diphenoxylate (Lomotil)
* class: opioid
* slows peristalsis via opioid receptors in intestine, and possibly decreased GI secretion
* treats diarrhea
* side effects: miosis, constipation, respiratory depression; dry mouth, N/V sedation, sweating; dreams, dysphoria, delerium, myoclonus, seizures, pruritis, urticaria, urinary incontinence
51
Naloxone (Narcan)
* class: opioid antagonist
* **competitive mu-, delta-, and kappa-opioid receptor antagonist**
* **treats acute opioid toxicity** (depressed RR best predicts reponse)
* side effects: **can precipitate withdrawal** (flu-like symptoms of N/V/D, piloerection, yawning, irritability)
* continuous parenteral infusion, as lasts only 15-30 minutes (oral almost completely metabolized by liver)
52
Naltrexone (Revia)
* class: opioid antagonist
* **mu-opioid receptor antagonist**
* **treats alcoholism**
* may produce a prolonged withdrawal state (N/V, piloerection, yawning)
53
Benzodiazepines
* **GABAa agonist; binds between a1 and y2 subunits;**"ceiling effect" due to augmenting action of GABA
* P450 metabolism
* treats: depression (short-term); maintenance of bipolar; severe bipolar
* side effects: daytime sedation and drowsiness, anterograde amnesia, synergistic depression of CNS with other drugs, psychologic and physiologic dependence (chronic use)
* **Diazepam:** muscle relaxant
* **Chlordiazepoxide**
* **Flurazepam:** longest t1/2
* **Lorazepam:** prevent withdrawal symptoms in alcoholics, anticonvulsant, anxiety
* **Alprazolam:** sedation, anxiety
* **Midazolam:** anesthesia (calming effects, anterograde amnesia)
* **Triazolam:** induces sleep
54
Zolpidem (Ambien)
* class: non-benzodiazepine receptor agonist
* BDZ-1 selective agonist
* sedation and hypnosis without muscle relaxation or anticonvulsant activity (unlike the other benzos)
* side effects: sleep-walking, next morning impairment
55
Flumazenil (Romazicon)
* class: competitive nonselective benzodiazepine antagonist
* treats benzodiazapine overdose
* side effects: withdrawal (may be life-threatening); seizures in mixed overdoses; non uniform in reversal of respiratory depression
56
Barbiturates
* GABAa agonist (binds a or b subunit)
* **Thiopental:** highly lipid soluble, fast-on, fast-off (redistribute from brain to muscle and fat, metabolized by liver; dosed based on lean body mass); induces anesthesia
* **Methohexital:** also antagonist of NMDA-glutamate receptor; induce general anesthesia (produce hypnosis & sedation, but is antianalgesic)
* **Phenobarbitol:** antiepileptic, anticonvulsant
* side effects: daytime sedation and drowsiness, dose-dependent depression of CNS, pyschologic and physiologic dependence (chronic use)
* abrupt withdrawal life-threatening
57
Buspirone (Buspar)
* may be partial agonist at 5HT1A, no GABAa interaction
* anxiolytic without marked sedation
58
Nitrous Oxide
* class: inorganic gas
* NMDA receptor antagonist
* **mask induction in children**; adjuvant to volatile anesthetics, opioids
* no muscle relaxation
* **v. insoluble/ works fast (don't need much to create equilibrium)**
* side effects: **postop N/V; inactivates B12** (abnormal embryonic development, abortion); accumulates in closed, air-containing spaces (bowel, middle ear, pneumothoraces, air emboli) because N2O insoluble in blood
59
Volatile Anesthetics
* **Isoflurane:** most potent; **gold standard for maintenance; pungent; can increase HR, resistant to metabolism**
* **Desflurane:** least soluble, least potent (allows for rapid emergence from anesthesia); maintenance of anesthesia; **most pungent (airway irritation)**
* **Sevoflurane:** less soluble, less potent (but **not irritating**); mask induction in **children** and adults; maintenance of anesthesia; can form CO if not combined with CO2 correctly
* side effects: dose dependent CNS depression, increase in cerebral blood flow and ICP, decrease in BP, decrease in respiratory function; relaxes skeletal muscle; increase in HR; **malignant hyperthermia**
60
Propofol
* class: Alkylphenol (atty acid)
* GABAa receptor agonist, antagonist of NMDA-glutamate receptor; some a2 receptor activity; rapid onset and offset
* **antiemetic** at low doses; induction and maintenance of general anesthesia; sedation in ICU, procedural sedation; no malignant hyperthermia
* **Propofol infusion syndrome:** use for several days→ met. acidosis, rhabdo, heart & renal failure, lowering of BP, bradycardia, and death
* side effects: painful injection site (administer in lipid emulsion); supports bacterial growth
61
Etomidate (Amidate)
* class: carboxylated imidazole
* GABAa receptor agonist (only D-isomer)
* used for hypnosis; **no analgesic activity**; minimal cardiorespiratory depression **(good for patients with minimal cardiac reserve)**
* side effects: pain on administration (due to solvent, propylene glycol); **involuntary myoclonic movements due to subcortical disinhibition (not seizure); postop N/V; single dose inhibits cortisol synthesis**
62
Ketamine (Ketalar)
* class: phencyclidine
* NMDA receptor antagonist, kappa opiate agonist; leads to dose-dependent unconsciousness, amnesia, **analgesia**
* **dissociative (intact CN signs)**
* use for: sedative/anesthetic for: peds/delayed patients, **induction in reactive airway disease** (bronchodilates), **hypovolemia** (increases HR and systemic vascular resistance), cardiac disease; **+ propofol procedural sedation**; adjuvant during/after surgery to reduce opiod use; part of multimodal pain therapy regimen; depression treatment
* side effects: stimulates symp outflow; increases cerebral blood flow (ICP); emergence delerium;
* metabolized by P450 (norketamine, less effective); **contraindicated in CAD and those with intracranial lesions**
63
Dexmedetomidine (Precedex)
* class: a2 adrenergic agonist
* binds a2a and a2b in locus coeruleus and spinal cord (**sedation, sympatholysis, and analgesia**)
* GABA not hit (easier to wake; similar to non-REM sleep); FDA approved only for ventilation of ICU patients for \<24 hrs
* **awake intubations and craniotomies;** adjunct to general anesthesia in patients susceptible to narcotic-induced post-op respiratory depression; withdrawal/ detox
* **limited respiratory depression (wide safety margin)**
64
Succinylcholine (Anectine)
* class: depolarizing NMB
* divalent ACh molecule; attaches and overstimulates all ACh receptors (fasiculations→ paralysis)
* used as a **skeletal muscle relaxant (intubation)**
* side effects: malignant hyperthermia; cardiac dysrhythmias, hyperkalemia, increased intraocular pressure, increased intracranial pressure; increased intragastric pressure, myalgias, masseter spasm
* hydrolyzed by pseudocholinesterase (in plasma); **blockade cannot be reversed;** only NMB with rapid onset and ultra-short duration of action
65
non-depolarizing NMBs
* competitive blockade of ACh (no depolarization)
* skeletal muscle relaxant, reverse with AChEI
* **Pancuronium:** vagolytic, avoid in patients with renal insufficiency; **can increase HR;** **long acting, low liver metabolism**
* **Vecuronium:** no cardiovascular effects; hepatic and renal excretion
* **Rocuronium:** can substitute succinylcholine in rapid sequence intubation, no cardiovascular effects; hepatic and renal excretion
* **Atracurium:** use in patients with liver/renal dysfunction; leads to histamine release→ hypotension and tachycardia
* **Cis-atracurium:** use in patients with liver/renal dysfunction; no histamine release; nonenzymatic degradation (hofman elimination)
66
Sugammadex (Bridion)
* class: selective relaxant binding agent
* **complexes with rocuronium**, rendering it inactive; no effect on AChE
* **not yet FDA approved**
* side effects: decrease in BP, N/V, dry mouth
67
Glycopyrrolate (Robinul)
* class: anti-muscarinic
* used for reversal of neuromuscular blockade's muscaranic effects
* side effects: DUMBELLS
68
Ester anesthetics
* used as local anesthesia, hydrolyzed by pseydocholinesterase (rapid)
* reversibly inactivates intracellular portion of voltage-gated Na channel; blocks nociceptive nerve impulses
* local side effects: transient neurologic symptoms (really bad pain), **neuronal injury**
* **Cocaine:** many side effects due to action as a CNS stimulant
* **Benzocaine: risk of methemoglobinemia**
* **Procaine**
* **Tetracaine**
* **Chlorprocaine: high pKa (not as potent)**
* systemic side effects (MC with long-acting local anesthetics): circumoral numbness, dizziness, tinnitis, blurred vision, CNS excitation (restlessness, agitation, seizures), followed by CNS depression (respiratory arrest, unconsciousness); hypotension; cardic toxicity with higher doses
69
Amide anesthetics
* **Lidocaine**
* **Mepivacaine**
* **Bupivacaine: highest cardiac toxicity potential**
* **Ropivacaine:** less potent than others (larger TI)
* used as local anesthesia; **transformed by hepatic carboxyl esterases and CYP450s (slow)**
* mechanism: reversibly inactivates intracellular portion of voltage-gated Na channel; blocks nociceptive nerve impulses; **effects more rapidly firing neurons vs. resting neurons, smaller more myelinated nerves are blocked faster**
* local side effects: transient neurologic symptoms (really bad pain), neuronal injury
* systemic side effects (MC with long-acting local anesthetics): circumoral numbness, dizziness, tinnitis, blurred vision, **CNS excitation (restlessness, agitation, seizures), followed by CNS depression (respiratory arrest, unconsciousness);** hypotension; **cardic toxicity with higher doses** (block Na channels in heart and increase myocardial contractility and vasodilation)
70
IFN-betas for MS
* inhibit T cell activation, shift reponse from Th1 to Th2; inhibit lymphocyte movement into CNS
* treats RRMS; decrease acute attacks by 1/3 and significantly reduces new and enhacing MRI lesions
* does not cross BBB (treats peripherally)
* side effects: anemia, leukopenia, increase LFTs and hypothyroidism (monitor every 3 mo.); injection site reactions
* **IFN-beta-1a:** available in low and high doses (high dose is 1st line; better than other IFNs and glatiramer acetate)
* **IFN-beta-1b:** high dose, more efficacious than low dose IFN beta 1a
71
Glatiramer acetate (Copaxone)
* class: myelin basic protein analog
* causes T-cell apoptosis (looks like MBP), induces anti-inflammatory Th2 cells (cytokine shift from Th1), induces Treg with induction of anergy
* treats RRMS
* **active in CNS** (decreases brain atrophy; no organ damage); try to use early; reduce relapse by 1/3, modest reduction in MRI lesion and reduction of atrophy, but no effect on disease progression
* side effects: injection site rxn, anxiety attack-like reaction
72
Natalizumab (Tysabri)
* class: monoclonal antibody
* **binds VLA4 (integrin subunit), inhibiting leukocyte migration across BBB**
* treats: 2nd line therapy for RRMS (relapse reduction by 2/3)
* most efficacious treatment for MS, 2nd line because it is also the most problematic
* side effects: **PML (JC virus);** acute urticaria, systemic HSN infusion rxn; headache, dizziness, fatigue, arthralgia, rigors
73
Fingolimod (Gilenya)
* class: sphingosine-1-phosphate analog
* prodrug; **sequesters lymphocytes in secondary lymph organs** via induction of intracellular internalization of receptors on lymphocytes (no effect on lymphocyte induction, proliferation, or memory function)
* treats RRMS; better than low dose IFN
* side effects: **bradycardia and heartblock; macular edema,** reduced FEV1, increased LFTs, lymphopenia, leukopenia, infections
* Patients **must be VZV immune** before prescription
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Teriflunomide (Aubagio)
* class: immunosuppressants
* reduces T and B proliferation and function against autoantigens; preserves replication and function of cells living on salvage pathway (e.g., hematopoietic cells, memory cells)
* treats RRMS; as good as IFNs but oral dosing
* black box warnings: **hepatotoxicity; teratogenicity (animal data)**
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Dimethyl fumarate (Tecfidera)
* neuroprotective (enhances Nrf2 pathway; some Th1→ Th2 shift)
* treats RRMS; comparible to fingolimod (better than low dose IFN)
* side effects: N/V/D, stomach pain, flushing, itching redness, rash
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Mitoxantrone (Novantrone)
* class: anthracenedione
* broad immune suppression and modulation of B cells, T cells and macrophages;
* treats: **SPMS, RRMS (2nd line);** decreases frequency of clinical relapse, reduces disease progress, and reduces disability
* side effects: **dose-dependent cardiac toxicity** (decreased LVEF, irreversible CHF); **leukemia**
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immunosuppressants for SPMS
* treats SPMS (resistant, or as combination with other therapies)
* side effects: systemic toxicity (monitor blood for changes)
* **Azathioprine**
* **Methotrexate**
* **Cyclophosphamide**
* **Mycophenolate mofetil**
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meds for acute MS attacks
* **1st line= methylprednisone:** corticosteroid (immunosuppressant)
* short-term: insomnia, mood changes, fluid retention, epigastric pain, HTN
* long-term: osteoporosis, cushingoid, secondary malignancies
* **2nd line= plasmaphoresis**
* **3rd line= ACTH** if patient is allergic to corticoseroids, poor IV access, MTP doesn't work
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Voltage-gated Na channel stabilizer
* stabilize inactive conformation of Na channel (nerve can still work but not repeatedly and v. fast)
* side effects: rash (rarely, Stevens-Johnson), mild myelosuppression, mild increase in LFTs; can cause contraceptive failure
* toxicity: dizzy drunk double vision
* **Phenytoin:** less effective for absence (esp pediatric), myoclonic, atonic seizures; **teratogen;** **gingival hyperplasia,** hirsutism, lupus-like reaction
* **Carbamazepine:** more effective for complex partial seizure than primary generalized; bipolar disorder; neuropathic pain; **hepatic enzyme inducer (auto and hetero) so much increase dose**
* **Oxcarbamazepine:** more effective for complex partial seizure than primary generalized; bipolar disorder; neuropathic pain; fewer interactions/ less toxic than carba
* **Lamotrigine:** primary generalized epilepsies, absence seizures; indicated in children; bipolar disorder; neuropathic pain; competes with valproate for excretion (synergism)
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Valproate (Depakote)
* likely affects Na-gated channels and GABA system
* treats: broad spectrum seizure treatment but not absence; IV for status epilepticus; bipolar treatment, **migraine and long-term cluster headache prophylaxis**
* side effects: **weight gain**, hair loss, hyperammonemia (can be mitigated with oral carnitine), **teratogenicity,** blood dyscrasias; pancreatitis
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GABAergic anti-epileptics
* **vigabatrin:** GABA transaminase binder (slows down intracellular breakdown of GABA); works on GABA-A
* **tigabine:** GABA reuptake inhibitor; works on GABA-A
* **benzodiazapines:** binds GABA-A in post synaptic membrane of inhibitory synapse); treasts status epilepticus; anesthesia
* LT usefulness limited by tolerance
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Gabapentin
Pregabalin
* class: GABA analog
* block presynaptic influx of Ca
* adjunct for partial complex epilepsy; more commonly used for neuropathic pain
* **gabapentin: v. safe (no metabolism or drug interaction so few side effects)**
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Topiramate
* class: glutamate receptor blockers
* partial AMPA, Kainate Ca receptor blocker; 2ndary effect on voltage-gated Na and GABA system
* treats partial onset seizures, 2ndary generalized seizures, generalized epilepsy, **migraine and LT cluster headache prevention**
* side effects: **mild met. acidosis**→ resp. comp.→ mild alk→ Ca ionization→ **tingling;** kidney stones; weight loss; **word-finding problems;** acute angle-closure glaucoma
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Felbamate
* class: glutamate receptor blocker
* NMDA receptor blocker; 2ndary effect at voltage-gated Na and Ca, GABA system
* treats: partial onset seizures w/or w/out 2nd generalization, medically refractory epilepsy
* side effects: uncommon but potentially fatal (aplastic anemia, acute hepatic failure); requires monitoring
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Levetiracetam
* class: synaptic vesicle binder
* binds synaptic vesicle protein 2→ less NT release
* treats: partial onset seizures, 2ndary generalized seizures
* side effects: **irritability**
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Ethosuximide
* class: voltage-gated Ca channel blocker
* blocks T-type Ca channels in thalamocortical circuits
* treats: **absence seizures only;** neuropathic pain
* side effects: nausea, irritability
* readly absorbed, minimal 1st pass metabolism
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Butalbital
* class: barbiturate
* acute treatment of migraines; use when more traditional therapies unavailable or contraindicted (no RCT show efficacy)
* side effects: drowsiness, dizziness; risk of overuse and withdrawal)
* use limited to 2-3x /week
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opioids for headache treatment
* acute treatment of migraines, patients with infrequent headaches; **generally for patients who wake up with a headache**
* side effects: drowsiness, constipatient
* physical dependence w/chronic use (rebound headaches); use \<3x/week
* pregnant women may use codeine or meperidine with caution
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corticosteroids for headache treatment
used for acute treatment of migraines, prolonged headache syndromes; **rescue treatment of cluster headache;** avoid chronic use
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ergot alkaloids for headache treatment
* **ergotamine, DHE**
* vasoconstriction possible; act as 5HT agonist in trigem vascular pathway
* contraindicated in: women planning pregnancy, uncontrolled HTN, sepsis, renal or hepatic failure, vascular disease
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triptans for headache treatment
* selective 5HT1 b-d agonists (blocks peptide release); penetrate CNS, constriction of extracerebral intracranial vessels, inhibition of trigem vascular system
* used for **acute treatment of migraines (premier option**); photo/phonophobia, N/V, **acute treatment of cluster headaches (subQ)**
* side effects: flushing, tingling, noncardiac chest discomfort
* contraindicated in: vascular disease, inctrolled HTN, complicated migraine
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onabotulinum toxin A
* prevention of migraines; unknown mechanism (possibly decreased afferent stimulation of trigem. vascular system or downreg of sensory and parasymp receptors)
* injection site pain (specific injection site protocol is FDA approved)
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TCAs for headache treatment
* used for migraine and tension headache prevention
* side effects: dry mouth, constipation, weight gain, cardiac toxicity, orthostatis hypotension
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SSRIs for headache treatment
* migraine and tension headache prevention; treatment for coexisting depression and chronic daily headache
* side effects: weight gain, sexual dysfunction, headache
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ß-blockers for headache treatment
* **only propranolol and timolol are FDA approved for migraine prevention**
* nadolol and atenolol sometimes preferred for long half-life and tolerability
* side effects: drowsiness, dpression, decreased libido, hypotension, memory disturbance
* **contrindicated in asthma, diabetes, CHF, or Raynaud's**
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verapamil
* Ca channel blocker for migraine prevetion **(esp. in prolongued/disabling aura or complicated migraine); LT prevention of cluster headaches**
* side effects: constipation dizziness
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Dextroamphetamine
Lisdexamfetamine
* class: stimulant
* mechanism: blocks DAT (may actuall reverse it); increases VMAT2
* treats: ADHD
* side effects due to NE and DA; addictive
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prostaglandin analogs
* latano**prast**, travor**prost**, bimato**prost**, uno**pros**tone isopryl (least effective)
* increase uveoscleral outflow (no effect on aqueous or trabecular flow)
* **primary agent for glaucoma**
* side effects: eyelash grow, iris color change, may cause cystoid macular edema in cataract surgery and activate herpes
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AChE inhibitors for Alzheimer's Disease
* **tacrine:** AChE and BuChE inhibition; can raise transaminase
* **donepezil:** mild-severe AD
* **rivastigmine:** not metabolized by P450 (hydrolyzed by cholinesterases)
* **galantamine:** AChE inhibition, allosteric modulator of N receptors
* side effects: N/V, sleep disturbance
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Memantine
* partial antagonist of NMDA receptor
* used for severe AD
* side effects: dizziness, confusion, headache, constipation
* excreted unchanged in urine
