Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Robert Kobelja Rite Review 2016 Go over major category of drugs along with mechanism of action, side effects and primary indication that have appeared on the RITE Will leave out pathophysiology given too much material Will highlight repeat questions (very few) Antidepressants Antipsychotic SSRI SNRI TCA MAOI Mechanism of action. Specific neurotransmitters involved and not involved Unique side effects Fluoxetine (Prozac)• Vilazodon (Viibryd)** Sertraline (Zoloft) • Vortoxetine (Brintellix)** Paroxetine (Paxil) Fluvoxamine (LuVox) Citalopram (Celexa) Escitalopram (Lexapro) **5HT1A partial agonist Most common first-line agents for: Major depression, dysthymia Panic disorder, generalized anxiety, social phobia Obsessive compulsive disorder (1st line) Eating disorders Mechanism of action: Inhibits CNS neuron serotonin reuptake; minimal or no effect on reuptake of norepinephrine or dopamine; does not significantly bind to alphaadrenergic, histamine, or cholinergic receptors Side effects tend to be mild, but may include: Dizziness, hypotension Nausea, diarrhea Serotonin syndrome – especially in the first few days of treatment Weight gain Sexual dysfunction (esp. decreased libido and inhibit oragasm) All QTC interaction, Citalopram highest QTC risk Delerium, hyperthermia, tachycardia, diaphoresis, clonus, hyperreflexia, tremor Caused by concombinate use of MAOI and SSRIs, TCA, SNRI, trazadone, dextromethorphan, tramadol. Venlafaxine (Effexor) Desvenlafaxine (Pristiq) Duloxetine (Cymbalta) Levomilnacipran (Fetzima) Trazodone (Desyrel, Oleptro) Tricyclic antidepressants (TCA) Same mechanism, Usually classified separately Mechanism of Action: neuronal serotonin and norepinephrine reuptake and a weak inhibitor of dopamine reuptake. No significant activity for H1-histaminergic, or alpha2-adrenergic receptors. Do not possess MAO-inhibitory activity. But mild anti-cholinergic activity. Side effects Insomnia or somnolence Weight loss or weight gain Cardiac conduction abnormalities HTN Duloxetine ALT elevations Sexual dysfunction Used for sleep and agitation Mechanism: Inhibits reuptake of serotonin, causes adrenoreceptor subsensitivity, and induces significant changes in 5-HT presynaptic receptor adrenoreceptors. Trazodone also significantly blocks histamine (H1) and alpha1-adrenergic receptors. Anticholinergic moderate properties. Side effects Sedation Hypotension Priapism Sexual dysfunction Tertiary Amines • Amitriptyline (Elavil) • Clomipramine (Anafranil) • Imipramine (Tofranil) • Doxepin (Sinequan) Secondary Amines • Amoxapine (Asendin) • Desipramine (Norpramine) • Nortriptyline (Pamelor) • Protriptyline (Vivactil) Headache, depression, anxiety, pain Mechanism of action: increase the synaptic concentration of serotonin and norepinephrine in the central nervous system by inhibition of their reuptake by the presynaptic neuronal membrane. Also blocks H1 and anticholinergic properties higher in tertiary amines. Tertiary Amines • More anticholinergic • More sedation • More hypotension Secondary Amines • Less anticholinergic • Less sedation • Less hypotension Side effects QT prolongation Sedation Lethal in high doses suicide Depression (not anxiety or OCD) Mechanism of action: unknown and poorly understood. But with weak inhibitor activity of the neuronal uptake of norepinephrine and dopamine, and does not inhibit monoamine oxidase or the reuptake of serotonin. Side effects No sexual dysfunction or cardiac compications Insomnia and dry mouth Lowers seizure threshold Indication: Depression, anxiety, panic disorder Mechanism: Blocks presynaptic alpha2 receptors, causing disinhibition of norepinephrine release. It is also a potent antagonist of 5-HT2 and 5-HT3 serotonin receptors and mild H1 histamine receptors and a moderate peripheral alpha1-adrenergic and muscarinic antagonist. (has TCA like structure) Side effects Weight gain and sedation MAO-A: peripherally located (bowel and liver), centrally located MAO-B: centrally located and located in platelets Tranylcypromine A>B Phenelzine A=B Selegiline B>A but at 20 mg daily selectivity disappears Used for major depression, panic disorder (especially with agoraphobia), generalized anxiety, and social phobia. Also for parkinson’s disease (lower dose) Mechanism: Blocks metabolism of norepinephrine, serotonin, dopamine, and tyramine Side effects sedation, hypotension, hypertensive crisis, anticholinergic effects, sexual dysfunction Hypertensive crisis with tyramine reaction Serotonin syndrome 5HT NE SSRI XX SNRI XX Trazadone X TCA Buproprion X X x Mertazepine X X MAOI X X D H1 XX Ach Alpha 1 x X x X X X X X x x Main mechanism: D2 receptor blocker through the mesolimbic pathway Other activity: D2 receptors in the mesocortical pathways cause sedation Alpha 1 antagonist decrease blood pressure Anti-cholinergic angonist consitpation and dry mouth Histamine antagonist weight gain and dowsiness No serotonin activity First generation: Higher D2 affinity More EPS and more TD Less cholinergic side effects Less metabolic dysregulation • Second generation: – Lower D2 affinity • less EPS and more TD – More cholinergic side effects – More metabolic dysregulation First generation High Potency • Droperidol (Inapsine) • Fluphenazine (Prolixin) • Haloperidol (Haldol) • Perphenazine (Trilafon) • Pimozide (Orap) • Thiothixene (Navane) Low Potency • Chlorpromazine (Thorazine) • Loxapine (Loxitane) • Thioridazine (Mellaril) • • • • • Second generation: • Paliperidone Aripiprazole (Invega) (Abilify) • Quetiapine Asenapine (Saphris) (Seroquel) Iloperidone (Fanapt) • Risperidone Lurasidone (Latuda) (Risperdal) Olanzapine* • Ziprasidone (Zyprexa) (Geodon) • Clozapine (Clozaril) Side effects Sedation Weight gain Sexual dysfunction Metabolic Dysregulation: DM, elevated LDL, elevated triglycerides, HDL decreased Clozapine Side effects: Agranulocytosis Increased risk of seizures Parkinsonism and Antipsychotics Worsened by first and second generation medication First generation is contraindicated in Lewey body dementia They easily get neuroleptic malignant syndrome. Psychosis in Parkinson's can be treated with clozapine Neuroleptic malignant syndrome Hyperthermia, tachycardia, HTN, delerium, board like rigidity Treat with Bromocriptine: dopamine agonist Or Dantrolene: prevents release of calcium from the sarcoplasmic reticulum. Know carbamazepine Know spectrum of medication Most seizure types Valproate Lamotrigine Topiramate Zonisamide Levetiracetam Felbamate Phenobarbital • Partial seizures – Carbamazepine (Oxcarbazepine) – Gabapentin (Pregabalin) – Perampanel – Lacosamide – Tiadabine Absence Ethosuxamide (only) Valproic acid (2nd line) • Infantile spams – Vigabatrin Absence seizures Gabapentin Tiagabine vigabatrin • Myoclonic seizures – Carbamazepine – Gabapentin – Pregabalin – Tiagabine – Vigabatrin Blockade of voltage-gated sodium channels Structurally similar to TCAs Side effects: Aplastic anemia SIADH Steven’s Johnson Rash: Associted with HLA-b1502 allele with 10 fold increase Metabolism: Inhibits metabolism of phenytoin, cimetidine, diltiazem, erythromycin, verapamil, fluoxetine, and isoniazid. Induces metabolism of itself, oral contraceptives, sodium valproate, ethosuximide, corticosteroids, anticoagulants, antipsychotics, cyclosporine, and methylphenidate Levels raised by isoniazid, erythromycin, cimetidine, verapamil, propoxyphene Levels lowered by phenobarbital, phenytoin, and primidone. Glucuronidation: Adding on a glucuronic acid How lamotrigine is cleared from the body Induced by Carbamazepine lowers Lamotrigine levels. Topamax Blocks voltage-sensitive Na channels, and highvoltage calcium channels; potentiates GABAmediated inhibition at the GABA-A-R; reduces excitatory actions of glutamate via the AMPA receptor Side effects: inhibits carbonic anhydrase causes a metabolic acidosis Parasthesias, weight loss, Cognitive impairment Kidney Stones: calcium phosphate Phenytoin Mechanism: Blockade of voltage-dependent sodium channels Zero order kinetics Side effects: Purple glove syndrome from pH Use fosphenytoin to avoid this (can also be used IM) Gingival hyperplasia, morbiliform rash, hypotension Induces Glucuronidation Perampanel Mechanism: antagonist of the AMPA receptor Side effects:dizziness somnolence and headache. As well as hostility and aggression Lamotrigine Mechanism: Blockade of voltage-dependent slowinactivated sodium channels Also can block calcium channels and K channels Cleared by Glucuronidation Elevated levels of lamotrigine with VPA Decreased levels of lamotrigine with Carbamazepine, Phenytoin, and phenobarbital Side effects No effect on vitamin D metabolism Steven’s Johnson rash Valproic acid Mechanism: not well defined Side effects: Liver injury (increased risk in POLG mutation) Hyperammonemia (independent of liver injury) Birth defects mainly spina bifida only rarely anencephaly (NTD), cardiac, craniofacial, skeletal and limb defects and a possible set of dysmorphic features, the "valproate syndrome" with decreased intrauterine growth Weight gain, hair loss, tremor Zonisamide blockade of sodium channels, blockade of T-type calcium channels, potentiation of GABAergic transmission, and inhibition of carbonic anhydrase Side effects Kidney stones Allergies to sulpha Levels lowered by Carbamazepine, phenytoin and barbituates Pregabalin Mechanism: Modulates neurotransmitter release by binding to the a2-d subunit of voltage-gated calcium channels GABA analogue but no activity on GABA or benzodiazepine receptors More used for neuropathic pain through same mechanism. No Drug-Drug interactions Weight gain Symptomatic treatment Dalfampridine (Ampyra) Potassium channel blocker improves nerve conduction on demyelinated axons Used for motor weakness, gait trouble and fatigue in MS Side effects Cleared by the kidneys and contrainicated in GFR <50 Causes seizures at higher doses. Immune modifying drugs Injectable Interferon Beta Flu like symptoms Glatiramer acetate Four peptide polymer similar to myelin basic protein Injection site reactions with little other side effects Immune modifying drugs: oral medications Dimethyl fumerate (Tecfidera) Unclear mechanism but thought to be from activation on nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway Side effects: flushing, diarrhea, PML with persistent lymphopenia Immune modifying drugs: oral medications Fingolimod (Gilenya) activates sphingosine-1 phosphate-receptor reduces lymphocyte recirculation in lymph nodes Side effects PR prolongation Macular edema Liver injury AST and ALT VZV infection PML Immune modifying drugs: oral medications Teriflunomide (Abagio) inhibits dihydroorotate dehydrogenase in mitochondria needed for pyrimidine synthesis reducing B and T cell count. But spars slow dividing cells through exogenous supplies of pyrimidine. Side effects: diarrhea, hair thinning, liver injury with ALT increase Immune modifying drugs: IV medications Superior to orals and injections Natalizulmab monoclonal antibody against the alpha-4 subunit of integrin molecules Side effects Increased risk of PML Risk increased to 1/1000 after 2 years with PCR negative Risk increased to 11/1000 if seropositive after 2 years Immune modifying drugs: IV medications Alemtuzumab Monoclonal antibody to CD 52 causes B and T cell depletion. Spares hematopoietic cells Side effects: Thyroid dysfunction (30%) Thrombocytopenia (bone marrow suppression) Goodpasture Malignancy risk Parkinson’s Drugs COMT inhibitors – prevent conversion of levodopa to 3-0 methyldopa Tolcapone Small risk of liver failure Entacopone Common side effects Nausea, diarrhea Urine discoloration (orange) Parkinson’s Drugs Dopamine Agonists Ropinirole and pramipexole Compulsive gambling, hypersexuality Tremor predominant Treat with trihexyphenidyl Anticholinergic Avoid in patients over 60 or with cognitive impairment Orthostatic hypertension Midodrin: converted to an alpha agonist Supine hypertension Used for patient unresponsive to fludrocortisone Tardive dyskenesias Treat with amantidine Caused by long term anti-psychotic use but also prochlorperazine and metoclopramide Tourette’s First line agents: guanfacine or clonidine Alpha 2 receptor agonists Haldol more effective but more troublesome side effects Essential tremor Propranolol: non specific beta blocker Don’t use if the patient has asthma, COPD, or CHF Primadone: converted to phenobarbital Restless legs First line is ropinirole Causes intrauterine growth retardation and digit malformation In pregnancy use Carbidopa/Levodopa Triptans Blood vessel constriction due to seratonin receptor agonists 5HT1B and 5HT1D fast onset peak at 2 hours sumatriptan, zolmitriptan, rizatriptan, almotriptan, and eletriptan Slow onset naratriptan and frovatriptan use for headaches that recur within 24 hours Tramadol Mechanism: binds to Mu receptors but inhibits serotonin and norepinephrine reuptake Two enantomers: both affect Mu receptors. Tramadol inhibits serotonin reuptake And the metabolite O-desmethyl-tramadol inhibits norepinephrine reuptake