Analgesics, also known as painkillers, are drugs that relieve pain. There are two main types: non-narcotic analgesics for mild pain and narcotic or opioid analgesics for severe pain. Commonly used analgesics include acetaminophen (Tylenol), acetaminophen plus oxycodone (Percocet), celecoxib (Celebrex), tramadol (Ultram), ibuprofen (Advil, Motrin), and aspirin.
NSAIDS or non-steroidal anti-inflammatory drugs are commonly used as analgesics and antiinflammatory drugs. NSAIDS block the cyclooxygenase 1 and/or 2, also called COX enzymes, and decrease prostaglandin production. NSAIDS like ibuprofen, diclofenac, ketorolac, indomethacin, and naproxen are non-selective, reversible inhibitors of COX 1 and 2. Celecoxib, rofecoxib, and valdecoxib are selective COX 2 inhibitors. The antiplatelet effect of aspirin is by reduction in thromboxane A2 production. Adverse effects include gastric upset, peptic ulcers, gastrointestinal bleeding and perforation, sodium retention, edema, renal failure, and chronic kidney disease. Diclofenac and COX 2 selective blockers like celecoxib are associated with increased risk of cardiovascular events and stroke. Children treated with aspirin during a viral infection may develop Reye’s syndrome with liver failure. Examples of NSAIDS include aspirin (Bayer, St. Joseph), ibuprofen (Advil, Motrin), naproxen (Aleve), celecoxib (Celebrex), diclofenac (Voltaren), indomethacin (Indocin) and ketorolac (Toradol).
Acetaminophen inhibits the PGH2 synthase enzyme. It has antipyretic and analgesic effects by central mechanism but is not anti-inflammatory. Overdose may cause liver failure. N-acetylcysteine is used as an antidote. The maximum daily dose of acetaminophen for a healthy adult of average weight is 4000 mg. Brands include Tylenol, Mapap, and many combination products for cold and flu, like Delsym, Excedrin, Robitussin, Theraflu, and Sudafed.
Opioid or narcotic analgesics are strong analgesics that are used in the management of severe and chronic pain. They are controlled drugs. They bind to opioid receptors in the human body to produce their effects. They include heroin, morphine, fentanyl, buprenorphine, tramadol, dextromethorphan, codeine, oxycodone, and methadone. Methadone and buprenorphine are also used to manage opioid addiction. Adverse effects include euphoria, sedation, constipation, dry mouth, respiratory depression, bradycardia, vomiting, and heavy extremities. Long-term use causes addiction and tolerance. Common brands include hydrocodone (Vicodin), oxycodone (OxyContin, Percocet), oxymorphone (Opana), hydromorphone (Dilaudid), tramadol (ConZip, Qdolo), fentanyl (Fentora, Actiq) and morphine (Kadian, Avinza). Naloxone (Narcan, ReVive, Kloxxado, Zimhi) and nalmefene (Opvee) are FDA-approved for the reversal of opioid overdose. They are available as nasal sprays and injectable forms.
Medications for migraine: Chronic and severe migraine headaches can cause disruptions in daily life and can be medically managed by two types of therapy - abortive treatment treats the acute headache, while preventive treatment is given to avoid migraine attacks. All types of analgesics are effective to varying degrees in the abortive treatment of migraine. Other drugs include triptans like sumatriptan (Imitrex, Tosymra), rizatriptan (Maxalt), ergot alkaloids like dihydroergotamine (Migranal, Trudhesa), lasmiditan (Reyvow) and CGRP or calcitonin gene-related peptide antagonists or gepants like ubrogepant (Ubrelvy) and rimegepant (Nurtec ODT). Preventive drugs include antidepressants like amitriptyline (Elavil), anti-epileptics like valproate (Depakote) and topiramate (Topamax), calcium channel blockers like verapamil (Verelan, Calan), beta blockers like propranolol and timolol, atogepant (QULIPTA) and Botox injections. Triptans may cause drowsiness, tingling, flushing, and chest tightness. Topiramate may cause decreased sweating and increased body temperature. CGRP antagonists may cause severe constipation and high blood pressure. Ergot alkaloids may cause nausea, fatigue, insomnia, dizziness, hypertension, tingling and numbness, bradycardia, and depression. They are contraindicated with certain antimicrobials like erythromycin, clarithromycin, HIV protease inhibitors, and azole antifungals.
Antidepressants modulate levels of neurotransmitters like serotonin and norepinephrine in the brain. They are used to treat clinical depression, anxiety disorders, obsessive compulsive disorder, and post traumatic stress disorder. Several classes are available like selective serotonin reuptake inhibitors or SSRIs, serotonin-norepinephrine reuptake inhibitors or SNRIs, norepinephrine-dopamine reuptake inhibitors or NDRIs, noradrenergic and specific serotonergic antidepressants or NaSSAs, tricyclic antidepressants or TCAs, heterocyclics, monoamine oxidase inhibitors or MAOIs and serotonin antagonist and reuptake inhibitors or SARIs.
SSRIs prevent the reuptake of serotonin in the synapses of the brain hence increasing serotonin levels in the brain. They include fluoxetine (Prozac), paroxetine (Paxil), fluvoxamine (Luvox), sertraline (Zoloft), citalopram (Celexa) and escitalopram (Lexapro). Adverse effects include nausea, vomiting, weight gain, drowsiness, decreased libido and sleep disturbances.
SNRIs prevent the reuptake of both serotonin and norepinephrine. They include duloxetine (Cymbalta), venlafaxine (Effexor), desvenlafaxine (Pristiq), and levomilnacipran (Fetzima). They may increase blood pressure. Other adverse effects are similar to SSRIs.
NDRIs increase the levels of both norepinephrine and dopamine in the brain synapses. The most commonly used drug in this class is bupropion (Wellbutrin). It may cause jitteriness, tachycardia, seizures, and insomnia. It is also used to treat ADHD and smoking cessation.
Like SNRIs, NaSSAs increase both serotonin and norepinephrine. Side effects include drowsiness, dizziness, weight gain, dry mouth, and constipation. An example is mirtazapine (Remeron). It is used in patients who cannot tolerate SSRIs and SNRIS, and to treat patients with depression, anxiety disorders, or insomnia.
Serotonin antagonists and reuptake inhibitors, or SARIs increase serotonin levels in the brain and block serotonin receptors. They include trazodone (Desyrel) and nefazodone. Adverse effects include sedation, headache, dry mouth, blurred vision, nausea, dizziness, agitation and diarrhea. Nefazodone may cause liver failure a few weeks after starting therapy.
Heterocyclics and tricyclic antidepressants, or TCAs, increase the concentration of serotonin and norepinephrine in the brain. Examples include amitriptyline, nortriptyline (Aventyl), clomipramine (Anafranil), desipramine (Norpramin), imipramine (Tofranil), and amoxapine. Mirtazapine (Remeron) can also be classified as a TCA. Adverse effects are severe and include cardiac arrhythmias, heart attack, seizures, glaucoma, dry mouth, sedation, and retention of urine.
Monoamine oxidase inhibitors or MAOIs include moclobemide (Manerix), isocarboxazid (Marplan), phenelzine (Nardil), and tranylcypromine (Parnate). MAOIs inhibit an enzyme called monoamine oxidase, causing an increase in the levels of neurotransmitters such as dopamine, serotonin, and norepinephrine. They may cause weight gain, orthostatic hypotension, insomnia, and swelling. Dietary restrictions are needed when taking MAOIs. Foods high in tyramine, such as cheese and fermented products, may cause a dangerously high elevation in blood pressure when taken together with MAOIs. Moclobemide is the newest MAOI, and dietary restrictions are generally not required.
Special precautions while using antidepressants: The risk of suicidal tendencies is higher in children and young adolescents taking antidepressants. This can occur even when patients are feeling less depressed. The highest risk is with SSRIs. Serotonin syndrome is a rare but life-threatening adverse effect of certain antidepressants that increase serotonin levels, e.g., SSRIs, SNRIs, MAOIs, TCAs, and bupropion. It presents as high fever, rigidity of muscles, shivering, fast and irregular heart rate, seizures, agitation, dilated pupils, high blood pressure, and unconsciousness.