Comprehensive Guide to NSAIDs, Antidepressants, Antipsychotics, and Anxiolytics
NSAIDs
Salicylates
- Aspirin
- Sodium Salicylate
Para-aminophenol Derivatives
- Acetaminophen
Pyrazolones and Pirazolindiones
- Dipyrone
- Phenylbutazone
Acetic Acid Derivatives
- Indomethacin
- Diclofenac
- Ketorolac
- Etodolac
- Tolmetin
- Sulindac
Propionic Acid Derivatives
- Ibuprofen
- Naproxen
- Ketoprofen
- Flurbiprofen
Oxicams
- Piroxicam
Anthranilic Acid Derivatives
- Mefenamic Acid
- Flufenamic Acid
- Meclofenamic Acid
Alkanones
- Nabumetone
Sulfonanilides (COXIBs)
- Celecoxib
- Etoricoxib
Mechanism of Action
NSAIDs inhibit the enzyme cyclooxygenase (COX), thereby inhibiting the biosynthesis of prostaglandins (PGs) in cells undergoing inflammation. There are two COX isoenzymes:
- COX-1: Constitutive enzyme
- COX-2: Inducible enzyme
Selectivity for COX
- Relatively Selective for COX-1: Aspirin and Sodium Salicylate
- Less Selective for COX-1: Ibuprofen and Paracetamol
- Preference for COX-2: Naproxen, Diclofenac, and Piroxicam
- COX-2 Inhibition Exclusive: COXIBs
Pharmacodynamic Actions
Analgesic
- Effective for mild to moderate pain
- Less potent than opioid analgesics but without the risk of addiction
Anti-inflammatory
- All NSAIDs except paracetamol
Antipyretic
- Effective in reducing fever
Adverse Effects
Gastrointestinal
- Gastroduodenal ulcers
- Bleeding
- Perforation risk of GI mucosa
Renal
- Acute renal insufficiency
- Edema due to water retention
- Increased reabsorption of chloride
- Enhanced action of antidiuretic hormone (ADH)
- Analgesic nephropathy
Salicylates
Aspirin and Sodium Salicylate
Therapeutic Effects
- Decrease elevated body temperature
- Increase oxygen consumption and metabolic rate
Toxic Effects
- Increase body temperature
- Profuse sweating and risk of dehydration
High Therapeutic Doses
- Stimulate the respiratory center to increase ventilation
- Decrease PCO2, favoring the presence of respiratory alkalosis
- As compensation, renal elimination of HCO3 increases
- If sustained high doses are administered, stimulation of the respiratory center is followed by depression, preventing the removal of CO2 and leading to mixed acidosis
Antiplatelet Activity
- Aspirin has antiplatelet activity, indicated for the prevention of thrombosis
Anti-inflammatory Effects
- Aspirin has a beneficial effect on rheumatic and inflammatory processes by two mechanisms: inhibition of PG synthesis and suppression of antigen-antibody reactions and modification of connective tissue metabolism
Therapeutic Uses
- Antipyretic
- Analgesic
- Acute rheumatic fever
- Rheumatoid arthritis
- Prophylaxis of diseases that present with increased platelet aggregation
Adverse Effects
Gastrointestinal
- Nausea and vomiting
- Gastrointestinal bleeding
- Reye Syndrome (children with chickenpox)
Poisoning
Chronic
- Mild symptoms appear: Salicylism (tinnitus, diarrhea, mental confusion, headache)
Severe Acute
- The central nervous system (CNS) is affected, moving from excitement to central depression
- High fever
- Altered acid-base balance and electrolytes
Treatment of Poisoning
- Gastric lavage
- Activated charcoal administration for drug adsorption
- Correction of hyperthermia, acid-base, and electrolyte imbalances with appropriate intravenous solutions
- Symptomatic treatment of hypoglycemia, bleeding, and vomiting
- Barbiturates or opiates should not be used to treat hyperventilation due to the risk of respiratory acidosis and coma
Paracetamol
Alternative to Aspirin
- Good tolerance and bioavailability
- No anti-inflammatory effects
Nephrotoxicity
- Can cause acute severe kidney damage, which can be deadly
Adverse Effects
- Hepatic necrosis (dose-dependent, treated with N-acetylcysteine)
- Methemoglobinemia
- Thrombocytopenia
- Hypoglycemic coma
- Renal tubular necrosis
Therapeutic Uses
- Analgesic-antipyretic
- Substitute if aspirin is contraindicated
Phenylbutazone
Anti-inflammatory
- Treatment limited to short periods due to its high toxicity
- Penetrates very well into healthy and swollen joints
Adverse Effects
- Gastrointestinal intolerance
- Bleeding
- Rash
- Edema
- Aplastic anemia
- Agranulocytosis
Limited Use as an Anti-inflammatory
- Acute phases of gout
- Exacerbation of rheumatoid arthritis
- Osteoarthritis
- Ankylosing spondylitis
Antidepressant Drugs
Mechanism of Action
- Inhibition of norepinephrine (NE), serotonin (5-HT), and dopamine (DA) reuptake
- After exercising their function, 95% of the amines are reuptaken into the presynaptic neuron, and 5% are metabolized by the enzyme monoamine oxidase (MAO)
- Metabolites are active, and the antidepressant efficacy is equivalent to the original drug
Classification of Antidepressants
Tricyclic Antidepressants (TCAs)
- Imipramine
- Amitriptyline
- Nortriptyline
- Desipramine
- Doxepin
Mechanism of Action
- Block the reuptake of NE, 5-HT, and DA
Pharmacological Actions
- Improve mood
- Promote sleep
- Improve appetite
Indications
- Depression
- Bedwetting
- Hyperactive child syndrome
- Agoraphobia
Adverse Effects
- Dry mouth
- Blurred vision
- Drowsiness
- Tachycardia
- Urinary retention
- Confusion
- Delusions
- Decreased libido
Interactions
- Potentiate the effects of alcohol, sedatives, antiparkinsonian drugs, and antipsychotics
Selective Serotonin Reuptake Inhibitors (SSRIs)
- Paroxetine
- Sertraline
- Citalopram
- Fluoxetine
Fluoxetine
- A selective inhibitor of serotonin reuptake
- Indicated for depression, obsessive-compulsive disorder, panic disorder, and bulimia nervosa
- Contraindicated with MAOIs as they lead to increased serotonin, which can lead to serotonin syndrome
Adverse Effects
- Same as tricyclic antidepressants
MAO Inhibitors (MAOIs)
- Tranylcypromine
- Phenelzine
Mechanism of Action
- Increase the levels of NE and 5-HT by inhibiting their metabolism
Adverse Effects
- Headaches
- Orthostatic hypotension
- Weight gain
- Decreased libido
Antipsychotics or Neuroleptics
Antipsychotics produce sedation and relaxation. They are effective in treating acute and chronic psychosis, fear, and aggression. They can cause extrapyramidal reactions but do not lead to physical or psychic dependence.
Classification
Phenothiazines
- Chlorpromazine: Less potent
- Thioridazine: More potent with fewer extrapyramidal effects
- Perphenazine: More potent, with more extrapyramidal side effects and less sedative
Actions
- Sedation
- Decreased reactivity to external stimuli
- Decreased emotional displays
- Disappearance of agitation and aggression
Indications
- Schizophrenia
- Opiate withdrawal syndrome
- Alcoholic psychosis
Adverse Effects
- Sedation
- Dry mouth
- Blurred vision
- Orthostatic hypotension
- Neuroleptic malignant syndrome
- Gynecomastia
Butyrophenones
- Haloperidol: Indicated in psychoses
- Droperidol: Used in neuroleptanalgesia
Pimozide
- Good antipsychotic with few side effects
- Chronic and prolonged action
Lithium Salts
- Suitable for manic-depressive psychosis
Adverse Effects
- Gastrointestinal
- Trembling hands
- Memory loss
- Skin reactions
Poisoning
- Lethargy
- Disorientation
- Convulsions
- Coma
Anxiolytics
Anxiolytics are drugs that relieve anxiety selectively without causing sedation or sleep.
Benzodiazepines
Classification by Duration of Action
Long-Acting (> 30 hours)
- Diazepam
- Clorazepate
- Flurazepam
- Clobazam
- Chlordiazepoxide
- Quazepam
Intermediate-Acting (25-30 hours)
- Bromazepam
- Flunitrazepam
- Nitrazepam
- Ketazolam
Short-Acting (6-24 hours)
- Alprazolam
- Lorazepam
- Lormetazepam
- Oxazepam
- Clotiazepam
- Temazepam
Ultrashort-Acting (< 6 hours)
- Midazolam
- Triazolam
Benzodiazepine Analogues
- Zopiclone
- Zolpidem
- Zaleplon
Pharmacological Actions
- Anxiolysis
- Anticonvulsant
- Antiepileptic
- Hypnotic
- Muscle relaxant
- Mild central antiarrhythmic action
Mechanism of Action
- Facilitate the action of the neurotransmitter GABA by binding to a GABA receptor subunit that is associated with a chloride channel, causing the entry of chloride into the cell, making it refractory to stimuli
- GABA receptors act on both central and peripheral nervous systems
Adverse Effects
- Tolerance
- Dependence: Physical (4 weeks) and mental (4 months)
Clinical Uses
: Anxiety, alcohol addiction, epilepsy, muscle spasms and dystonia.