Steroidal Anti-inflammatory Drugs and Cancer Therapies
Steroidal Anti-inflammatory Drugs
Major Hormones Secreted by Adrenals
Major hormones secreted by adrenals are: cortisol, corticosterone, and aldosterone. They are classified into glucocorticoids and mineralocorticoids.
Glucocorticoids
Glucocorticoids act on the metabolism of carbohydrates, stimulating gluconeogenesis and regulating inflammatory response. The main representative is cortisol.
Among its purposes are:
- Lipid metabolism (body fat distribution)
- Abnormal bone tissue (high doses cause osteoporosis)
- Inhibit growth in children
- Decreased immune response
Mechanism of Action
They inhibit phospholipase A2 and cytokines. They completely inhibit the production of arachidonic acid, reducing prostaglandins and leukotrienes (important in inflammation). Net effect decreases the action of neutrophils, mast cells, eosinophils, and macrophages.
Clinical Uses
Administration and discontinuation should be gradual. They are used in:
- Obstructive respiratory crisis
- Chronic rheumatism
- Anaphylaxis
- Immune diseases
- Inflammation unresponsive to NSAIDs
- Protection from external injuries
ADME
Good oral absorption, high protein binding (90%). Hepatic metabolism and renal excretion.
Adverse Effects
- Renal: Fluid and electrolyte disorder; retains sodium, edema.
- GI: Peptic ulceration
- Endocrine: Cushing’s syndrome, irregular menstruation.
- Ophthalmic: Cataract
- Dermatological: Difficult healing, thin fragile skin (anti-anabolic action for loss of nitrogen and formation of protein)
- Immunological: Increased immunosuppression infections.
- CNS: Psychic disorders, euphoria, insomnia, mood swings, severe depression.
Contraindications and Precautions
Diabetes mellitus, arterial hypertension, peptic ulcers, epilepsy, renal disease, pregnancy (1st trimester), osteoporosis, psychiatric diseases, myasthenia gravis.
Uses in Dentistry
As powerful anti-inflammatories, prednisone is used. (Patients using them for a long time may have dental problems, lowered resistance to infections, and poor healing response).
It is also used in anaphylactic shock via IV betamethasone as an immunosuppressant and anti-inflammatory.
Digestive System: Nervous Regulation
Innervated by the autonomic nervous system (ANS), also abundant cholinergic innervation, vagal afference, and alpha2 adrenergic receptors. The neurotransmitters involved are:
- Serotonin (5HT3 and 5HT4 receptors): Stimulate muscle cells and secretory
- Norepinephrine (alpha2 and beta1-adrenergic receptors): Relaxing action
- Dopamine (D2 receptors): Inhibition of motility
Coadjuvants
Peptides, substance P, opioid peptides, VIP, and nitric oxide.
GI Motility Regulating Drugs
1-Pro-kinetic
Increase wall and sphincter tone. D2 receptor agonists (metoclopramide and domperidone, being dopamine antagonists, are antiemetics with adverse effects at the central level), 5HT3 (metoclopramide), and 5HT4 (Cisapride is more pro-kinetic). They are used in gastroesophageal reflux, nausea relief (migraine), and dyspepsia relief.
2-Inhibitors of Esophageal Dyspnea
Improve esophageal motility (nitrates, calcium agonists, and anticholinergics)
3-General Antispasmodics
Relax GI smooth muscle wall. Cholinergic antagonists such as papaverine, atropine, and scopolamine. May cause hypotension.
Drugs in Control of Gastric Acidity and Peptic Ulcers Treatment
1-Antihistamines H2
Inhibit HCl secretion. (Ranitidine has side effects like gynecomastia and inhibits cytochrome p450 and decreases absorption of famotidine and antacids that do not have these effects)
2-Proton Pump Inhibitors
Omeprazole and lansoprazole inhibit ATPase H/K and are effective in the treatment of ulcers. Adverse effect: inhibits cytochrome p450, therefore inhibits the metabolism of warfarin, phenytoin, diazepam (prolongs its effects).
3-Antacids
Weak salts neutralized in the presence of HCl, but produce compensatory HCl secretion. We have NaHCO3, CaCO3, Al(OH)3, Mg(OH)2. The most used are aluminum hydroxide and magnesium hydroxide. They interact by interfering with the absorption of tetracycline, iron, ranitidine, and prednisone, forming complexes.
4-Protective Gastric Mucosa
A protective layer formed on contact with water interacts, preventing the absorption of ciprofloxacin, theophylline, aminophylline, tetracycline, and warfarin.
Antineoplastic Therapy
Cancer
Abnormal cell growth that can invade other normal tissue or spread to other organs (metastasis). Its malignancy is based on the degree to which cells invade and spread from a distance. Cancer therapies: radiotherapy, surgery, and chemotherapy. The latter may be curative or palliative, depending on the tumor.
Potentiation of Oncolytic Agents
It is understood as increasing efficiency by the combined use of two or more agents that result in increased patient survival and no increase in toxicity. There are cycle-specific and cycle-nonspecific drugs. The latter affects cells in any stage, lengthening the S phase (DNA replication) and irreversibly blocking the G2 phase (RNA synthesis).
Toxicity
Bone marrow produces a decrease in platelets and leukocytes, as gastrointestinal ulceration is. At the hair follicle, there is temporary hair loss. The most terrible adverse effect is nausea and vomiting in 60% of cases. Other effects are suppression of ovarian activity and spermatogenesis, cardiac toxicity, and tumor formation (alkylating agents by modifying the DNA).
Drugs
- Alkylating agents: Transferring alkyl groups to cellular constituents, altering its function.
- Antimetabolites: Structural analogs of normal metabolites, altering the rate of cell growth.
- Vegetable alkaloids: Block mitosis at metaphase.
- Antibiotics: Inhibit cell growth by blocking DNA transcription.
- Enzymes: Destroys L-asparagine, inhibiting cell growth dependent on this.
- Steroidal hormones: Alter the hormonal balance, which affects cell growth.
- Biological response modifiers: Alter interactions between a tumor and the body.
- Immunomodulatory agents: Increase the activity of macrophages, NK cells.
- Cytokines: Stimulate NK cells, lymphokine, interrupt cell proliferation.
- Growth factors and differentiation factors: Modulate tumor growth.
- Monoclonal antibodies