Pharmacological Treatments for Acne and Other Disorders

• Pharmacological treatments available for skin disorders, gout, bone issues, and the autonomic nervous system

Acne Treatment Options

• Mild acne responds well to topical treatments like Tretinoin and Benzoyl Peroxide.
• Tretinoin increases cell turnover and reduces comedones.
• Benzoyl Peroxide attacks acne-causing bacteria with its antibacterial properties.
• Moderate acne is often treated with oral antibiotics, such as Minocycline.
• Minocycline, a tetracycline antibiotic, lessens inflammation and bacterial growth.
• Severe nodulocystic acne typically requires Isotretinoin.
• Isotretinoin is a potent retinoid that dramatically lowers sebum production.
• Isotretinoin carries a high risk of adverse effects, including teratogenic effects, necessitating strict pregnancy prevention.
• BE TIM(my) is an acronym to recall acne treatments: Benzoyl Peroxide, Tretinoin, Isotretinoin, Minocycline
• Patients taking Isotretinoin need regular monitoring of CBC, lipid levels, and liver function because of potential side effects.
• Isotretinoin may be considered for severe acne unresponsive to topical treatments after discussing potential risks and benefits.

Psoriasis Treatment Options

• Topical treatments for psoriasis include Betamethasone (a steroid) and Tazarotene (a vitamin A analog).
• Both Betamethasone and Tazarotene help reduce inflammation and skin cell turnover.
• Calcipotriene, a Vitamin D analog, is another effective topical treatment that regulates skin cell production.
• Systemic treatments, including biologics targeting specific immune response pathways, may be required for severe cases.
• Patients should know psoriasis is chronic and understand the importance of adhering to treatment plans.
• Plaque psoriasis may improve with a combination of topical Betamethasone and Calcipotriene.
• Regular follow-ups are needed to assess treatment effectiveness and make therapy adjustments.

Gout Treatment Options

• Acute gout attacks are primarily treated with NSAIDs and Colchicine.
• Colchicine can cause gastrointestinal side effects like explosive diarrhea, requiring monitoring.
• Allopurinol is used for long-term prevention of gout attacks by lowering uric acid levels in the blood.
• Patients should modify their diet to lower purine intake, which can worsen gout.
• Consistent monitoring of uric acid levels is crucial for gout management.
• Managing recurrent gout attacks might need a blend of NSAIDs for immediate relief and Allopurinol for prevention.
• Patients should know about potential Allopurinol side effects, including skin rashes and liver abnormalities.

Adverse Effects and Management of Corticosteroids

• Corticosteroid usage can result in several adverse effects, which can be remembered using the acronym FORTH WI(d)TH: Fluid retention, Osteoporosis, Thin skin/bruising, Hyperglycemia, Weight gain, Infections, Hypokalemia.
• Fluid retention can lead to hypertension and edema, necessitating monitoring of blood pressure and weight.
• Long-term use increases fracture risk; patients should supplement with calcium and vitamin D to counter Osteoporosis
• Patients may experience thinning skin and easy bruising, so gentle skin care is needed.
• Corticosteroids can induce Hyperglycemia/diabetes, so blood glucose levels should be monitored in at-risk patients.
• Immunosuppression increases the risk of infections; patients should be educated on signs of infection.

Bone Disorder Medications

• Alendronate is used for osteoporosis, with osteonecrosis of the jaw as a notable side effect, so dental evaluations are needed before treatment.
• Calcitonin-Salmon is used for Paget's disease and osteoporosis, but is contraindicated in patients with fish allergies and administered via the nasal route.
• Calcitriol boosts calcium absorption, particularly in patients with renal disease and low serum calcium levels.
• Methotrexate, used for psoriasis, can cause bone marrow suppression, leading to anemia and increased bleeding risk.
• Raloxifene is used for osteoporosis but is contraindicated in patients with a history of deep vein thrombosis (DVT).
• Consistent medication adherence and regular follow-ups are essential for monitoring bone density.

Autonomic Nervous System Drugs

• Adrenergic and cholinergic drugs affect the autonomic nervous system.
• Adrenergic and cholinergic receptors are two major classes of receptors in the autonomic nervous system (ANS).
• Norepinephrine/epinephrine (adrenergic) and acetylcholine (cholinergic) are neurotransmitters, and their effects are mediated by these receptors.
• Drugs targeting these receptors have a wide range of therapeutic applications.

Adrenergic Drugs

• Albuterol, a beta-2 agonist for asthma, can cause tachycardia and headaches due to beta-1 stimulation.
• Epinephrine stimulates multiple adrenergic receptors and is used in anaphylaxis and cardiac arrest.
• Metoprolol, a beta-1 blocker, lowers heart rate; watch for bradycardia and hypotension.
• Phenylephrine, an alpha-1 agonist used as a decongestant, is contraindicated in closed-angle glaucoma due to vasoconstriction.
• Prazosin, an alpha-1 blocker for hypertension and BPH, requires monitoring for orthostatic hypotension.
• Patients should know how to take medications as prescribed and recognize the side effects.

Adrenergic Receptors

• Adrenergic receptors are G protein-coupled receptors (GPCRs) that are activated by catecholamines like norepinephrine (noradrenaline), epinephrine (adrenaline), and dopamine.
• These receptors are divided into two main types: alpha (α) and beta (β) receptors.
• Both α and β receptors are further subdivided into subtypes: α₁, α₂, β₁, β₂, and β₃.

Alpha (α) Receptors

• α₁ Receptors:
  • Primarily located on postsynaptic effector cells.
  • Activation leads to smooth muscle contraction (vasoconstriction, increased blood pressure), pupillary dilation (mydriasis), and increased glycogenolysis.
  • Found in blood vessels, iris, and bladder.
• α₂ Receptors:
  • Located on presynaptic nerve terminals and postsynaptic locations.
  • Presynaptic α₂ receptors inhibit further norepinephrine release (negative feedback).
  • Postsynaptic α₂ receptors can cause smooth muscle contraction.
  • Found in blood vessels and platelets.
• α-Adrenergic Agonists:
  • Phenylephrine: α₁-selective agonist used as a decongestant and to raise blood pressure.
  • Clonidine: α₂-selective agonist used as an antihypertensive by reducing sympathetic outflow from the brain.
• α-Adrenergic Antagonists (Blockers):
  • Prazosin: α₁-selective antagonist used to treat hypertension and benign prostatic hyperplasia (BPH) by relaxing smooth muscle in blood vessels and the prostate.
  • Yohimbine: α₂-selective antagonist that increases norepinephrine release; has limited clinical use due to side effects.

Beta (β) Receptors

• β₁ Receptors:
  • Predominantly located in the heart.
  • Activation increases heart rate (chronotropy), contractility (inotropy), and conduction velocity (dromotropy).
  • Also found in the kidneys, where they stimulate renin release.
• β₂ Receptors:
  • Found in smooth muscle of bronchioles, blood vessels, and the uterus.
  • Activation causes smooth muscle relaxation (bronchodilation, vasodilation, uterine relaxation).
  • Also involved in glycogenolysis and gluconeogenesis in the liver and skeletal muscle.
• β₃ Receptors:
  • Primarily found in adipose tissue.
  • Activation promotes lipolysis (breakdown of fats).
  • Also found in the bladder, where they cause relaxation of the detrusor muscle.
• β-Adrenergic Agonists:
  • Isoproterenol: Non-selective β-agonist that increases heart rate and causes bronchodilation.
  • Albuterol: β₂-selective agonist used as a bronchodilator in asthma.
  • Dobutamine: β₁-selective agonist used as a cardiac stimulant in heart failure.
• β-Adrenergic Antagonists (Beta-Blockers):
  • Propranolol: Non-selective β-blocker used to treat hypertension, angina, and arrhythmias.
  • Metoprolol: β₁-selective blocker (cardioselective) used to treat hypertension and angina, with fewer side effects related to bronchodilation.

Cholinergic Drugs

• Atropine, an anticholinergic for bradycardia, may cause dry mouth and urinary retention (DDUCCT).
• Bethanechol, a cholinergic agonist for urinary retention can cause diarrhea and increased salivation (DUMBELLS).
• Edrophonium distinguishes between myasthenia gravis and cholinergic crisis with its rapid onset.
• Oxybutynin, an anticholinergic for overactive bladder, requires monitoring for dry mouth and constipation.
• Succinylcholine, a depolarizing neuromuscular blocker for short surgeries, carries a risk of malignant hyperthermia.
• Inform patients of overdose signs and the importance of reporting side effects.

Cholinergic Receptors

• Cholinergic receptors are activated by the neurotransmitter acetylcholine (ACh).
• There are two main types: nicotinic and muscarinic receptors.

Nicotinic Receptors

• Nicotinic receptors are ligand-gated ion channels.
• They are located at the neuromuscular junction (NMJ) in skeletal muscle, autonomic ganglia, and in the central nervous system (CNS).
• Activation of nicotinic receptors leads to an influx of sodium ions, causing depolarization and excitation.
• Subtypes include:
  • Nm: found at the neuromuscular junction
  • Nn: found in autonomic ganglia and the CNS
• Nicotinic Agonists:
  • Nicotine: Stimulates nicotinic receptors in the brain and autonomic ganglia.
  • Succinylcholine: Nm agonist used as a muscle relaxant during surgery (depolarizing neuromuscular blocker).
• Nicotinic Antagonists (Blockers):
  • Tubocurarine: Nm antagonist, a non-depolarizing neuromuscular blocker used to cause muscle paralysis.
  • Hexamethonium: Nn antagonist, blocks nicotinic receptors in autonomic ganglia.

Muscarinic Receptors

• Muscarinic receptors are G protein-coupled receptors (GPCRs).
• Located on target organs of the parasympathetic nervous system, as well as in the CNS.
• There are five subtypes: M₁, M₂, M₃, M₄, and M₅.
• M₁ Receptors:
  • Located in the CNS, gastric parietal cells, and salivary glands.
  • Activation leads to increased gastric acid secretion, increased salivation, and CNS excitation.
• M₂ Receptors:
  • Located in the heart.
  • Activation leads to decreased heart rate (chronotropy), decreased contractility (inotropy), and decreased conduction velocity (dromotropy).
• M₃ Receptors:
  • Located in smooth muscle, exocrine glands, and the endothelium.
  • Activation leads to smooth muscle contraction (bronchoconstriction, increased gut motility, bladder contraction), increased secretions (salivation, sweating), and vasodilation (via nitric oxide release from endothelial cells).
• M₄ and M₅ Receptors:
  • Primarily located in the CNS.
  • Involved in various functions including motor control and cognition.
• Muscarinic Agonists:
  • Pilocarpine: Non-selective muscarinic agonist used to treat glaucoma and dry mouth (xerostomia).
  • Bethanechol: Selective M₃ agonist used to stimulate bladder contraction and treat urinary retention.
• Muscarinic Antagonists (Blockers):
  • Atropine: Non-selective muscarinic antagonist used to treat bradycardia, reduce secretions before surgery, and dilate pupils (mydriasis).
  • Scopolamine: Non-selective muscarinic antagonist used to prevent motion sickness.
  • Ipratropium: Non-selective muscarinic antagonist used as a bronchodilator in asthma and COPD.

Clinical Applications

• Adrenergic and cholinergic drugs are used to treat a wide variety of conditions.
• Cardiovascular Diseases: Beta-blockers for hypertension and angina, alpha-agonists for hypotension.
• Respiratory Diseases: Beta-agonists and muscarinic antagonists for asthma and COPD.
• Urological Conditions: Alpha-antagonists for BPH, muscarinic agonists for urinary retention.
• Ophthalmic Conditions: Alpha-agonists for pupillary dilation, muscarinic agonists for glaucoma.
• Neurological and Psychiatric Conditions: Centrally acting adrenergic and cholinergic drugs for various conditions.

Overview of pharmacological treatments for skin disorders like acne, gout, bone issues, and autonomic nervous system conditions. Acne treatments range from topical applications like Tretinoin and Benzoyl Peroxide for mild cases, to oral antibiotics such as Minocycline for moderate acne. Severe nodulocystic acne often requires Isotretinoin.