Exophthalmic Goitre -  

Exophthalmos - abnormal protrusion of one or both eyes anteriorly out of the orbit due to increase in orbital contents

Mechanism of Exophthalmos- Activation of Orbital Fibroblasts - The autoantibodies produced in Graves' disease can bind to TSH receptors on orbital fibroblasts, which are the cells surrounding the eye. This binding leads to the activation of orbital fibroblasts, causing them to proliferate and secrete various substances, including glycosaminoglycans (GAGs) and cytokines.

Abnormal accumulation of hyaluronic acid and the buildup of edema within the retro-orbital space lead to the enlargement of the extraocular muscles and the expansion of orbital adipose tissues leading to exophthalmos.

Goitre - Goitre is a medical term used to describe the enlargement of the thyroid gland, which is located in the front of the neck. This enlargement is often visible as a swelling or lump in the neck.

Mechanism of Goitre - 

a) Autoimmune Stimulation: Graves' disease is an autoimmune disorder where the immune system mistakenly produces antibodies, such as thyroid-stimulating immunoglobulins (TSI) which belongs to IgG class of antibody, which act like thyroid-stimulating hormone (TSH). These antibodies bind to thyroid(TSH) receptors and stimulate the thyroid gland to produce excessive amounts of thyroid hormones (T3 and T4). 

b) Excessive Thyroid Hormones: The overproduction of thyroid hormones by the thyroid gland leads to a condition known as hyperthyroidism. Elevated levels of these hormones can result in the enlargement of the thyroid gland (goitre).

Goitrogens - Thioamide antithyroid drugs like Propylthiouracil, Carbimazole, Methimazole and Ionic inhibitors like Thiocyanates, Perchlorates, Nitrates are called goitrogens because, if given in excess, they cause enlargement of thyroid by feedback release of TSH.

Goitrogenic foods - Cabbage, Turnip, Mustard, Cassava, Rutabagas.

Merseburg triad, including palpitations (due to hyperthyroidism), goiter, and exophthalmos (Graves’ orbitopathy), characterizes the classical description of Graves’disease

Treatment - Graves’ disease is treated with any of three effective and relatively safe initial treatment options: antithyroid drugs (ATDs), radioactive iodine ablation (RAIU), and surgery(Total thyroidectomy)

antithyroid drugs (ATDs)  used prior to surgery - Carbimazole, Lugol's iodine

Lugol's solution (LS) was created in 1829 by the French physician Jean Guillaume August Lugol with its initial purpose being a treatment for tuberculosis. The solution consists of elemental iodine (5%) and potassium iodide (KI, 10%) combined with distilled water.

In India, Carbimazole is commonly used for the treatment of hyperthyroidism, whereas Methimazole is not available on the market. The use of Propylthiouracil is generally limited due to its shorter duration of action and the increased risk of severe hepatitis, making it a preferable option for early pregnancy when there is a need to minimize placental transfer compared to Carbimazole.

To prevent the potential onset of a thyroid storm during surgery, it is advisable to initiate pretreatment with antithyroid drugs (ATDs) to promptly attain a euthyroid (normal thyroid function) state. In most cases, euthyroidism can be achieved within a few weeks of ATD therapy. Additionally, beta-blockers like propranolol are often added to the treatment regimen to effectively manage hyperthyroid symptoms. Prior to surgery, the use of a saturated solution of potassium iodide (SSKI) or potassium iodine (Lugol's solution) for a short duration is recommended. This helps reduce both the release of thyroid hormones and the vascularity of the thyroid gland, ultimately leading to a decrease in intra-operative blood loss.

Carbimazole - Plasma t1/2 - 6 - 10 hours and duration of action - 12 to 24 hours. so single daily dosing. Doesn't inhibit peripheral conversion of T4 to T3. Large amounts cross placenta and enter breast milk.

PTU - Plasma t1/2 - 1-2 hours and duration of action - 4 to 8 hours. so 2 to 3 daily doses needed. Inhibit peripheral conversion of T4 to T3. Small amounts cross placenta and enter breast milk.

Cretinism - 

Cretinism is a severe condition caused by untreated congenital deficiency of thyroid hormones, also known as congenital hypothyroidism. 

There are two main types of cretinism: neurological and myxedematous. 

Neurological endemic cretinism is characterized by extremely severe mental deficiency, along with squint, deaf mutism, and motor spasticity. Goiter, an enlargement of the thyroid gland, is often present in these cases. The underlying neurological abnormalities include underdevelopment of the cochlea, which leads to deafness, maldevelopment of the cerebral neocortex resulting in mental retardation, and maldevelopment of certain parts of the brain, like the corpus striatum, contributing to motor disorders. This form of cretinism is primarily associated with maternal hypothyroidism due to iodine deficiency, and there may also be a genetic predisposition. 

Myxedematous cretinism, on the other hand, is characterized by severe growth retardation and various physical features like underdeveloped facial structures, puffy appearance, thickened and dry skin, and delayed sexual maturation. Notably, goiter is usually absent, and the thyroid may be atrophied. Blood tests reveal extremely low levels of thyroid hormones (T4 and T3), high levels of thyroid-stimulating hormone (TSH), and reduced thyroidal uptake of radioiodine. Additionally, some individuals with myxedematous cretinism may have markedly enlarged sella turcicae. In summary, cretinism is a serious condition resulting from thyroid hormone deficiency at birth. It can manifest as neurological or myxedematous cretinism, each with distinct clinical features and underlying causes. Neurological cretinism is linked to maternal hypothyroidism and genetic factors, while myxedematous cretinism is characterized by physical and hormonal abnormalities, often without a goiter.

another classification - 

Endemic cretinism - due to extreme Iodine deficiency

Sporadic cretinism - due to thyroid gland underdevelopment or defect in thyroid hormone synthesis

Treatment - Thyroxine(8-12 micrograms/kg) daily started as soon as possible, because mental retardation that has already set in is only partially reversible. It is crushed on a spoon and mixed in milk or water, but not put in the bottle so as to ensure full dose delivery. The tablets are sweet. In most cases of congenital hypothyroidism the duration of therapy is lifelong

Alopecia areata - 

Alopecia areata typically begins with a round or oval, smooth bald spot on the scalp. This bald patch is often the initial indication of the condition, and it doesn't exhibit any signs of irritation such as swelling or changes in color.

Alopecia areata vs Telogen effluvium vs anagen effluvium

Alopecia Areata: It is an autoimmune condition where the body's immune system mistakenly attacks hair follicles, leading to hair loss in well-defined, often round or oval patches. The exact cause of this autoimmune response is not fully understood but is thought to involve genetic and environmental factors. 

Telogen Effluvium: This type of hair loss is usually triggered by a specific event or circumstance, such as a significant physical or emotional stress, illness, surgery, childbirth, medication, or nutritional deficiencies. It disrupts the normal hair growth cycle, leading to excessive shedding of hair.

Anagen effluvium: It is an atypical and swift hair loss occurring during the initial growth phase (anagen) of the hair cycle. It can result from the use of cancer treatment medications or exposure to specific harmful chemicals.

Drug induced alopecia - anticancer drugs, Heparin, Warfarin

Incidence of alopecia associated to the main chemotherapic drug categories

a) Anti-microtubule agents - 80%

b) Topoisomerase inhibitors - 60%-100%

c) Alkylators - >60%

d) Antimetabolites -10%-50%

Hair-shaft shedding due to chemotherapy can occur days to weeks after treatment begins, and various shedding patterns may be observed, such as dystrophic anagen effluvium and telogen effluvium. 

It often affects the frontal or occipital hairlines selectively. 

The shedding pattern is influenced by the hair follicle's mitotic activity at the time of chemotherapy exposure. The main targets of cancer drugs are the highly proliferative matrix keratinocytes and their pigmentary system during the anagen phase, making them sensitive to toxins and drugs. Catagen and telogen phases are not affected since they are mitotically inactive, but late anagen phase hair is accelerated into telogen. 

Scalp hair is most frequently affected because a significant portion is typically in the anagen phase. Other body hairs, like those in the beard, eyebrows, eyelashes, and pubic regions, are affected based on the percentage of hairs in the anagen phase. Generally, this type of hair loss is reversible, with hair typically regrowing within 3-6 months. However, in rare cases, permanent alopecia can occur, often associated with high-dose chemotherapy or specific drug administrations, possibly due to damage to hair-follicle stem cells.

Alopecia totalis is a chronic condition of complete hair loss of the scalp

Alopecia universalis (AU) is a condition characterized by the complete loss of hair on the scalp and body including eyebrows, eyelashes, chest hair, armpit hair, and pubic hair.

Gingival hyperplasia - 

Drugs causing Gingival Hyperplasia - Phenytoin, Nifedipine, Cyclosporine A

Mechanism - 

a. Phenytoin disrupts calcium ion (Ca2+) influx, leading to reduced folic acid uptake and limited production of active collagenase. 

b. Phenytoin reduces collagen endocytosis by decreasing the expression of α2β1-integrin in fibroblasts. 

c. Phenytoin stimulates myofibroblasts, contributing to gingival overgrowth. 

d. Cytokines, such as IL-6, IL-1, and IL-8, produced by phenytoin-activated fibroblasts, activate T cell proliferation and neutrophil recruitment, linking the immune system to connective tissue, a common feature in fibrotic diseases. 

e. Dental plaque can induce a local inflammatory response, which is essential for the development of gingival overgrowth. 

f. Growth factors, including CTGF, PDGF, FGF, and TGF-β, are found in higher levels in fibrotic tissues and play a role in phenytoin-induced gingival overgrowth. 

g. Phenytoin affects the production of IL-13 by activating Th2 cells and induces the release of TGF-β, CTGF, and other growth factors by macrophages. 

h. These actions synergistically lead to fibroblast proliferation, increased collagen production, activation of tissue inhibitors of metalloproteinases (TIMPs), inhibition of matrix metalloproteinases (MMPs), and enhanced extracellular matrix (ECM) synthesis, which are characteristic processes observed in fibrotic lesions.

Phenytoin - route of administration - Phenytoin is available in oral and parenteral formulations

Phenytoin can be given iv for digoxin induced cardiac arrhythmias. Phenytoin is a Class 1B antiarrhythmic that can be used in digoxin toxicity, it inhibits digitalis binding to the sodium-potassium-ATPase pump and antagonizes digitalis induced delayed after depolarization. The effective dose is 5–15 mg/kg/day infusion with a targeted serum level of 10–18 mcg/mL. The recommended of infusion rate is 10–25 mg/min in patients with a cardiovascular problem and 30–40 mg in patients without cardiovascular disease.

Scabies - 

The most common presenting lesions are papules, vesicles, pustules, and nodules. The pathognomonic sign is the burrow; a short, wavy, scaly, grey line on the skin surface . These burrows are most easily found on the hands and feet, particularly in the finger web spaces, thenar and hypothenar eminences, and on the wrists.

Scabies is an intensely itchy dermatosis caused by the mite Sarcoptes scabiei.

Crusted scabies : It is also known as Norwegian scabies because of its initial description in Norwegian patients with leprosy. In patients with neurological disorders or immunosuppression the number of mites can escalate rapidly. This may be due to the impaired immune response, the lack of pruritus, or the patient's physical inability to scratch. Clinically, the eruption is suspected when there is marked thickening and crusting of the skin (fig 3), particularly on the hands, although the entire body including the face and scalp is often involved.

Drugs - 

Permethrene 5% cream

Ivermectin 0.2mg/kg single dose

Benzyl benzoate 25% lotion

Read more about scabies in - click here

Trachomatous eye -

The WHO grading system for trachoma classifies the disease in 5 grades: (FISTO Classification)

Trachomatous Inflammation – Follicular (TF) - which mostly requires topical treatment. 

Trachomatous Inflammation – Intense (TI) - during which topical and systemic treatments are considered.

 Trachomatous Scarring (TS) - when scars are visible as in the tarsal conjunctiva and which may obscure tarsal blood vessels. 

Trachomatous Trichiasis (TT) - when an individual is referred for eyelid surgery; and 

Corneal Opacity - a stage during which a person is irreversibly blind.

Trachoma is associated mainly with infection by serovars A, B, Ba, and C of Chlamydia trachomatis. Serovars D-K are conventionally associated with adult inclusion conjunctivitis. Other species of the Chlamydiaceae family, such as Chlamydophilia psittaci and Chlamydophila pneumoniae, have also been implicated.

SAFE Strategy Trachoma treatment - 

The SAFE strategy recommended by WHO encompasses surgery for trichiasis, antibiotics, facial hygiene, and environmental improvement. 

Surgery may be required for relieving entropion and trichiasis and maintaining complete lid closure.

Antibiotics should be administered to the patient as well as to all the family members. A single dose of azithromycin (20 mg/kg up to 1g) is the treatment of choice. Erythromycin 500 mg twice daily for 14 days or doxycycline 100 mg twice daily for 10 days may be considered (use tetracyclines with caution in pregnancy/breastfeeding/children). 1% tetracycline ointment may be used topically. However, it is less effective than oral treatment. 

Facial cleanliness is important.

Environmental improvement, for example, proper sanitation, access to clean drinking water, and control of flies, etc.

X-ray of Acute Gout -

The tophus, a cardinal feature of gout, is a complex mass comprised of monosodium urate (MSU) crystals, a variety of immune and inflammatory cells, and a fibrous capsule. Tissue deposition of urate crystals initiates tophus formation with a local inflammatory and subsequent fibrotic tissue response.

Treatment of acute gout - 

Colchicine - Colchicine modulates multiple pro- and antiinflammatory pathways associated with gouty arthritis. Colchicine prevents microtubule assembly and thereby disrupts inflammasome activation, microtubule-based inflammatory cell chemotaxis, generation of leukotrienes and cytokines, and phagocytosis.

Sie effects - Most commonly GI related side effects - Diarrhoea>Vomiting>Nausea

others - 

Neurologic - sensorimotor neuropathy 

Dermatologic - alopecia, maculopapular rash, purpura, rash 

Gastrointestinal - abdominal cramping, abdominal pain, lactose intolerance 

Hematologic - leukopenia, granulocytopenia, thrombocytopenia, pancytopenia, aplastic anemia 

Hepatobiliary - elevated AST, elevated ALT 

Musculoskeletal - myopathy, elevated CPK, myotonia, muscle weakness, muscle pain, rhabdomyolysis.

 Reproductive - azoospermia, oligospermia

NSAIDs - Indomethacin, Ibuprofen, Naproxen, Diclofenac.

The most common side effects of NSAIDs are gastrointestinal problems, including stomach irritation and reflux, Peptic ulcers.

Brownish discoloration of teeth by Tetracycline

One of the side-effects of tetracyclines is incorporation into tissues that are calcifying at the time of their administration. They have the ability to chelate calcium ions and to be incorporated into teeth, cartilage and bone, resulting in discoloration of both the primary and permanent dentitions.

Tetracycline uses -

1st line for  - Lymphogranuloma venerum, Granuloma inguinale, Brucellosis, Plague, Relapsing Fever, Rickettsial infections(Q fever, Typhus, Rocky mountain spotted fever)

DNA Dependent RNA Polymerase inhibition - Rifampicin - uses - Tuberculosis, Leprosy, Prophylaxis for Meningococcal meningitis and Hemophilus influenza meningitis.

Rifampicin + Doxycycline - first line for brucellosis

2nd line for MRSA, Diphtheroids, Legionella infections

Cell membrane leakage - Polymyxin B, Colistin, Amphotericin B, Bacitracin - uses - Polymyxin B sulfate is a drug of choice in the treatment of infections of the urinary tract, meninges, and bloodstream caused by Pseudomonas aeruginosa. Polymyxins comprise a class of antibiotics targeting gram-negative bacterial infections. Polymyxin B and Polymyxin E (colistin). Bacitracin and polymyxin B is used to prevent infections caused by minor cuts, scrapes, or burns. other uses - skin and soft tissue infections, conjunctivits, corneal ulcers.

30s Ribosomes inhibition - Tetracyclines, Streptomycin 

Tetracyclines - They specifically inhibit the 30S ribosomal subunit, hindering the binding of the aminoacyl-tRNA to the acceptor site on the mRNA-ribosome complex. When this process halts, a cell can no longer maintain proper functioning and will be unable to grow or further replicate.

Aminoglycosides - Streptomycin - The site of streptomycin action is the ribosome subunit small or 30S, in particular the ribosomal protein S 12 and 16S rRNA. Streptomycin functions by interfering with the synthesis of ribosomal proteins. Most c ommon side effect is ototoxicity.Some of the common side effects of aminoglycoside antibiotics, including streptomycin, are ototoxicity, nephrotoxicity, paralysis(neuromuscular blockade), and skin rashes. uses of aminoglycosides - TB(Streptomycin), SABE(Subacute bacterial endocarditis - Gentamicin)

50s Ribosomes inhibition - Macrolides, Chloramphenicol(side effect - Gray baby syndrome is an adverse reaction to chloramphenicol that is characterized by abdominal distention, hemodynamic collapse, and ashen-gray skin discoloration in neonates.)

DNA gyrase inhibitor - Quinolones(Nalidixic acid). Nalidixic and oxolinic acids inhibit DNA gyrase activity and induce formation of a relaxation complex analogue. It is bactericidal. Nalidixic acid is active against Gram negative bacteria especially coliforms - E.coli, Klebsiella, Proteus, Enterobacter, Shigella but not pseudomonas. 

Tetracycline molecules comprise a linear fused tetracyclic nucleus (4 rings). Tetracycline examples -  Doxycycline, Oxytetracycline, Minocycline, Demeclocycline, Tigecycline

The basic chemical structure of all penicillins consists of a beta-lactam ring, a thiazolidine ring, and a side chain (6-aminopenicillanic acid)

Dihydropteroate synthetase inhibitors - 

a)Sulphonamides - example - sulfadiazine(short acting), sulfamethoxazole(intermediate acting), sulfadoxine, sulfamethopyrazine(long acting), sulfacetamide sodium, sulfasalazine, silver sulfadiazine, Mafenide(special purpose)

Cotrimoxazole - Sulfamethoxazole(400mg/800mg) + Trimethoprim(80mg/160mg)

Cotrimazine - Sulfadiazine + Trimethoprim

All sulphonamides are derivatives of sulfanilamide(p-aminobenzene sulfonamide)

b) PAS

c) Dapsone

Dihydrofolate reductase inhibitor - Trimethoprim, Pyrimethamine, Methotrexate

Rifampicin - Red color is due to naphthoquinone chromophore.

uses - Tuberculosis, Leprosy, Prophylaxis for Meningococcal meningitis and Hemophilus influenza meningitis.

Rifampicin + Doxycycline - first line for brucellosis

2nd line for MRSA, Diphtheroids, Legionella infections

Side effects - 

Hepatitis, 

Cutaneous syndrome - Pruritus + Rash(especially on face and scalp), redness, flushing, redness and watering of eyes.

Flu syndrome - Fever, chills, headache, malaise, Bone pain

Abdominal syndrome - Abdominal cramps, nausea, vomiting, diarrhoea

Urine and Secretions may become orange red color

rare and serious - hemolysis, shock, renal failure

Red man syndrome - The anaphylactic reaction is mediated by IgE. Red man syndrome, an anaphylactoid reaction, is caused by the degranulation of mast cells and basophils, resulting in the release of histamine independent of preformed IgE or complement. Anaphylactoid reactions are immediate systemic reactions that mimic anaphylaxis but are not caused by IgE-mediated immune responses.

drugs causing red man syndrome - ciprofloxacin, amphotericinB, rifampcin, vancomycin and teicoplanin.

Red man syndrome - The anaphylactic reaction is mediated by IgE. Red man syndrome, an anaphylactoid reaction, is caused by the degranulation of mast cells and basophils, resulting in the release of histamine independent of preformed IgE or complement. Anaphylactoid reactions are immediate systemic reactions that mimic anaphylaxis but are not caused by IgE-mediated immune responses.

drugs causing red man syndrome - ciprofloxacin, amphotericinB, rifampcin, vancomycin and teicoplanin.

Vancomycin uses - MRSA, Pseudomembranous enterocolitis

Digitalis purpurea(Foxglove plant) - 

Na+ - K+ ATPase inhibitor - Cardiac glycosides like Digoxin(Digitalis lanata), Digitoxin(Digitalis purpurea), Ouabain(Strophanthus gratus), Bufotoxin( Toad skin)

Cardiac glycosides - consists of an aglycone(genin) and sugar moeities. aglycone consists of cyclopentanoperhydrophenanthrene(steroid) ring to which attached 5 or 6 membered unsaturated lactone ring.

digoxin - increase myocardial contractility(positive inotropic effect) and increase cardiac output without a proportionate increase in oxygen consumption, thus increase efficiency of failing heart.

what are other glycosides you know apart from cardiac glycosides ? ans - Aminoglycosides, coumarin glycosides

Inotropy - cardiac contractility

Chronotropy - Heart rate(SA node)

Dromotropy - Conduction(AV node)

Bathmotropy - Cardiac excitability

Lusiotropy - Myocardial relaxation

side effects of digitalis - 

cardiac - arrhytmia (pulsus bigeminus - most common) others like nodal and ventricular extrasystoles, ventricular tachycardia, ventricular fibrillation, AV blocks

extracardiac - anorexia, nausea, vomiting, abdominal pain, headache , delirium, disorientation, psychosis, visual disturbances, restlessness, hyperapnea

ACE Inhibitors inhibit ACE(Angiotensin converting enzyme) thus preventing conversion of angiotensin 1 to angiotensin 2(go through image mechanism of RAAS) 

ACE Inhibitors - Captopril, enalapril, lisinopril, Ramipril, Perindopril, Fosinopril

Side effects - mnemonic - captopril

cough(dry cough), angioedema, proteinuria, taste change, others(Rash, Fatigue), pregnancy changes, renal insufficiency, increased potassium(hyperkalemia), and lower blood pressure(hypotension)

contraindications - pregnancy and bilateral renal artery stenosis, c1 esterase inhibitor deficiency(hereditary angioedema).

Diuretics - site of actions

a) Carbonic anhydrase inhibitors - PCT(Proximal convoluted tubule) - inhibit carbonic anhydrase enzyme

b) Loop diuretis - Thick ascending limb of loop of henle - Na+-K+-2Cl- symporter

c) Thiazides - Distal convoluted tubule(DCT) - Na+-Cl- symporter

d) Epithelial sodium channel inhibitors - Late distal tubule and collecting ducts - ENaC receptor

e) Aldosterone antagonists - Late distal tubule and collecting ducts - Mineralocorticoid receptors(indirectly ENaC)

Loop diuretics / High ceiling diuretics - Furosemide(20-80mg OD oral/IV), Bumetanide(1-5mg oral OD, 2-4mg IM/IV), Torsemide(2.5-5mg OD in hypertension, 5-20mg/day in edema upto 100mg/day in renal failure).

Thiazide diuretics - Hydrochlorthiazide(12.5-100mg)  uses of thiazide diuretics are Edema, Hypertension, Diabetes insipidus, Hypercalciuria with recurrent calcium stones in kidney(acts by reducing ca2+ excretion)

Atropine - moa - competitive, reversible antagonist of muscarinic receptors: an anticholinergic drug, it blocks the effects of neurotransmitter acetylcholine.

Antidote - Anticholinesterase - Physostigmine (Because it enhances the transmission of acetylcholine signals in the brain and can cross the blood–brain barrier, physostigmine salicylate is used to treat anticholinergic poisoning caused by overdoses of atropine, scopolamine and other anticholinergic drugs. It is also used to reverse neuromuscular blocking drugs.)

The tertiary amine structure of physostigmine allows it to penetrate the blood-brain barrier and exert central cholinergic effects as well. Neostigmine, a quaternary ammonium compound, is unable to penetrate the CNS.

Optic disc cupping seen in glaucoma 

drugs for glaucoma - 

Timolol - 0.25 to 0.5% - non-selective(beta1 and beta2) beta blocker

Pilocarpine (miotics)- 1 to 4%

Physostigmine - 0.25 to 0.5%

classification - 

a) beta adrenergic blockers - (moa - decrease aqueous secretion )- timolol, betaxolol, levobunolol, carteolol 

b) alpha adrenergic agonists - apraclonidine, brimonidine, dipivefrine

c) prostaglandin analogues - (moa - increase trabecular outflow and uveoscleral outflow)- latanoprost, travoprost, bimatoprost

d)carbonic anhydrase inhibitors - (moa - decrease aqueous secretion) - dorzolamide, brinzolamide

e) miotics - (moa - increase trabecular outflow) - pilocarpine, physostigmine, ecothiophate

Centrally acting antihypertensives - Central sympatholytics (e.g., methyldopa, guanabenz, guanfacine, clonidine, moxonidine, and rilmenidine) have a variety of antihypertensive actions that result in increased sodium excretion and decreases in the cardiac output, heart rate, total peripheral resistance, and renin release.

Clonidine acts by stimulating the pre-synaptic alpha 2 adrenoceptors, thereby decreasing noradrenaline release from both central and peripheral sympathetic nerve terminals.

Alpha-methyldopa is converted to methyl norepinephrine centrally to decrease the adrenergic outflow by alpha-2 agonistic action from the central nervous system, leading to reduced total peripheral resistance and decreased systemic blood pressure.

Phocomelia (seal like limbs) - caused by Thalidomide administration during pregnancy. 

Phocomelia remains the most striking limb deformity caused by thalidomide, and remains the stereotypical image of thalidomide embryopathy. Phocomelia occurs through a severe shortening of the limb/s, due to proximal elements (long bones) being reduced or missing and leaving distal elements (handplate) in place.

Thalidomide uses - Thalidomide is used to treat and prevent erythema nodosum leprosum(Lepra reaction), a painful skin disease associated with leprosy. It is also used together with dexamethasone (eg, Decadron®) to treat patients with multiple myeloma (a cancer of the blood). Thalidomide works on the immune system to reduce inflammation.

Leprosy nodules 

3-drug regimen with rifampicin, dapsone and clofazimine for all leprosy patients, with a duration of treatment of 6 months for PB leprosy and of 12 months for MB leprosy.

Adults - Rifampicin 600mg once a month + clofazimine 300mg once a month and 50mg daily + Dapsone 100mg daily 6 months for PB leprosy and of 12 months for MB leprosy.

Children (10-14 years) - Rifampicin 450mg once a month + clofazimine 150mg once a month and 50mg alternate days + Dapsone 50mg daily 6 months for PB leprosy and of 12 months for MB leprosy.

Children(<10 years or 40kg) - Rifampicin 10mg/kg once a month + clofazimine 100mg once a month and 50mg twice weekly + Dapsone 2mg/kg daily 6 months for PB leprosy and of 12 months for MB leprosy.

Rifampicin reduces infectivity of M.leprae quickly than other drugs

Iron deficiency anemia - Microcytic Hypochromic anemia 

Oral iron preparations - Ferrous sulfate(200mg), Ferrous gluconate(300mg), Ferrous fumarate(200mg), Ferrous succinate(100mg), Ferrous aminoate, Iron choline citrate, Ferric ammonium citrate, Ferric glycerophosphate, Ferric hydroxy polymaltose.

Parenteral iron preparations - Iron dextran(IM/IV), Ferrous sucrose(IV), Ferrous carboxymaltose(IV), Iron isomaltoside-1000(IV), Iron sodium gluconate complex, Iron sorbitol citric acid complex(only IM)

Iron requirement (mg) = 4.4 * body weight(kg) * HB deficit(g/dl)

Macrocytosis, Poikilocytosis, Anisocytosis, cell fragments seen in pernicious anemia

Pernicious anemia is a complex disease, with a clear autoimmune basis. The anemia is megaloblastic and is caused by vitamin B12 deficiency secondary to intrinsic factor (IF) deficiency. IF is a glycoprotein produced and secreted by parietal cells that binds B12 and facilitates its transport to the terminal ileum for absorption. Anti-IF antibodies inhibit B12 from binding to IF, preventing B12/IF complex formation or binding to the B12/IF complex, preventing intestinal absorption.

Treatment - 

Cyanocobalamine - 100micrograms IM/SC - daily for 1 week followed by weekly for 1 month followed by monthly doses for maintenance

Hydroxycobalamin 1mg - IM/SC - for 2 weeks till neurological symptoms are relieved followed by 1mg every 2 months

Transdermal patch behind the ear -

Examples of Drugs delievered by this route - 

Scopolamine/Hyoscine - Motion sickness

Nicotine - Smoking cessation

Fentanyl - Chronic Pain relief patch

Norelgestromin-Ethinyl estradiol - Contraception

Nitroglycerine - Angina pectoris

Testosterone - Hypogonadism in males

Diclofenac diethylamine - Antiinflammatory

Clonidine - Hypertension

Rotigotine - Early stage Idiopathic parkinson's disease

Oxybutynin - Overreactive bladder

Methylphenidate - ADHD(Attention deficit hyperactivity disorder)

Selegiline - Major depressive disorder

Rivastigmine - Dementia

Lidocaine/tetracaine - Local dermal analgesia

Lidocaine - Post-herpetic neuralgia pain

Estradiol - Menopausal symptoms

Mechanism - The drug initially penetrates through the stratum corneum and then passes through the deeper epidermis and dermis without drug accumulation in the dermal layer. When drug reaches the dermal layer, it becomes available for systemic absorption via the dermal microcirculation

These designs characteristically are composed of four layers: an impermeable backing membrane; a drug reservoir; a semi-permeable membrane that may serve as a rate-limiting barrier; and an adhesive layer.

Moon face , Reddish purple striae(abdominal stretch marks) and other features suggestive of Cushing's syndrome

There are two main etiologies of Cushing syndrome: endogenous hypercortisolism and exogenous hypercortisolism. 

Exogenous hypercortisolism, the most common cause of Cushing syndrome, is mostly iatrogenic and results from the prolonged use of glucocorticoids. 

Endogenous Cushing syndrome results from excessive production of cortisol by adrenal glands and can be ACTH-dependent and ACTH-independent. 

ACTH-secreting pituitary adenomas (Cushing disease) and ectopic ACTH secretion by neoplasms are responsible for ACTH-dependent Cushing. 

Adrenal hyperplasia, adenoma, and carcinoma are major causes of ACTH-independent Cushing syndrome.

Glucocorticoids classification based on duration of action - 

a) Short-acting(t1/2 is < 12hr) - Hydrocortisone(Cortisol)

b) Intermediate acting (t1/2 is 12-36hrs) - Prednisolone, Methylprednisolone, Triamcinolone, Deflazacort

c) Long acting (t1/2 is >36hrs) - Dexamethasone, Betamethasone

Dexamethasone(0.5-5mg/day oral for antiinflammatory and antiallergic action, 4-20mg/day IV infusion or IM for Shock and Cerebral edema)

Betamethasone(same as dexamethasone)

Ringworm Infestation - The rash is usually ring-shaped, but it may look different on your face, neck or scalp.

Tinea corporis - It is a superficial fungal skin infection of the body caused by dermatophytes. Tinea corporis is present worldwide. It is defined explicitly by the location of the lesions that may involve the trunk, neck, arms, and legs. 

scalp (tinea capitis), 

the face (tinea faciei), 

hands (tinea manuum), 

the groin (tinea cruris), 

 feet (tinea pedis). 

Treatment - 

Suggested topical regimens include one of the following: 

Clotrimazole: 1% cream/ointment/solution applied topically twice daily 

Ketoconazole: 2% cream/shampoo/gel/foam applied once daily 

Miconazole: 2% cream/ointment/solution/lotion/powder applied twice daily 

Naftifine: 1% cream, applied once daily or 1% or 2% gel twice daily 

Terbinafine: 1% cream/gel/spray solution once or twice daily 

Oral therapy is necessary in more widespread infections or cases that have failed topical treatment.  Oral terbinafine or itraconazole is usually the preferred first-line treatments and is expected to clear the condition in about 2 to 3 weeks. 

Suggested oral regimens include one of the following (for adults): 

Terbinafine: 250 mg orally once daily for two weeks 

Itraconazole: 100 mg once daily for 2 weeks or 200 mg once daily for one week; give capsules with food

 Fluconazole: 150 to 200 mg once weekly or 50 to 100 mg/day for 2 to 4 weeks 

Griseofulvin: 500 to 1000 mg once daily for 2 to 4 weeks

Ptosis reversal during Edrophonium test(Tensilon test) in Myasthenia gravis- 

Edrophonium, diagnostic tool for myasthenia gravis (MG), is a reversible acetylcholinesterase inhibitor with rapid onset and short duration of action resulting in an increase of acetylcholine in the neuromuscular junction (NMJ).

MG is a neuromuscular disorder characterized by muscular weakness due to antibody production that inhibits or destroys post-synaptic nicotinic acetylcholine receptors in the NMJ. Muscle weakness in MG presents as ptosis, diplopia, dysarthria, and dysphagia and can progress to fatal respiratory depression in critically ill patients. For many years, edrophonium, marketed as the Tensilon test, was FDA-approved to be utilized to diagnose MG.

Mechanism - 

Acetylcholine synthesis and storage occur in the presynaptic neurons of the NMJ. Acetylcholine binds to postsynaptic nicotinic acetylcholine receptors upon its release from the presynaptic neurons. In the NMJ, acetylcholine is metabolized by acetylcholinesterases via hydrolysis, attenuating its physiological effects. Edrophonium is a synthetic short-acting acetylcholinesterase competitive inhibitor that functions by forming non-covalent bonds at the serine-103 allosteric site of acetylcholinesterase enzymes. Thus, edrophonium increases the amount of acetylcholine in the NMJ synapses. The higher amounts of acetylcholine in the NMJ synapses overcome the antibodies on the nicotinic receptors in MG, resulting in a brief improvement of muscular strength. 

Edrophonium has a rapid onset of action occurring within 1 minute of administration and a short duration of action lasting 10 minutes

Picture of an infant showing Spina bifida(Neural tube defect) - 

Spina Bifida is a congenital anomaly that arises from incomplete development of the neural tube. It is commonly used as a nonspecific term referring to any degree of neural tube closure. It can be further subdivided into spina bifida occulta and spina bifida aperta.

Etiology - 

Defects in neural tube development are thought to be multifactorial including environmental and genetic influences. 

The most common environmental cause is folate deficiency with most cases deemed “folic acid-sensitive”

maternal obesity, 

maternal diabetes, and 

teratogens such as valproic acid(Valproic acid has the highest association with the development of NTDs carrying about a tenfold increase in risk)

Some genetic factors have also been correlated with poor neuralization including several chromosomal syndromes and genetic polymorphism. Research has implicated polymorphism of the gene encoding the MTHFR enzyme, involved in folate metabolism, as a likely genetic risk factor. While NTDs are typically isolated defects, some are associated with chromosomal syndromes, most often Trisomy 13 and 18.

Valproic acid(Sodium Valproate) mechanism of action - 

VPA acts on γ amino butyric acid (GABA) levels in the brain, blocks voltage-gated ion channels, and also acts as an HDAC inhibitor. 

It increases GABA synthesis by increasing activity of GABA Synthetase enzyme

It decreases GABA Metabolism by inhibiting GABA Transaminase enzyme

It blocks voltage-gated sodium channels

It decreases low threshold calcium current in thalamus

Recently, VPA was demonstrated to be an inhibitor of HDAC1 as well as other HDACs, which potentially increases the expression of genes involved in apoptosis and antitumor action. Therefore, VPA has been proposed to be a potential antitumor agent.

Fetal alcohol syndrome from above facial characteristics like Microcephaly, Small eye openings, Smooth philtrum, Thin upper lip

Etiology - Prenatal alcohol exposure

There is no cure for FAS

Stimulants (methylphenidate and amphetamine derivatives) are first-line medications primarily used to target symptoms of ADHD common in children with an FASD including but not limited to hyperactivity, inattentiveness, and impulsivity.

Gynecomastia - Gynecomastia relates to any condition in which the male breast volume is enlarged due to an increase in ductal tissue, stroma, or fat. Gynecomastia is derived from the Greek terms gyne and masto, gyne meaning feminine and masto meaning breasts.

The cause of most cases of gynecomastia is idiopathic. However, it has been proven to be associated with imbalances in the hormones estrogen and testosterone.

Drugs causing gynecomastia are - 

digoxin, 

thiazides, 

estrogens, 

phenothiazines, 

theophylline

recreational drugs including marijuana 

Chemotherapeutic drugs known to cause gynecomastia include  - methotrexate, alkylating agent, imatinib and vinca alkaloids. 

The most common drugs, however, have estrogen-like activity and include cimetidine, spironolactone, ketoconazole, and finasteride.

Colchicine is derived from the bulb-like corms of the Colchicum autumnale plant, also known as autumn crocus shown above.

MOA - Colchicine modulates multiple pro- and antiinflammatory pathways associated with gouty arthritis. Colchicine prevents microtubule assembly and thereby disrupts inflammasome activation, microtubule-based inflammatory cell chemotaxis, generation of leukotrienes and cytokines, and phagocytosis.

The most common adverse reactions are related to the gastrointestinal tract. Diarrhea is the most commonly reported symptom (23%), followed by vomiting (17%) and nausea (4% to 17%).

uses - 

a) Prophylaxis of gout: Colchicine dosing is 0.6 mg once or twice a day in adults and adolescents older than 16 years old; the maximum dose is 1.2 mg per day. 

b) Treatment of acute gout flare: 1.2 mg at the first sign of a gout flare followed by 0.6 mg one hour later. 

c) Familial Mediterranean fever: 1.2 mg to 2.4 mg for adults and children over 12 years old; the daily dose gets administered in one or two doses.

Rauvolfia serpentina( Indian snakeroot, devil pepper, or serpentine wood) - Reserpine is the alkaloid which is obtained from this plant.

MOA - Reserpine irreversibly blocks VMAT-2 (vesicular monoamine transporter-2) in the adrenergic neurotransmission pathway. The inhibition of catecholamine pumps results in blockage of the uptake of serotonin, norepinephrine, and dopamine into presynaptic storage vesicles. This action will then lead to their depletion by cytoplasmic monoamine oxidase from peripheral and central synapses. Reserpine is lipid-soluble, so it can cross the blood-brain barrier and slow the activity of the nervous system, resulting in decreased heart rate, decreased cardiac output, decreased peripheral resistance, and lowered blood pressure.

Uses - Treatment of high blood pressure and also severe agitation in patients with mental disorders.

Claviceps Purpurea - Claviceps purpurea is an ergot fungus that grows on the ears of rye and related cereal and forage plants. Consumption of grains or seeds contaminated with the survival structure of this fungus, the ergot sclerotium, can cause ergotism in humans and other mammals. C. purpurea most commonly affects outcrossing species such as rye (its most common host), as well as triticale, wheat and barley. It affects oats only rarely.

ergot alkaloids are obtained from claviceps purpurea. They are classified primarily as 

ergoline alkaloids (e.g., lysergic acid, lysergol, lysergic acid amide and ergonovine(ergometrine)) 

ergopeptine alkaloids (e.g., ergotamine, ergocristine, ergosine, ergocryptine, ergocornine and ergovaline)

Ergopeptine alkaloids are potent D2-dopamine receptor agonists which decrease prolactin secretion by the anterior pituitary (Evans et al., 2004), and the most sensitive indicator of ergopeptine alkaloid exposure in animals is hypoprolactinemia.

Uses - Migraine, Headache, Postpartum hemorrhage, symptomatic control of carcinoid syndrome.

Amanita muscaria - Muscarine is obtained from this mushroom.

MOA - Muscarine is the prototypical agonist for all muscarinic receptors. Muscarine acts in the peripheral nervous system, where it competes with acetylcholine at its receptor binding sites. Once bound to the receptor, muscarine mimics the effect of acetylcholine. Muscarine is unable to inactivate acetylcholinesterase (Young, 1994), and uncontrolled overstimulation of receptors occurs.

muscarinic agonists have serious side effects, including SLUD syndrome (salivation, lacrimation, urination, defecation). Moreover, they are contraindicated in patients with asthma because they cause bronchoconstriction and increase mucous secretions. Muscarinic-induced hypotension can lead to serious problems associated with reduced coronary blood flow. In addition, these drugs are contraindicated in patients with hyperthyroidism because the body reacts to hypotension by releasing norepinephrine. Patients with hyperthyroidism are very sensitive to norepinephrine and can develop atrial fibrillation.

Antidote - Atropine (Organophosphate or muscarinic poisoning: 2 mg to 3 mg every 20 to 30 minutes (may require doses up to 20 mg, titrate to effect for secretion control))

Roundworm infestation in the intestine (ex- ascaris lumbricoides) -  

Treatment - 

Albendazole - 400mg OD Oral

Mebendazole - 100mg BD oral for 3 days

MOA of albendazole and mebendazole - They bind to beta tubulin unit of parasitic microtubules and inhibit polymerization or assembly of microtubules and thus stop egg production and prevent existing eggs hatching.

Pyrantal Pamoate - 1mg single dose

MOA - Pyrantel pamoate is a pyrimidine derivative which is believed to act by depolarizing the neuromuscular junction of nematodes, resulting in their paralysis and expulsion in stool. The drug is poorly absorbed from the intestine and is usually effective in a single dose

Levamisole - 150mg single dose

MOA - 

a) Ganglia in worms are stimulated causing tonic paralysis and expulsion of live worms. 

b) Interference with carbohydrate metabolism i.e.., inhibition of Fumarate reductase

Hookworm infestation in intestine - 

Treatment - 

Albendazole - 400mg OD Oral

Mebendazole - 100mg BD oral for 3 days

MOA of albendazole and mebendazole - They bind to beta tubulin unit of parasitic microtubules and inhibit polymerization or assembly of microtubules and thus stop egg production and prevent existing eggs hatching.

Pyrantal Pamoate - 1mg single dose

MOA - Pyrantel pamoate is a pyrimidine derivative which is believed to act by depolarizing the neuromuscular junction of nematodes, resulting in their paralysis and expulsion in stool. The drug is poorly absorbed from the intestine and is usually effective in a single dose

Tapeworms - 

Treatment - 

Niclosamide - The mechanism of action of niclosamide has been demonstrated to block glucose uptake, thus acting as an uncoupling(inhibiting) agent for energy-generating oxidative phosphorylation in mitochondria of intestinal worms, starving the worms of ATP. Niclosamide is a vermicidal medication used to directly kill parasitic worms.

Mepacrine - Mepacrine inhibits phospholipase A2 and subsequently leukotrienes, which are calcium ionophores. Mepacrine also has an inhibitory effect on phospholipase C and subsequent inositol phosphate formation, which mobilizes cytosolic calcium from intracellular stores. Mepacrine is thought to have a vermifugal action, which means it weakens or paralyzes worms rather than directly killing them. This effect can make it easier for the body to expel the worms naturally.

Amebic liver abscess - 

Treatment - 

Metronidazole(drug of choice) - Metronidazole diffuses into the organism, inhibits protein synthesis by interacting with DNA, and causes a loss of helical DNA structure and strand breakage. Therefore, it causes cell death in susceptible organisms. Metronidazole kills trophozoites of Entamoeba histolytica in intestines and tissue but does not eradicate cysts from intestines. side effects - Metronidazole may cause dry mouth, an unpleasant or sharp metallic taste, and a change in taste sensation, GI intolerance

Tinidazole

Chloroquine

Emetine

For eradication - 

Diloxanide furoate is a dichloroacetamide derivative that is a luminally active agent used to eradicate cysts of E. histolytica in asymptomatic carriers and in those who have mild, noninvasive disease, as well as after treatment with metronidazole in those who have invasive amebiasis.

The researchers discovered that beta1 receptors are located all over the surface of cardiac muscle cells, but beta2 receptors are only located on what is known as T-tubules.

Once beta-blockers bind to the B1 and B2 receptors, they inhibit these effects. Therefore, the chronotropic and inotropic effects on the heart undergo inhibition, and the heart rate slows down as a result. Beta-blockers also decrease blood pressure via several mechanisms, including decreased renin and reduced cardiac output. The negative chronotropic and inotropic effects lead to a decreased oxygen demand; that is how angina improves after beta-blocker usage. These medications also prolong the atrial refractory periods and have a potent antiarrhythmic effect. 

Administration of a beta-blocker is not generally associated with symptomatic postural hypotension

Examples - Non-selective agents bind to both beta-1 and beta-2 receptors and induce antagonizing effects via both receptors. Examples include propranolol, carvedilol, sotalol, and labetalol. 

Beta-1 receptor-selective blockers like atenolol, bisoprolol, metoprolol, and esmolol only bind to the beta-1 receptors; therefore, they are cardio-selective

Ulcer crater - Gastric ulcer

Treatment - 

1) Gastric acid secretion inhibitors - 

a) PPIs - Omeprazole, esomeprazole, Lansoprazole, Pantoprazole, Rabeprazole, Dexrabeprazole, Ilaprazole

b) H2 antihistamines - Cimetidine, Rantidine, Famotidine, Roxatidine, Lafutidine

c) Anticholinergics - Pirenzepine, Propantheline, Oxyphenonium

d) Prostaglandin analogue - Misoprostol

2) Gastric acid neutralizers(antacids) - 

a) Systemic - Sodium bicarbonate, Sodium citrate

b) Non systemic - Magnesium hydroxide, Magnesium trisilicate, Aluminum hydroxide, Calcium carbonate, Magaldrate

3) Ulcer protectives - Sucralafate, Colloidal bismuth subcitrate(CBS) 

4) Anti H.pylori drugs - Amoxicillin, Clarithromycin, Metronidazole, Tinidazole, Tetracycline, CBS

For healing of gastric ulcers - 

Carbenexolone sodium 

Important notes on sodium nitroprusside -

Sodium nitroprusside - Vasodilator(Both Arteriolar dilator and venodilator) . Rapid action and short duration of action(2 to 5 min). It relaxes both resistance and capacitance vessels. RBCs and Endothelial cells split sodium nitroprusside to generate NO(nitric oxide) which relaxes vascular smooth muscle.

It is 2nd line drug for Hypertensive emergencies