2. SKIN The skin has multiple layers of ectodermal tissue guards the underlying muscles, bones, ligaments and internal organs Human skin is similar to that of most other mammals, except that it is not protected by a fur. Though nearly all human skin is covered with hair follicles, it can appear hairless. There are two general types of skin, hairy and glabrous skin.

3. The adjective cutaneous literally means "of the skin" (from Latin cutis, skin). Because it interfaces with the environment, skin plays a key role in protecting the body against pathogens and excessive water loss. Its other functions are insulation, temperature regulation, sensation, synthesis of vitamin D, and the protection of vitamin B folates. Severely damaged skin will try to heal by forming scar tissue. This is often discolored and depigmented.

5. Anatomy Skin has three layers:  The epidermis: the outermost layer of skin, provides a waterproof barrier and creates our skin tone.  The dermis: beneath the epidermis, contains tough connective tissue, hair follicles, and sweat glands.  The deeper subcutaneous tissue (hypodermis) is made of fat and connective tissue.

6. Epidermis This tough layer of cells is the outermost layer of skin. It gets its toughness from a protein called keratin. The epidermis has five layers:  Stratum corneum is made up of dead, mature skin cells called keratinocytes. These cells are constantly shed and replaced by cells from the lower layers of the epidermis. These cells have lost most of their internal structures and organelles.  Stratum lucidum is found in thicker skin and helps reduce friction between the stratum corneum and the stratum granulosum. It’s composed of dead, flattened cells.

7. The skin is thicker in some areas (like the soles of your feet) and thinner in others; women also tend to have thinner skin than men do.  Stratum granulosum is where keratin is formed. The cells in this layer also produce materials that prevent evaporation, which helps waterproof the skin.  Stratum spinosum contains the keratin-producing cells that were formed in the stratum basale. Keratin is a major structural component of the outer layers of skin.  Stratum basale forms the deepest layer. The cells of this layer continuously divide and form new keratinocytes to replace the ones that are constantly shed. This layer also contains melanocytes, which are the cells that produce skin coloring.

9. Dermis This lower layer of the skin contains collagen and elastic fibers that give strength to the skin. This layer is also where the vasculature and nerves live. Together the epidermis and dermis form the cutaneous layer. The subcutaneous layer (area below the skin) lies underneath the cutaneous layer and is sometimes called the hypodermis. It holds most of the body’s fat, so it varies in thickness from one person to another. Creases form over joints because the skin always folds the same way as the joints bend. The skin is thinner in those areas and is firmly attached to the underlying structures by connective tissue.

10. The integument also includes the structures that grow out of the skin, plus a couple of glands: Hair: The protein keratin forms hair. Hair has an inner layer (the cortex), which contains pigments that give it color, and an outer layer (the cuticle). It grows out of follicles, which are little pockets of epidermis in the dermis. The shape of the follicle determines whether hair is curly or straight. Each follicle contains a hair bulb from which the hair develops. Errector pili muscles connect the hair follicle to the skin. Nails: Keratin shows up again in the form of plates found on ends of the fingers and toes.

11. Sebaceous glands: These glands are connected to the hair follicles. They produce sebum, which is an oily substance that helps keeps the hair flexible. Sweat glands: Sweat glands are coiled tubular glands found in most of the skin. The secretory portion (the part that secretes the sweat) of each gland lies in the fascia with a duct that runs up to the surface of the skin.

12. Hypodermis The fascia is divided into two types: the superficial fascia and the deep fascia, which forms the following structures: Investing fascia: This part of the fascia covers deeper structures, such as muscles and ligaments. Intermuscular septa: The septa divide muscles into various groups. Subserous fascia: This part of the fascia lies between the body walls such as the thoracic wall (or abdominal wall and the membranes that line corresponding body cavities.

13. Hypodermis Retinacula: These band-like structures hold tendons in place while joints move. Bursae: These fluid-filled sacs are made of fibrous tissue; they’re lined with membranes and contain a bit of viscous fluid. They reduce friction between body tissues. Major bursae are located near joints between the tendons and bone.

14. Functions Protection: an anatomical barrier from pathogens and damage; Langerhans cells in the skin are part of the adaptive immune system. Sensation: contains a variety of nerve endings that react to heat and cold, touch, pressure, vibration, and tissue injury; Heat regulation: the skin contains a blood supply far greater than its requirements which allows precise control of energy loss by radiation, convection and conduction. Dilated blood vessels increase perfusion and heat loss, while constricted vessels greatly reduce cutaneous blood flow and conserve heat. Control of evaporation: the skin provides a relatively dry and semi- impermeable barrier to fluid loss. Loss of this function contributes to the massive fluid loss in burns. Aesthetics and communication: others see our skin and can assess our mood, physical state and attractiveness.

15. Storage and synthesis: acts as a storage center for lipids and water, as well as a means of synthesis of vitamin D by action of UV on certain parts of the skin. Excretion: sweat contains urea, however its concentration is 1/130th that of urine, hence excretion by sweating is at most a secondary function to temperature regulation. Absorption: the cells comprising the outermost 0.25–0.40 mm of the skin are "almost exclusively supplied by external oxygen", although the "contribution to total respiration is negligible". In addition, medicine can be administered through the skin, by ointments or by means of adhesive patch, such as the nicotine patch or iontophoresis. The skin is an important site of transport in many other organisms. Water resistance: The skin acts as a water resistant barrier so essential nutrients aren't washed out of the body.

16. Absorption the act of taking up or in by specific chemical or molecular action; especially the passage of liquids or other substances through a surface of the body into body fluids and tissues, as in the absorption of the end products of digestion into the villi that line the intestine.

17. Classification of Topical agents : Topical Agents : Compounds used on body surfaces 1.Protectives 2. Antimicrobial and Astringent compounds.

18. Protectives Protectives are substances that are usually applied to areas of the skin that are subject to constant irritation or areas that have already become irritated or inflamed due to moisture and /or friction. Criteria of an ideal protective: They must be insoluble to limit absorption of compounds through skin, make it difficult to wash them off and reduces metallic properties on tissue. They must be chemically inert to prevent interactions between the protective substance and tissue.

19. Criteria of an ideal protective (contd.): They must be efficient adsorbents since adsorbing moisture from the surface of the skin lessens mechanical friction and irritation. They must be composed of small particles because small particles offer a large surface area, allowing them to adhere to the surface of the skin more efficiently and also offers a smooth substance that is soothing to apply and helps in preventing irritation due to friction or rubbing.

20. Protectives are generally applied as Dusting powders Suspensions /Lotions containing the insoluble protective substance Ointments Therefore, protectives are substances that may be applied to skin to protect certain areas from irritation (due to moisture, friction and allergy etc).

21. Talc Talc USP XVIII is hydrated magnesium silicate. Contains 28.1% to 31.2 % MgO, 57 to 61.7% SiO 2, 3 to 7% H 2 O Properties: - Very fine white or grayish white crystalline powder. - Smooth, greasy feeling to the touch (unctuous) - Adheres readily to the skin - Free from grittiness - odorless, tasteless, insoluble and chemically inert - low adsorptive properties Uses: - useful as a lubricating, protective dusting powder - as a filtering aid

22. Calamine Calamine USP XVIII is zinc oxide (ZnO) with a small proportion of ferric oxide (Fe 2 O 3, iron(III)oxide). It contains not less than 98% and not more than 100.5% of ZnO. Preparation: - The official calamine is obtained by calcination (powdered by heating) of the natural ore. - The calcined product is then passed through a 100-mesh sieve to get a finely powdered material for good adhesive and cohesive properties. Uses : - topical protective used in dusting powders, ointments & lotions for its soothing, adsorbent properties.

23. Popular form of calamine: - Calamine lotion USP XVIII that contains equal quantities of Calamine and Zinc Oxide. - It is a protective, with good drying effect and mild astringent action. - Phenolated Calamine lotion USP XVIII contains 1% liquified phenol that provides local anesthetic and antipruritic action (anti itching action).

24. Titanium Dioxide Properties : Titanium Dioxide USP XVIII is a white, amorphous, odorless, tasteless, infusible powder. Neutral to litmus Insoluble in water, HCl, nitric acid but soluble in hydrofluoric acid. Uses : Topical protective Used in sun creams and sun screen products for its opacity. Its high refractive index (2.7) is useful for screening out ultraviolet radiation. White pigment in cosmetics

25. Antimicrobial Terminology Antiseptic : Agent which either kills or inhibits growth of microorganism e.g bacteria, fungus etc. Germicide : Agent which kills microorganisms e.g bactericide, fungicide etc Those which does not kill but inhibit growth of microorganism are bacteriostat, fungistat. Disinfectant : kills microorganisms but used on inanimate objects e.g. instruments, equipments, rooms Sterilization : use of a disinfectant or other procedure (e.g heat) to render an object completely free from microorganisms.

26. Mechanism of action of Inorganic Antimicrobial agents Inorganic antimicrobials act by 3 ways : 1. Oxidation 2. Halogenation 3. Protein precipitation based on the primary chemical interactions or reactions that occur between the agent and the microbial protein. This results in the death of the microbe or inhibition of its growth. Site of action of inorganic antimicrobials are nonspecific i.e. it will interact with all proteins in a similar fashion and in high concentrations and will affect both microbial and host proteins.

27. Oxidation Nonmetals and certain types of anions function through oxidative mechanisms. Examples are hydrogen peroxide, metal peroxides, permanganates, halogens (e.g chlorine and iodine) and oxo- halogen anions. Oxidative action of these compounds involves the reducing groups present in most proteins e.g the sulfhydryl (-SH) group in cysteine. Illustration of reaction between oxidizing antiseptic and a sulfhydryl- containing protein.

28. Oxidation The formation of the disulphide bridge will alter (change) the conformation (shape) of the protein. Thereby alters the function of the protein. The overall change or destruction of the function of the protein is responsible for the ultimate destruction of the microorganism. Chemical result of oxidizing the protein is destruction of the antimicrobial agent.

29. Halogention This is a reaction occurring with antiseptics of the hypohalite type i.e. Hypochlorite, OCl - Since these types of compounds can serve as reagents in the chlorination of primary and secondary amides, e.g it is expected that a similar reaction can take place under appropriate conditions with the peptide linkage between the amino acid groups comprising the protein molecule.

30. Halogention Example of the reaction is shown below : O O ││ OCl - ││ Protein- C - N- Protein ─ › Protein- C – N-Protein │ H Cl

31. Halogention This reaction is ultimately destructive to the function of proteins. The substitution of the chlorine atom for the hydrogen produces changes in the forces (hydrogen bonding) that is responsible for the proper conformation of the protein molecule. Changes in the conformation result in destruction of function of proteins.

32. Protein Precipitation This type of mechanism involves the interaction of proteins with metallic ions having large charge/radius ratios or strong electrostatic fields. This property is available in transition metal cations e.g. Cu(II), Ag(I), Zn(II). Al(III) due to its charge and small ionic radius is also an effective protein precipitant. Except alkali and alkaline earth metals, most metal cations will demonstrate protein precipitant activity.

33. Protein Precipitation The nature of the interaction is complexation of the metal ion with various polar groups on the protein that act as ligands. The complexation of the metal ion with the protein results in radical changes in properties of the protein or protein precipitant. Certain metals have affinity for particular enzymes. The metal ‘ties up’ important functional groups at the active site on the enzyme by forming the complex. Increasing the concentration of the metal cations can increase antimicrobial and astringent properties.

34. Protein precipitation

35. Astringents The application of a very dilute solution of a metal cation to tissue primarily involves a local or surface protein precipitant action. This activity is known as astringent. As it is a surface phenomenon it does not usually result in the destruction of host tissue. Its effect can be observed or felt when applied to skin or mucous membranes. The effect can be described as a ‘shrinkage’ or ‘firming’ of the tissue.

36. Uses of astringents: used as styptics to stop bleeding from small cuts as astringents cause constriction of capillaries and small blood vessels to reduce the volume of exudates from wounds and skin eruptions. as antiperspirants in deodorants due to their ability to constrict pores and destroy microorganisms that produce body odors may stimulate growth of new tissue when applied topically to wounds. higher concentrations can provide corrosive effect on contact with tissue that can be used to remove undesirable tissue.e.g warts.

37. Control of antimicrobial/astringent action The concentration of protein precipitants needed for astringent activity is higher than that needed for antimicrobial activity. Very high concentrations can produce an irritant action and corrosive action. For water soluble compounds control of activity is done by making solutions of a appropriate concentrations for the desired use. The concentrations will depend on the area of use - e.g higher concentrations may be used on skin than on eye.

38. Control of antimicrobial/astringent action Soluble compounds may be controlled by placing them in a vehicle/ solutions (e.g glycerin or polyethylene glycol) that will slow their release to the site of action. Complexation with a ligand (e.g. Povidone-Iodine) also provides controlled release. Other compounds may be synthesized in an insoluble form and used in suspensions, creams or ointments for their antimicrobial action and slow release of the agent.

39. Oxidative Antimicrobial Agents 1. Hydrogen Peroxide Solution USP XVIII Uses : Used as a mild oxidizing antiseptic in contact with open or abraded tissue, exposing the chemical to the enzyme, catalase. Catalase causes decomposition of H 2 O 2 to water and oxygen. 2H 2 O 2 ——> 2H 2 O + O 2 The foaming release of oxygen provides mechanical cleansing action to remove dirt, bacteria, debris from the surface of the wound. When diluted with one part of water it can be used as a gargle or mouthwash for the treatment of throat and mouth infections.

40. Potassium Permanganate USP XVIII (KMnO 4 ) Odorless, dark purple crystalline compound Soluble in water When heated at 240° C, it decomposes with the liberation of oxygen, leaving manganese oxide (MnO 2 ) and potassium manganate (K 2 MnO 4 ). Strong oxidizing agent both in dry state and in solution Great care must be taken in handling it as dangerous explosives may occur if it is brought in contact with organic or readily oxidizable substances, either in solution or in dry state.

41. Potassium Permanganate USP XVIII (KMnO 4 ) Acid solutions of potassium permanganate reduces the permanganate ion (MnO 4 - / Mn +7 ) to the manganous ion with the evolution of oxygen. 2KMnO 4 + 3H 2 SO 4 ──> K 2 SO 4 +2MnSO 4 +3H 2 O+5[O] Neutral or alkaline solution produces a brown precipitate of manganese dioxide (MnO 2 ). 2KMnO 4 + H 2 O ──> 2MnO 2 + 2KOH + 3[O] The antibacterial action is dependant upon its oxidation of protein or other bioorganic substances. The oxygen released is the effective agent.

42. Uses: Used for both their antibacterial and antifungal actions Used externally in concentrations ranging from 0.2% to about 0.006%. Used for skin infections (dermatitis) caused by bacteria and fungi and for poisoning produced by plant and animal toxins. Used in the treatment of vesicular (small blisters/raised areas containing fluids) stage of eczema, tinea pedis (fungal infection of the foot). Potassium Permanganate USP XVIII (KMnO 4 )

43. Sodium Hypochlorite Solution N.F. XIII (Dakin’s solution) NaOCl is very unstable and usually found only in solutions Contains not less than 4% and not more than 6% by weight of NaOCl Clear, pale greenish yellow liquid having an odor of chlorine Has an alkaline pH coloring red litmus blue Not suitable for application to wounds since its alkalinity and oxidizing action is too strong for use on tissues In addition, the solution dissolves blood clots and delays healing A diluted form is known as Labaraque’s solution and consists of Sodium Hypochlorite Solution that has been diluted with an equal volume of water (approx. 2.5% NaOCl) This solution is used a disinfectant on inanimate (nonliving) objects.

44. Sodium Hypochlorite Solution N.F. XIII (Dakin’s solution) Uses: Useful as a disinfectant and laundry bleach Effective as an germicidal agent that can be used to disinfect areas, instruments and utensils exposed to pathogenic microorganisms Diluted form is used as a mouthwash Disadvantages : Prolongs clotting time, can lead to secondary hemorrhage Instability of solution requires storage in tight, light-resistant containers and avoidance of excessive heat.

45. Iodine Preparations and Compounds : Iodine Solution N.F XIII Iodine Tincture U.S.P. XVIII Both the solutions contain the same concentration of ingredients. In each 100ml they contain not less than 1.8g and not more than 2.2g of iodine (I) and not less than 2.1g and not more than 2.6g of sodium iodide (NaI). They differ only in the nature of the solvent i.e. – Iodine solution is aqueous, having being prepared with purified water, and Iodine Tincture contains approximately 50% alcohol as the final solvent.

46. Uses of Iodine Tincture and Iodine Solution : Effective topical antiseptic agents Used as antiseptics on the skin prior to surgery – Iodine Tincture is more suitable for this purpose as the alcohol can improve the penetration of the iodine due to a wetting or spreading effect and also provides additional antibacterial effect. Can be diluted with water for applications to wounds and abrasions – Iodine solution is preferred since the alcohol in the tincture is very irritating to the open tissues and causes stinging when applied to wounds.

47. Povidone-Iodine N.F. XIII (Aerosol and Solution) Povidone-Iodine is a complex of iodine with Povidone N.F XIII which is a polymer also known as polyvinylpyrrolidone or PVP. Both the aerosol and solution contains not less than 85% and not more than 120% of the labeled amount of iodine. Acid to litmus Soluble in water and in alcohol and insoluble in organic solvents. The Povidone- Iodine solution is a transparent liquid having a reddish brown color and a pH of not more than 6.

48. Povidone-Iodine N.F. XIII (Aerosol and Solution) Povidone-Iodine is a member of a class of compounds referred to as iodophors. Iodophors are complexes of iodine with carrier organic molecules serving as a solubilizing agent. These complexes slowly liberate iodine in solution. Advantages of Povidone-Iodine complex over elemental iodine solutions: Nonirritating effect on tissues Its comparatively low oral toxicity Water solubility Low iodine vapor pressure making it stable to possible iodine loss Nonstaining and can be washed clear from skin & clothing.

49. Povidone-Iodine N.F. XIII (Aerosol and Solution) Uses: Lack of tissue irritation makes it useful for application to sensitive areas and mucous membranes Recommended for surgical scrubs and preoperative antisepsis of the skin Used in gargles and mouthwashes Examples : Betadine solution (concentrations of 0.1% to 1% of available iodine).

50. Protein Precipitant Antimicrobial Agents 1. Silver Nitrate U.S.P. XVIII Properties: Colorless or white crystals which become gray or grayish black on exposure to light in the presence of organic matter Very soluble in water, sparingly soluble in alcohol and freely soluble in boiling alcohol pH of 1% solutions is between 4.5 and 6 and must be clear or colourless Solutions of silver nitrate in concentrations between 0.5 and 1% are used as antibacterial agents.

51. Silver Nitrate U.S.P. XVIII When a protein solution is treated with a solution containing a soluble silver salt, a heavy precipitate is formed involving a complex interaction between the silver ions and protein. This type of reaction is the basis for the antimicrobial action of the silver compounds. The protein precipitant action of silver ion is not selective i.e. it will precipitate both bacterial and human proteins. Silver ion precipitation of protein involves interactions between the cation and various polar groups on the protein molecule e.g - SH, -COOH, -NH 2 and heterocyclic residues e.g histidine.

52. Silver Nitrate U.S.P. XVIII When applied to tissue in a concentration of 0.1% silver the activity is rapidly bactericidal. Sustained action: A bactericidal action continues after the initial application due to the slow production of silver ions from the silver proteinate and silver chloride. This sustained action at the tissue levels has given rise to colloidal products of silver proteinate and halide as antibacterials.

53. Silver has oligodynamic action, meaning it is active in small quantities. Silver preparations are bacteriostatic at concentrations of silver ion below that required for protein precipitation. Solutions of silver nitrate are bacteriostatic at concentration of 1:30,000 and bactericidal at 1:4000 in the presence of organic matter. Irritation of the skin becomes a factor at concentrations above 1:1000. Extended use of silver preparations causes a darkening of the skin due to the deposition of free silver below the epidermis a condition known as argyria. Silver Nitrate U.S.P. XVIII

54. Uses: Employed as an antibacterial in solutions ranging from 0.01 to 10% (higher concentration present astringent and irritant properties to the tissues). Used in concentration of about 1:10,000 on sensitive membranes e.g. irrigation of the urethra and bladder. Used in treatment of infected ulcers in the mouth (10% solution of silver nitrate). Silver Nitrate Opthalmic solution U.S.P XVIII is a 1% solution for instillation into the eyes of newborn babies. Used as a prophylactic measure against infections caused by gonococcal organisms.

55. 0.5% aqueous solution of silver nitrate is used in the form of wet dressing on burned areas of patients suffering from third-degree burns. - This form of therapy involves the mechanism of sustained action in that the silver ions are precipitated by tissue protein and chloride ion. The antibacterial activity is then dependant upon a low but minimal concentration of ions in equilibrium with the insoluble forms. - This is a good initial treatment due to both the antibacterial effect and the reduction in fluid evaporation and the heat loss produced by the wet dressing. - Side effects of this treatment: electrolyte imbalance due to precipitation of chloride such as low serum sodium, metabolic acidosis and diarrhea. Silver Nitrate U.S.P. XVIII

56. Astringents Aluminium Chloride N.F. XIII White or yellowish white, deliquescent, crystalline powder Nearly odorless Very soluble in water, freely soluble in alcohol and soluble in glycerin Acid to litmus in aqueous solutions Uses: local external astringent and mild antiseptic used in aqueous solutions in concentrations ranging from 10 to 25%. Initially employed for use as antiperspirant but was found to be too irritating.

57. Soluble Zinc Compounds Zinc Chloride U.S.P XVIII Uses : Zinc chloride is used for the activity of zinc ion which is a very strong protein precipitant. The compound is a powerful astringent in solution and mild antiseptic. The strong astringent properties makes it useful as an escharotic (an agent that causes the sloughing of tissue, thus helping in the formation of scar tissue to improve healing). It is applied as a solution containing from 0.5% to 2% of zinc chloride. The lower concentration may be applied to mucous membranes and can be used as a nasal spray to aid drainage from infected sinuses. It is applied topically (10% solution) as a desensitizer of dentine.

58. Zinc Sulphate U.S.P.XVIII Colorless, transparent prisms or as small needles. May also be a granular, crystalline powder. Very soluble in water, freely soluble in glycerin and insoluble in alcohol. Acid to litmus Uses : Used externally as an ophthalmic astringent (Zinc Sulphate Ophthalmic Solution U.S.P.XVIII) in 0.25% aqueous solution. The acidic nature of the solution requires buffering. The pH should be between 5.8 and 6.2. It is usually applied in 0.1 ml doses to the conjuctiva. Used internally as an emetic (1 to 2 g doses in a 1% solution).

59. White Lotion N.F. XIII Preparation : This is a topical preparation prepared by adding a solution of Sulfurated Potash (40g in 450 ml of water) slowly to a solution of Zinc Sulphate (40g in 450 ml of water) and then adding water to a volume of 1000 ml. When completed the resulting product is a suspension of zinc sulphides. K 2 S + ZnSO 4 ——> ZnS + K 2 SO 4 The order of addition of the compounds is very important. If the order is reversed, the hydroxide ions in the Sulfurated Potash cause the formation of basic zinc salts and zinc hydroxide, rather than zinc sulphides. The precipitate tends to become lumpy upon standing so the suspension should be freshly prepared and shaken thoroughly before using. Uses: used topically for the effects of sulphide ion and the astringent action of the zinc ion. Has been used in the treatment of acne vulgaris, seborrhea dermatitis and other dermatological problems.