External Analgesic Products. The Gate-control theory of pain.

Presentation on theme: "External Analgesic Products. The Gate-control theory of pain."— Presentation transcript:

1 External Analgesic Products

2 The Gate-control theory of pain

3 How the theory of chronic pain works…. The brain commonly blocks out sensations that it knows are not dangerous, such as when the feel of tight-fitting shoes that are put on in the morning has all but vanished by the second cup of coffee…

4 Mechanism of Muscular Pain Perception The Gate-control theory of pain: - Neural mechanism in the spinal cord acts like a gate that controls transmission of pain impulses to the brain  integrate and evaluate as pain - Pain signals are carried from pain receptors to spinal cord via 2 types of nerve fibres: 1. Small un-myelinated fibres (C type) 2. Large-myelin containing fibres (A delta type)

5 Mechanism of Muscular Pain Perception 1. Type C- fibres: conduct impulses slowly, associated with dull, aching and lingering pain 2. A-delta fibres: linked with immediate pain, which is sharp and precise with pricking sensation. Small and large fibres can oppose each other  mild stimulation of the large fibres can attenuate pain felt from activation of small fibres  MOA of topical counterirritants (e.g. sport-related knee injury)

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7 Types of Musculoskeletal pain Overuse Injuries Soft Tissue Injury Arthritis Lower Back Pain Other types of Muscular Pain

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9 Types of Muscular pain Overuse injuries: - skeletal muscle pain that is quite common in persons who are not accustomed to strenuous exercise - Such injuries result from equal and opposite reactions: 1. Macrotrauma 2. Microtrauma

10 Overuse Injuries Trauma comes in two varieties: Macrotrauma: sudden catastrophic injury, occurs when an equal and opposite force exceeds the inherent tensile strength of a body structure (e.g. bone, tendon, ligament, muscle) causing the structure to collapse. E.g. falls and sport injuries Microtrauma: microscopic subclinical injury, results from repeated activity that, over a period of time, overwhelms the tissue’s ability to repair itself - described as: “overuse syndrome”- repetitive microtrauma > break-down structure (e.g. nerve, bursae etc.) - Most commonly encountered in form of tendi/onitis

11 Overuse Injuries 1. Tendinitis Results from strain or injury of tendons Often seen at times of maximum physical effort (e.g. athletic competitions) 3 phases: inflammation  excessive proliferation of CT  chronic inflammation (CT overgrowth + tendon degeneration)  rupture Common sites: Achilles tendon (most common injury in sports), shoulder, biceps (football; baseball), patellar- kneecap (volleyball, basketball players)

12 Example: Carpal tunnel syndrome Tingling or numbness of the first digits of hands caused by repetitive use of hands and wrists. Tendon sheets become inflamed which constricts median nerves in the tunnel between the wrist bones

13 Overuse Injuries Factors contributing to producing an overuse injury In industry Poorly designed equipment Awkward working position Lack of job variation Long working hours Inadequate rest breaks Bonuses for overtime

14 Overuse Injuries Factors contributing to producing an overuse injury In athletics Age Poor technique Exercise of prolonged intensity/duration Poorly designed equipment (e.g. shoes) Fluoroquinolones > associated with tendon repture> FDA warning! (what is it?)

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17 Overuse Injuries 2. Bursitis Definition: Bursae Overuse  trauma (either friction or external pressure)  inflammation with fluid build-up. Localised pain, tenderness and swelling Pain acute: macrotrauma or microtrauma chronic : infection (Dx: by aspiration of fluid) Symptoms can mimic arthritis pain (how to distinguish?)

18 Bursitis vs. arthritis Location: bursae within joints (knee, shoulder and big toe; weight bearing joints (knee, hips, low back, hands) Signs: warmth, edema, erythema, and possible crepitus; noninflmmatory joints, narrowing of joint space, restructuring of bone and cartilage and possible swelling Sx: Constant and worsens with movement or application of pressure over the joint; dull joint pain relieved by rest, joint stiffness < 20-30 minutes, localized symptoms to joint

19 Bursitis vs. arthritis Onset: acute with injury, recurs with precipitant use of joint; insidious development over years Exacerbated by: movement of affected joints; obesity, lack of activity or heavy physical activity, repetitive movement and trauma

20 Bursitis

21 Overuse Injuries 3. Occupational Repetition Strain: Muscle and tendon injuries of the upper limbs, shoulders and neck. Due to overload on particular muscles (due to awkward working positions or repeated use) Overload  pain, fatigue, decline in work performance The most likely candidates: - Assembly line workers - Typists “the new industrial epidemic”

22 Soft Tissue Injury A sprain is a partial or complete rupture of a ligament A bruise is a rupture of tissue resulting in haematoma A strain is a partial tear of muscles

23 Soft Tissue Injury Sprains Strains: - occurs mostly during forceful muscle action - occurs soon after an activity has begun (e.g. when race has just started) - muscle: sore, painful, movement difficult joint being forced beyond its normal range of motion (e.g. hyper-extended knee) Joint forced in a plane through which little or no motion actually exists (e.g. lateral ankle sprain)

24 Arthritis Joint pain may be caused by either rheumatoid arthritis (RA) or osteoarthritis (DJD) Endogenous neuropeptides (e.g. substance P) are involved in the pathogenesis, the inflammation and cartilage destruction in both diseases

25 Lower Back Pain 70% at least once in their lives Primarily: due to sedentary life style, (particularly the one disrupted by bursts of activity) Poor posture Improper shoes Excess body weight Poor mattress and sleeping posture Improper technique in lifting heavy objects injuries

26 Lower Back Pain In addition to injuries, causes of backache includes: 1. Congenital anomalies 2. Osteoarthritis 3. Spinal tuberculosis 4. Referred pain from kidneys, pancreas, liver or prostate

27 Other Types of Muscular Pain Acute, temporary stiffness and muscle pain can result from: cold, dampness, rapid temperature changes or air currents Sometimes, referred pain in the skeletal muscles of the shoulder may result from: Cardiovascular Disease (e.g. angina pectoris) Gastrointestinal complaints (e.g. gallbladder or oesophagus)

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31 Patient Assessment Pharmacists should enquire about: Duration and type of pain if pain > 7 days underlying serious condition?? Cause of pain muscular/joint pain caused by overexertion  valid indication for OTC ext. anal. Use Severity/location of pain If mild, located  OTC ext. anal. Otherwise, may be referred from viscera  OTC X X X

32 Patient Assessment If the pain is in the joint Is joint red, swollen, warm and tender to the touch??? May be a fracture or rupture in ligament or tendon and/or arthritic involvement NO YES OTC ext. anal. X X X OTC would delay an accurate Dx  see Dr.

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34 Patient Assessment If patient is under medical s/v for arthritic condition  - recommend only a counterirritant as an adjunctive therapy - arthritic conditions should not be self-diagnosed or self-treated Pharmacist should record all the patient’s medication (Rx + OTC) in order to minimise the risk of duplication of therapy or D#D If condition not relieved by OTC within 7 days or relieved but recurred  D/C OTC drug  see Dr. Arrange follow-up: to prevent prolonged ineffective self- treatment that allows a more serious disease to progress

35 Treatment/Non-pharmacologic Usually 1-2 days ASAP; 10- 15 min. tid to qid (1-3 days) 2-3 hours/d

36 Treatment/pharmacologic External analgesics (Definition) 1. Local anaesthetics; 2. Local analgesics; 3. Local antipruritics; 4. Counterirritants Depress cutaneous sensory receptors for pain, burning and itching. act directly on skin to diminish symptoms result from cuts, abrasions, insect bites etc.

37 Treatment Counterirritation: the paradoxical pain-relieving effect achieved by producing less severe pain to counter a more intense one. Relieve pain indirectly by stimulating cutaneous receptors to induce sensations such as cold, warmth or sometimes itching These induced sensations distract from deep- seated pain in muscles, joints, tendons etc., which are distant from skin, where counterirritant is applied. Some counterirritants effect  dose dependent (e.g. menthol)

38 Counterirritants Menthol if < 1.0%  depress receptors > 1.25%  stimulate receptors The intensity of response to counterirritant depends on the irritant used, its concentration, the solvent used and duration of its contact with skin Increased risk of irritation, redness or blistering with tight bandaging or occlusive dressing Their action  has strong psychological component Rubifacients are counterirritants that cause vasodilatation of cutaneous vessels

39 Analgesics, Anaesthetics & Antipruritics Act by overcoming stimulus that causes pain Must be percutaneously absorbed first Same action as internal analgesics Their effect is systemic in nature Relieve any deep-seated pain, provided their interstitial fluid concentration is sufficiently high

40 Pharmacologic Agents

41 Classification of OTC counterirritant external analgesics (Category I) GroupCharacteristicsIngredientsConc. (%) AInduce redness and irritation, more potent than other used C/I Allylisothiocyanate Ammonia water Methyl salicylate Turpentine oil 0.5-5.0 1.0-2.5 10-60 6-50 BProduce cooling sensation, have strong organoleptic properties Camphor Menthol 3-11 1.25-16

42 Classification of OTC counterirritant external analgesics (Category I) GroupCharacteristicsIngredientsConc. (%) CCause vasodilatation Histamine dihydrochloride Methyl nicotinate 0.025-0.1 0.25-1.0 DIncite irritation without rubefaction; are equal in potency to group A ingredients Capsicum Capsicum oleoresin Capsaicin 0.025-0.25 Same

43 Counterirritants (Group A) Allylisothiocyanate “essence of mustard” Derived from seeds of black mustard plant In high concentration (or if applied for a long period of time) Absorbed rapidly from intact skin and mucous membranes ulceration if not removed soon after application “Mustard Plaster”: home remedy Should never be inhaled/tasted undiluted  toxic

44 Counterirritants (Group A) Stronger Ammonia Water If not diluted  caustic  vapour Sneezing, coughing In concentration: pulmonary oedema Asphyxia because of glottis spasm Eye irritation Weeping conjunctival swelling temporary blindness - Should be handled with care and never inhaled. - Dilute before use

45 Counterirritants (Group A) Methyl Salicylate “wintergreen oil” The most widely used counterirritant. At v low conc.  used as flavouring agent/aroma in candies, chewing gum, toothpastes etc Ingestion of more than small amounts in hazardous because of the high salicylate content. Liquid preparations of > 5%  child-resistant containers Avoid using with heat or after strenuous exercise (why?) Caution is patients allergic to ASA, having asthma or nasal polyps

46 Counterirritants (Group A) Turpentine Oil Prepared from Turpentine oleoresin collected from pine trees As an irritant: acts by defatting the skin causing dryness and fissuring May cause eczema for sensitive skin Systemic absorption may cause GIT upset, skin and respiratory symptoms in susceptible people Ingestion can be fatal ( 15mL in children and 140mL in adults)

47 Counterirritants (Group B) Menthol Obtained either from peppermint or synthetically In small quantities  flavouring agent in candies, chewing gums, cigarettes Dose dependent effect: < 1.0%  depress receptors > 1.25%  counterirritant Some patients may have reactions to menthol: wheezing, urticaria,erythema, contact dermatitis

48 Counterirritants (Group B) Camphor Obtained either from camphor tree or synthetically Dose-dependent effect: < 3%  topical analgesic, anaesthetic, antipruritic >3%  counterirritant if applied vigorously  rubefacient action Concentrations >11% are unsafe and toxic if ingested.

49 Counterirritants (Group C) Histamine Dihydrochloride Histamine: causes vasodilatation is also absorbed percutaneously

50 Counterirritants (Group C) Methyl Nicotinate This ester has a marked power to penetrate the cutaneous barrier In a very low concentrations, ~ causes vasodilatation and elevation of temperature Indomethacin, ibuprofen and ASA  significantly reduces the skin’s vascular response to ~  conclusion? If applied over large areas  drop in BP, pulse rate and syncope  due to generalised vascular dilation. Vasodilatation response due to ~ is mediated at least in part by prostaglandin biosynthesis

51 Counterirritants (Group D) Capsicum Preparations1 Capsicum  Capsicum oleoresin  Capsaicin Are derived from the fruit of various species of plants of the nightshade family The major compound is capsaicin, which is also the major ingredient in the hot (chile) pepper Elicits transient feeling of warmth In high concentrations  burning pain which will rapidly diminish due to tachyphylaxis

52 Counterirritants (Group D) Capsicum Preparations 2 DO NOT CAUSE reddening or blisters even at high conc. (WHY??) Capsaicin  depletion of substance P from sensory neurons that have been implicated in mediating cutaneous pain Substance P Because they do not work on blood vessels pain vasodilatation Pruritic stimuli X X X X= capsaicin effect

53 Counterirritants (Group D) Capsicum Preparations 3 Because it depletes substance-P, capsaicin has an increasing role in the treatment of: 1. Postherpetic neuralgia 2. Psoriasis 3. Post mastectomy pain 4. Reflex sympathetic dystrophy 5. Diabetic neuropathy (e.g. alleviate aching and burning foot pain)

54 Combination Products Two or more safe and effective ingredients (category I) may be combined: (1) when each active ingredient contributed to the claimed effect & (2) if this combination does not decrease the safety or effectiveness of any individual active ingredient It is irrational to combine counterirritants with local anaesthetics, topical antipruritics or topical analgesics (WHY?) Because these agents depress sensory cutaneous receptors which opposes the effect of counterirritants. = Methylsalicylate+ turpine oil+menthol

55 Dosage Forms Finished product= active ingredient(s)+ vehicle The ideal topical drug vehicle should be: 1. Easy to apply and remove 2. Nontoxic, nonirritating and nonallergenic 3. Cosmetically acceptable, nongreasy & nondehydrating 4. Homogenous 5. Bacteriostatic 6. Chemically stable 7. Pharmacologically inert 8. Keep skin penetration to a minimum

56 Dosage Forms Liniments: solutions or mixtures of various substances in oil, alcoholic solutions of soap, or emulsions. Applied by friction or rubbing (the oil, soap base facilitates massage) The vehicle selected in basis of desired action: Alcoholic/hydroalcoholic vehicle when rubefacient or counterirritant action is desired Oleoginous vehicles are used when massage is required

57 Dosage Forms Gels: generally clear, composed of water-soluble ingredients and are of more uniform and semisolid consistency Provide greater sensation of warmth than lotions or ointments (gels promote more rapid and extensive penetration of medication into skin and hair follicles) Excessive amounts or rubbing should be avoided (WHY?) because increased penetration may cause an unpleasant burning sensation

58 Dosage Forms Lotions: suspensions of solids in an aqueous medium, applied to skin without friction for the protective or therapeutic value of their constituents Intended to dry on the skin after application Fluidity  uniform and rapid application over wide areas  especially suited for hairy body areas Should be shaken before each use (WHY?) Because suspensions tend to separate while standing

59 Dosage Forms Ointments: semisolid preparations particularly desirable for counterirritation because they are applied with massage (just like liniments) Clinical Consideration: - oil/water formulations are preferred for day time use (because they are washable from skin) - Protect clothing with a cover but not tight (irritation, reddening and blistering)

60 Non-drug Measures 1 1. Heat: The most frequently used Heat lamp Hot water bottle Heat pad Moist steam pack - After a stretch injury, collagen does not return to its resting length…

61 Non-drug Measures 2 Heat: 1. Helps to restore the elastic properties of collagen by increasing the viscous flow 2. Increases threshold in free nerve endings  analgesic effect However, heat should not be used simultaneously with counterirritant preparation (WHY?) Severe burning, blistering, skin necrosis and interstitial nephritis

62 Non-drug Measures 2 2. Massage Increases flow of lymph and blood in skin and underlying structures > warmth> same effect as heat

63 Patient Counselling Precautions: For external use only D/C if condition worsens or last > 7 days Don’t apply to open wound or broken skin Don’t apply with tight bandage Wash hands thoroughly after application Do not handle or insert contact lenses following application without washing your hands Don’t apply to children < 2 years old

64 Adverse effects: - simple irritation (rashes and blisters) and - sensitisation Drug interactions: Topical salicylates may increase the PT time if used with warfarin

65 Myalgia OTC analgesics should be started soon after the injury. Adjunctive: heat, massage. Remobilisation after injury healed is important, otherwise: weak, tight, overly contracted muscles, trigger points may arise

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67 Periarticular Pain: Injury or inflammation to the tissues surrounding the joint ( joint capsule, ligaments, tendons, bursae) Localised tenderness, pain associated with movement of structure. knee, shoulder, elbow Responds well to OTC analgesics and limitation of movement

68 Arthralgia: Joint pain often caused by synovitis (inflammation of synovial membrane). Cartilage loss may occur (e.g. in DJD, RA). Osteoarthritis (DJD) -In wt bearing joints: hips, knee, lumbar spine -Paracetamol is analgesic of choice, wt loss -For acute flares: NSAIDs, local heat Reumatoid Arthritis (RA) -mainly: multiple joints, fingers, hands, wrist and feet - joints warm, red, swollen, motion limited > deformity -more than OTC (NSAIDs): education, physical therapy,

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