Summer Training Guide 4th Stage Pharmacy Students PDF

Summer Training Guide For Fourth Stage Pharmacy Students Second Edition 2022 I II ‫ص َذقَ ٍخ‬ ‫س ‪َ ٍِِْ :‬‬ ‫بد ا ْث ُِ آ َد ًَ ا ّْقَطَ َع َع ََئُُ إِال ٍِِْ صَال ٍ‬ ‫(إِ َرا ٍَ َ‬ ‫ح ٌَ ْذ ُع٘ ىَُٔ)‬ ‫َجب ِسٌَ ٍخ ‪ ،‬أَ ْٗ ِع ْي ٌٍ ٌُ ْْزَفَ ُع ثِ ِٔ ‪ ،‬أَ ْٗ َٗىَ ٍذ َ‬ ‫صبى ِ ٍ‬ ‫حذٌش ّج٘ي ششٌف‬ ‫"ال يؤلف أحد كتابا إال في أحد أقسام سبعة‪ ،‬و ال‬ ‫يمكن التأليف في غيرها‪ ،‬وهي‪ :‬إ ّما أن يؤلف من‬ ‫شيء لم يسبق إليه فيخترعه‪.‬أو شيء ناقص يتممه‪.‬‬ ‫أو شيء مستغلق يشرحه‪.‬أو طويل يختصره‪ ،‬دون‬ ‫أن يخل بشيء من معانيه‪.‬أو شيء مختلط يرتبه‪.‬أو‬ ‫شيء أخطأ فيه مصنف يبينه‪.‬أو شيء مفرق‬ ‫يجمعه"‪.‬‬ ‫شَظ اىذٌِ اىجبثيً سحَٔ هللا‬ ‫إٕذاء‪.....‬‬ ‫إىى ‪....‬‬ ‫صٗجزً ٗأٗالدي (ٌبعش ٗحَضح)‪....‬‬ ‫عيى ٍب أخزد ٍِ ٗقذ ٕ٘ ٍِ حقٌٖ ‪....‬‬ ‫إٔذي عَـــــــــــــــــــيً ٕـــــــــــــــــــزا ‪....‬‬ ‫ظٍبء‬ ‫‪0200‬‬ ‫‪III‬‬ ‫رٍَٖـذ‬ ‫ٌٍ‬ ‫َِ اى َّش ِح ِ‬ ‫غ ٌِ هللاِ اى َّش ْح ِ‬ ‫ث ْ‬ ‫ش ًذا)‬‫ع ٰى َٕ ْو أَرَّجِ ُعلَ َعيَ ٰى أَُْ رُ َعيِّ ََ ِِ ٍِ ََّب ُعيِّ َْذَ ُس ْ‬ ‫(قَب َه ىَُٔ ٍُ٘ َ‬ ‫ع٘سح اىنٖف اٌَخ ﴿‪﴾٦٦‬‬ ‫ٌَضو اىزذسٌت اىصٍفً ىطالة اىَشحيخ اىشاثعخ فً ميٍبد اىصٍذىخ اىقغٌ‬ ‫اىضبًّ ٍِ ٍزطيجبد اىزذسٌت اىصٍفً ثعذ رذسٌت اىَشحيخ اىضبىضخ ٗرأرً‬ ‫إٍَزٔ ٍِ مُ٘ اىطبىت ٌذخو ٕزا اىقغٌ ٗقذ اعزنَو دساعخ عيٌ االدٌٗخ‬ ‫مبٍال ٍع دساعخ صٍذىخ اىَجزَع ٗ قغَب ٍَٖب ٍِ اىصٍذىخ اىغشٌشٌخ‬ ‫ٗثبىزبىً فأُ اغيت ٍب ٌشآ ٍِ ادٌٗخ ٗاٍشاض عزنُ٘ ٍَب عجق ىٔ‬ ‫دساعزٖب ّظشٌب ٗعَيٍب فً اىنيٍخ‪...‬اُ اىطبىت فً ٕزٓ اىَشحيخ ٌنُ٘ قذ‬ ‫اٗشل عيى اىزخشط‪ٗ..‬ثبىزبىً فأُ االّخشاغ فً اج٘اء اىَْٖخ ٗاىزَبط‬ ‫اىَجبشش ٍع عبىٌ االدٌٗخ ٗاى٘صفبد ٗاىَشظى ‪..‬رحذ اششاف اىصٍذىً‬ ‫غجعب‪ٌ..‬صجح ظشٗسح ٍيحخ ىيزٍٖؤ ىجٍئخ اىعَو مصٍذالًّ ٍغؤٗه عِ‬ ‫صحخ ٗعالٍخ اىَشٌط‪..‬اُ ٕزا اىنزبة ٌعذ اعزنَبال ىنزبة (دىٍو اىزذسٌت‬ ‫اىصٍفً‪..‬ىطالة اىَشحيخ اىضبىضخ فً ميٍبد اىصٍذىخ)‪..‬رٌ اىز٘عع ثٔ امضش‬ ‫اّغجبٍب ٗاىَشحيخ اىذساعٍخ‪..‬غٍش اُ اىز٘عع ىٌ ٌخشط عِ اىز٘جٔ اىعبً‬ ‫ىينزبة ٕٗ٘ رشمٍضٓ عيى (اىَعيٍ٘بد االعبعٍخ‪ٗ..‬اىََٖخ‪..‬راد اىطبثع‬ ‫اىعَيً ٗاىقبثو ىيزطجٍق) اىخبصخ ثنو ٍجَ٘عخ دٗائٍخ اٗ احذ ادٌٗزٖب‪ٗ...‬قذ‬ ‫حبفظْب عيى اعي٘ة ٗرشرٍت دىٍو اىَشحيخ اىضبىضخ ٍِ ّبحٍخ رقغٌٍ اىفص٘ه‬ ‫ٗرجٌ٘ت اىَجبٍٍع اىذٗائٍخ ٗعشض اىَعيٍ٘بد ٗاىجذاٗه اىَيحقخ اىخبصخ‬ ‫ثأعَبء االدٌٗخ اىزجبسٌخ (االمضش شٍ٘عب) ٗاشنبىٖب اىصٍذالٍّخ ٗاىزً رَأل‬ ‫ٍِ قجو اىطبىت اىَزذسة‪..‬إُ عَيً ٕزا قذ ال ٌخي٘ ٍِ قص٘ ٍس‪ٗ ،‬ىنِ ٗمَب‬ ‫ت إّغبٌُ مزبثًب فً ٌ٘ ٍِٔ؛ إالَّ‬ ‫ٌق٘ه اىقبظً اىفبظو‪ ":‬إًِّّ سأٌذُ أَّّٔ ال ٌنزُ ُ‬ ‫غُِ ‪ٗ ،‬ى٘ قُ ِّذ ًَ‬‫أحغِ‪ٗ ،‬ى٘ ِصٌ َذ مزا ىنبُ ٌُغزَح َ‬ ‫َ‬ ‫قب َه فً َغ ِذ ِٓ‪ :‬ى٘ ُغٍِّ َش ٕزا ىنبُ‬ ‫ٕزا ىنبُ أفع َو‪ٗ ،‬ى٘ رُ ِشكَ ٕزا ىنبُ أجَ َو‪ٕٗ.‬زا ٍِِْ أعظَ ٌِ اى ِعجَ ِش‪ ٕ٘ٗ ،‬دىٍ ٌو‬ ‫ش ِش "‪ٗ..‬أخٍشا الثذ ٍِ اإلشبسح إىى إُ‬ ‫ص عيَى ُجَي ِخ اىجَ َ‬ ‫عيَى اعزٍال ِء اىَّْق ِ‬ ‫ٕزا اىذىٍو قذ اعذ ىٍنُ٘ ٍغبعذا ىطيجزْب األعضاء فً اىزذسٌت اىصٍفً ٕٗ٘‬ ‫ىٍظ ثذٌال عِ اىزذسٌت فً إي حبه اّغجبٍب ٍع اىحنَخ اىزعيٍٍَخ‬ ‫اىقبئيخ‪(:‬قو ىً‪ٗ..‬ع٘ف أّغى‪..‬أسًّ ‪ٗ..‬ع٘ف أرزمش ‪..‬أششمًْ ‪ٗ..‬ع٘ف‬ ‫أرعيٌ)‪ ٍِٗ..‬اىيــــــــــــــــــٔ اىز٘فٍـــــــــــــــق‬ ‫ظٍــــــبء‬ ‫‪0200‬‬ ‫‪IV‬‬ Contents Chapter's Title Page number 1 Dosage form-specific counseling points 1 0 Cardiovascular System 11 7 Gastro-intestinal System 73 4 Respiratory System 73 7 Central nervous system 31 6 Infections 98 3 Endocrine system 110 9 Genito-urinary system 177 8 Immune system and malignant disease 177 12 Nutrition and blood 166 11 Musculoskeletal and joint diseases 190 10 Eye 187 17 Ear, nose, and oropharynx 023 14 Skin 016 V Chapter One: Dosage form-specific counseling points 1.1-Administration of ear drops and sprays (1, 2) 1. Wash hands with soapy water. 2. Clean and dry the ear gently with a facecloth. 3. If necessary, shake the bottle of drops or spray. Some drops and sprays are suspensions and will need shaking; if applicable, this direction will be on the label. 4. Warm the ear drops or spray by holding the bottle in the hand for a few minutes. 5. Remove the lid. 6. Lie down on side with the affected ear uppermost (or tilt the head to one side). 7. Gently pull the ear lobe backward and upward to open the ear canal (see drawing A). If the patient is a child younger than 3 years old, pull the ear backward and downward (see drawing B). 8. Drop the drops or spray into the ear canal. 9. Gently massage just in front of the ear. 10. Stay lying down or with the head tilted for five minutes to allow the medication to run down the ear canal. 11. Return to the upright position and wipe away any excess medication. 12. Repeat if necessary in the other ear. 13. Replace the lid. 1 1.2-Administration of nasal preparations (1). How to use nasal drop How to use nasal sprays 1. Gently blow the nose to clear the nostrils. 1. Gently blow nose to clear nostrils. 2. Wash hands. 2. Wash hands with soapy water before using the 3. Shake the bottle of drops. Some are spray. suspensions and will need shaking; if 3. Gently shake the spray. Some are suspensions applicable, this direction will be on the and will need shaking; if applicable, this label. direction will be on the label. 4. Remove the lid from the bottle. If the lid 4. Remove the cap from the spray. includes an integral dropper draw some 5. Tilt head slightly forward (look down at feet). liquid into the dropper. 6. Close one nostril; gently press against the side 5. Position the head as shown in figure of the nose with one finger. below. The easiest way to do this is to lie on 7. Insert tip of nasal spray into open nostril and a bed with your head hanging over the edge. slowly breathe in through the open nostril, and Bending forward or kneeling is an while breathing in squeeze the spray to deliver alternative but maintaining the position for 2 one dose. It is important to keep the spray minutes after using the drops is more upright (do not sniff hard as the spray will travel difficult. Tilting the head back is not a straight to the back of the throat, failing to suitable position as the drops will not cover deposit any medication in the nostril). the upper surface of the nostril. 8. Remove spray from the nose and breathe out 6. Drop the required number of drops into through the mouth. Tilt head backwards for each nostril. The intention is to spread the about a minute to prevent the liquid spray drop(s) evenly over the surface of the running out of the nose. nostril. Do not allow the dropper to touch 9. Repeat in other nostril as directed. the nose. 10. Replace cap on spray. 7. Stay in this position for 2 minutes to 11. Try not to blow nose for several minutes prevent the drops running out of the nose after using the spray. and down the back of the throat. 8. Replace the lid. 2 1.3-Administration of drugs to the eye (1): How to use eye drops How to use eye ointment 1. Wash hands with soapy water. 1. Wash hands with soapy water. 2. If necessary, clean the eyes with boiled and 2. Clean your eye if necessary (as with eye cooled water and a tissue (one tissue for each drops) eye) to remove any discharge or remaining 3. Sit in front of a mirror. wateriness (do not use cotton wool as it may 4. Remove the cap from the eye ointment leave fibers behind that may irritate the eye). tube. Applying the ointment (see figure): 3. Shake the bottle of drops if necessary. Some 5. Gently pull down the lower eyelid, eye drops are suspensions and will need forming a pocket between the lid and the eye. shaking; if applicable, this direction will be on 6. Hold the tube above the eye without the label. touching it. 4. Remove the cap from the bottle. 7. Gently squeeze the tube and place about 1 5. Either sit down or lie down and tilt the head cm of ointment into the pocket, starting from backwards so that you are looking at the ceiling. nearest the nose to the outer edge. 6. Gently pull down the lower eyelid with a 8. Twist the wrist to break the strip of finger to make a pocket between the eye and the ointment from the tube. lower lid. 9. Close the eye and blink to help spread the 7. Look upwards. eye ointment over the eyeball. Body 8. Rest the dropper bottle on the forehead above temperature will help to melt the ointment so the eye (see figure). that it will spread over the surface of the eye. 9. Squeeze one drop inside the lower eyelid (do 10. Vision will be blurred for a few not allow the dropper tip to touch the eye). moments. Keep blinking and the vision will 10. Close the eye and gently blot away any clear. excess drops on a clean tissue. 11. Wipe away excess ointment using a clean 11. Apply slight pressure to the inner corner of tissue. the eye for about 30 seconds. This will prevent 12. Replace the cap of the tube. the drops running down the tear duct and into 13. Remember to discard any remaining the back of the throat, avoiding any unpleasant ointment four weeks after opening. after taste and also minimizing any absorption into the body, reducing the risk of possible side- effects. 12. Replace the cap on the bottle. 13. Remember to discard any remaining drops four weeks after opening. 3 1.4-Respiratory system drug delivery devices (1). An example of a metered A metered dose inhaler A metered dose inhaler attached dose inhaler. attached to a spacer to a spacer device with a mask device. An example of a Breath actuated inhaler An example of an Accuhaler. Turbohaler Figure 3-1: Examples of respiratory system drug delivery devices (1). 4 Device-specific patient counseling (1). How to use a metered dose inhaler How to use a metered dose inhaler with the aid of a spacer device 1. First assemble the spacer device if necessary as directed by the manufacturer (with or without a 1. Remove the cap covering the mouthpiece and face mask). check that there is no fluff or dirt in the 2. Remove the cap from the inhaler and insert the mouthpiece. mouthpiece of the inhaler into the opening at the 2. Shake the inhaler. end of the spacer. 3. If the inhaler is new or has not been used for 3. Hold the spacer and inhaler together and shake. some time it will need to be tested. To test: Hold 4. Breathe out. the inhaler away from body. Press the top of the 5. Put the spacer mouthpiece in the mouth and seal aerosol canister once. A fine mist should be with the lips. puffed into the air. The inhaler is now ready to 6. Press the inhaler once and then breathe in and use. out four or five times. 4. Tilt head back slightly. 7. Further doses may be taken waiting a few 5. Breathe out gently. seconds between puffs. 6. Place the mouthpiece in the mouth between the 8. Separate the spacer and inhaler. Replace the teeth (do not bite). Close lips around the inhaler cap and store until next dose. mouthpiece. 7. Start to breathe in slowly through the How to use an Accuhaler mouth, at the same time press down on 1. With the Accuhaler mouthpiece facing you, slide the inhaler to release the medicine in to the lungs. the lever away until it clicks. This will have loaded 8. Hold breath for between 5 and 10 seconds, then a dose ready for inhalation and the Accuhaler will breathe out slowly. move the dose counter on. 9. If a second dose is required, wait approximately 2. Hold the Accuhaler flat and breathe out 30 seconds and repeat the process. away from the inhaler. 10. Replace the cap and if the inhaler is a 3. Seal lips around the Accuhaler mouthpiece and corticosteroid inhaler, rinse the mouth out with inhale deeply. water. 4. Remove inhaler from the mouth and hold breath as long as is comfortable. 5. Slide the thumb grip back towards you to close the inhaler. 6. For further doses repeat above steps. How to use a Turbohaler How to use a Breath actuated inhaler 1. Unscrew the cover and remove it. 1. Shake the inhaler. 2. Hold the Turbohaler upright with one hand and 2. Hold the inhaler upright and open the cap. with the other twist the grip in one direction as far 3. Breathe out, away from the inhaler. as it will go. 4. Put the mouthpiece in the mouth, seal lips 3. Now twist back as far as it will go – a click around the mouthpiece. should be heard, showing the inhaler is primed 5. Breathe in steadily through the mouthpiece. and ready for use. 6. Hold breath for about ten seconds. 4. Breathe out gently. 7. Keeping the inhaler upright, close the cap. 5. Place the mouthpiece between the lips and 8. For further doses repeat the above steps. breathe in through the mouth as deeply and as hard as possible. 6. Remove the inhaler from the mouth and breathe out slowly. 7. Replace the cover. 8. Repeat the above steps if more than one puff is required. 5 How to use a HandiHaler (3) 1-Immediately before use, open one sealed blister foil and HandiHaler device, insert capsule, press HandiHaler button once to pierce capsule. 2-Exhale completely before placing mouthpiece into mouth with head upright. 3-Then breathe in slowly and deeply at a rate fast enough to hear capsule vibrate, until lungs are full. 4-Holding breath as long as comfortable take HandiHaler device out of mouth. 5-Then place device back in mouth and inhale again to get full dose. 1.5-Applying vaginal products (pessaries or vaginal cream) (1): 1.Wash hands with soapy water before using the pessaries/cream. 2.Remove any external foil or plastic packaging from the pessary and applicator. 3.If an applicator is provided, load the applicator as directed by the manufacturer. 4.Stand with one leg on a chair or lie down with knees bent and legs apart. 5.Press the applicator plunger to insert the pessary or cream into the vagina (see the figure ). If no applicator is provided, insert the pessary as high into the vagina as is comfortable by pushing gently but firmly in an upwards and backwards direction using the middle finger. (If pregnant, do NOT use an applicator to insert pessaries; insert using finger method.) 6.If an applicator is used, wash it ready for next use. 7.Wash hands once more. 6 1.6-Administration of rectal suppositories and enemas (2) : Suppositories 1-Gently squeeze the suppository to determine if it is firm enough to insert. Chill a soft suppository by placing it in the refrigerator for a few minutes or by running it under cool running water. 2-Remove the suppository from its wrapping. 3-Dip the suppository for a few seconds in lukewarm water to soften the exterior. 4-Lie on your left side with knees bent or in the knee-to-chest position (see drawings A and B). Position A is best for self-administration of a suppository. Small children can be held in a crawling position. 5-Relax the buttock just before inserting the suppository to ease insertion. Gently insert the tapered end of the suppository high into the rectum. If the suppository slips out, it was not inserted past the anal sphincter (the muscle that keeps the rectum closed). 6-Continue to lie down for a few minutes, and hold the buttocks together to allow the suppository to dissolve in the rectum. The parent/caregiver may have to gently hold a child's buttocks closed. 7-Remember that the medication is most effective when the bowel is empty. Try to avoid a bowel movement after insertion of the suppository for up to 1 hour so that the intended action can occur. Enemas 1-If someone else is administering the enema, lie on your left side with knees bent or in the knee-to-chest position (see drawings A and B). Position A is preferred for children older than 2 years. If self-administering the enema, lie on your back with your knees bent and buttocks raised (see drawing C). A pillow may be placed under the buttocks. 2-If using a concentrated enema solution, dilute solution according to the product instructions. Prepare 1 pint (500 mL) for adults and 1/2 pint (250 mL) for children. 3-Lubricate the enema tip with petroleum jelly or other non-medicated ointment/cream. Apply the lubricant to the anal area as well. 4-Gently insert the enema tip 2 (recommended depth for children) to 3 inches into the rectum. 5-Allow the solution to flow into the rectum slowly. If you experience discomfort, the flow is probably too fast. 6-Retain the enema solution until definite lower abdominal cramping is felt. The parent/caregiver may have to gently hold a child's buttocks closed to prevent the solution from being expelled too soon. 7 1.7-Administration of drugs to the skin: How to use patches (1): 1. Freshly wash and dry the area of skin where the patch is to be applied. Do not use talc, oil, moisturizers or creams as this may prevent the patch sticking. 2. Tear open the patch package where indicated (use the fingers rather than scissors to prevent accidental damage to the patch). 3. Remove the protective backing from the patch. Try not to touch the adhesive with fingers. 4. Press the adhesive side of the patch to the prepared skin site firmly. Ensure that there is good skin contact, particularly at the edges of the patch. 5. Wash hands thoroughly with soap and water to remove any possible contamination with medicament. Special considerations when using patches (1): Hormone replacement patches should be applied below the waist on the buttocks or thighs; NOT on the breasts. Contraceptive patches should be applied to the buttocks, abdomen, upper outer arm or upper torso; NOT on the breasts. Andropatch skin patches containing testosterone should be applied on the back, abdomen, upper arms or thighs. Avoid bony areas such as shoulders and hips that may be subjected to prolonged pressure during sleeping or sitting, as this may cause burn-like reactions of the skin. Do not apply the patches to the scrotum. Glyceryl trinitrate patches for angina should be applied to the chest or upper arm. Nicotine replacement patches should be applied to the chest, upper arm or hip. The site of application for fentanyl patches (an analgesic) depends on the brand of product used. Read the individual patient information leaflet for more details. Tips when using patches (1): Choose an area of skin that is not hairy, scarred, calloused or broken. Try to choose an area where the patch is unlikely to be rubbed off by tight clothing (for example, avoid the waist). Remove the old patch each time you apply a new one. Try not to reuse the same area to apply patches as this will make irritation more likely. Skin patches should be covered and protected from sunlight. The application of heat may increase the amount of medication absorbed. Make sure the edges of the patch are well sealed with no air pockets. This will ensure that you can bathe, shower or swim without removing the patch. (Not all patches allow this; the patient information leaflet will give guidance as to whether or not the patch will remain in place after bathing, etc.) Problems with the patch ‗sticking‘ may be due to the fact that the skin is too hot when the patch is applied. After washing the skin, dry carefully and allow the skin to cool before applying. This may improve the adhesive properties. If the skin feels sticky once the old patch has been removed this can be cleaned away using baby oil. 8 1.8-Administration of drugs by mouth: How to take tablets and capsules (1): How to take sublingual tablets (1): 1. Ideally the tablets or capsules should 1. Sit down. be taken while standing or at least 2. Take a sip of water to moisten the sitting upright. mouth if it is dry. 2. Place the tablet or capsule in the 3. Swallow or spit out the water. mouth. 4. Place the tablet under the tongue. 3. Swallow with the aid of a glass of 5. Close the mouth and do not swallow water. (Plenty of water ensures that the until the tablet has dissolved completely. tablet or capsule reaches the stomach Do not hasten the process by moving the and does not feel that it is ‗stuck‘ in the tablet around the mouth with the tongue. throat.) Do not chew or swallow the tablet and 4. Do not lie down flat for at least 2 do not eat drink or smoke while the minutes. tablet is dissolving. 6. Do not rinse out the mouth for several How to take soluble tablets (1): minutes after the tablet has dissolved. 1. Place the tablet or tablets into a small glassful of water. 2. Stir to dissolve the tablets. 3. Drink the resultant solution. How to take buccal tablets (1): 1. Sit down. 2. Take a sip of water to moisten the mouth if it is dry. 3. Swallow or spit out the water. 4. Place the tablet between the cheek and the upper or lower gum (or alternatively between the upper gum and the lip) 5. Close the mouth and do not swallow until the tablet has dissolved completely. Do not hasten the process by moving the tablet around the mouth with the tongue. Do not chew or swallow the tablet and do not eat drink or smoke while the tablet is dissolving. 6. Do not rinse out the mouth for several minutes after the tablet has dissolved. 9 References 1-Christopher A Langley, Dawn Belcher. Applied Pharmaceutical Practice. Pharmaceutical Press. 2009. 2-American pharmacists association. Handbook of Non-prescription drugs: An Interactive Approach to Self-Care. 18th edition. 2016. 3-Nursing Spectrum Drug Handbook. 2016. 11 Chapter Two: Cardiovascular System 2.1-Angiotensin-converting enzyme inhibitors (ACE inhibitors) 1-They inhibit ACE, thereby inhibiting the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor (1). 2- Members of the drug class include: (captopril, enalapril, fosinopril, imidapril, lisinopril, perindopril, quinapril, ramipril, and trandolapril) (2). 3-The main uses of ACE inhibitors are in the management of heart failure, hypertension, and myocardial infarction (3). In addition, they are used for the prevention and treatment of diabetic nephropathy (1) (early evidence of nephropathy is the presence of albumin in the urine) (4). 4-It may take several weeks before the full antihypertensive effects of ACEIs are seen. Therefore, evaluating BP response 2 to 4 weeks after starting or changing the dose of an ACEI is appropriate (5). 5-Pronounced hypotension may occur at the start of therapy with ACE inhibitors (first dose hypotension) (3). Therefore: A-Therapy should be started with low doses followed by gradual titration as tolerated to target doses (6). B-For hypertension the first dose should preferably be given at bedtime (2). 6-Other adverse effects include persistent dry cough (3)[see Angiotensin II receptor blocker (ARBs) below]. (Occurs in up to 20% of patients and is thought to be due to inhibition of bradykinin breakdown) (6). 7-Angioedema is a serious potential complication of ACEi therapy. It occurs in less than 1% of the population. Symptoms include lip and tongue swelling and possibly difficulty breathing. Drug withdrawal necessary. An is Angiotensin II receptor blocker (ARBs) can generally be used in patients with a history of ACE inhibitor-induced angioedema, with careful monitoring (6) (cross-reactivity 2.5%)(7). 8-Monitoring requirements: Renal function and electrolytes should be checked before starting ACE inhibitors (or increasing the dose) and monitored during treatment (2). Patients with an increase in serum creatinine of greater than 30% should have their ACEI therapy temporarily discontinued (5) until further evaluation can be made (4). 9-An ACEi, as well as an ARB or direct renin inhibitor, are contraindicated in pregnancy (6). 10-Counseling points for the drug class Notify a healthcare professional if a cough develops (1). For hypertension the first dose should preferably be given at bedtime (2). 11 ACE inhibitors Scientific name Trade names Dosage form 1 2 3 4 5 Any extra notes: 2.2-Angiotensin II receptor blockers(ARBs). 1-They block the binding of angiotensin II to the AT1 receptor, thereby inhibiting the effects of angiotensin II, a potent vasoconstrictor (1). 2-Members of the drug class include: (azilsartan, candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan, and valsartan) (sartans) (2). 3-They are used for hypertension, heart failure, diabetic nephropathy, and myocardial infarction (1). 4-As with ACE inhibitors, initiate therapy with low doses and then titrate to target doses (6). 5-In select situations, the addition of ARBs (Candesartan and valsartan) to ACE- Is (Combination therapy) for patients with heart failure has demonstrated additional incremental benefits (4). 6-Imortant: unlike ACE inhibitors, they are less likely to cause the persistent dry cough (2) (less than 1%) (7) which can complicate ACE inhibitor therapy. They are therefore a useful alternative for patients who have to discontinue an ACE inhibitor because of persistent cough (2). 7-Like ACE inhibitors, they may cause renal insufficiency, hyperkalemia, and orthostatic hypotension (6). 8-Monitoring requirements: Monitor potassium concentration, particularly in the elderly and in patients with renal impairment (2). 12 Angiotensin II receptor blockers Scientific name Trade names Dosage form 1 2 3 4 5 Any extra notes: 2.3-Angiotensin receptor–neprilysin inhibitor (ARNI) 1-Sacubitril (a neprilysin inhibitor) inhibits the breakdown of natriuretic peptides resulting in varied effects including increased diuresis, natriuresis, and vasodilation (2). 2-The combination of (ARNI) is indicated for chronic heart failure with reduced ejection fraction (Systolic HF) (2). 3-Discontinue ACE inhibitors 36 hours prior to initiating the ARNI (6) (due to an increased risk for angioedema) (4); no waiting period is needed in patients receiving an ARB (6). 4-Sacubitril/valsartan is contraindicated in patients with a history of angioedema associated with an ACE inhibitor or ARB. It is also contraindicated in pregnancy and should not be used concurrently with ACE inhibitors or other ARBs (6). 5-Monitoring requirements: Monitor renal function and potassium 1–2 weeks after initiating therapy or increasing the dose (7). Scientific name Trade name Dosage form 1 Valsartan/sacubitril Any extra notes: 13 2.4-Renin inhibitor 1-Aliskiren is a renin inhibitor that is licensed for the treatment of hypertension(2). 2-Aliskiren role in the management of hypertension is limited (6). 3-Many of the cautions and adverse effects seen with ACE inhibitors and ARBs apply to aliskiren. It is contraindicated in pregnancy due to known teratogenic effects (6). Scientific name Trade name Dosage form 1 Any extra notes: 2.5-Beta-adrenoceptor blocking drugs (beta-blockers) 1-Beta blockers block response to beta-adrenergic stimulation at the receptor level, which results in decreases in heart rate, myocardial contractility, blood pressure, and myocardial oxygen demand (1). 2-Members of the drug class include (atenolol, bisoprolol, carvedilol, metoprolol, nadolol, oxprenolol, pindolol, and propranolol) (2). 3- Table 2-1: Different properties of β-blockers. Criteria Examples Water solubility Atenolol , Nadolol, Bisoprolol Lipid soluble Oxprenolol, Metoprolol, Propranolol, Carvedilol Intrinsic sympathomimetic Oxprenolol, Pindolol activity(ISA) β1-Selectivity Atenolol , Metoprolol, Bisoprolol, Nebivolol Nonselective Oxprenolol, Nadolol, Pindolol , Propranolol Mixed α and β blocker Carvedilol 4-Usage for the drug class: Cardiovascular uses: Angina, arrhythmias, heart failure (bisoprolol, carvedilol, metoprolol(1) and nebivolol(2)), hypertension, and myocardial infarction (1). Noncardiovascular uses: Essential tremors, prophylaxis of migraine and of variceal bleeding associated with portal hypertension, management of alcohol withdrawal, anxiety disorders, and treatment of thyrotoxicosis symptoms. Some beta blockers are used as eye drops in the management of glaucoma and ocular hypertension (1, 3). 5-Important: when β-blockers are used for heart failure: 14 Initiate β-blockers in stable patients who have no or minimal evidence of fluid overload (6). Because of their negative inotropic effects, start β-blockers in very low doses with slow upward dose titration to avoid symptomatic worsening (doses should be doubled no more often than every 2 weeks, as tolerated, until the target or maximally tolerated dose is reached) (6). When used in heart failure, carvedilol should be taken with food to reduce the risk of hypotension (3). 6-Esmolol is a relatively cardioselective beta-blocker with a very short duration of action, used intravenously for the short-term treatment of supraventricular arrhythmias (2). 7-Sotalol, a non-cardioselective beta-blocker with additional class III anti- arrhythmic activity, is used for prophylaxis in paroxysmal supraventricular arrhythmias (2). 8-Important: A-β-blockers are effective for reducing blood pressure but other antihypertensives are usually more effective for reducing the incidence of stroke, myocardial infarction, and cardiovascular mortality, especially in the elderly (2). Therefore, for patients with hypertension but without compelling indications, a β-blocker should not be used as the initial first-line agent (6). B-A β-blocker is only an appropriate first-line agent in hypertension when used to treat specific compelling indications (e.g., ischemic heart disease, heart failure) (6). 9-Oxprenolol, and pindolol have intrinsic sympathomimetic activity (ISA); they tend to cause less bradycardia than the other beta-blockers and may also cause less coldness of the extremities (2). 10-Atenolol, and nadolol are the most water soluble; they are less likely to enter the brain, and may therefore cause less sleep disturbance and nightmares. They are excreted by the kidneys and dosage reduction is often necessary in renal impairment (2). 11-Beta-blockers can precipitate bronchospasm and should therefore usually be avoided in patients with a history of asthma (2). 12-Atenolol, bisoprolol, metoprolol, and nebivolol, have less effect on the β2 (bronchial) receptors and are, therefore, relatively cardioselective. They have a lesser effect on airways resistance but are not free of this side-effect (2). 13-Beta-blockers are also associated with fatigue, coldness of the extremities (may be less common with those with ISA), and sleep disturbances with nightmares (may be less common with the water-soluble beta-blockers) (2). 15 14-Beta-blockers can mask the signs and symptoms of hypoglycemia (such as tachycardia) (except sweating). However, beta-blockers are not contra-indicated in diabetes, although the cardioselective beta-blockers may be preferred (2, 5). 15-Abrupt cessation of β-blocker therapy may produce unstable angina, MI, or even death in patients with coronary disease. In patients without heart disease, abrupt discontinuation of β-blockers may be associated with tachycardia, sweating, and generalized malaise in addition to increased BP. For these reasons, the dose should always be tapered gradually over 1 to 2 weeks before discontinuation (6). 16-Counseling points for the drug class: Do not abruptly stop taking medication. Beta blockers should be gradually tapered when stopping (1). Beta-blockers Scientific name Trade name Dosage form 1 2 3 4 5 6 Any extra notes: 2.6-Calcium-channel blockers (CCBs) 1-These agents block calcium channels in the peripheral blood vessels and/or the heart (8). A-Dihydropyridine CCBs (examples: amlodipine, felodipine, nifedipine, isradipine, nicardipine, nimodipine, nisoldipine) (1) : They have a greater selectivity for vascular smooth muscle than for heart and therefore their main effect is vasodilatation (3). B-Non-Dihydropyridine CCBs (examples diltiazem and verapamil): They have a greater selectivity for heart than for vascular smooth muscle (3). Verapamil decreases heart rate. Diltiazem decreases heart rate to a lesser extent than verapamil (6). 2-The main use of CCBs is in the management of angina pectoris and hypertension (both types of CCBs) ; some are also used in cardiac arrhythmias (non-dihydropyridine CCBs) (3). All are valuable in forms of angina associated 16 with coronary vasospasm (2). 3-Nimodipine is related to nifedipine but the smooth muscle relaxant effect preferentially acts on cerebral arteries. Its use is confined to prevention and treatment of vascular spasm following aneurysmal subarachnoid hemorrhage (2). 4-Verapamil is used also as prophylaxis of cluster headache (2) and migraine prophylaxis (1). Nifedipine is also indicated for Raynaud’s syndrome, postponement of premature labour, hiccup in palliative care, and chronic anal fissure (by rectum using ointment). Diltiazem is also indicated for chronic anal fissure (by rectum using ointment) (2). 5-Amlodipine and felodipine have a longer duration of action and can be given once daily (2). 6-Side-effects associated with vasodilatation such as flushing and headache (which become less obtrusive after a few days), and ankle swelling (which may respond only partially to diuretics) are common (2). Constipation is the most common side- effect of verapamil (2). 7- Calcium channel blockers, with the exception of amlodipine, should be avoided in heart failure as they can further depress cardiac function and exacerbate symptoms (2). 8-Amlodipine tablets from various suppliers may contain different salts (e.g. amlodipine besilate, amlodipine maleate, and amlodipine mesilate) but the strength is expressed in terms of amlodipine (base); tablets containing different salts are considered interchangeable (2). 9-Different versions of modified-release preparations may not have the same clinical effect. To avoid confusion between these different formulations of nifedipine and diltiazem, prescribers should specify the brand to be dispensed (2). 10-Tablet membrane of (Tildiem retard ® and Adalat ® LA) may pass through gastro-intestinal tract unchanged, but being porous has no effect on efficacy (2). CCBs Scientific name Trade names Dosage form 1 2 3 4 5 6 17 Any extra notes: 2.7-Diuretics 1-The principal groups of diuretics are as follows (Table 2-2). Table 2-2: Types of diuretics Diuretic type examples Thiazide and related diuretics Hydrochlorothiazide, Chlortalidone Loop Diuretics Furosemide, Bumetanide and Torasemide Potassium (K+)-sparing diuretics Amiloride and triamterene Aldosterone antagonist Spironolactone Carbonic anhydrase inhibitors Acetazolamide (mainly for glaucoma) Osmotic diuretics Mannitol (used in cerebral edema) 2-Diuretics promote the excretion of water and electrolytes by the kidneys. They are used in the treatment of heart failure, hypertension and other diseases when salt and water retention has resulted in edema (3). (6) 3-Thiazides are the preferred type of diuretic for hypertension. Loop diuretics are the most widely used diuretics in heart failure (4). 4-The loop diuretics are more potent than thiazides, and retain their effectiveness in renal insufficiency. Thus, in most patients with HF, loop diuretics are preferred (5). 5-Thiazides are believed to lose their effectiveness when creatinine clearance decreases to less than 30 mL/minute. Metolazone is an exception in that its activity may be preserved in these patients (5). Unlike thiazides, loop diuretics maintain their effectiveness in the presence of impaired renal function, although higher doses may be necessary (6). 6-Potassium-sparing diuretics are weak antihypertensives when used alone. Their primary use is in combination with another diuretic to counteract potassium- wasting properties (6). 7-Because they do not alter disease progression or prolong survival, diuretics are not required for HF patients without fluid retention (6). 8-Chlortalidone, a thiazide-related compound, has a longer duration of action than the thiazides and may be given on alternate days to control edema. Metolazone is particularly effective when combined with a loop diuretic (even in renal failure) (2). 9-Xipamide and indapamide are chemically related to chlortalidone. Indapamide is claimed to lower blood pressure with less metabolic disturbance, particularly less aggravation of diabetes mellitus (2). 18 10-Spironolactone is of value in the treatment of edema and ascites caused by cirrhosis of the liver; furosemide can be used as an adjunct. Low doses of spironolactone are beneficial in moderate to severe heart failure (2). 11-Mannitol is an osmotic diuretic that can be used to treat cerebral edema and raised intra-ocular pressure (2). 12-I.V Furosemide doses greater than 50 mg given by intravenous infusion only. Give continuously in sodium chloride 0.9% ; glucose solutions are unsuitable (2). 13-Hypokalemia can occur with both thiazide and loop diuretics. Potassium- sparing diuretics may cause hyperkalemia (6). 14-Spironolactone is given after food (2). It has an anti-androgenic properties, therefore: A-It may cause side effects like gynecomastia (breast enlargement), and impotence in men (3). B- It has been used for its anti-androgenic properties in some cases of acne and for women with hirsutism (hair on the face) (3). 15-In concentrations of 15% or greater, mannitol may crystallize when exposed to low temperatures. Do not use a mannitol solution containing crystals. If such crystallization occurs, the recommended procedure for resolubilization is to heat the mannitol in a dry heat cabinet to 70 °C for flexible plastic containers with the overwrap intact or to 80 °C for glass containers with vigorous shaking. The use of a water bath is not recommended (9). Diuretics Scientific name Trade names Dosage form 1 2 3 4 5 6 Any extra notes: 19 Note : Fixed-dose combination products 1-Several fixed-dose combination products are available , their use can reduce the number of tablets or capsules taken by patients. This has been demonstrated to improve adherence compared with using two separate single-drug products. Improved adherence may increase the likelihood of achieving goal BP values (5). 2-Most fixed-dose combinations include a thiazide diuretic. Other fixed-dose combination products combine a CCB with either an ACEI or ARB (5). Fixed-dose combination products Scientific name Trade name Dosage form 1 2 3 4 5 2.8-Lipid-regulating drugs 1-Lipid regulating drugs are used to modify blood lipid concentrations in the management of dyslipidemias and for the reduction of cardiovascular risk (3). 2-The principal groups of lipid regulating drugs are (Table 2-3) (2, 6): Table 2-3: Types of lipid regulating drugs (2, 6) Class Examples 1 Statins Atorvastatin, Fluvastatin, Pravastatin, Rosuvastatin, and Simvastatin 2 Fibrates Bezafibrate, Ciprofibrate, Fenofibrate, and Gemfibrozil 3 Nicotinic acid Acipimox, and Nicotinic acid. derivatives 4 Bile acid sequestrants Colesevelam, Colestipol, and Colestyramine., 5 Absorption inhibitors Ezetimibe 6 Others Alirocumab, Evolocumab, Lomitapide , Mipomerson and Omega-3 fatty acid compounds 2.8.1-Statins 1-Statins inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, interrupting conversion of HMG-CoA to mevalonate, the rate-limiting step in cholesterol biosynthesis (6). 21 2-Statins are more effective than other lipid-regulating drugs at lowering LDL-cholesterol concentration but they are less effective than the fibrates in reducing triglyceride concentration (2). 3-Statins are used adjunct to diet and exercise for various dyslipidemias and for the treatment of various dyslipidemia disorders in patients with no evidence of cardiovascular disease (primary prevention) and in patients with documented coronary artery disease (secondary prevention) (1). 4-Rosuvastatin and atorvastatin have the longest half-lives. The long half-life also allows for administration at any time of day rather than at bedtime for maximum effect, which is recommended for simvastatin, lovastatin, pravastatin, and fluvastatin (5) (Cholesterol synthesis in the liver peaks during the early morning (midnight to 3 a.m.) (3). 5-Relative LDL–lowering efficacy of statins are shown in table 2-4 (7). Table 2-4: Relative LDL–lowering efficacy of statins (7). 6-The most common adverse effects reported include muscle pain and weakness (myalgias), headache, GI symptoms, including dyspepsia, flatus, constipation, and abdominal pain, and skin rashes. These symptoms are usually mild and often dissipate with continued therapy (5). 7-Less common adverse effects include myopathy, elevated hepatic transaminases, and diabetes (5). 8-Muscle toxicity can occur with all statins, however the likelihood increases with higher doses. Therefore, advise patients to report promptly unexplained muscle pain, tenderness, or weakness (2). 9-Liver enzymes should be measured before treatment, and repeated within 3 months and at 12 months of starting treatment, unless indicated at other times by signs or symptoms suggestive of hepatotoxicity (2). 10-Avoid drinking grapefruit juice with statins metabolized by the CYP3A4 system (1)[ lovastatin, simvastatin, atorvastatin (avoid excess quantities :> 1.2 L/day)] (7). 21 2.8.2-Fibrates 1-Fibrates are mainly used for the treatment of hypertriglyceridemia (1). 2-Fenofibrate is the preferred agent when used in combination with statins due to the potential for fewer drug interactions (1). 3-Bezafibrate and fenofibrate are given with or just after food while gemfibrozil is given 30 to 60 minutes before food (2). 2.8.3-Bile acid sequestrants (BAS) 1-Bile acid sequestrants act by binding bile acids, preventing their reabsorption; this promotes hepatic conversion of cholesterol into bile acids; the resultant increased LDL-receptor activity of liver cells increases the clearance of LDL- cholesterol from the plasma (2). 2-May increase TG concentrations (7). 3-Older BAS (colestyramine, colestipol) are not well tolerated due to numerous GI side effects and the unpleasant granular texture of the powder. Therefore, colesevelam is currently the preferred agent (5). 4-Other uses: A-Colesevelam is also approved by the FDA for use in type 2 diabetes to improve glycemic control (5). B-Colestyramine is also used for pruritus associated with partial biliary obstruction and primary biliary cirrhosis. It also used for diarrhea associated with Crohn‘s disease, ileal resection vagotomy, diabetic vagal neuropathy, and radiation (2). 5-They interfere with the absorption of fat-soluble vitamins (supplements of vitamins A, D, K, and folic acid may be required when treatment is prolonged) (2). 6-Colestyramine and colestipol may reduce or delay the absorption of medications when co-administered. This can be minimized by administering other medications 1 hour before or 4 hours after the resin dose (5). 7-Adminstarion: A-Colesevelam tablet is given with or just after food (2). B-Colestipol Granules: The contents of each sachet should be mixed with at least 100 mL of water or other suitable liquid such as fruit juice or skimmed milk. Alternatively it can be mixed with thin soups, cereals, yoghurt, or pulpy fruits ensuring at least 100 mL of liquid is provided (2). C-Colestyramine Powder :The contents of each sachet should be mixed with at least 150 mL of water or other suitable liquid such as fruit juice, skimmed milk, thin soups, and pulpy fruits with a high moisture content (2). 22 2.8.4-Cholesterol absorption inhibitor (Ezetimibe) 1-Ezetimibe inhibits the intestinal absorption of cholesterol. If used alone, it has a modest effect on lowering LDL-cholesterol, with little effect on other lipoproteins(2). 2-Ezetimibe should not be prescribed as a first-line agent. It is specifically used in combination with a statin to lower LDL. An additional lowering of approximately 25% in LDL can be seen when ezetimibe is combined with a statin(1). 3-Ezetimibe is taken without regard to meals (1). 2.8.5-Nicotinic acid (niacin )derivatives 1-Nicotinic acid and its derivatives reduce triglycerides and increases HDL cholesterol and may also modestly reduce LDL-cholesterol (3). 2-Niacin is indicated for patients with elevated triglycerides, low HDL cholesterol, and elevated LDL cholesterol (4). 3-Adverse events frequently limit niacin use (6). A-Niacin use is limited by cutaneous reactions such as flushing and pruritus of the face and body. The use of aspirin (4) (325 mg (6)) or a nonsteroidal anti-inflammatory drug (NSAID) 30 minutes prior to taking niacin can help alleviate these reactions because they are mediated by an increase in prostaglandin (4). B-In addition, taking niacin with food and avoiding hot liquids or alcohol at the time niacin is taken is helpful in minimizing flushing and pruritus (4). C-Lastly, slow titration of the niacin dose to minimize and/or prevent flushing (4). D-Rise in serum transaminase values are seen with all niacin formulations, but the worst cases have been reported with slow-release niacin (slow-release products should not be recommended due to increased hepatotoxicity risk) (1). E-Immediate-release products have the least hepatotoxicity; however, they must be dosed three times daily and can cause significant flushing (1). F-Most experts prefer Niaspan (extended-release niacin) because it causes less flushing than immediate-release niacin, is dosed once daily, and is associated with less liver toxicity than sustained-release (1). 4-Acipimox capsule is given with or just after food (2). 2.8.6-Others 1-Fish oil supplementation (omega-3 polyunsaturated fatty acids) lowers TG by 26%–45% (10). Used as adjunctive therapy to treat hypertriglyceridemia and as adjunct in secondary prevention in those who have had a myocardial infarction in the preceding 3 months (2). 23 2-PCSK9 Inhibitors: Alirocumab and evolocumab reduce LDL-C by as much as 60% when added to statin therapy. The drugs are administered by subcutaneous injection either biweekly or once monthly. The most common adverse effect is injection site reactions, which can be minimized by allowing the injection to come to room temperature before use and icing the site before injecting. PCSK9 inhibitor use has been limited because of high cost (6). 3-Lomitapide and Mipomersen are indicated as an adjunct to diet and lipid- lowering treatments to reduce cholesterol in patients with homozygous familial hypercholesterolemia. Their labeling contain black box warnings for severe hepatotoxicity (6). 4-Volanesorsen lowers serum triglycerides. It is indicated for familial chylomicronaemia syndrome (2). 5-Bempedoic acid inhibits cholesterol synthesis in the liver, thereby lowering LDL-cholesterol. It is indicated for primary hypercholesterolemia or mixed dyslipidemia in patients who have not responded adequately to other appropriate measures (2). Lipid-regulating drugs Scientific name Trade names Dosage form 1 2 3 4 5 6 Any extra notes: 2.9-Nitrates 1-Nitrates are peripheral and coronary vasodilators used in the management of angina pectoris, heart failure, myocardial infarction (3), for anal fissure (by rectum using ointment), and prophylaxis of phlebitis and extravasation (‗5‘ patch only) (2). 2-Sublingual Glyceryl trinitrate (GTN)(Nitroglycerin: NTG) is effective for providing rapid symptomatic relief of angina. The aerosol spray provides an 24 alternative method of rapid relief of symptoms for those who find difficulty in dissolving sublingual preparations (2). 3-If using the GTN spray, patient should apply the spray on or under the tongue and not swallow or inhale it (5). 4-Patient education about sublingual glyceryl trinitrate (Table 2-5) Table 2-5: Patient education about sublingual glyceryl trinitrate 1-In the event of an acute attack, patients should be instructed to sit or lie down, place the dose (spray or tablet) under the tongue, and not swallow the tablet. Relief of pain should occur within 5 minutes (10). If the pain persists or is unimproved 5 minutes after the first dose of GTN, the patient should call an ambulance transport as they may be experiencing an MI. If patient needs more than one tablet, he can take a maximum of three tablets in 15 minutes (5). 2-SL NTG can also be used to prevent acute episodes of angina. When patients want to participate in activities which they know lead to angina, they can take a dose of SL NTG 2 to 5 minutes in advance. This prophylactic dose provides up to 30 minutes of protection and allows patients to participate in activities that they might otherwise be unable (6). 3-The tablets should be dispensed in the original, unopened manufacturer‘s container and stored in the original brown bottle (5). 4-The bottle should be stored in a cool, dry place, but not refrigerated. The bottle should be closed tightly after each opening (5). 5-GTN tablets should be supplied in glass containers of not more than 100 tablets closed with a foil-lined cap, and containing no cotton wool wadding; they should be discarded after 8 weeks in use (2). 6-Expiration dating should be monitored closely, and tablets should be replaced immediately if they are exposed to excessive light, heat, moisture, or air (5). 5-Transdermal GTN patches, isosorbide dinitrate (ISDN) and isosorbide mononitrate (ISMN) are most commonly prescribed for long-term prevention (prophylaxis) of angina episodes (6). 6-ISMN is the primary metabolite of ISDN. To minimize the potential development of nitrate tolerance, ISMN should be used in a twice-daily (the first dose is taken on awakening and the second dose about 7 hours later) (5). 7-Modified release formulations of ISMN should only be given once daily (dose to be taken in the morning), and used in this way do not produce tolerance (2). 8-Despite the availability of ISMN, oral ISDN is still commonly used. ISDN needs to be dosed three times a day (7 AM, noon, and 5 PM ) (5). In the case of modified release tablets of ISDN, the second of the two daily doses should be given after about 8 hours rather than after 12 hours (2). 9-Common side effects of nitrate therapy include hypotension, dizziness, and headache (5). Headache usually resolves after about two weeks of continued therapy (4) and may be treated with acetaminophen (5). 25 10-Concomitant administration with phosphodiesterase type 5 inhibitors (within 24 hours for sildenafil and vardenafil, 48 hours for tadalafil) is contraindicated due to the risk of life-threatening hypotension (5). 11-Rectal ointment should be discarded 8 weeks after first opening (2). 12-With intravenous GTN: use glass or polyethylene apparatus is preferable; loss of potency will occur if PVC is used (2). 13-Transdermal patch: Apply once daily to skin site that is free of hair and not subject to excessive movement. Avoid areas with cuts or irritations. Do not apply to distal parts of the extremities. Use caution when discarding to keep out of the reach of children or pets. Remove at night for a 12-hour ―nitrate-free interval.‖ May contain metal; remove prior to MRI (1). 14-Patients using transdermal nitroglycerin may experience skin erythema and inflammation. Initiating therapy with smaller doses and rotating the application site can mitigate some of the adverse effects of transdermal NTG (6). Nitrates Scientific name Trade names Dosage form 1 2 3 Any extra notes: 2.10-Antiplatelet drugs 1-Antiplatelet drugs reduce platelet aggregation and are used to prevent further thromboembolic events in patients who have suffered myocardial infarction, ischemic stroke or transient ischemic attacks, or unstable angina, and for primary prevention of a thromboembolic event in patients at risk (3). 2-Antiplatelet drugs include aspirin, P2Y12 inhibitor antiplatelet [cangrelor (I.V), clopidogrel, prasugrel, ticagrelor), dipyridamole, and Glycoprotein IIb/IIIa inhibitors (abciximab, eptifibatide and tirofiban) (2). 3-Aspirin is given following coronary bypass surgery. It is also used in atrial fibrillation, for intermittent claudication, for stable angina and acute coronary syndromes, for use following placement of coronary stents and for use in stroke (2). 26 4-Clopidogrel monotherapy may be an alternative when aspirin is contra- indicated, for example in those with aspirin hypersensitivity, or when aspirin is not tolerated despite the addition of a proton pump inhibitor (2). 5-Clopidogrel, in combination with low-dose aspirin (dual antiplatelet therapy) are used in patients with non-ST elevation acute coronary syndromes, in patients with ST elevation acute coronary syndromes, and following percutaneous coronary intervention. The duration of antiplatelet therapy vary according to these indications. Aspirin therapy should continue indefinitely (2). Clopidogrel is also licensed, in combination with low-dose aspirin, in patients with atrial fibrillation (and at least one risk factor for a vascular event), and for whom warfarin is unsuitable (2). 6-Both prasugrel and ticagrelor are more potent than clopidogrel. Prasugrel has the fewest significant drug–drug interactions of the oral P2Y12 inhibitors (4). 7-Abciximab, eptifibatide, or tirofiban may be administered for some patients undergoing percutaneous coronary intervention (PCI) (2). 8-Aspirin is also used as an analgesic and antipyretic (2). 9-Pregnant women are at high risk of developing preeclampsia if they have chronic kidney disease, diabetes mellitus, autoimmune disease, chronic hypertension, or if they have had hypertension during a previous pregnancy; these women are advised to take aspirin once daily [unlicensed indication] from week 12 of pregnancy until the baby is born (2). 10-Owing to an association with Reye’s syndrome, aspirin-containing preparations should not be given to children under 16 years, unless specifically indicated, e.g. for Kawasaki disease (2). 11-Contra-indications of aspirin include: Active peptic ulceration, bleeding disorders, children under 16 years (risk of Reye‘s syndrome), haemophilia. previous peptic ulceration (analgesic dose) and cardiac failure (analgesic dose) (2). 12-Aspirin is contraindicated in history of hypersensitivity to aspirin or any other NSAID—which includes those in whom attacks of asthma, angioedema, urticaria, or rhinitis have been precipitated by aspirin or any other NSAID (2). 13-Aspirin tablet commonly formulated as enteric coated tablet to decrease GIT irritation. Antiplatelet drugs Scientific name Trade names Dosage form 1 2 3 27 4 5 Any extra notes: 2.11-Anticoagulants 1-Anticoagulants are used in the treatment and prophylaxis of thromboembolic disorders (3). 2-Different types of anticoagulants are available (Table 2-6) (2). Table 2-6: Types of anticoagulants (2). Parenteral anticoagulants Oral anticoagulants 1 Unfractionated Heparin (UFH) 1 Warfarin 2 Low molecular weight heparins Direct Oral Anticoagulants (LMWHs) (dalteparin, enoxaparin and (DOACs) Dabigatran, tinzaparin) Rivaroxaban, apixaban , 3 Parenteral direct thrombin inhibitor 2 betrixaban, and edoxaban (lepirudin, bivalirudin, argatroban, and desirudin) 4 Fondaparinux 2.11.1-Unfractionated heparin (UFH) 1-UFH can be administered via the intravenous (IV) or subcutaneous (SC) route (4). 2-For the treatment of Venous thromboembolism (VTE), UFH is generally given as a continuous IV infusion (4). 3-The activated partial thromboplastin time (aPTT) is the most widely used test in clinical practice to monitor UFH. Traditionally, therapeutic aPTT range is defined as 1.5 to 2.5 times the control aPTT value (4). 4-Side effects associated with UFH include bleeding, thrombocytopenia, and with prolonged use, alopecia, hyperkalemia, and osteoporosis (4). A-Bleeding is the most common adverse effect associated with antithrombotic drugs including UFH therapy. Patients receiving UFH therapy should be closely monitored for signs and symptoms of bleeding, including epistaxis, hemoptysis, hematuria, hematemesis, and melena (4). B-If major bleeding occurs, discontinue UFH immediately and give IV protamine sulfate (6). C-Heparin-induced thrombocytopenia (HIT) is a very serious adverse effect associated with UFH use (4) that requires immediate intervention (discontinue 28 heparin and initiate alternative anticoagulation with a parenteral direct thrombin inhibitor) (6). 2.11.2-Low-molecular-weight heparins 1-Advantages of LMWHs over UFH include: (A) predictable anticoagulation dose response, (B) improved SC bioavailability, (C) dose-independent clearance, (D) longer biologic half-life, E) lower incidence of thrombocytopenia, and (F) reduced need for routine laboratory monitoring (6). 2-LMWHs can be easily administered in the outpatient setting, thus enabling the treatment of VTE at home (4). 3-Because LMWH anticoagulant response is predictable when given SC, routine laboratory monitoring is unnecessary (6). 4-As with other anticoagulants, bleeding is the most common adverse effect of LMWH therapy, but major bleeding may be less common than with UFH. If major bleeding occurs, administer protamine sulfate IV, although it cannot neutralize the anticoagulant effect completely (6). 5-Thrombocytopenia can occur with LMWHs, but the incidence of HIT is three times lower than with UFH (6). 2.11.3-Warfarin 1-Warfarin inhibits the production of vitamin K–dependent clotting factors. Warfarin has no effect on circulating coagulation factors that have been previously formed, and its therapeutic antithrombotic activity is delayed for 5 to 7 days (4). 2-Warfarin also inhibits the anticoagulant proteins C and S. Reductions in the concentration of natural anticoagulants before the clotting factors are depleted can lead to a paradoxical hypercoagulable state during the first few days of warfarin therapy. It is for this reason that patients with acute thrombosis should receive a fast-acting anticoagulant (heparin, LMWH, or fondaparinux) while transitioning to warfarin therapy (4). 3-Monitor warfarin therapy by the international normalized ratio (INR); the recommended target INR for treatment and prevention of VTE is 2.5, with an acceptable range of 2 to 3(4). 4-In patients with acute VTE, a rapid-acting anticoagulant (UFH, LMWH, or fondaparinux) should be overlapped with warfarin for a minimum of 5 days and until the INR is greater than 2 and stable (4). 5-Similar to other anticoagulants, warfarin’s primary side effect is bleeding. Bleeding in the gastrointestinal tract is most common. Intracranial hemorrhage (ICH) is one of the most serious complications because it often causes severe disability and death (4). 6-Warfarin is prone to numerous clinically significant drug–drug and drug–food interactions. Patients on warfarin should be questioned at every encounter to 29 assess for any potential interactions with foods, drugs, herbal products, and nutritional supplements (4). 7-Vitamin K is the antidote of warfarin (1). In cases of life-threatening bleeding, fresh-frozen plasma or clotting factor concentrates should also be administered, in addition to IV vitamin K (4). 2.11.4-Direct oral anticoagulants: 1-These currently include two categories, direct thrombin (factor IIa) inhibitor (DTI) (dabigatran) and direct Xa inhibitors (rivaroxaban, apixaban, and edoxaban) (11). 2-As compared to warfarin, these oral anticoagulants have a more rapid onset, shorter half-life, wider therapeutic window, and more predictable pharmacokinetics (11). 3-These features allow for sole oral therapy without the need for an overlapping parenteral agent (with the exception of edoxaban for VTE), no need for titration or dose adjustments in patients with normal renal function, and no need for routine monitoring (11). 4-When used for the treatment or prophylaxis of recurrent VTE, edoxaban and dabigatran must be given only after at least 5 days of subcutaneous (SC) anticoagulation with UFH, LMWH, or fondaparinux (2, 6). 5-Compared to warfarin, the target-specific anticoagulants have a lower risk of intracranial hemorrhage (11). 6-Idarucizumab is a monoclonal antibody fragment used to reverse dabigatran anticoagulation (7). 7-Andexanet alfa is a recombinant form of human factor Xa protein which binds specifically to apixaban or rivaroxaban, thereby reversing their anticoagulant effects (2). 2.11.5-Parenteral direct thrombin inhibitors 1-Several injectable DTIs are available including lepirudin, bivalirudin, argatroban, and desirudin (4). 2-Parenteral DTIs are considered the drugs of choice for the treatment of VTE in patients with a diagnosis or history of HIT (4). 2.11.6-Parenteral Xa inhibitor (Fondaparinux) 1-Fondaparinux is a safe and effective alternative to LMWH for treatment of VTE (6). It is also is approved for prevention of VTE following orthopedic or abdominal surgery (2). 2-Patients receiving fondaparinux do not require routine coagulation testing (6). 31 Anticoagulants Scientific name Trade names Dosage form 1 2 3 4 5 6 7 Any extra notes: 2.12-Anti-arrhythmic drugs 1-Anti-arrhythmic drugs can be classified clinically into those that act on supraventricular arrhythmias (e.g. verapamil), those that act on both supraventricular and ventricular arrhythmias (e.g. amiodarone), and those that act on ventricular arrhythmias (e.g. lidocaine) (2) (Table 2-7) (12). Table 2-7: classification of Anti-arrhythmic drugs according to principal site of action 2-Atropine is used for bradycardia and AV nodal blockade. In patients with hemodynamically unstable or unresponsive to atropine, epinephrine or dopamine may be administered (4). 31 3-Adenosine is the drug of choice for pharmacologic termination of paroxysmal supraventricular tachycardia (PSVT) (4). 4-Hemodynamically stable torsades de pointes should be treated with I.V magnesium (4). 5-Hemodynamically unstable PSVT, ventricular tachycardia, atrial fibrillation, torsades de pointes, or ventricular fibrillation (already hemodynamically unstable) should be terminated immediately using direct current cardioversion (DCC) (4). 6-Amiodarone is the most commonly used antiarrhythmic agent. It is used for rate and rhythm control of atrial fibrillation and to treat and prevent ventricular arrhythmias (1). 7-Although amiodarone is the most commonly used antiarrhythmic, it should be reserved for patients with life-threatening arrhythmias due to its substantial toxicity (1). 8-Adverse Reactions: A-Most Common: Bradycardia, corneal microdeposits, hypotension (more common with IV), hypothyroidism, nausea, vomiting (especially with higher doses), phlebitis (IV form), photosensitivity, prolonged QTc interval (1). B-Rare/Severe/Important: Blue/gray skin discoloration, hyperthyroidism, liver toxicity, pulmonary toxicity (1). C-Monitoring requirements (2): Thyroid function tests should be performed before treatment and then every 6 months. Liver function tests required before treatment and then every 6 months. Serum potassium concentration should be measured before treatment. Chest x-ray required before treatment. With intravenous use ECG monitoring 9-Because of the possibility of phototoxic reactions, patients taking amiodarone should be advised to shield the skin from light during treatment and for several months after discontinuing amiodarone; a wide-spectrum sunscreen to protect against both long-wave ultraviolet and visible light should be used (2). 10-Digoxin is a cardiac glycoside that increases the force of myocardial contraction (so used for HF) and reduces conductivity within the atrioventricular (AV) node (so used for atrial fibrillation or flutter) (2). 11-Digoxin does not improve survival in patients with HF but does provide symptomatic benefits only (6) (digoxin is added for patients who remain symptomatic despite an optimal HF regimen consisting of an ACE inhibitor or ARB, β-blocker, and diuretic). In patients with concomitant atrial fibrillation, digoxin may occasionally be added to slow ventricular rate (4). 32 12-Loading dose of digoxin (Rapid digitalization) is usually given for atrial fibrillation or flutter (2) (Roughly half of the total loading dose administered as the first dose, with the remaining portion divided and administered every 6–8 hours initially) (1). 13-Sotalol is used for ventricular and supra- ventricular arrhythmias (2). Anti-arrhythmic drugs Scientific name Trade names Dosage form 1 2 3 4 Any extra notes: 2.13-Miscellaneous cardiovascular drugs 2.13.1-Fibrinolytic drugs 1-Thrombolytic drugs are indicated for any patient with acute ST-segment elevation myocardial infarction (STEMI) for whom the benefit is likely to outweigh the risk of treatment (2). 2-Alteplase should be given within 6–12 hours of MI symptom onset, reteplase within 12 hours of symptom onset, but ideally all should be given within 1 hour; use after 12 hours requires specialist advice. Tenecteplase should be given as early as possible and usually within 6 hours of symptom onset (2). 3-Alteplase can be used for other thromboembolic disorders such as deep-vein thrombosis and pulmonary embolism (2). 4-Alteplase is also used for acute ischaemic stroke (2). 5-Serious bleeding calls for discontinuation of the thrombolytic and may require administration of coagulation factors and antifibrinolytic drugs (2). 2.13.2-Antifibrinolytic drugs 1-Fibrin dissolution can be impaired by the administration of tranexamic acid, which inhibits fibrinolysis. It can be used to prevent bleeding or to treat bleeding associated with excessive fibrinolysis (e.g. in surgery, dental extraction, and obstetric disorders) and in the management of menorrhagia (2). 33 2-Tranexamic acid may also be used in hereditary angioedema, epistaxis, and in thrombolytic overdose (2). Scientific name Trade names Dosage form 1 2 2.13.3-Vasodilator antihypertensives (hydralazine, minoxidil, sodium nitroprusside) 1-Vasodilators have a potent hypotensive effect (2). 2-Hydralazine (i.v infusion) is used for hypertensive emergencies (including during pregnancy) (2). 3-Hydralazine is given by mouth as an adjunct to other antihypertensives for the treatment of resistant hypertension but is rarely used; when used alone it causes tachycardia and fluid retention (2). 4-Hydralazine in combination with long acting nitrate is also used for heart failure (2). 5-Sodium nitroprusside is given by i.v infusion to control severe hypertensive emergencies when parenteral treatment is necessary (2). 6-Minoxidil should be reserved for the treatment of severe hypertension resistant to other drugs (2). Scientific name Trade names Dosage form 1 2 2.13.4-Centrally acting antihypertensive drugs 1-Methyldopa is a centrally acting antihypertensive; it may be used for the management of hypertension in pregnancy (2). 2-Clonidine has the disadvantage that sudden withdrawal of treatment may cause severe rebound hypertension. (Note: Clonidine is also used for prevention of recurrent migraine, prevention of vascular headache, and for menopausal symptoms, particularly flushing and vasomotor conditions) (2). Scientific name Trade names Dosage form 1 2 34 2.13.5-Sympathomimetics (inotropic sympathomimetics, vasoconstrictor sympathomimetics) 1-The profound hypotension of shock must be treated promptly to prevent tissue hypoxia and organ failure. Volume replacement is essential to correct the hypervolemia associated with hemorrhage and sepsis but may be detrimental in cardiogenic shock (2). 2-Depending on hemodynamic status, cardiac output may be improved by the use of sympathomimetic inotropes such as adrenaline/epinephrine, dobutamine or dopamine (2). 3-In septic shock, when fluid replacement and inotropic support fail to maintain blood pressure, the vasoconstrictor noradrenaline/norepinephrine may be considered (2). 4-Midodrine is a sympathomimetic agent, which acts on peripheral α-adrenergic receptors to increase arterial resistance, resulting in an increase in blood pressure. It is indicated for severe orthostatic hypotension due to autonomic dysfunction when corrective factors have been ruled out and other forms of treatment are inadequate (2). 5-Metaraminol is a vasoconstrictor sympathomimetic indicated for acute hypotension (2). 2.13.6-Coagulation proteins 1-Human prothrombin complex, Factor IX fraction, Factor VIIa, Factor VIII fraction are used to treat hemorrhage especially that associated with congenital deficiencies of these factor proteins (2). 2.13.7-Peripheral vasodilators (e.g. cilostazol, pentoxifylline) Peripheral vascular disease can be either occlusive (e.g. intermittent claudication) in which occlusion of the peripheral arteries is caused by atherosclerosis, or vasospastic (e.g. Raynaud’s syndrome) (2). 2-Cilostazol is licensed for use in intermittent claudication to improve walking (2). 3-Pentoxifylline is another agent approved by the FDA for the treatment intermittent claudication (limited role) (5). Scientific name Trade names Dosage form 1 2 2.13.8-Others antianginal agents 1-Ranolazine is indicated as adjunctive therapy in the treatment of stable angina in patients inadequately controlled or intolerant of first line antianginal therapies(2). Because it does not substantially affect heart rate (HR) and BP, it is recommended 35 as add-on therapy to traditional antianginal agents for patients who achieve goal HR and BP and still have exertional angina symptoms (6). 2-Nicorandil a potassium-channel opener. It is indicated for Prophylaxis and treatment of stable angina (second-line) (2). 3-Ivabradine lowers the heart rate by its action on the sinus node. It is licensed for the treatment of angina in patients who are in normal sinus rhythm and for mild to severe chronic heart failure (2). 2.13.9-Drugs for pulmonary arterial hypertension 1-Ambrisentan, bosentan, iloprost , macitentan, sildenafil, and tadalafil are licensed for the treatment of pulmonary arterial hypertension (2). 2-Bosentan is also licensed to reduce the number of new digital ulcers in patients with systemic sclerosis and ongoing digital ulcer disease (2). 3-Riociguat is licensed for the treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension (2). Scientific name Trade names Dosage form 1 Any extra notes: References 1-Michael AM, Jason. Frequently prescribed medications. Third edition 2019. 2-BNF-81 (2021) 3-Martindale: The Complete Drug Reference, 38th Edition. Pharmaceutical Press 2014. 4- Marie A. Chisholm-Burns.Pharmacotherapy Principles & Practice. 5th edition. 2019. 5-Zeind, Caroline S and Carvalho, Michael G. Applied Therapeutics: The clinical use of drugs, 11th ed., 2018. 6-Joseph T. DiPiro, Robert L. Pharmacotherapy: A Pathophysiologic Approach, 11th Edition. 2021. 7-ACCP Updates in Therapeutics® 2021: The Pharmacotherapy Preparatory Review and Recertification Course. 8-Roger Walker. Clinical Pharmacy and Therapeutics. Sixth edition 2019. 9-Lawrence A. Trissel. Handbook on injectable drugs. 15th ed. 2009. 10-David J Quan, Richard A Helms. Textbook of Therapeutics: Drug and Disease Management. 8th edition. 2006. 11-Pavan Bhat, et al. Washington Manual of Medical Therapeutics, The, 35th Edition. Copyright 2016. 12-Helen Williams.V Arrhythmia : part 1. The pharmaceutical journal (VOL 271) (2003):368-370. 36 Chapter Three: Gastro-intestinal System 3.1-Drugs for inflammatory bowel disease. Notes: 1-Chronic inflammatory bowel diseases (IBD) include crohn’s disease (CD) and ulcerative colitis (UC) (1). UC is confined to the rectum and colon, while CD can involve any part of the gastrointestinal (GI) tract (2). 2-The major drug therapies used in IBD are aminosalicylates; corticosteroids; immunomodulators (azathioprine, mercaptopurine, and methotrexate); immunosuppressive agents (ciclosporine and tacrolimus); antimicrobials (metronidazole and ciprofloxacin) monoclonal antibodies (infliximab, adalimumab, golimumab, certolizumab, natalizumab, ustekinumab, and vedolizumab) or Janus kinase function (tofacitinib) (2). 3.1.1-Aminosalicylates 1-Aminosalicylates include Sulfasalazine [a combination of 5-aminosalicylic acid, (‗5-ASA‘) and sulfapyridine (acts as a carrier and believed to be responsible for many of the adverse reactions to sulfasalazine)], and the safer sulfa-free compounds [mesalazine (mesalamine)(5-ASA), balsalazide (a pro-drug of 5-ASA) and olsalazine (a dimer of 5-ASA)] (1-3). 2-The aminosalicylates are among the most commonly used drugs for inducing and maintaining remission in patients with mild to moderate IBD (4). 3-Enemas are appropriate for patients with left-sided disease because the medication will reach the splenic flexure. Suppositories deliver mesalamine up to approximately 20 cm and are most appropriate for treating proctitis (4). 4-Oral and topical mesalamine preparations may be used together for maximal effect. Oral mesalamine may also be used for patients who are unwilling or unable to use topical preparations (4). 5-The extent of disease should be considered when choosing the route of administration. If the inflammation is distal, a rectal preparation is adequate but if the inflammation is extended, systemic medication is required (1). 6-Enemas or suppositories (when given once daily) are preferably administered at bedtime, preferably after a bowel movement (1). 7-Oral aminosalicylates for the treatment of ulcerative colitis are available in different preparations and release forms. The preparation and dosing schedule should be chosen taking into account the delivery characteristics and suitability for the patient (1). 37 8-Unlike sulfasalazine, sulfa-free compounds are safe to use for patients with sulfonamide allergies (3). 9-Blood count should be performed and the drug stopped immediately if there is suspicion of a blood dyscrasia (1). 10-Patients receiving aminosalicylates, and their carers, should be advised to report any unexplained bleeding, bruising, purpura, sore throat, fever or malaise that occurs during treatment (Blood disorders) (1). 11-Regarding mesalazine: A-If it is necessary to switch a patient to a different brand of mesalazine, the patient should be advised to report any changes in symptoms (1). B-The manufacturers of some mesalazine gastro-resistant and modified-release medicines (Asacol MR tablets, Ipocol, Salofalk granules) suggest that preparations that lower stool pH (e.g. lactulose) might prevent the release of mesalazine (1). C-Granules should be placed on tongue and washed down with water without chewing (1). 12-Olsalazine is associated with a higher incidence of secretory diarrhea than other aminosalicylates (4). 13-Aminosalicylates are contra-indicated in salicylate hypersensitivity (1). 14-Balsalazide and olsalazine are taken after food (1). 15-Note: sulfasalazine is also used for rheumatoid arthritis [it is one of the Disease-Modifying Antirheumatic Drugs (DMARDs)] (1). Aminosalicylates Scientific name Trade names Dosage form(s) 1 2 3 4 Any extra notes: 38 3.2-Proton pump inhibitors (PPIs) 1-Drug action: Proton pump inhibitors inhibit gastric acid secretion by blocking the H+/K+-ATPase (the ‗proton pump‘) of the gastric parietal cell (1). 2-PPIs are the most potent inhibitors of gastric acid secretion. PPIs include omeprazole, lansoprazole, rabeprazole, pantoprazole, and esomeprazole (2). 3-PPIs are used for the treatments of gastric and duodenal ulcers; they are also used in combination with antibacterials for the eradication of Helicobacter pylori (a bacteria that is common cause of ulcer). PPIs can be used for the treatment of dyspepsia and gastro-oesophageal reflux disease. They are also used for the prevention and treatment of NSAID-associated ulcers (1). 4-A PPI can be used to reduce the degradation of pancreatic enzyme supplements in patients with cystic fibrosis. They can also be used to control excessive secretion of gastric acid in Zollinger–Ellison syndrome; high doses are often required (1). 5-PPIs are most effective when taken 30 to 60 minutes before meals (3).The once daily dose usually given in the morning before meals. Large doses should be given in 2 divided doses (1) (for divided dosing, give evening dose before evening meal instead of at bedtime) (5). 6-PPIs may take up to 72 hours to achieve optimal effectiveness and symptom improvement (6). 7-Newer PPIs (omeprazole-sodium bicarbonate and dexlansoprazole) offer dosing flexibility in relation to meals (5). 8-Controversial PPI drug interaction involves the antiplatelet drug clopidogrel. Clopidogrel is converted to its active form through CYP2C19. PPIs may attenuate the antiplatelet effect of clopidogrel by inhibiting or competing for this metabolic pathway. FDA safety guidelines recommend that the coadministration of omeprazole, omeprazole/sodium bicarbonate, or esomeprazole with clopidogrel be avoided because they reduce the effectiveness of clopidogrel (2). The 2013 ACG guidelines consider the PPI/clopidogrel interaction not clinically significant (5). Given the limitations of existing studies, administration of clopidogrel with PPIs should be balanced based upon cardiovascular and gastrointestinal risk (2). 9-PPIs are formulated as delayed-release enteric-coated dosage forms that have pH-sensitive granules contained in gelatin capsules (omeprazole, esomeprazole, and lansoprazole), rapidly disintegrating tablets (lansoprazole), and delayed-release enteric-coated tablets (rabeprazole, pantoprazole, and nonprescription omeprazole). Omeprazole is also available in a delayed-release tablet and in a combination product with sodium bicarbonate in an immediate-release capsule and oral suspension (Zegerid®) (2). The sodium bicarbonate raises intragastric pH, permitting rapid absorption of omeprazole from the duodenum (7). 39 10-Special administration: A-Orodispersible lansoprazole tablets should be placed on the tongue, allowed to disperse and swallowed, or may be swallowed whole with a glass of water. Alternatively, tablets can be dispersed in a small amount of water and administered by an oral syringe or nasogastric tube (1). B-Losec MUPS®: Tablets (Losec MUPS®) or capules (Losec ®) containing enteric-coated pellets can be dispersed in non-carbonated water or a slightly acidic liquid e.g. fruit juice or apple sauce; do not use milk or carbonated water. The dispersion should be stirred just before drinking and taken immediately, rinsed down with half a glass of water. The enteric-coated pellets must not be chewed (1). C-For patients who are unable to swallow the capsule or for pediatric patients, there are several alternative administration methods available. The contents of the delayed-release capsules can be mixed in applesauce or placed in orange juice. If a patient has a nasogastric tube, the contents of an omeprazole capsule can be mixed in 8.4% sodium bicarbonate solution. Esomeprazole granules can be dispersed in water. Esomeprazole, omeprazole, and pantoprazole are also available in a delayed-release oral suspension powder packet, and lansoprazole is available as a delayed-release, orally disintegrating tablet (2). 11-PPIs can increase the risk of fractures (particularly when used at high doses for over a year in the elderly). Patients at risk of osteoporosis should maintain an adequate intake of calcium and vitamin D and if necessary, receive other preventative therapy (1). 12-PPIs are generally considered interchangeable; selection of agent is usually based on cost and formulary considerations (6). PPIs Scientific names Trade name Dosage form Any extra notes: 41 3.3-Histamine-2 receptor antagonists (H2RAs) 1-Drug action: H2RAs reduce gastric acid output as a result of histamine H2- receptor blockade (1). 2-H2RAs include cimetidine, ranitidine, famotidine, and nizatidine (2). 3-H2RAs are used for the treatments of gastric and duodenal ulcers. They can be used for the treatment of dyspepsia and gastro-oesophageal reflux disease (1). 4-Aspiration of gastric contents (Mendelson‘s syndrome) is a potential cause of morbidity and mortality associated with anesthesia, especially in obstetrics and in emergency surgery (8). H2RAs also reduce the risk of acid aspiration (1). 5-Cimetidine has been used alone or with an antihistamine (H1-antagonist) in various skin disorders. H2RAs such as cimetidine and ranitidine have produced improvement in certain types of urticaria (8). 6-Cimetidine inhibits several CYP450 isoenzymes, resulting in numerous drug interactions (e.g., theophylline, warfarin, and clopidogrel) (2). Avoidance of the combination, or a reduction in the dosage of these drugs may be required (8). 7-Ranitidine has less potential for hepatic CYP450 drug interactions, while famotidine and nizatidine do not interact with drugs metabolized by the hepatic CYP450 pathway (3). 8-Cimetidine has demonstrated weak antiandrogenic effects, and its use in high doses has been associated with gynecomastia and impotence in men. This effect is reversible with discontinuation of the medication or by switching to another H2RA (3). 9-Regaeding H2RAs use for gastro-oesophageal reflux disease (GERD): Tolerance to the antisecretory effect may develop after several days of regularly scheduled (continuous) use but can be avoided by taking the H2RA only when needed (3). H2RAs Scientific names Trade name Dosage form Any extra notes: 41 3.4-Treatment of H. pylori–associated ulcers 1-H. pylori is a common cause of both gastric and duodenal ulcer. General recommendations, are to include an antisecretory agent (preferably a PPI) plus at least two antibiotics in the eradication regimen (5). (5) 2-Therapy duration is usually 10–14 days. 3-Several first-line therapies are recommended, but bismuth quadruple therapy (bismuth subsalicylate, metronidazole, tetracycline, and a PPI ) for 10-14 days should be used preferentially (2). (Table 3-1) 4-Another recommended first line therapy is concomitant therapy (PPI, clarithromycin, with amoxicillin and metronidazole) for 10 to 14 days (2). 5-Clarithromycin triple therapy is no longer recommended in areas where H. pylori resistance exceeds 15% (2). 6-Sequential therapy: Sequential therapy involves administration of a PPI and amoxicillin given for the first 5 days, followed by a PPI, clarithromycin, and tinidazole for an additional 5 days (5). 7-Quadruple-based therapy: A-Bismuth subsalicylate, metronidazole, tetracycline, and a PPI (5). B-Nonbismuth quadruple therapy (also called ―concomitant‖ therapy) contains a PPI, amoxicillin, clarithromycin, and metronidazole taken together at standard doses for 10 -14 days (2). 8-Hybrid therapy (combines the strategies of concomitant and sequential therapy) involves 7 days of dual therapy (PPI and amoxicillin) followed by 7 days of quadruple therapy (PPI, amoxicillin, clarithromycin, and metronidazole) (2). 9-Levofloxacin-Based Therapy Levofloxacin has been studied as first-line therapy and (after initial treatment failure) for H. pylori eradication. Three regimens using levofloxacin have been suggested (levofloxacin triple therapy, levofloxacin sequential therapy and Quadruple therapy) (Table 3-1). Concerns about using fluoroquinolones to treat H. pylori include development of resistance and adverse effects (e.g., tendonitis and hepatotoxicity) (2). 42 Table 3-1. Recommended Treatment Regimens for Helicobacter pylori Infection (5). BID: twice daily; PPI : proton pump inhibitor; QID : four times daily; TID : three times daily. 43 3.5-Antacids: 1-Antacids are basic compounds that neutralize hydrochloric acid in the gastric secretions. They are used in the symptomatic management of gastrointestinal disorders associated with gastric hyperacidity such as dyspepsia, GERD, and peptic ulcer disease (8). 2-Antacid agents include a variety of aluminum, magnesium, and calcium products available as single and combination therapy preparations in multiple dosage forms (6). 3-Antacids are best given when symptoms occur (i.e. when required) or are expected, usually between meals and at bedtime (1). When taken 1 h after a meal, antacids may act for up to 3 h compared with only 30 min–1 h if taken before meals (9). 4-Liquids and powders generally provide faster relief and have greater neutralizing capacity than tablets. Advantages of tablets over liquids include ease of portability and administration (10). It might be appropriate for the patient to have both; the liquid could be taken before and after working hours, while the tablets could be taken during the day for convenience (9). 5-Tablets should not be swallowed whole; they should be chewed to initiate disintegration or sucked to provide a relatively slow but sustained delivery of antacid to the stomach (10). 6-Interactions: A-Antacids can affect the absorption of a number of drugs (via chelation and adsorption) (11). This interactions can usually be avoided when potentially interacting drugs are separated by at least 2 hours (7). B-Antacids also interact with enteric-coated tablets, capsules and granules (Enteric coatings may be disrupted prematurely in the presence of antacids, causing unwanted release of the drug in the stomach) (10). 7-Side effects of antacids: A-AL-containing antacids tend to be constipating. Mg-containing antacids tend to cause osmotic diarrhea and are useful in patients who are slightly constipated. Thus combination products of AL and Mg salts cause minimum bowel disturbances (9). B-Antacids containing sod. Bicarbonate: The high sodium content may cause fluid overload in patients with congestive heart failure, renal failure, cirrhosis, or pregnancy, and in those on sodium restricted diets (7). C-Calcium carbonate: It acts quickly, has a prolonged action and is a potent neutralizer of acid. It can cause acid rebound and, if taken over long periods at high doses, can cause hypercalcaemia and so should not be recommended for long-term use (9). 44 8-Other drugs that may be combined with antacid formulations include simeticone, which acts as a defoaming agent to reduce excess gas in the stomach, and alginates, which form a gel or foam on the surface of the stomach contents thereby impeding reflux and protecting the oesophageal mucosa from acid attack (8). Antacids (including those combined with simethicone, and alginate) Scientific names Trade names Dosage form 1 2 3 4 5 6 Any extra notes: 3.6-Laxatives: 1-Laxatives (purgatives or cathartics) promote defecation and are used in the treatment of constipation and for bowel evacuation before investigational procedures such as endoscopy or radiological examination, or before surgery (8) to ensure the bowel is free of solid contents (1). (10) 2-Laxatives can be classified into groups depending on their mode of action (Table 3-2). Table 3-2: types of laxatives Type of laxative Example(s) Approximate onset of action Senna, Bisacodyl, Sodium Oral:6-12hours (9) 1-Stimulant laxative picosulfate, and Glycerin (supp.) Rectal: within 1 hour (9) Methylcellulose, Bran , Sterculia 12 -24 hours, but 2-Bulk-forming and Ispaghula (Metamucil®) onset may be laxative delayed as long as 72 hours (7) 4-Osmotic laxative Lactulose 1-2 days (9) 45 Linaclotide (guanylate cyclase-C receptor agonist), 5-Othrs Prucalopride (selective serotonin 5HT4-receptor agonist with prokinetic properties) (1). 3.6.1-Stimulant laxatives: 1-Stimulant laxatives are thought to act mainly by stimulating the intestinal mucosa to secrete water and electrolytes (12). 2-The main adverse effects of stimulant laxatives are griping and intestinal cramps. Prolonged use may result in loss of colonic smooth muscle tone (10). However, many experts now believe that the risk of long-term use of stimulant laxatives use have been overestimated and they are safe for daily use) (13). 3-Bisacodyl tablet is enteric-coated; therefore, it should be swallowed whole and should not be taken within one hour of antacid or milk as this will lead to dissolution of the coating and release of the drug into the stomach and cause gastric irritation (10). 4-Senna is excreted via the kidney and may color the urine a yellowish-brown to red color depending on its PH (12). 5-Senna is secreted in breast milk, and large dosages may cause increased gastric motility and diarrhea in breastfed infants. Breastfeeding mothers should, therefore, avoid this laxative (12). (However BNF-81 states that specialist sources indicate suitable for use in breast-feeding in infants over 1 month (1)). 6-Usual doses: Bisacodyl 5 mg tab. Adult dose: usually 1-2 tablets (dose to be taken at night). While the dose of supp. Is one supp. (usually in the morning) (1). Senna tab. Adult dose: usually 2 tablets (preferably at bedtime) (11). Glycerin suppositories: Glycerol suppositories are normally used when a bowel movement is needed quickly. The patient should experience a bowel movement in 15 to 30 minutes. Varying sizes are made to accommodate use for different ages. The 1-g suppositories are designed for infants, the 2-g for children and the 4-g for adults. (11). 3.6.2-Bulk-forming laxative: 1-Bulk laxatives are those that most closely resemble the normal physiological m

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