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EXERCISE 5: CASE STUDY ON TUBERCULOSIS ANTITUBERCULAR DRUG REGIMENS

Standard treatment (intensive phase)
ANTI-TUBERCULOSIS DRUGS 1st 2 months - ISONIAZID + RIFAMPIN +
TUBERCULOSIS PYRAZINAMIDE
 An infectious disease of humans and animals caused +
by the tubercle bacillus and characterized by the 2 months - ETHAMBUTOL or STREPTOMYCIN
formation of tubercles on the lungs and other tissues
of the body, often developing long after the initial Standard treatment (continuation phase)
infection. 1st 2 months- ISONIAZID + RIFAMPIN + PYRAZINAMIDE
+
FIRST LINE AGENTS 4 months ETHAMBUTOL or 2 months STREPTOMYCIN
RIFAMPIN (enzyme inducer)
 Semisynthetic derivative of rifamycin FIRST LINE AGENTS
 MOA: inhibits DNA-dependent RNA polymerase  These drugs are always used in combination due to
 Pharmacokinetics: undergoes enterohepatic recycling its resistance when used alone.
and is partially metabolized in the liver, orange-
colored REGIMEN DURATION IN MONTHS
 Can be used as the sole drug in treatment of latent Isoniazid, Rifampin,
6
TB in INH-intolerant patients, PREVENT Pyrazinamide
EMERGENCE OF DRUG-RESISTANCE Isoniazid, Rifampin 9
MYCOBACTERIA Rifampin, Ethambutol,
6
 S/E: light chain-proteinuria, impair antibody Pyrazinamide
responses, skin rashes, nephritis and liver Rifampin, Ethambutol 12
dysfunction, ORANGE URINE Isoniazid, Ethambutol 18
 Daily adult dose: 10mg/kg All Others ≥24
 Max: 600 mg ISONIAZID
ALTERNATIVE DRUGS
ISONIAZID (enzyme inhibitor)  Used in cases that are resistant to the first line
 A structural congener of pyridoxine (Vit. B6) drugs, failure of clinical response to 1st line, and
 MOA: inhibition of mycolic acid (component of cell serious tx-limiting ADR. Their toxicities are more
wall) serious.
 Single most important drug used in TB  Amikacin
 Pkinetics: INH half-life ○ Fast acetylators (Asian) =  Ciprofloxacin and Ofloxacin
60-90 mins ○ Slow acetylators (European / African) =  Ethionamide
3-4 hrs  p-Aminosalicylic Acid (PAS)
 S/E: Peripheral neuritis, Hepatotoxicity, Drug-induced  Capreomycin and Cycloserine
SLE  Linezolid
 Combined with pyridoxine to prevent symptoms of  Rifabutin and Rifapentine
peripheral neuritis
 Daily adult dose: 5mg/kg Amikacin (Aminoglycoside)
 Max: 400 mg  For TB caused by streptomycin-resistant of multidrug-
resistant mycobacterial strains
PYRAZINAMIDE
 MOA: which is believed to act by inhibiting energy Ethionamide
metabolism across the cell membrane, is a prodrug  Used in the treatment of isoniazid-resistant TB
requiring acidic conditions for activation  Congener of INH, also blocks synthesis of mycolic
 Active form: Pyrazinoic Acid acid
 Effective against slow replicating bacilli.  S/E: GI irritation, neurologic effects, HEPATOTOXIC
 S/E: Hepatic dysfunction, myalgia, GI irritation, p-Aminosalicylic Acid (PAS)
maculopapular rash, HYPERURICEMIA, porphyria,  Folate syn blocker, similar to PABA - Rarely used due
and photosensitivity reactions to its primary resistance
 Daily adult dose: 25 mg/kg  S/E: severe gastric irritation. Crystalluria, ulceration
 Max: 2 g Capreomycin
 A peptide CHON syn inhibitor
ETHAMBUTOL  For TB resistant to Streptomycin or Amikacin
 MOA: inhibits arabinosyl transferases (for the  S/E: ototoxicity, renal dysfunction Cycloserine -
synthesis of mycobacterial cell wall) Inhibition of cell wall synthesis
 Pkinetics: dose reduction for renal impairment  S/E: peripheral neuropathy, CNS dysfunction
 Use: Higher dose is needed for TB Meningitis
Linezolid
 S/E: RETROBULBAR NEURITIS (red-green color
 Used in combination with other second- and third-line
blindness, optic neuritis, possible retinal damage)
drugs to treat patients with multi-drug resistant
 Daily adult dose: 15mg/kg
tuberculosis
 S/E: bone marrow suppression and irreversible
STREPTOMYCIN (in IV)
peripheral and optic neuropathy
→ aminoglycoside used in TB
 Considered as a drug of last resort
 For the treatment of life-threatening TB disease
including meningitis, military dissemination Rifabutin
 Treatment of drug-resistant strains  Indicated in place of Rifampin for treatment of TB in
 S/E: ototoxic and nephrotoxic patients with HIV infection who are receiving
 Daily adult dose: 15mg/kg antiretroviral therapy
 Max: 1g
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Rifapentine  Bacillus-Calmette-Guerin
 For the treatment of tuberculosis caused by rifampin-  People who have had BCG vaccine will often have
susceptible strains during the continuation phase only positive result for TB skin test
 Should not be used to treat patients with HIV infection  Giving BCG vaccine to someone who already has
because of an unacceptably high relapse rate with some immunity provides no benefit and could cause
Rifampin-resistant organisms. unpleasant side effects
 Use of BCG in children who are immune
Kanamycin (aminoglycoside) compromised could result in them having an infection
 Treatment of TB caused by Streptomycin-resistant caused by the BCG vaccine itself.
strains
TB PREVENTION
Fluoroquinolones  The use of the BCG vaccine;
 Levofloxacin - More active than Cipro against TB  drug treatment to prevent people with latent TB from
 Moxifloxacin - Most active against TB by weight in developing TB disease;
vitro  infection control measures to prevent health care
 Ciprofloxacin - More active against atypical TB workers and other people in contact with people with
active TB disease, from becoming infected;
MDR TB vs XDR TB  and drug treatment for people with active TB disease
MDR TB XDR TB will also prevent transmission of TB bacteria to other
Strains that are resistant to Recently strains (XDR TB) people, as drug treatment makes a person less
at least isoniazid and have appeared that are infectious.
rifampin are referred to as resistant to a very large
“multi-drug resistant” (MDR number of products; those MANAGING MINOR SIDE EFFECTS
TB). that are resistant to DRUG
SIDE EFFECTS MANAGEMENT
isoniazid, rifampin, RESPONSIBLE
fluoroquinolones, and at Anorexia, PZA, Give drug with
least one 2nd line injectable Nausea, RIFAMPICIN, small meals or at
drug (capreomycin, Abdominal Pain INH bedtime
kanamycin, and amikacin) Joint Pain (from Give aspirin or
PZA
hyperuricemia) NSAID
DRUGS FOR MDR TB 100 mg daily for
Group 1: First line Oral Agents Peripheral treatment/ 10 mg
 Pyrazinamide INH Pyridoxine
Neuropathy daily for
 Ethambutol prevention
 Rifamycin Orange / Red Reassure The
Rifampicin
Group 2: Injectable Agents Colored Urine Patient
 Kanamycin Reassure the
 Amikacin patient and give
Drowsiness INH
 Capreomycin the drug at bed
 Streptomycin time
Group 3: Fluoroquinolones Flu-Like
Rifampicin Give Antipyretic
 Levofloxacin Symptoms
 Moxifloxacin
 Ofloxacin MANAGING MAJOR SIDE EFFECTS
Group 4: Oral Bacteriostatic Second Line Agents DRUG
SIDE EFFECTS MANAGEMENT
 Para-aminosalicylic Acid RESPONSIBLE
 Cycloserine Any drug
Severe Skin Rash
 Terizidone especially
(Hypersensitivity)
 Thionamide Streptomycin
 Prothionamide Any drug
Jaundice Due To
Group 5: Agents with an unclear role in the treatment of especially INH,
Hepatitis
drug-resistant TB Rifampicin, PZA
Visual Impairment Discontinue
 Clofazimine Ethambutol taking the
 Linezolid (for XDR TB) (Optic Neuritis)
medications and
 Amoxicillin/Clavulanate Deafness, Tinnitus,
Streptomycin refer to the
 Thiacetazone And Dizziness
clinician urgently
 Imipenem/Cilastatin Decrease Urine Streptomycin,
 High Dose Isoniazid Output Rifampicin
 Clarithromycin Psychosis And
INH
Convulsion
NEW TB DRUG Thrombocytopenia ,
Rifampicin
 Sirturo (Bedaquiline) Anemia, Shock
 Used as part of combination therapy to treat
adults with MDR TB when no other alternatives NOTES
are available.  TB DOTS
 Nitroimidazoles  Philhealth 4,000 for 6 months course (2013)
 X alcohol acute (enzyme inhibitor) chronic
BCG VACCINE (enzyme inducer)
 The only vaccine available for the prevention of  August - National TB awareness month
human forms of TB  March 24 - World TB day
 Normally given to children
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EXERCISE 6: CASE ON PEPTIC ULCER DISEASE  Infrequent or absent remissions

 Small % become cancerous
Drugs Used in the Treatment of Peptic Ulcer Disease  Severe ulcers may erode through stomach wall
PEPTIC ULCER
 A circumscribed loss of the mucous membrane of the DIFFERENTIATING BETWEEN H. PYLORI AND NSAID-
GIT system exposed to gastric juices containing acid INCLUDED ULCER
and pepsin.  Ulcers associated with H. pylori
 Signs and Symptoms: Characterized by gnawing,  More often in duodenum
burning or aching pain (worsen at night), N/V,  Often superficial
belching and weight loss, Dyspepsia, heartburn,  Less severe GI bleeding
bloating, cramping, nausea, vomiting, anorexia
 Ulcers associated with NSAIDs
 Excessive secretion of gastric acid
 More often in stomach
 Gastric Ulcer (Stomach)
 Often deep
 Duodenal Ulcer (Duodenum)
 More severe GI bleeding
 Esophageal Ulcer (Esophagus)
 Sometimes asymptomatic
 There is an excessive secretion of the gastric acid
causing ulceration in the duodenum, stomach, and
TWO TYPE OF ACID SECRETION
esophagus
 Meal Stimulated = Gastrin
 Gastric Distention (prolonged emptiness)
Causes of PUD: presence of Helicobacter pylori; gram (-)
 Specific food constituents such as amino acids,
– displace a role of PUD
CHON (protein) hydrolysates, ethanol and
 NSAID Induce interaction of prostaglandin synthesis
calcium
can impair mucosal defense and can lead to mucosal
 Elevation of gastric pH
injury
 Basic stomach can cause the growth of bacteria
 Use of steroid: alcohol and nicotines- can cause PUD
 Basal Stimulated = Acetylcholine
 Patient suffering from suffering physiologic stress
 Exhibits circadian rhythm (sleeping pattern)
 Patient suffering from burn surgery patients, CNS
 Importance:
trauma patients, surgery patients, receiving
 Accounts for the characteristics nighttime
severe medical treatment (eg. ICCU – receive a
 awakening with peptic ulcer pain
PPIs (such as pantoprazole) – to prevent PUD
 It serves as the rationale for single night time
dosing with H2 receptor antagonists
Hydrochloric acid
 Peptic ulcer usually happens at night 11 pm to 1 am
 Secreted from the PARIETAL CELLS in the body of
 Advise the patient to have a minimal intake of food at
the stomach
night
 Regulated by:
 Endocrine secretes Gastrin, Somatostatin
Goal Therapy
(hormones secreted in the delta cells of the
1. Reduce Gastric Acid Production
pancreas in order to equalize HCl whether there
 H2 antihistamines (H2 RAs), PPIs (drug of choice
is low levels of HCL acid; neutralizes stomach
for peptic ulcer disease), Anticholinergics,
acidity)
Prostaglandin analogs
 Paracrine secretes Histamine (is the most
2. Neutralize Gastric pH
powerful potent stimulus of Hydrochloric acid
 Antacids
secretion), PGE2 (Prostaglandin E2- potent
3. Protect The Walls of The Stomach from the Acid and
inflammatory mediator that is generated COX-2
Pepsin Release
conversion of arachidonic acid)
 Ulcer protectives
 Neurocrine (CNS) secretes Acetylcholine
4. Treat Peptic Ulcer And Reflux Esophagitis
DUODENAL ULCERS VS GASTRIC ULCERS
H2 Receptor Antagonist
 Usual etiology are due to the presence of
 Competitive inhibition at the parietal cells at the h2
Helicobacter pylori and NSAID induced injury
receptor, they suppress acid secretion
 Usually used in combination with PPIs to increase
DUODENAL ULCERS
activity
 Usual location is at the first portion of the duodenum,
 Promote healing of gastric and duodenal ulcers
within 3 cm at the pylori
 Recurrence occurs in 90% of px when used
 Age 25-27 years
alone
 Gnawing or burning upper abdomen pain relieved by
 Used to treat hypersecretory states
food but reappears 1-3 hours after meals.
 Inhibiting stomach acid production- used as
 Worse pain when stomach is empty
prophylaxis for recurrent ulcers in px at risk
 Bleeding occurs with deep erosion
 Control of reflux esophagitis and bile reflux
 Hematemesis - vomiting of blood
gastritis and the prevention of aspiration
 Melena - dark black stool
pneumonia
 Most discriminating symptoms is the pain that
 ADR: diarrhea, headache, fatigue, myalgias,
awakens the patient to sleep between midnight and
constipation
3am.
 They are relatively safe
 The oldest and most widely used in the treatment of
GASTRIC ULCERS
PUD
 Usual location is distal to the junction between atrium
and acid secretory mucosa
Cimetidine (Tagamet®)
 Age 55-65 years
 Prototype, anti-androgenic = gynecomastia
 Relieved by food but pain may persist even after
(enlargement of breast tissue in men) and
eating
galactorrhea (there is a milky discharge in women
 Sometimes precipitated by food
who are not breastfeeding)
 Anorexia, weight loss, vomiting
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Ranitidine (Zantac®)  Inhibits gastric acid secretion and increases mucosal

 5-1-x more potent than cimetidine, most widely resistance
prescribed because of good Bioavailability  FOR NSAID INDUCED ULCER
 ADE: hepatotoxicity/rashes  It is not registered in the Philippine FDA because it
can induce abortion - indicated in the black box
Famotidine (H2-bloc®) warning - not given in pregnant
 Most potent
Rebamipide (Mucosta®)
Nizatidine (Accid®)  Available as 100 mg tablet and is given 3 times a day
 100% BA, allows once a day dosing; hepatotoxic (morning, afternoon, evening before bedtime)
 gastric mucosal lesions, acute gastritis, and chronic
Proton Pump Inhibitors (PPIs) gastritis 1 tab orally
 Proton pump inhibitor are now the most widely  Stimulates prostaglandin production in gastric
prescribed drugs worldwide due to their outstanding mucosa
efficacy and safety  Improves quality and speed of ulcer healing
 Inactivate the transporter that is primarily  Side Effects: dizziness, drowsiness, constipation,
responsible for producing stomach acid nausea and vomiting
 most potent acid inhibitory agent
 maximum efficacy if taken is 30-60 minutes ANTACIDS
before meal  Acid-neutralizing capacity (ANC)
 Can only heal gastric and duodenal ulcers  Weak bases that are orally taken and that are
independent, whether NSAIDs is discontinued or partially neutralizes gastric acid and reduce pepsin
not activity
 Lacks androgenic effect, given once daily  Reduce pain associated with ulcers and may promote
healing
Omeprazole (Omepron®) (International brand is LOSEC®)
 Ideal antacids - should be rapid in onset and it should
 most potent
provide a continuous buffering action
Lansoprazole (Prevacid®)  Includes: Magnesium hydroxide, Calcium
Rabeprazole (Pariet®) carbonate
 newest PPIs (another is dexlansoprazole)  Slow onset antacid - like Magnesium trisilicate
and Aluminum compounds
Pantoprazole (Pantoloc®)
 S/E: electrolyte imbalance (caused by systemic
 parenteral pump available
antacids) and alkalosis, hypercalcemia (caused by
Esomeprazole (Nexium®) Calcium carbonate), renal failure, diarrhea and
 S-enantiomer of omeprazole hypermagnesemia (caused by Magnesium containing
antacids- should be avoided in patients with CKD),
Dexlansoprazole (Dexilant®)
phosphate depletion and constipation (caused by
 R-enantiomer of lansoprazole
Aluminum-containing antacids), osteoporosis,
osteomalacia, neurotoxicity
Anticholinergics
 Systemic Antacids (systemic action) - not for long
 Include propantheline, isopropamide and
term management
scopolamine
 Sodium bicarbonate
 Decrease acetylcholine-stimulated secretion and
 contraindicated with Hypertension and
motility in the gastrointestinal tract (GIT)
edema
 Required doses produce systemic anticholinergic
 abrupt withdrawal of systemic antacids can
effect
 cause a rebound hyperacidity
 They are rarely used alone but they are useful as
 Calcium bicarbonate
adjuncts in patients resistant to H2 blockers
 Non-systemic Antacids (peripheral action)
 Aluminum Hydroxide (Amphojel®)
Cytoprotective Agents
 Dihydroxyaluminum sodium (Rolaids®)
Sucralfate (Carafate®, Iselpin®)(aluminum sucrose
 Calcium carbonate (Tums®)
sulfate)
 Magaldrate (Riopan®)
 A complex polysaccharide complexed with aluminum
 Mg(OH)2 + AI(OH)2 (Maalox®, Mylanta®,
 hydroxide
Gelusil®)
 Has affinity for exposed proteins in the crater of
 Maalox plus - combination product antacids and
peptic
simethicone - that is to balance between the agents’
 ulcer (coats the ulcer bed)
adverse effects on bowel system
 becomes a viscous paste within the stomach and the
 Simethicone -anti-foaming agent ( it decreases the
duodenum- binds primarily to the side of active
surface tension of the stomach, used to defoam
ulceration they act as physico-chemical barrier
gastric juices.Thus, it prevent flatulence
 Protects ulcerated areas from further damage and
promotes healing
Colloidal Bismuth Compounds
 ADR: osteoporosis, osteomalacia, flatulence, dry
 Axns: Formation of protective coating on ulcerated
mouth, constipation, aluminum toxicity in renal
tissue, stimulation of mucosal protective mechanisms,
insufficiency
direct antimicrobial effects and sequestration of
 Given 1gram QID (4 times a day)
enterotoxins
 Combined with Metronidazole and Tetracycline in
Misoprostol (Cytotec®)
Management of H. Pylori
 A PGE1 (prostaglandin 1) analog
 ADR: Blackening of gums and stools
 More water soluble and it has a t1/2 (half life) than
 Bismuth Subsalicylate (Pepto-bismol®- given 300 mg
naturally occurring prostaglandin
qid, long term used can cause neurotoxicity; also
 Enhances mucosal defense and repair
used in irritable bowel syndrome), Bismuth Subcitrate
and Bismuth Dinitrate
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Somatostatin EXERCISE 7: DRUGS FOR DIABETES MELLITUS

 14 amino acid peptide that is released in the GIT and
pancreas from paracrine cells, D-cells, and enteric PANCREAS is a mixed gland
nerves as well as from the hypothalamus  Exocrine Portion
 Suppress gastric acid, universal inhibitory of  Releases pancrelipase and chymotrypsin
secretory cell, cause hyperglycemia  Endocrine Portion
 Short t1/2 in the cisculation (3 mins) when it is  1 million islets of Langerhan cell cluster
administered by IV injection  have at least 4 hormone-producing cells

Octreotide Endocrine Pancreas

 Brand name is Sandostatin® Cell Type % Islet Hormone
 Synthetic octapeptide with actions similar to Glucagon
somatostatin 20
A (Alpha) ↑ Blood Sugar
 IV: t1/2 = 1.5 hrs Proglucagon
 SC: DOA = 6-12 hrs Insulin
 IM: t1/2 = 1 month 75
B (Beta) ↓ Blood Sugar
 Causes STEATORRHEA (fatty stool) and Pro-Insulin
hyperthyroidism Somatostatin
 DO NOT induce hyperglycemia D (Delta) 3-5 Regulates Alpha
And Beta Cells
Carbenoxolone Pancreatic
 Synthetic derivative of GLYCYRRHIZIC ACID F (PP Cell) <2
Polypeptide (PP)
 Heals both gastric and duodenal ulcers
 MOA: increases production, secretion and viscosity of INSULIN
intestinal mucus  The storage and anabolic hormone of the body
 A/E: Aldosterone Effect and diarrhea  Produced by the Beta-cells of the pancreas
 Principal hormone required for proper glucose use in
Triple Therapy normal metabolic processes
 Omeprazole / Lansoprazole - 20/ 30 mg bd  previously extracted from beef/pork pancreas
 Clarithromycin - 500 mg bd  now is produced via recombinant DNA technology
 Amoxicillin / Metronidazole - 1g/ 500 mg bd
 Given for 14 days followed by PPI for 4-6 weeks INSULIN - EFFECTS
 Short regimen for 7-100 days no veyt effective 1. It facilitates transport of glucose across cell
 BEST or drug of choice in eradication of H. pylori membrane
 Bismuth Subsalicylate - 2 tabs qid 2. In the liver, it promotes glycogenesis and INHIBITS
 Metronidazole - 250 mg qid gluconeogenesis
 Tetracycline - 500 mg qid 3. In the muscles, it increases amino acid transport,
 Ranitidine / Bismuth Citrate - 400 mg bd protein synthesis, and glycogenesis
 Tetracycline - 500 mg bd 4. In adipose tissues, it increases triglyceride storage.
 Clatithromycin / Metronidazole - 500 mg bd
 Under the influence of insulin, In liver, skeletal
 Antibiotic Resistance Strains - most common cause muscles sore and absorb glucose in the form of
for the treatment failure in compliant patients. glycogen and many other cells quickly breakdown the
glucose to form ATP for energy
 The choice of antibiotics is based on the:  Insulin Effects - key for the entrance of glucose into a
1. Resistance Pattern cell which either use immediately for energy or stored
2. Local Recommendation to meet the body future demands
3. Availability
INSULIN
 Testing successful eradication is recommended using CARBOHYDRATES
the: ↓ Glucose Release From Liver
1. Urea Breath Test ↓ Glycogenolysis
2. Fecal Antigen Test ↑ Glycogen Synthesis
3. Biopsy Based Test ↑ Glycolysis
↓ Ketogenesis
 AT LEAST 4 WEEKS AFTER THE COMPLETION
OF ANTIBIOTICS WITH 1-2 WEEKS OF LIPIDS
WITHHOLDING PPI THERAPY ↓ Adipose FFA Release
↑ FFA Synthesis

PROTEINS
↑ aa transport to liver and muscle
↑ Protein Synthesis Facilitate entry of glucose into cell

Tissue Anabolic Effects

Liver Glucose Uptake and Storage
 Glycogen Synthesis
Increased
 Gluconeogenesis Decreased
Muscle Protein synthesis increased
 Amino Acid Transport
Increased
 Protein Synthesis Increased
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 Glycogen Synthesis 3. Gestational DM

Increased  defined as any degree of glucose intolerance that
 Glucose Transport has its onset during pregnancy
Increased 4. Secondary DM
 Glycogen Synthase Activity  broad term used to classify patients who have
 Increased unusual causes of DM due to certain diseases of
 Phosphorylase Activity the pancreas, endocrinopathies or drugs
Decreased  usually goes away after having a baby but there’s
Adipose Triglyceride Storage Increased a likelihood of developing diabetes later in life
 Lipoprotein Lipase Activated  Diabetes in 2nd or 3rd trimester of pregnancy
 Triglyceride Hydrolysis that was not clearly overt diabetes prior to
Increased gestation
 Glucose Transport Secondary causes of Diabetes mellitus include:
Increased  Acromegaly
 Intracellular Lipase Inhibited  Cushing Syndrome
 Thyrotoxicosis
 Pheochromocytoma
DIABETES MELLITUS (DM)  Chronic Pancreatitis
 diabetes = Greek “siphon”  Pancreatic Cancer
 Latin “mellitus” = sweet as honey
 “something sweet is passing through or siphoning 3 Cardinal Signs of DM
from the body” 1. Polyuria - excessive urination to flush out the
 A metabolic and chronic disorder in which glucose glucose and
levels in the blood are too high and begins to spill in 2. ketones
the urine because the kidney tubule cells cannot 3. Polydipsia - excessive thirst resulting from water
reabsorb it fast enough loss
 Characterized by high levels of glucose in the 4. Polyphagia - excessive hunger due to inability to use
blood that either results from insulin production or sugars and the loss of fats and proteins from the
resistance of the body cells to the action of body
insulin
Drugs associated with HYPERGLYCEMIA
TYPES OF DM  Beta-blockers
1. Type 1  Fluoroquinolones are the only class of antibiotics
 Insulin-Dependent DM (IDDM) consistently associated with the development of
 Juvenile-Onset DM hyperglycemia
 Ketosis-Prone diabetes  Gatifloxacin - commonly implicated
 Most common in children fluoroquinolones, can also cause hypoglycemia
 Insulin secretion is destroyed  Statins
 Dependent upon exogenous insulin to sustain life  Corticosteroids
 The insulin-producing cells are destroyed  Thiazide and thiazide-like diuretics
thus eliminating the production of insulin  Immunosuppressants Tacrolimus, tacrolin, cyclizine
caused by autoimmune destruction of the  Niacin
beta cells in the pancreas.  Protease inhibitors
 Linked to obesity and family history  Second Generation Antipsychotics particularly
 Must be treated to insulin Olanzapine and Clozapine most likely to increase the
 Caused by autoimmune destruction of risk of diabetes mellitus used in patients with
the beta cells in the pancreas schizophrenia.
2. Type 2
 Non-Insulin-Dependent DM (NIDDM) DIAGNOSIS CRITERIA
 Adult-Onset DM A. PRE-Diabetes
 Not Insulin Dependent  Fasting Plasma Glucose (FPG) = 100-125 mg/dL
 endogenous insulin levels may appear normal or  2-Hour Plasma Glucose = 140-199 mg/dL after
increased but beta-cell dysfunction is manifested 75-gram OGTT
by a relative insulin insufficiency  A1C = 5.7 - 6.4
 there is an insulin resistance and gradual  Refers to increased risk that the patient will
insulin deficiency develop
Risk Factors:  Impaired glucose - homeostasis
 1st Degree Relative
 Physical Inactivity B. DIABETES
 HTN  Polyuria, Polydipsia, Polyphagia
 Hx of CVD  Random Glucose: ≥ 200 mg/dL
 Race (Non-whites) High risk ethnicity-  FPG = ≥ 126 mg/dL
African, American, Latino, Native American,  2-hour PG ≥ 200 mg/dL after 75-gram OGTT
Asian American, Pacific Islander  A1C ≥ 6.5%
 Overweight - BMI > 25, > 23 (Asians)
 HDL <35 mg/dL The Normal Values:
 LDL > 250 mg/dL  FPG - less than 100 mg/dL
 A1C ≥ 5.7 % on previous testing  2-HPG - less than 140 mg/dL
 Hx of GDM Gestational diabetes mellitus  A1C - less than 5.7%
 Polycystic Ovarian Syndrome (PCOS)
DISPENSING 2 LABORATORY (Medication-related CERDA, A.J.
Problems, Medication Safety, Medication Counseling
and other Pharmacy Services)

Stability of Insulin  SQ: 5 min before meals

 Insulin when refrigerated 2-8 degrees Celsius. In an  Rapid onset of action in 5-15 minutes
open insulin is still available in the expiration date  Available in Vials usually 10 mL, PHEN- 3 mL
indicated in the label of the product. Once open or  DOA: 2 to 4 hours
once used, room temperature varies 12- 42 days the  Peak effect: 30- 90 minutes
most. But the usual or common is 28 days. It is a
must to check in every drug product to check stability SHORT-ACTING INSULIN (Bolus Insulin)
and days requirement.  Regular Insulin C
 SQ/IVV; 20 mins before meals
Chronic Complications of DM  USES: To prevent Postprandial Hyperglycemia
 Macrovascular Target Postprandial
 CVD  Glucose: < 180mh/Dl Target Preprandial Glucose
 CAD = 90-130 mg/Dl
 PAD  Target HbA1C: < 7%
 Microvascular  Bolus Insulin - they are required to cover the
 Retinopathy (most common) glycemic excretion following a meal
 Nephropathy  Must be given 20-30 minutes before meals
 Peripheral Neuropathy  Onset of action: 30-60 minutes
 Peak effect: 2-3 hours
Acute complications of DM:  DOA: 3 to 6 hours
 Diabetic Ketoacidosis
 Hyperglycemic INTERMEDIATE ACTING INSULIN (Basal Insulin)
 Hyperosmolar State 2.1.1 ISOPHANE INSULIN
2.1 ADDED WITH / NPH
ADA Treatment Goals PROTAMINE AND ZINC 2.1.2 HUMULIN N
 A1C: <7% (Q3 months) 2.1.3 NOVOLIN N
 Pre-Prandial: 80-130 mg/dL 2.2 WITH DIFFERENT
 Post-Prandial: < 180 mg/dL SIZES OF INSULIN 2.2.1 LENTE INSULIN
CRYSTAL
Diabetes in Pregnancy:
 Fasting: ≤ 95 mg/dL  USES: Insulin basal, insulin secretion
 1-Hour Post-Meal: ≤ 140 mg/dL  DOSE: BID AM 2/3 of the dose PM 1/3 of the dose
 2-Hour Post-Meal: ≤ 120 mg/dL  Lente Insulin prepared by mixing 30% Semilente &
 70% Ultralente Insulin
PHARMACOLOGIC TREATMENT  Basal insulin- required to regulate metabolic
 Oral Medications processes even in the absence of meal
 Injectable Medications  Slower onset of action: 2 to 4 hours
 Peak effect 4 to 10 hours
INSULIN AND ITS ANALOGS  DOA 10-16 hours
 Previously extracted from beef/pork pancreas
 Now is produced via recombinant dna technology LONG ACTING INSULIN (Basal Insulin)
 Insulin - is a polypeptide susceptible to degradation of Insulin Glargine
SQ, OD
git that is why insulins are not given orally (Lantus®, Toujeo®)
 Insulin contains 100 Units per mL USES: Provide basal
 Delivery 1 Unit per increment insulin requirement
 Duration of action up to
What gives the analog to act quickly? 24 hours
 Insulin molecules naturally like to stick together  Insulin Glargine (peak-
forming hexomers. Hexomers are too large to cross Insulin Detemir (Levemir®) less insulin) has a
subcutaneous tissue in the bloodstream. So scientists Onset of action (1-24 character release
altered the amino acid sequence of insulin molecules hours) pattern that shows no
to make them less likely to aggregate analogs which Insulin Degludec (Tresiba®) peak & a plateau
resulted into faster absorption and more rapid in Onset of action 30- 90 serum insulin level that
action. minutes is maintained for about
24 hours.
Insulin - Indicators  Do not mixed long
1. Diabetes Mellitus Type 1 acting insulin with
2. Diabetes Mellitus Type 2 that cannot be controlled by other insulin Onset of
diet, exercise and Oral Hypoglycemic Agents (OHAs) action (2 to 4 hours)
3. Ketoacidosis
4. Diabetic Coma AMYLIN ANALOGUE
 activates amylin receptors
RAPID ACTING INSULIN (Bolus Insulin)  Pramlintide the only amylin mimetic available in the
1.1. DERIVED FROM PIG market. Given in disposable multidose single patients
1.1.1 ILETIN II use only.
PANCREAS
1.2.1. INSULIN ASPART  Given SQ; co-secreted w/ insulin
1.2 INSULIN ANALOG (NOVOLOG)  Enhances the effect of insulin
CREATED BY RDMA 1.2.2. INSULIN GLULISINE  MOA: Analog of amylin activates amylin receptors
TECHNOLOGY (APIDRA)  CLINICAL USE: Type 1 and type 2 diabetes
1.2.3. INSULIN LISPRO  SE: risk of hypoglycemia, nausea, modest weight
(HUMALOG)  Delay gastric emptying time to suppress the post
fragile glucagon secretion, blunts pancreatic and
promotes satiety.
DISPENSING 2 LABORATORY (Medication-related CERDA, A.J.
Problems, Medication Safety, Medication Counseling
and other Pharmacy Services)

Incretin - stimulates pancreas to stimulate or produce 2. INSULIN SENSITIZERS

more insulin. Group of metabolic hormones that is A. BIGUANIDES
secreted from the gut in response to the food ingestion.  MOA:
 Liver: Decrease the amount of glucose made by
INCRETIN MIMETICS the liver
 GLP-1 analogue (Glucagon-like peptide-1) activate  Muscles and Fat Tissue: Increase insulin
GLP1 receptor sensitivity of muscle and adipose tissue
 Exenatide (Byetta®), Liraglutide (Saxenda®,  1st line initial treatment of type 2 DM esp. Among
Victoza®) obese patients
 ADMINISTRATION: Parenteral (SQ)  S/E: Diarrhea, Weight loss, Inc. risk of lactic acidosis
 Risk: hypoglycemia  CI: Chronic Alcoholics, Renal Failure, Hepatitis
 MOA: Analog of glucagon-like peptide-1 (GLP-1) 1. Metformin (Glucophage®) – very low risk of lactic
activates GLP-1 receptors resulting in glucose- acidosis First line treatment in type 2 DM.
dependent insulin secretion. Discontinue before imaging procedure and start
 SE: GI disturbances, headache, increased risk of 48 hours after. advised to be taken with food.
pancreatitis Leaves go shed in stool
 It can cause weight loss 2. Phenformin – high risk of lactic acidosis (out in
 Glucose dependent, inc. insulin secretion, dec. the market)
Glucagon secretion Slowing down GET causes
B. THIAZOLIDINEDIONE
weight loss.
 MOA: Regulates gene expression by binding to PPAR
 Insulin secretion; glucagon secretion; GI motility;
 Activate PPAR (Peroxisome Proliferator-acting
Gastric Emptying Time
receptor) Gamma
 Taken without regard to meal. may take several
ORAL HYPOGLYCEMIC DRUGS
weeks to work
1. Insulin Secretagogues
 SE: Hepatotoxicity, May inc. HDL levels, Peripheral
A. Sulfonylureas
Edema
B. Meglitinides
 Rosiglitazone (Avandia®) – risk of cardiovascular
2. Insulin Sensitizers
mortality
A. Biguanides
 Pioglitazone (Actos®) – inc bladder cancer risk
B. Thiazolidinedione derivatives TZD or Glitazones
 Troglitazone
3. Alpha-Glucosidase Inhibitors
4. Incretin-Acting Drugs
3. ALPHA-GLUCOSIDASE INHIBITORS
 DPP-4 inhibitor (Dipeptidyl peptidase 4) inhibitors
 May be given to Type 1 DM patients as a combination
5. SGLT2 Inhibitors (Sodium glucose co-transporter 2
therapy with insulin
inhibitors)
 MOA: Inhibit intestinal-glucosidases Inhibit a variety
of enzymes present in the brush-border of the
1. INSULIN SECRETAGOGUES
mucosa of the wall intestine that are responsible for
A. SULFONYLUREAS
the breakdown of complex polysaccharides and
 MOA: block outward K+ channel lead
sucrose into absorbable monosaccharides
todepolarization of cells to release Insulin
 It can be treated by sucrose
 CI: Liver disease, Renal disease
 SE: Flatulence, Hepatotoxicity (Acarbose)
 Common S/E: Hypoglycemia, Weight Gain
 ADMINISTRATION: After 1st bite of food (must be
 Reduce both fasting and post-prandial glucose
taken with food)
 Should be taken shortly before meals 30 mins
 Acarbose (Glucobay®, Gluconase®)
before breakfast
 Voglibose (Basen®)
 Glyburide - should be avoided by patients with
 Miglitol (Glyset®)
renal impairment
1st generation  Less potent, More side 4. INCRETIN-ACTING DRUGS
 Chlorpropamide – effects  DPP-4 inhibitor (Dipeptidyl peptidase 4)
longest t1/2  SE: Disulfiram - like  Sitagliptin (Januvia®); Linagliptin (Trajenta®)
 Tolbutamide – most reaction  Saxagliptin (Onglyza®); Alogliptin (Nesina®)
cardiotoxic  Tolazamide – safest for  ADMINISTRATION: Oral in the morning
 Acetahexamide elderly  MOA: Inhibitor of the dipeptidyl peptidase-4
2nd Generation (DPP-4) that degrades GLP-1 and other incretins
Glibenclamide (Euglucon®)  SE: Similar to GLP-1 mimetics, Rhinitis, upper
 Most Potent, Less Side respiratory infections, rare allergic reactions
Glipizide (Minidiab®)
Effect  Major side effect: pain and inflammation in the
Gliclazide (Diamicron®)
Glimepiride (Solosa®) pancreas
 It can cause weight loss
B. MEGLITINIDES  INC. Insulin secretion; dec. glucagon secretion;
 MOA: Increase pancreatic insulin secretion GI motility; Slow Gastric Emptying time thus
 Short duration of action: 1 to 3 hours promoting satiety
 CLINICAL USE: Control 2 hours post-prandial
hyperglycemia 5. SGLT2 INHIBITORS
 S/E: Hypoglycemia (Sodium glucose co-transporter 2 inhibitors)
 Must be taken 15-30 mins before meals. Skip  Dapagliflozin (Farxiga®) Philippine: Forxiga
dose if skipping meals  Empagliflozin (Jardiance®)
 Never use sulfonylureas and Meglitinides  Canagliflozin (Invokana®) Must be monitor because it
together, they will cause hypoglycemia can can cause leg and foot amputation
 ADMINISTRATION: Oral
 MOA: Reduced glucose reabsorption in renal
tubules; increased glucose excretion
DISPENSING 2 LABORATORY (Medication-related CERDA, A.J.
Problems, Medication Safety, Medication Counseling
and other Pharmacy Services)

 SE: Thirst, increased urination, Increased UTI EXERCISE 8: CASE STUDY ON TONSILLITIS
dehydration due to urination, genetic yeast  It refers to the inflammation of tonsils due to viral and
infection bacterial infection.
 Tonsils are involved in guarding against infection by
ADA Treatment Guidelines for Type-2 Diabetes filtering the foreign organism. This will result to
Monotherapy Lifestyle Modification + swelling which causes tonsillitis.
Metformin (unless C/I)  Viral Tonsillitis - Epstein Barr virus
Dual Treatment Start if the A1C is ≥ 8.5% at  Acute Tonsillitis - Gradual onset of sore throat
baseline Lifestyle modification + and usually accompanied by fever
Metformin + Second drug Select  Symptoms is usually last for 3 to 4 days but
second drug based on the can last up to 2 weeks if not treated
patient co-morbid risks:  Subacute Tonsillitis - Actinomyces bacterium
 Px has ASCVD: Choose  last between 3 weeks to 3 months if not treated
drug with CV benefit, either  Chronic Tonsillitis - Group A Streptococcal (S.
a GLP-1 agonist or an pyogenes)
SGLT-2 inhibitor -Px has  can for a long time if not treated
heart failure or CKD: SGLT-  Symptoms usually resolve within 7-10 days whether
2 inhibitor antibiotic is used or not.
 Px has no ASCVD, HF, or  Appropriate antibiotic treatment for full 10 days
CKD: Choose any drug prevents the development of rheumatic fever.
from the remaining  If your prescribed antibiotics, it is important to change
medication classes. your toothbrush after starting treatment
Different MOA should be
selected, consider HOW CAN IT BE PREVENTED?
comorbidities  This action may help to stop the spread of germs and
Triple Treatment MOST 3-drug combinations are alleviate tonsillitis:
acceptable, EXCEPT:  Frequent hand wash
 Metformin + DPP-4 + GLP-  Use of separate cutlery and crockery
1  Don’t smoke and drink alcohol
 Metformin + Basal insulin +  At home you can:
SU  Rest and drink plenty of fluids
Combination Injection  Try to gargle warm salty water
Start basal insulin + basal  Try throat lozenges - especially for adults
Treatment (If BG ≥ 300
insulin OR GLP-1 agonist  Pain reliever when needed
mg/dl or A1C ≥ 10%)
 Soft diet
LIFESTYLE MODIFICATIONS  If pediatric patient, counseling to be done is with the
1. Reduce weight, BP, Cholesterol guardian.
2. Reduce calories to < 3500 to lose 1 pound a week
3. Waist circumference < 35 inches (F) and < 40 inches TONSILLECTOMY
in male  Surgery to stop tonsillitis from coming back
4. Use Omega-3 FA + Omega-3 linoleic acid  This procedure usually take about 30 minutes
5. Type-1 DM patient needs to count carbs  Typically done in children
6. Moderate exercise 150 minutes/ week at least 3 days  Post surgery advice: Patient need to stay home for 2
/ week weeks to prevent catching of germs that may trigger
7. Vaccines (Flu, Pneumonia, Hepatitis B) Diabetes are the wound surgery - to avoid infection or complication
more susceptible to inflammation Fluvax, Pneumovax
MEDICATION ADVICE
 Metformin can also be used in the normal test. the
 OTC pain medicine like paracetamol, ibuprofen or
normal test should be retested after or every 2 years
naproxen must follow the instructions written. Make
sure that the cold preparation doesn't contain
HYPOGLYCEMIA TREATMENT
paracetamol if already taking other pain medicines.
GLUCAGON
 Try an OTC throat spray to relieve throat pain
 Parenteral
 Drink plenty of water to soothe irritated throat
 Useful for reversing the cardiac effects of an
 Don’t smoke and avoid secondhand smoke
overdose of blocking agents because of its ability to
 Use a vaporizer or humidifier to add moisture to
increase CAMP production in the heart.
bedroom
 MOA: Activates glucagon receptors
 If antibiotic is being prescribed, stick to the medication
 CLINICAL USE/S:
order. Make sure comply to prevent complications
1. Severe hypoglycemia (NOT responding well to
 Ice cream can help to soothe painful throat- it will
glucose),
ease the pain
2. Blocker overdose (by increasing CAMP levels as
it binds to Glucagon Receptors in the Heart)
 SE: GI Disturbances, Hypotension, Flatulence (most
common)
 For hypoglycemia, (mostly with the use of
Sulfonylureas, Maglitinides and Pramlatidine) may
lead to seizure, coma or death.
 D50 in water (50% dextrose Injection) - used to treat
insulin hypoglycemia.
 First lay the patient in recumbent position and give 1
mg SQ IV glucagon and check blood glucose for 15
mins