Clinical Pharmacy Concepts PDF

​ CLINICAL PHARMACY CONCEPTS Pharmaceutical Care Abridged Definition...

​ CLINICAL PHARMACY CONCEPTS Pharmaceutical Care Abridged Definition ​ It is the responsible administration of medication therapy to reach certain goals that enhance or ​ Clinical pharmacy is defined as that area of pharmacy concerned with the science and practice preserve a patient’s quality of life of rational medication use. Unabridged Definition ​ Clinical pharmacy is a health science discipline in which pharmacists provide patient care that Clinical Pharmacy Pharmaceutical Care ○​ Optimizes medication therapy ○​ Promotes Place Clinical Setting Everywhere ​ Health, ​ Wellness, and Target Healthcare providers Patient ​ Disease prevention Goal Clinical Outcomes, Patient-Related Outcomes CLINICAL PHARMACY Pharmacoeconomic outcomes ​ Embraces the philosophy of pharmaceutical care ​ It blends a caring orientation with specialized therapeutic knowledge, experience, and judgement for the purpose of ensuring optimal patient outcomes. Clinical Pharmacists CORE, PRIME, SOAP/FARM ​ Clinical pharmacists care for patients in all healthcare settings. Documentation of Pharmaceutical Care ​ Possess in-depth knowledge of medications that is integrated with a foundational understanding of ​ CORE the: ​ PRIIME ○​ Biomedical ​ FARM/SOAP ○​ Pharmaceutical ​ ○​ Sociobehavioral, and ​ Develop or identify the CORE ○​ Clinical sciences ○​ Condition of the patient ○​ Outcomes desired in the specific patient Expertise of Clinical Pharmacists ​ Therapeutic Use of Drugs ○​ Regimen selected ​ Providing Consultancy Services ○​ Evaluation parameters ○​ Medication Therapy Evaluation ​ Identify the PRIME pharmacotherapy need ○​ Medication Use Review ○​ Pharmaceutical based problems ○​ Drug Utilization Evaluation ○​ Risk to the patient ​ Providing scientific and clinically valid information for the ○​ Interactions ○​ Safety ○​ Mismatch between medication and condition or patient needs ○​ Appropriateness ○​ Efficacy issues ○​ Cost-effectiveness of medications ​ Formulate a FARM/SOAP note Basic Components of Clinical Pharmacy Practice ○​ Findings- - patient-specific information ​ Taking part in Prescribing Drugs ○​ Assessment - evaluation of findings e.g. severity, duration ​ Administration of Drugs ○​ Resolution (including prevention) - rationale for the intervention should be mentioned ​ Documentation ○​ Monitoring (and follow up) - assess efficacy, safety and outcome of the intervention ​ Reviewing Drug Use ​ Communication ​ Counseling ​ Consulting ​ Preventing Medication Errors  Sample Consideration Based on Timing of Collection MEDICATION RECONCILIATION 1.​ Trough Concentration Medication Reconciliation 2.​ Peak Concentration ​ A process of comparing a patient’s medication orders to all the medications the patient has been taking. ​ Goal: To avoid Medications Errors ○​ Omissions ○​ Duplications ○​ Dosing errors ○​ Drug interactions ​ Done at every transition of care in which new medications are ordered, or existing orders are rewritten. ​ Transition in Care includes changes in ○​ Setting ○​ Service ○​ Practitioner ○​ Level of Care Five Steps of Medication Reconciliation 1.​ Develop a list of current medications; 2.​ Develop a list of medications to be prescribed; 3.​ Compare the medications on the two lists; 4.​ Make clinical decisions based on the comparison; and 5.​ Communicate the new list to appropriate caregivers and the patient 1.​ Trough Concentration ​ Reflects the lowest level of drug in the blood THERAPEUTIC DRUG MONITORING ​ Samples are drawn immediately (or 30 minutes) before the next dose ​ It is affected by the drug clearance rate Therapeutic Drug Monitoring (TDM) ○​ If the clearance rate increases, the trough level decreases ​ A quantitative procedure performed for drugs with a narrow therapeutic index. ​ It allows for the safe use of drugs that would otherwise be potentially toxic. 2.​ Peak Concentration ​ The Mixed function oxidase (MFO) system is the biochemical pathway responsible for the ​ The best specimen for initial investigation of therapeutic drug toxicity greatest portion of drug metabolism. ○​ Since it is most likely to exceed the upper therapeutic limit ​ Sample is drawn one hour after an orally administered dose (except for Digoxin) Indications for TDM ​ For IV drugs - peak levels are determined after the infusion is completed 1.​ Consequences of overdosing and underdosing are serious. ​ Increasing the dose rate may result in peak drug levels in the toxic range 2.​ Small differences between a therapeutic and toxic dose. 3.​ Poor relationships between the dose of the drug circulating concentrations but a good correlation between circulating concentrations and therapeutic toxic effects. 4.​ Change in the patient’s physiologic state that may unpredictably affect circulating drug concentrations. 5.​ Drug interaction is or may be occuring. 6.​ Monitoring patient compliance. Common Drug Classes requiring TDM 1.​ Digoxin ​ Cardioactive drugs ​ Cardiac glycoside - tmt of martial arrhythmia and CHF ​ Antibiotics ​ Serum electrolytes affect its therapeutic action and toxicities ​ Anti-epileptic Drugs ​ Large dose - inh. Na-K-ATPase = dec K and Mg; inc. Ca ​ Psychoactive Drugs ​ 0.8-2 ng/mL - cardiac contractility-inotropic effect ​ Bronchodilator ​ Timing of blood collection after the last dose is critical in the interpretation of drug levels ​ Immunosuppressive Drugs ○​ Absorption: in GIT = variable ​ Antineoplastic Drugs ○​ Distribution: 25% is protein bound ​ Anti-Inflammatory/Analgesics ​ Free drug is sequestered into muscle cells ​ Neuroleptics (Antipsychotic Major Tranquilizers) ○​ Excretion: eGFR affects serum concentration ​ Hyperthyroid patients = resistant to digoxin Route of Administration ​ The circulatory system is a convenient route that can effectively deliver most drug to their site of Elimination ​ Renal filtration of the plasma free form action. ​ IV route of administration had 100% BA or 1 Bioavailable fraction. Peak serum level ​ 8 hours after PO ​ PO-administered drugs should achieve a 0.7 bioavailability fraction. ​ IV-administered drugs have constant distribution and elimination rates. t½ ​ 38 hours Therapeutic level ​ 0.5-2 ng/mL Toxic level ​ > 2 ng/mL Causes of Drug Toxicity Toxic effects ​ N/V ​ Elevated concentration of free drug ​ Visual disturbances ​ Abnormal response to drug after administration ​ Premature ventricular contractions ​ The presence of active drug metabolites ​ AV node blockade Cardioactive Drugs 2.​ Lidocaine ​ Used to correct VT for the tmt of MI ​ Used for the treatment of arrhythmia and CHF ​ Administration = 1st loading dose, 2nd IV infusion ​ Classification ​ Used as a local anesthetic ○​ Class I - rapid sodium channel blockers (Quinidine, Procainamide, Lidocaine) ​ Bound to Albumin & AAG ○​ Class II - beta receptor blockers (Propanolol) ​ Cannot be given PO - almost complete hepatic removal of absorbed drug ○​ Class III - potassium channel blockers (Amiodarone) ○​ Class IV - calcium channel blockers (Verapamil) 1.​ Digoxin Elimination ​ Hepatic Met, changes in eGFR have little effect 2.​ Lidocaine Primary product of Hep. Met ​ Monoethylglycinexylidide (MEGX) 3.​ Quinidine 4.​ Procainamide Therapeutic level ​ 1.5-4.0 ug/mL 5.​ Disopyramide 6.​ Propranolol Toxicity level ​ > 4.0 ug/mL 7.​ Amiodarone 8.​ Verapamil CNS Depression ​ 4-8 ug/mL  5.​ Disopyramide Seizure and dec BP/CO ​ > 8 ug/mL ​ Used to treat cardiac arrhythmias ​ Administered PO = GIT Absorption is complete and rapid Toxic Effect ​ CHF and Heart Block ​ Anticholinergic effect = >4.5 ug/mL (Dry mouth and Constipation) Elimination ​ Renal filtration 3.​ Quinidine ​ Naturally occurring - used for tmt of arrhythmia Therapeutic Level ​ 3-5 ug/mL ​ Almost 85% protein bound Toxic Level ​ 10 ug/mL Elimination ​ Hepatic Metabolism Toxic Effect ​ Bradycardia ​ AV node blockade Route of Delivery ​ Oral Administration Common Formulations ​ Quinidine sulfate & Quinidine gluconate 6.​ Propranolol Peak serum level ​ 2 hrs after PO (sulfate); 4-5 hrs PO (gluconate) ​ Non-selective Beta receptor antagonist ​ Used for = Angina, HPN, CAD, Thyrotoxicosis Therapeutic level ​ 2.3-5 ug/mL ​ Suppressed conversion of T4 to T3 Toxic level ​ > 5 ug/mL Therapeutic Range ​ 50-100 ng/mL Toxic Effects ​ Cinchonism ​ Blood dyscrasia Toxic Effects ​ Bradycardia ​ Hepatitis ​ Arterial Insufficiency (Reynaud’s type) ​ Platelet disorder ​ Pharyngitis 4.​ Procainamide ​ Used to treat Ventricular Arrhythmia ​ GIT absorption = rapid and complete 7.​ Amiodarone ​ 20% protein bound = eliminated by Renal abd Hepatic Met. ​ Blocks potassium channel in the cardiac muscle ○​ Used to treat Ventricular Arrhythmias ​ Iodine-containing = causes Hyperthyroidism or Hypothyroidism Common Route ​ Oral Hepatic Metabolite ​ N-acetyl procainamide (NAPA) Therapeutic Level ​ 1.0-2.5 ug/mL Peak serum level ​ One hour after the dose Toxic Level ​ >2.5 ug/mL Therapeutic level ​ 4-10 ug/mL Toxic Effects ​ Bradycardia ​ Hepatitis Toxic Level ​ > 12 ug/mL ​ Photodermatitis ​ Thyroid dysfunction Toxic Effects ​ Reversible lupus-like syndrome (ANA) ​ Nephrotic syndrome ​ Urticaria  8.​ Verapamil Elimination ​ Renal filtration ​ Used to treat Angina, HPN, Supraventricular Arrhythmias Toxic Levels ​ >30 ug/mL (Amikacin & Kanamycin) - peak levels Therapeutic Range ​ 80-400 ng/mL ​ 12-15 ug/mL (Gentamicin & Tobramycin) - peak levels Toxic Effects ​ Hypotension Toxic Effects ​ Nephrotoxicity ​ Peripheral Edema ​ Ototoxicity ​ Ventricular fibrillation 2.​ Vancomycin ​ Glycopeptide Abx effective against Gram-positive cocci and bacilli ​ Poor oral BA - administered by IV Infusion ​ Toxic side effects = occur in the therapeutic range (5-10 ug/mL) ​ Only trough levels are monitored ○​ To ensure serum drug concentrations is within the therapeutic range Elimination ​ Renal filtration and excretion Toxic Levels ​ >10 ug/mL - nephrotoxicity ​ >40 ug/mL - ototoxicity Toxic Effects ​ Red man syndrome ​ Nephrotoxicity ​ Ototoxicity 3.​ Chloramphenicol ​ Distributes to all tissues and concentrates in the CSF ​ 50% protein bound ​ Rapidly absorbed in GIT Antibiotics 1.​ Aminoglycosides Toxic Levels ​ >25 ug/mL 2.​ Vancomycin 3.​ Chloramphenicol Toxic Effects ​ Blood dyscrasia ​ Cytoplasmic vacuolation (erythroid and myeloid cells) 1.​ Aminoglycosides ​ Used to treat Gram-negative bacterial infections ○​ Not given outpatient ​ Administration: IM, IV, not well-absorbed PO ​ May damage 8th cranial nerve at toxic levels = Hearing loss ​ Requires trough and peak measurements  ​ Free form = biologically active portion; 99% protein bound Anti-epileptic Drugs ​ Toxicity = can be seen at therapeutic level 1.​ Phenobarbital 2.​ Phenytoin Elimination ​ Hepatic Pathway (Zero-order kinetics) 3.​ Valproic Acid 4.​ Carbamazepine Therapeutic Range ​ 10-20 ug/mL 5.​ Ethosuximide 6.​ Gabapentin Toxic Level ​ >20 ug/mL Injectable proform ​ Fosphenytoin 1.​ Phenobarbital ​ Long acting barbiturate Major toxicity ​ Initiation of seizures ○​ Controls grand mal tonic-clonic seizure and focal seizures ​ Teratogenic (cleft lip and palate) ○​ Not used for petit mal seizures ​ Nystagmus ​ Treatment of withdrawal symptoms in infants ○​ Mothers who are addicted to opiate or barbiturate ​ Treat cases of congenital hyperbilirubinemia 3.​ Valproic Acid ○​ Enhances bilirubin metabolism ​ Used for treatment of ​ Absorption = slow but complete; 50% protein bound, majority stored in the brain ○​ Petit mal (absence seizure) ​ ↓eGFR = slows down the elimination process ○​ Atomic ​ Only trough levels are evaluated - unless there is toxicity ○​ Grand mal seizures ​ Administration = PO; GIT absorption is rapid and complete Elimination ​ Hepatic Metabolism ​ 93% protein bound ​ Prominent for causing Hepatic Dysfunction Inactive proform ​ Primidone (Mysoline) ○​ Monitor after 6 mos of therapy Peak serum level ​ 10 hours after PO Elimination ​ Hepatic Metabolism Therapeutic level ​ 20-40 ug/mL (Phenobarbital) ​ 5-12 ug/mL (Primidone) Therapeutic Level ​ 50-100 ug/mL Toxic Effects ​ Nystagmus Toxic Levels ​ >100 ug/mL ​ Stupor ○​ Nausea ​ Ataxia ○​ Lethargy ​ Respiratory Depression ○​ Weight gain ​ >200 ug/mL ○​ Pancreatitis ○​ Hallucinations 2.​ Phenytoin ○​ Hyperammonemia ​ Short-term prophylactic agent in brain injury ​ Controls seizure ○​ Tonic-Clonic ○​ Simple partial seizures ​ Not used for petit mal and atonic seizures ​ Decreases Na and Ca influx into hyperexcitable neurons ​ GIT absorption - incomplete; given IV 4.​ Carbamazepine 6.​ Gabapentin ​ Tricyclic Compound = related to Imipramine ​ Chemically similar to GABA ​ Effective for ​ Used for ○​ Grand Mal seizure ○​ Partial seizures ○​ Treatment of seizures accompanied by pain ○​ An adjunct to other seizure therapies ​ Antineuralgic action ​ Administration = PO; not bound to plasma proteins ​ 70-80% protein-bound ​ Excreted unchanged in the urine ​ Administration = PO; serious toxic effects and not frequently used ​ Not metabolized in humans Elimination ​ Hepatic Metabolism Adverse Effects ​ Dizziness ​ Ataxia Idiosyncratic Effects ​ Rashes ​ Fatigue ​ Leukopenia ​ Nystagmus ​ Nausea ​ Vertigo Therapeutic Level ​ 2-15 ug/mL ​ Febrile reactions Toxic effects ​ Ataxia Therapeutic Level ​ 4-16 ug/mL ​ Somnolence/drowsiness Toxic Level ​ >12 ug/mL Toxic effects ​ Hematologic dyscrasia Other Anti-Seizure Drugs ​ Aplastic anemia ​ Irregular pulse ​ Topiramate/Lamotrigine/Felbamate ​ Ataxia ○​ Adjunct drug for partial seizures 5.​ Ethosuximide Psychoactive Drugs ​ DOC for controlling Petit Mal (Absence seizure) 1.​ Lithium ​ Administered PO 2.​ Tricyclic Antidepressants (TCAs) ​ Free in serum and not protein bound 3.​ Fluoxetine Therapeutic Level ​ 40-100 ug/mL 1.​ Lithium Toxic Level ​ >100 ug/mL ​ Used for treatment of Manic-depressive illness (bipolar disorders) ​ DOC for prevention of chronic cluster headache Toxic effects ​ GI Disturbances ​ Inhibits Thyroid Hormone Synthesis and Release ​ Ataxia ○​ Inhibits iodine uptake, causing Hypothyroidism ​ SLE ​ Cationic metal that does not bind to proteins ​ Aplastic anemia ​ PO Administration - rapid and complete absorption ​ Pancytopenia ​ Distribution = uniform throughout the body water and is reabsorbed ​ When given with Demeclocycline = inhibit the action of ADH on the kidneys  Elimination ​ Renal Filtration 3.​ Fluoxetine Therapeutic Range ​ 0.8-1.2 mmol/L ​ Blocks the re-uptake of serotonin in Central Serotonergic Pathways ​ Used for treatment of Obsessive-compulsive disorder (OCD) Toxic Effects ​ Severe dehydration ​ Nephrotoxicity Therapeutic Level ​ 90-300 ng/mL ​ Hypothyroidism Toxic Effects ​ Attempted suicide Toxic Levels ​ 1.2-2 mmol/L ​ Decreased Libido ○​ Apathy ​ Decreased sexual function ○​ Lethargy ○​ Speech difficulties ​ >2 mmol/L ○​ Seizures ○​ Muscle rigidity Bronchodilator ○​ Coma 1.​ Theophylline ​ Methylated xanthine ​ Relaxes bronchial smooth muscle 2.​ Tricyclic Antidepressants (TCAs) ○​ Inhibits the release of histamine and other proinflammatory agents ​ Used for the treatment of ​ Used in the treatment of ○​ Depression ○​ Asthma ○​ Insomnia ○​ Chronic obstructive pulmonary disease (COPD) ○​ Extreme apathy ​ Therapeutic for ○​ Loss of Libido ○​ Primary apnea of prematurity ​ PO Administration = absorption is variable ​ Absence of respiratory effort in newborn infants ○​ Slow gastric emptying and intestinal motility ​ Administration: 1st IV; 2nd Orally; 50% protein bound ​ Highly protein-bound (85-95%) ​ Crosses the placenta = may be teratogenic in pregnant females ​ Examples ​ The best predictor of Toxicity ○​ Imipramine, Amitriptyline, Doxepin, Nortriptyline, Trazodone ○​ Blood level of the drug ○​ Not the early signs or symptoms of toxicity Elimination ​ Hepatic Metabolism Elimination ​ Renal filtration and hepatic metabolism Peak Serum Concentration ​ 2-12 hours Therapeutic Level ​ 10-20 ug/mL Therapeutic Level ​ 100-300 ng/mL Toxic Level ​ >20 ug/mL Major metabolite ​ Desipramine Toxic Effect ​ GI bleeding Toxic effects ​ Drowsiness ​ Seizures ​ Blurred vision ​ Tachycardia ​ Memory loss ​ Syncope ​ Seizure ​ Cardiac arrhythmia ​ Parkinsonian syndrome ​ Unconsciousness  3.​ Rapamycin Immunosuppressive Drugs ​ Similar to Tacrolimus 1.​ Cyclosporine ​ Major Side Effects 2.​ Tacrolimus ○​ Lipid abnormalities 3.​ Rapamycin ○​ Thrombocytopenia 1.​ Cyclosporine Other Immunosuppressive Drugs of Interest ​ Inhibits cellular immune response = blocking the production of IL-2 ​ Therapeutic uses ​ Mycophenolate mofetil - decreases renal allograft rejection ○​ Used to prevent rejection of allogenic organ transplants ​ Leflunomide (LFM) - inhibits lymphocyte proliferation ○​ Utilized for suppression of acute graft-versus-host disease (GVHD) ○​ For the tx of rheumatoid arthritis ​ When used for the Heart, Liver, and Pancreas ○​ Require High Dose (300 ng/mL) ​ Has marked affinity with RBC (Temperature dependent) ​ Administration = PO/5-50% absorption Antineoplastic Drugs 1.​ Methotrexate Elimination ​ Hepatic Metabolism 2.​ Busulfan Best Sample ​ Whole Blood (with lysis of RBC to yield the total amount) 1.​ Methotrexate Toxic Level ​ >500 ng/mL ​ Effective therapy for ○​ Various neoplastic conditions Toxic Effect ​ Renal tubular and Glomerular dysfunction ○​ Immunosuppression ​ GI disturbances ​ Mechanism ​ Hirsutism ○​ Inhibits DNA Synthesis - by blocking dihydrofolate reductase ​ Hematologic dyscrasia ​ Leucovorin - rescue drug for Methotrexate toxicity (“Leucovorin rescue”) Toxic Level ​ >0.01 umol/L 2.​ Tacrolimus (FK-506) ​ Macrolide lactone Abx Toxic Effect ​ Leucopenia ​ 100x more potent than cyclosporine ​ GI Ulceration ​ GIT uptake is variable ​ Thrombocytopenia ​ Levels will elevate in patients with cholestasis ​ Cirrhosis Elimination ​ Hepatic metabolism 2.​ Busulfan Specimen of choice ​ Whole blood ​ An alkylating agent used to treat ○​ Leukemias and Lymphomas before bone marrow transplantation Toxic Effects ​ Thrombus formation ​ Overdosage = Hepatic Occlusive Disease ​ Nephrotoxicity ​ Neurotoxicity  ​ Chronic Abuse Anti-Inflammatory/Analgesics ○​ Chronic toxicity and death 1.​ Salicylates/Aspirin ○​ Anemia 2.​ Acetaminophen ○​ Renal damage 3.​ Ibuprofen ○​ Gastrointestinal disturbances - with chronic toxicity ​ NAC - treats toxic effects of Acetaminophen/APAP 1.​ Salicylates/ASA ​ Direct stimulator of the Respiratory system Therapeutic Level ​ 25 ug/mL ​ Inhibitor of Kreb’s Cycle ​ Antiplatelet Toxic Levels ​ >50 ug/mL ​ Decrease TXA and PG ​ 100-300 ug/mL (hepatic cirrhosis) ​ Acute aspirin intoxication = common cause of fatal drug poisoning in children Toxic Effects ​ Cyanosis due to methemoglobinemia ​ CNS Depression Side Effects ​ GI disturbances ​ Seizure ​ Interference with platelet aggregation Method ​ HPLC Therapeutic Level ​ 5 mg/dL (treatment of HA) Toxic Level ​ >30 mg/dL 3.​ Ibuprofen Toxic Effects ​ Mixed acid-base disturbances (Met. Acidosis and Resp. ​ Analgesic/Anti-Inflammatory Alkalosis) ​ Lower risk of Toxicity than Salicylates and Acetaminophen ​ Hypoglycemia ​ Reye’s Syndrome Toxic Effects ​ Nausea/Vomiting ​ Blurred Vision Methods ​ Trinder Assay ​ Abdominal pain ​ Enzymatic Assay (Salicylate hydroxylase) ​ Edema ​ EMIT ​ HPLC Therapeutic Level ​ 10-50 ug/mL Toxic Level ​ >100 ug/mL 2.​ Acetaminophen ​ Inhibitor of PG Metabolism ​ Analgesic/Antipyretic ​ Overdosage = hepatotoxicity ​ Toxic Doses = Acute singe ingestion levels of 140 mg/kg ​ Very High Doses (with Suicide attempts) Neuroleptics (Antipsychotic Major Tranquilizers) ○​ Fulminant hepatic failure ○​ Maximum liver damage ​ Blocks action of DOPAMINE and SEROTONIN in the LIMBIC System ​ Not becoming apparent until 2-4 days after ingestion ​ Used in the treatment of = Schizophrenia ​ Severe Poisoning ​ Difficult to monitor in the serum due to ○​ CNS Stimulation followed by CNS Depression ○​ Abundant metabolites for each drug ○​ Vascular Collapse ○​ Extensive hepatic metabolism ○​ Shock ​ Typical Antipsychotics ○​ Total Seizure ○​ Phenothiazines = Chlorpromazine ○​ Coma preceded Death ○​ Butyrophenones = Haloperidol  ​ Atypical Antipsychotics Pancreas ○​ Risperdal ​ Islet of Langerhans ○​ Olanzapine 1.​ Beta Cells ○​ Quetiapine ​ Insulin ○​ Aripiprazole ​ Amylin ​ Toxic Effects 2.​ Alpha Cells ○​ Cholestasis ​ Glucagon ○​ Orthostatic Hypotension 3.​ Delta Cells ○​ Aplastic Anemia ​ Somatostatin ○​ Muscle rigidity 4.​ F Cells ​ Pancreatic polypeptide ​ Endocrine Gland ○​ Secretes insulin, glucagon, and somatostatin from different cells residing in the pancreatic islets of Langerhans CARBOHYDRATES ​ Exocrine Gland Carbohydrates ○​ Secretes amylase, which is responsible for the breakdown of ingested complex ​ Hydrates of aldehyde or ketone carbohydrates ​ Glucose ○​ The only carbohydrate to be directly used for energy or stored as glycogen Insulin ○​ Does not accumulate in the muscle ​ Primary hormone responsible for the entry of glucose to the cell ○​ Does not enter the muscle cell freely ​ Promotes ​ Brain ○​ Glycogenolysis ○​ Completely dependent on blood glucose for energy production ○​ Lipogenesis ○​ ⅔ of glucose utilization occurs in the CNS ○​ Glycolysis ​ Suppresses - glycogenolysis Reducing and Non-Reducing Sugars ​ Patient preparation ​ Reducing Sugars ○​ No MTV/Supplements 12 hours prior to collection of specimen ○​ Glucose ​ Sample Requirement ​ A double bond and a negative charge in the enol anion make glucose an active ○​ Serum reducing substance ​ Reference values: 2.6-24.9 mIU/mL ○​ Maltose ○​ Fructose Glucagon ○​ Lactose ​ Hyperglycemic agent ○​ Galactose ​ Released during stress and fasting states ​ Non-Reducing Sugars ​ Enhances catabolic functions during fasting periods ○​ Sucrose ○​ Promotes glycogenolysis ○​ Do not contain an active ketone or aldehyde group ​ FP Glucagon = 25-50 pg/mL Other Hormones that Tend to Increase Blood Glucose Concentration 1.​ Cortisol and Corticosteroids (Glucocorticoids) 2.​ Catecholamines 3.​ Growth Hormone (Somatotrophic) 4.​ Thyroid Hormones 5.​ Adrenocorticotropic Hormone (ACTH) 6.​ Somatostatin Clinical Conditions Related to Carbohydrate Metabolism Classification of Hypoglycemia ​ Hyperglycemia ​ Drug-induced ○​ Toxic to beta-cell function and impairs insulin secretion ​ Critical illnesses ○​ Causes ​ Hormonal deficiency ​ Stress ​ Endogenous hyperinsulinism ​ Severe Infection ​ Autoimmune hypoglycemia ​ Dehydration ​ Non-beta cell tumors ​ Pregnancy ​ Hypoglycemia of infancy and childhood ​ Pancreatectomy ​ Alimentary (reactive) hypoglycemia ​ Hemochromatosis ​ Insulin deficiency/Abnormal insulin receptor If Px is suspected of Endogenous Hyperinsulinism ○​ FPG = ≥ 126 mg/dL ​ Measure: ​ Hypoglycemia ○​ Plasma glucose ○​ Imbalance between glucose utilization and production ○​ Insulin & Proinsulin ○​ Warning signs and symptoms - related to CNS ○​ C-peptide ○​ Whipple’s Triad - needs to be met before Dx of Hypoglycemia ○​ Beta-hydroxybutyrate ​ Low blood glucose concentration ○​ Insulin antibodies ​ Typical symptoms ○​ Oral hypoglycemic drugs ​ Symptoms alleviated by glucose administration Clinical Hypoglycemia Interpretation of Plasma Glucose Values ​ Plasma/serum glucose concentration is low enough to cause symptoms/signs of impairment of brain ​ 65-70 mg/dL function. ○​ Glucagon and other glycemic hormones are released into the circulation ​ 50-55 mg/dL Factitious Hypoglycemia ○​ Observable symptoms of hypoglycemia appear ​ Intentional attempt to induce low blood glucose levels ​ ≤50 mg/dL ​ Results from exogenous self-administration of insulin/insulin-secretagogues ○​ Considered low value and abnormal for infants (req. further diagnostic test) ​ More common in women in 30s-40s ​ 180 mg/dL with normal renal fxn ○​ Diaphoresis ​ Ketosis ​ Neuroglycopenic ○​ Excessive synthesis of Acetyl-CoA leading to formation of Ketone Bodies ○​ Dizziness ○​ Severe DM ○​ Tingling ​ Β-hydroxybutyrate to acetate ratio 6:1 ○​ Blurred vision ​ Laboratory Findings in DM ○​ Confusion ○​ Inc. glucose in PLASMA and URINE ○​ Behavioral changes ○​ Inc. URINE Sp.gr. ○​ (+) Ketones in SERUM and URINE ○​ Acidosis in BLOOD and URINE ○​ Electrolyte Imbalance ​ Low sodium  ​ Increase potassium ​ Latent Autoimmune Diabetes of Adulthood (LADA) ​ Low bicarbonate ​ Type 1a or 1.5 DM ○​ High Serum Osmolality ​ Slow immune-mediated DM ​ Slowly progressive insulin-dependent type 1 DM (SPIDDM) ​ Characterized by: ○​ Moderate hyperglycemia with gradual autoimmune destruction of the pancreatic beta cells ○​ Common among adults CLASSIFICATION OF DM ​ Adult onset T1DM - Ketosis-resistant Classification of DM ​ Shares immunological features with both T1DM and T2DM 1.​ Type 1 DM (T1DM) ​ Distinguishing feature 2.​ Type 2 DM (T2DM) ○​ (+) single specific islet cell autoantibody 3.​ Gestational Diabetes Mellitus (GDM) ​ GAD 4.​ Other Types of DM (OTODM) ​ IA-2A (Insulinoma-associated protein 2) ​ ZnT8 ​ Insulin 1.​ Type 1 DM ​ Predisposing Factors ​ Insulin Dependent Diabetes Mellitus (IDDM) ○​ Low birth weight ​ Juvenile Onset Diabetes Mellitus ○​ Severe smoking ​ Brittle Diabetes ○​ Advanced age ​ Labile Diabetes ○​ FH of autoimmune disease ​ Ketosis-Prone Diabetes ​ Signs/Symptoms ​ It results from cellular-mediated autoimmune destruction of the β-cells of the pancreas ○​ Similar to T1DM ​ T1DM has insulinopenia (absolute insulin deficiency) ​ Polyuria ○​ Due to loss pancreatic B-cells ​ Polydipsia ​ Prone to Ketoacidosis ​ Weight loss ​ Other Detectable Autoantibodies ​ Other Clinical Manifestations ○​ Tyrosine phosphatase 1A-2 and IA-2B antibody ○​ Nocturia ○​ Zinc transporter 8 Antibody (ZnT8) ○​ Visual Impairment ○​ Islet autoantibodies ○​ Fatigue ​ Signs and Symptoms ○​ Polyuria ​ Fulminant Type 1 Diabetes (FT1D) ○​ Polydipsia ​ Formerly: Idiopathic Type 1 DM or Type 1b ○​ Polyphagia ​ Strongly inherited and associated with absence of B-cell autoantibodies ○​ Rapid weight loss ​ Characterized by remarkably rapid and complete B-cell destruction ○​ Hyperventilation ​ Aggressive progression of hyperglycemia and ketoacidosis ○​ Mental confusion ○​ Possible loss of consciousness ​ Complications ○​ Microvascular disorders ​ Endogenous Serum Insulin ○​ Very low or undetectable  3.​ Gestational Diabetes Mellitus ​ Impaired ability to metabolize carbohydrates 2.​ Type 2 Diabetes Mellitus (T2DM) ○​ Deficiency of insulin ​ Non-Insulin Dependent Diabetes Mellitus (NIDDM) ○​ Metabolic ​ Adult Type/Maturity Onset Diabetes Mellitus ○​ Hormonal ​ Stable Diabetes ​ Occurs during pregnancy and disappears after delivery ​ Ketosis-resistant Diabetes ○​ 2nd to 3rd trimester ​ Receptor-Deficient Diabetes Mellitus ​ Screening and Diagnosis ​ Hyperglycemia due to ○​ Through 2-hour OGTT ○​ Insulin resistance ​ Diagnostic Tests ○​ Defective insulin secretion ○​ One-step Method ​ Strong genetic predisposition ​ 75 grams glucose load, common ​ Not related to autoimmune disease ○​ Two-step Method ​ “Geneticist’s nightmare” ​ 50 grams 1st; 100 grams as follow up ​ Patient is at risk for: ​ Diagnostic Criteria for GDM ○​ Macrovascular and Microvascular complications 1.​ FBS = ≥ 92 mg/dL ​ Risk Factors 2.​ 1-hour sample = ≥ 180 mg/dL ○​ Obesity 3.​ 2-hour sample = ≥ 153 mg/dL ○​ Family history ​ Interpretation of OGTT in GDM ○​ Advanced age ○​ Infants born to diabetic mothers are at increased risk for respiratory distress ○​ Hypertension syndrome, hypocalcemia, and hyperbilirubinemia ○​ Lack of exercise ○​ After giving birth, women with GDM should be evaluated 6 to 12 weeks postpartum ○​ GDM ○​ Fetal insulin secretion is stimulated in the neonate of a mother with diabetes, but ○​ Impaired glucose metabolism upon delivery and the umbilical cord is severed, the infant’s oversupply of glucose is ​ Recommendation immediately terminated ○​ Adults aged 45 and above - screened for DM every three years Comparison between T1DM & T2DM 4.​ Other Types of DM 1.​ DM due to Pancreatic Disorder (pancreatogenic DM/Type 3c DM) ​ Chronic pancreatitis ​ Malignancy (pancreatic CA) ​ Pancreatectomy 2.​ DM related to endocrine disorders ​ Cushing’s syndrome ​ Pheochromocytoma ​ Acromegaly ​ Aldosteronoma ​ Hyperthyroidism 3.​ DM caused by genetic syndromes ​ Down syndrome ​ Klinfelter’s syndrome ​ Rabson-Mendengall Syndrome ​ Leprechaunism ​ Huntington’s chorea ​ Turner syndrome 4.​ DM associated with other exocrine diseases ​ Cystic fibrosis ​ Neoplasia ​ Hemochromatosis 5.​ DM due to viral infections such as CMV and Rubella 6.​ Drug-induced or Chemical induced DM ​ Drugs/chemical inducers of B-cell dysfunction ○​ Dilantin ○​ Pentamidine ​ Causes impaired insulin action ○​ Thiazides ○​ Glucocorticoids Sample for Glucose Measurement ○​ Monitor the effectiveness of lifestyle changes and stress management 1.​ Random Blood Sugar (RBS) ​ Increased Cholesterol 2.​ Fasting Blood Sugar (FBS) 1.​ Hyperlipoproteinemia types II, III, IV 3.​ Two-hour Post-Prandial BS (2-HPPBS) 2.​ Biliary cirrhosis 4.​ Glucose Tolerance Test (GTT) 3.​ Nephrotic syndrome 5.​ Glycosylated Hemoglobin (HbA1c) 4.​ Poorly controlled DM 6.​ Fructosamine 5.​ Alcoholism 7.​ 1,5-anhydroglucitol (1,5-AG) 6.​ Primary hypothyroidism ​ Decreased Cholesterol ○​ Severe hepatocellular disease ○​ Malnutrition ○​ Severe burns ○​ Hyperthyroidism LIPIDS AND LIPOPROTIENS ○​ Malabsorption syndrome Major functions of Lipids ​ Primary source of fuel Major Lipids in Plasma: TRIGLYCERIDE/TRIACYLGLYCEROL (Neutral Fat) ​ Provide stability to cell membrane ​ Very hydrophobic and water-insoluble ​ Sources of Hormones ​ Main storage lipid in humans (adipose tissue) ​ Used as a source of energy during fasting states and between meals Major Lipids in Plasma ​ Low calorie intake = low TG levels ​ Phospholipids ​ Function: ​ Cholesterol ○​ When TAG are metabolized their FA are released into the cells and converted into energy ​ Triglycerides ○​ Provides excellent insulation ​ Fatty Acid ​ Breakdown is facilitated by: ​ Fat Soluble vitamins (ADEK) ○​ Epinephrine ○​ Cortisol Major Lipids in Plasma: PHOSPHOLIPIDS (Conjugated lipid) ○​ Lipoprotein lipase ​ The most abundant lipid derived from phosphatidic acid ​ Fasting requirement: 10-12 hours ​ Originates in the liver and intestine ​ Reference range: 500 mg/dL (Very High) - acute and recurrent pancreatitis ​ Unsaturated steroid alcohol ​ Diagnostic Significance ​ Synthesized in the liver and it is found on the surface layer of lipoproteins ○​ Evaluates suspected atherosclerosis and measures the body’s ability to metabolize fat ​ Does not serve as a source of fuel/energy ○​ Fasting TAG ≥ 200 mg/dL is at risk for CAD ​ Transport & Excretion are promoted by estrogen ○​ TAG and Cholesterol are the most important lipids in the management of CAD​ ​ Ref. value =