Blood Gases Clinical Chemistry 2 PDF

7P| BLOOD GASES CCHM312 LEC Ma’am Dianne Rose Mendoza RMT Clinical Chemistry 2 Caluag, Cruz, Mendoza, Nicoleta, Quines, Rubete...

7P| BLOOD GASES CCHM312 LEC Ma’am Dianne Rose Mendoza RMT Clinical Chemistry 2 Caluag, Cruz, Mendoza, Nicoleta, Quines, Rubete Third Year Second Semester BLOOD GASES PROTEIN BUFFER SYSTEM TERMS AND ABBREVIATIONS  Proteins can also help in maintaining the buffer due Acids to charges present on their surfaces. Proteins are  substance that can yield a hydrogen ion (H) or made up of amino acids which has carboxyl end hydronium ion when dissolved in water and amino end; consisting of (+) and (-) charge end.  +  represents (+) charge molecules Proteins can exist in 2 forms: H protein, B Protein Base o Their characteristics depend on the pH of the environment  substance that can yield hydroxyl ions (OH)  More (+) in acidic environment  represents (-) charge molecules  More (-) in basic/alkaline Buffer  Has capability to bind or release excess Hydrogen  combination of a weak acid or weak base and as required within blood circulation its salt, is a system that resists changes in pH  Plasma proteins (Charges on their surface)  Effectiveness of a buffer is determined based o pH > pI – (-) charge on: o pH < pI – (+) charge o Ionization constant/ pKa of the TERMS buffering system BICARBONATE (HCO3) o pH of the environment  The second largest fraction of the anions in the  Function: maintain or prevent sudden plasma. fluctuations in pH  Conjugate base representative of major buffer  Major buffer system: Plasma – bicarbonate- system carbonic acid buffer system; pK of 6.1  Classified under electrolytes. It includes:  Normal blood pH: 7.35-7.45, to achieve this the o ionized bicarbonate (HC03) – measured to body uses buffers determine pH BUFFER SYSTEMS o Bicarbonate molecules linked with amino BICARBONATE-CARBONIC ACID BUFFER SYSTEM acid: carbonate and the carbamino  Principal mammalian buffer system compounds. Normal range is from 21 - 28  Acids combine with Bicarbonates in the blood mmol/L (21 - 28 meq/L) o Neutral Salts (Bicarbonate Salts) – CARBONIC ACID (H2CO3) conjugate base  Weak acid representative of major buffer system o Carbonic Acid (Weak Acid)  readily dissociated into H2O and CO2 once it  In blood circulation, bicarbonate and carbonic acid reaches the blood circulation exists in 2 different forms.  This fraction of blood, plasma or serum includes the Bicarbonate Carbonic Acid undissociated carbonic acid and the physically (unstable) dissolved anhydrous C02. Form Bicarbonate Changes to  In blood circulation, CO2 concentration is higher H2O and CO2 than HCO3, the symbol cdCO2 (conc. of dissolved once it reaches C02) is frequently used and measured from pCO2 the plasma. multiplied by the solubility coefficient (0.03) of CO2. o Other references: the complete solubility Regulation Primary Measurement: coefficient is 0.0307 or 0.0306 regulation is based on pCO2  Normal range: 1.05 –1.45 mmol/L. thru kidneys, PARTIAL PRESSURE OF C02 (PCO2) renal  pressure or tension exerted by C02 gas regulation dissolved in blood  3 H2CO unstable, changing to H2O and CO2 in fluid  It is an index of efficiency of gas exchange in the lungs and not a direct measurement of total CO2 PHOSPHATE BUFFER SYSTEM concentration in the blood.  2,3-diphosphoglycerate – phosphate form that  Function: used to determine (H2CO3) level by acts as a buffer multiplying it with solubility coefficient  Primary utilization is in RBCs. It is 16% of the non-  Normal range: 35 - 45 mmHg. bicarbonate buffer value of erythrocytes CARBON DIOXIDE COMBINING POWER (CO2  It increases the amount of NaHCO3 in ECF (more COMBINING POWER) alkaline)  Amount of CO2 bound within the blood o Sodium bicarbonate (NaHCO3) is a circulation depending on the sample used negatively charged molecule which makes  The value of the CO2 combining power Is an index blood pH to be more alkaline, but still of the amount of CO2 that can be bound by serum, maintaining the normal blood pH plasma, or whole blood as HCO3 at a pCO2 of 40 mmHg at 25 degrees Celcius. HEMOGLOBIN-OXYHEMOGLOBIN BUFFER SYSTEM  Normal range: 24 - 30 mmol/L.  maintains pH level (Venous and Arterial Blood) TOTAL CARBON DIOXIDE CONCENTRATION  Hemoglobin is considered to be an effective buffer (ctCO2) because it is responsible for carrying oxygen so it Formerly known as C02 content has the ability to off load O2 replacing it with CO2  Sum of major buffer system or total concentration  helps in the maintenance of CO2; it facilitates its of C02 in the blood consisting of ionized HC03, diffusion across different gradients C03, carbamino compound) and unionized fraction  1 gram of Hemoglobin carries 1.39 mL of Oxygen. (H2C03) and physically dissolved C02. Each mole of Hgb binds with 1 mole of O2 (primarily  Normal range: 21-28 mmol/L. more than 95% of Hgb binds with O2) 1   Arterialization – process by which pH vasodilation is induced to maintain good  The negative logarithm of hydrogen ion activity with blood flow. Sample from capillary puncture a normal average range of 7.35-7.45 undergoing arterialization will be near arterial sample. MAJOR FACTORS REGULATING BLOOD PH: Procedure  Could be subdivided into 2 levels – primary line in  Warm up first the area of blood order to prevent drastic fluctuation in pH, and extraction. (i.e in finger/heel stick, dip o second line which acts when major disturbances, it first in water bath with 42 C temp changes or deviations from normal pH occurs. and leave it for at least 10mins. Primary line  Alternative: use warming pad 1) Chemical buffers (with charges) Exceptions in Arterialization  bicarbonate and carbonic acid buffer  If patients have low blood pressure: system systolic with Venous blood: bc in 𝐵𝑖𝑐𝑎𝑟𝑏𝑜𝑛𝑎𝑡𝑒 venous blood, O2 level is significantly 𝑝𝐻 = lower compared to arterial blood. Blood 𝐶𝑎𝑟𝑏𝑜𝑛𝑖𝑐 𝑎𝑐𝑖𝑑 passing thru the veins are deoxygenated blood, so the body has already distributed 𝐻𝐶𝑂3 the O2 content into different cells and 𝑝𝐻 = 𝑃𝐶𝑂2 tissues, therefore it is lower.  ↓ low O2 = ↑ pCO2 (2-8mmHg BLOOD COLLECTION FOR BLOOD GAS AND PH higher in venous compared to ANALYSIS arterial)  Blood gas analysis may not be encountered by MTs  ↑ pCO2 = acidic (0.02-0.05 units anymore because there are other healthcare lower in venous blood sample) professionals that are responsible for this procedure 2. MTs are not trained to perform arterial blood sample as they are capable and trained to perform. collection. Either physicians or respiratory therapists REMINDERS are the ones responsible.  Keep the sample at anaerobic technique in 3. Ideal syringe (but not used anymore): glass blood collection; at least prevent its exposure to syringe – less porous than plastic syringe so it ambient air because the concentration of O2 lessens amount of exposure and difference in and CO2 is different in blood and in air. amount of CO2 and O2 in ambient air.  The pCO2 of air (0.2mmHg) Is much 4. Anticoagulant: heparin (lyophilized/freeze dried) – less than that of the blood (38 mmHg) powdered heparin. The use of liquid heparin is not so that when blood is exposed to air, advisable because it causes dilution of sample. the ctCO2 and pCO2 decreases; and  Always follow anaerobic technique. the pH increases, thus it is a must to collect, transfer and manipulate blood METHOD OF DETERMINATION for blood gas analysis in condition where air is avoided or at least kept at a minimum level.  Preferred sample: whole blood  Arterial blood is the more preferred specimen for blood gas analysis because it is of more uniform composition than venous blood. This is due to the metabolic diversity composing venous samples  Venous and Capillary (Skin punctured) Blood  These specimens can also be used for blood gas analysis provided that they undergo arterialization.  Arterialized capillary blood – used as an alternative if arterial sample from the patient cannot be possibly collected or if the patient does not have arterial cannula yet. 2  pO2 2 Types of Gasometric Analysis  ISE Method  vary depending on the volume of blood  Clark/e p02 electrode sample which will be utilized  Principle: Based on amperometric or  Macrogasometric method – >1mL of sample polarographic measurement of oxygen.  Microgasometric method - 45 respiratory acidosis HCO3 Metabolic acidosis 29 mmol/L  < 22 - metabolic acidosis pCO2 represent Respiratory alkalosis 26 – metabolic alkalosis H2CO3 Determine which is the Primary (1°) and Respiratory acidosis >45 mmHg compensating disorder (35-45mmHg)  pH Determine the degree of compensation 3. Degree of Compensation  non- compensatory  Compensation – body’s mechanism which  partial compensatory allows it to revert back the pH level into normal  complete compensation range pO2 = 81 - 100 mmHg (adequate oxygenation)  One buffer system adjusts for the other buffer system which has primary disturbance  p02 Hypoxemia:  mild = 61 - 80 Degree of Compensation pH pCO2 HCO3 H2CO3  moderate = 41 - 60  severe = 40 or less Non-compensatory A A or N A or N Partial compensatory A A A BLOOD GASES CALCULATION HENDERSON-HASSELBACH EQUATION Complete compensatory N A A  pH is based on HCO3- and H2CO3  N = normal [𝑐𝑜𝑛𝑗𝑔𝑎𝑡𝑒 𝑏𝑎𝑠𝑒]  A = abnormal 𝑝𝐻 = 𝑝𝐾𝑎 + 𝑙𝑜𝑔 Non-compensatory 𝑤𝑒𝑎𝑘 𝑎𝑐𝑖𝑑  No compensation HCO3 −  Either pCO2/ HCO3 H2CO3 is normal; pH is pH = 6.1 + log abnormal H2CO3  Ex: Respiratory acidosis - pCO2 is abnormal, while H HCO3 2CO3 did not adjust and  H2CO3 = pCO2 x 0.03 (solubility coefficient; is normal. Since this is acidosis, pH in other references: 0.029) effect will be acidic or in abnormal range. Partial compensatory Formula to be used:  With compensation but insufficient to HCO3 − compensate pH → abnormal pH = 6.1 + log  pCO2 and H HCO3 2CO3 are abnormal; pH is pCO2 x 0.03 abnormal - Complete compensatory Can HCO3 be measured in blood circulation?  With sufficient compensation; thus  Yes, as explained in anion gap, normalizing pH bicarbonate is used together with chloride as representatives of anions. 4. Degree of Oxygenation (pO2 = 85-105mmHg) Alternative Formula: if incase the given is only tCO2  Evaluate according to the given result based on and pCO2 tCO2 = HCO3 + H2CO3 normal range  ↓ pO2 (61; 41; 4.0 ug/ml ng/ml CNS depression >4-8 ug/ml  GIT absorption is variable; change in GFR affect Seizure, Decrease BP >8 ug/ml serum concentration of Digoxin and cardiac output  The absorption is affected by several  Usually, the upper limit off therapeutic dose is factors such as dietary factors, GIT the lower limit of toxicity. motility, and actual formulation of drug QUINIDINE  In blood circulation, about 25% is protein bound Ex: Quinidex, Extentabs, Cardioquin, Quinora while the remaining percentage is free which will be  Na protein bound naturally occurring drug for the sequestered by the muscle cells. The tissue treatment of arrhytmia. concentration of Digoxin is about 15-30x higher  Route of delivery is by oral administration than plasma.  GIT absorption is complete and rapid for the sulfate.  One of the significant considerations in the  85% protein bound; eliminated by hepatic distribution of Digoxin is that if there’s slow release metabolism of tissue Digoxin (inside muscle) the half-life is Therapeutic Range 2.3 – 5 ug/ml extended more.  + ↓ Mg and K = potentiate the activity of Digoxin Toxic Range >5 ug/ml Half Life 6-8hrs  Hyperthyroid individuals = resistant to digoxin action quinidine sulfate and  Elimination is by renal filtration of the plasma free Common formulation quinidine gluconate form Peak Serum Level 8hrs after an oral dose  differs in peak serum lvl Half Life 38 hours (adult)  2 hours after an oral Toxic Level >2 ng/ml Peak serum level dose - sulfate Nausea, vomiting, visual  4-5 hours - gluconate disturbances, premature nausea, vomiting, abdominal Toxic Effects: contractions and Toxic Effects discomfort, cardiovascular atrioventricular node toxicity blockage PROCAINAMIDE Two commonly used cardiac glycosides Ex: Pronestyl, Procanbid, Procan Sr Digoxin (more  Sodium channel blocker commonly used) Digitoxin  Used to treat cardiac arrhythmia and Wolff- Onset Rapid Slower Parkinson White Syndrome Half life Short Longer  Oral administration is the common route TSL 0.5 – 2 ng/ml 9-25 ng/ml  GIT absorption is rapid and complete  Half – life – time required to reduce the drug to half  20% protein bound; eliminated by renal filtration and of its initial value hepatic metabolism  If half-life is shorter, it will readily reach the  Hepatic metabolite: N-acetyl procainamide therapeutic dose in its peak effect at (NAPA) shorter period of time.  As little as 200mg given intravenously may prove  TSL – specific level that needs to be in the blood fatal circulation/serum for the drug to take effect. TSL 4-8 ng/ml Half Life 4hrs Epidemiology Peak serum level 1 hour after the dose  Digoxin Toxicity is common (Incidence: 7-20%) Reversible lupus like syndrome o Patients who are taking Digoxin Toxic Effects (↑ANA), Nephrotic syndrome, beyond 2ng/ml they will exhibit toxic Urticaria 2  DISOPYRAMIDE (ex: Norpace) FLECAINIDE  Used to treat cardiac arrhythmias; used as a  highly potent drugs used only for serious substitute for quinidine ventricular arrhythmias that fail to respond to  Administered orally other medications and  GIT absorption is complete and rapid  Never in patients with a history of heart attack or  It binds to several plasma proteins congestive heart failure (bc the adverse effect of  Eliminated by filtration Flecainide is cardiac arrhythmia, cardiac arrest, and  It has anticholinergic effects = dry mouth and possible heart failure)  + constipation Works by decreasing Na entry into cardiac cells 3-5 ug/ml which causes prolongation of the cardiac action Therapeutic Range potential In Bishop: 3-7.5 ug/ml Toxic Range 10 ug/ml  Effects: Suppresses vigorous potentially dangerous Half Life 7hrs ventricular arrhythmias. bradycardia and atrioventricular  Digoxin levels should be reduced in conjunction Toxic Effects with flecainide. node blockage ALPHA BLOCKERS PROPANOLOL  Another group which has significant effect on the  A beta receptor blocking drug (Class II); used in the heart function and circulatory system activity. treatment of angina pectoris, hypertension,  Alpha receptors normally promote constriction of coronary artery disease. the arterioles.  Suppress the conversion of T4 to T3 = helpful in  Blocking constriction promotes dilation of vessels patients with thyrotoxicosis and lowers blood pressure as well as reducing the  Therapeutic Range: 50-100 ng/ml heart work in some situations.  Toxic Effect: bradycardia, arterial insufficiency  Alpha-blocking drugs also inhibit the actions of one (Raynauds type), pharyngitis, and platelet disorder of the adrenal hormones, norepinephrine, that for those given toxic dose of propanolol raise blood pressure as part of the fight-or-flight  Raynaulds type – have several episodes response. with blockage in the blood distribution on Generic names (trade names): doxazosin particular part of the body such as in (Cardura), prazosin (Minipress), fingers, toes, nose, and ears. This terazosin (Hytrin) blockage leads to insufficient blood supply,  Effects: They lower high blood pressure and may turning the body part into white → blue reduce the heart workload in heart failure. (cyanotic) → after few mins, there will be  Possible side effects: One major side effect of blood flow again (very reddish and almost alpha blockers is a drop in blood pressure when a have the feeling of burning). person stands up abruptly (orthostatic hypotension);  This is a phenomenon which last for few this can result in dizziness or fainting. mins and reverts back into normal circulation in that particular part. ACE INHIBITORS AMIODARONE (ex: Cordarone)  act to prevent production of a hormone,  It blocks potassium channels in the cardiac muscle. angiotensin II, which constricts blood vessels  Amiodarone blocks several channels (e.g., leading to vasodilation K+ and inactivated Na+ channels) and β-  They belong to the class of drugs called adrenoceptors. vasodilators—drugs that dilate blood vessels, an  An iodine containing drug which can cause effective way to lower blood pressure. hypothyroidism or hyperthyroidism Generic names (trade names): captopril  use for treatment of ventricular arrhytmias (Capoten), enalapril (Vasotec),  Therapeutic range: 1 – 2.5 ug/ml Lisinopril (Prinivil, Zestril)  Toxic effects: bradycardia, hepatitis photodermatitis  Effects: They dilate the blood vessels and improve  It is the most potent antiarrhythmic agent in use. the flow of blood, thus lowering high blood pressure,  Often effective when other drugs have failed, but relieving vascular muscle spasm, and reducing the should be used sparingly, as it causes serious side- workload of the heart. effects (e.g., photosensitivity, thyroid disorders,  Possible side effects: Common side effects are neuropathy, and pulmonary alveolitis). dizziness or weakness, loss of appetite, a rash,  Sotalol has both Class III and Class II (β-blocking) itching, a hacking, unpredictable cough, and actions, but lacks the side-effects of amiodarone, swelling. but has the side-effects of β-blockers. ANTIBIOTICS VERAPAMIL AMINOGLYCOSIDES  For treatment of angina, hypertension and Ex: Gentamicin, Tobramycin, Amikacin, supraventricular arrhythmias. Kanamycin, Neomycin, Streptomycin)  Verapamil blocks L-type Ca channels, especially on  Used for treatment of gram negative bacterial the AVN, where conduction is entirely dependent on infections Ca2+ spikes.  Administered IM or IV  Therapeutic range: 80- 400 ng/ml  Not well absorbed from the GIT (used only in an IN  Toxic effects (>400): hypotension, peripheral PATIENT setting) edema, ventricular fibrillation.  Eliminated by renal filtration  Ventricular fibrillation – heart rhythm  Half Life: 2-3hrs problem which has rapid and erratic heart  Toxic Range: rate/beat. This causes the ventricles to  >30 ug/ml (amikacin & kanamycin) quiver uselessly instead of acting the  12-15 ug/ml (gentamicin & tobramycin) actual action of pumping blood. 3  Toxic Effects: Nephrotoxicity & ototoxicity on 1 side only and spreads to the other (irreversible condition with impaired hearing and half of brain. This causes muscle stiffening balance) and face twitching/jerking of muscle act.  Cause damage to the 8th cranial nerve at  short term prophylatic agent in brain injury toxic levels (hearing loss)  phenytoin helps in preventing the loss of functional tissue in the brain VANCOMYCIN  It decreases sodium and calcim influx into Ex: Vancomycin HCl hyperexcitable neurons  glycopeptide effective against gram (+) cocci and  IV administered; GIT absorption is incomplete bacilli.  87-97% protein bound  It has a poor oral absorption; administered by IV  Eliminated by hepatic pathway infusion  Phenytoin is an inducer of MFO hepatic  Eliminated by renal filtration and excretion pathway; therefore, they might be  Only the trough level (lowest concentration of drug saturation of elimination pathway causing obtained in dosing interval) are monitored to ensure toxic effects when given a certain amount to serum drug concentration is within the 10-20 ug/ml therapeutic range Therapeutic range Toxicity is seen at the level of Toxic side effect occur in the the therapeutic range. Therapeutic Range therapeutic range (5-l0 ug/ml) >20 ug/ml Toxic Range  >10 ug/ml – nephrotoxicity 6-24 hrs Toxic Range Half Life  >40 ug/ml - ototoxicity Fosphenytoin (need to be Half Life 4-6 hrs Injectable proform metabolized to be active) red-man syndrome , initiation of seizures, teratogenic Toxic Effects Major Toxicity nephrotoxicity and ototoxicity action (cleft lip & palate) Other adverse RED MAN SYNDROME – erythemic flushing of Vitamin D and folate deficiency effect extremities VALPROIC ACID (ex: DEPAKENE)  used for treatment of petit mal (absence of seizure) and grand mal  Orally administered  GIT absorption is rapid and complete.  It is highly protein bound (93%)  Eliminated by hepatic metabolism CHLORAMPHENICOL  Hepatic dysfunction is observable which requires  Distributes to all tissues and it concentrates in the monitoring after 6 months of therapy. CSF  Therapeutic range: 50 -120 ug/ml  50% protein bound; rapidly absorbed in the GIT  Half Life: 11-17hrs  Toxic Effects: Blood dyscrasia, cytoplasmic  Toxic level: vacuolation (erythroid & myeloid cells)  120 ug/ml = nausea, lethargy & weight  Toxic Level: >25 ug/ml pain  >200 ug/ml = pancreatitis, hallucinations, ANTI-EPILEPTIC DRUG hyperammonemia  Involves conditions such as epilepsy, convulsions, and seizures which are prevalent neurologic CARBAMAZEPINE (ex: TEGRETOL) disorders.  Effective for the treatment of various seizure  AEDs are given as prophylactic agents. These are disorder taken regularly by patients who were prescribed  tricyclic compound chemically related to imipramine which such drugs.  The antiepileptic action similar to phenytoin. PHENOBARBITAL  It has a serious toxic effect and not frequently used Ex: Luminal, Solfoton  70-80% protein bound; eliminated by hepatic  long acting barbiturate that controls several types of metabolism seizures Therapeutic Range 50-120 ug/ml  Used for treating withdrawal symptoms in infants Toxic Range >150 ug/ml (hematologic born to opiate or barbiturate addicted mothers dyscrasias, aplastic anemia)  Used to treat cases of congenital hyper Half Life 10-20 hrs bilirubinemia, since this drug enhances bilirubin  unpredictable and not metabolism. explained in pharmacologic  Absorption is slow but complete; 50% protein bound property of particular drug.  Eliminated by hepatic metabolism and renal Idiosyncratic effects These effects may occur function; renal impairment slows down even at therapeutic dose. elimination process.  rashes, leukopenia, nausea, Inactive form Primidone (mysoline) vertigo, febrile reactions Half life 70-100 hrs Peak Serum Level 10 hours after an oral dose ETHOSUXIMIDE (ex: ZARONTIN) Therapeutic range 20-40 ug/ml  The drug of choice for controlling petit mal (absence) seizure. PHENYTOIN (ex: DILANTIN)  Orally administered  controls seizures (tonic-clonic, simple partial  It is free in serum and not protein bound seizures) Therapeutic Range 40-100 ug/ml o Tonic-clonic – type of seizures which Toxic Range >100 ug/ml begins either on both sides of the brain or Half Life 40-60 hrs 4  GI disturbances, ataxia, SLE,  Organs such as heart, liver and pancreas require Toxic effects aplastic anemia, pancytopenia high dosage (300 mg/ml)  Eliminated by hepatic metabolism GABAPENTIN (ex: NEURONTIN) Therapeutic level 100-300 ng/ml  Chemically similar to neurotransmitter Gamma Toxic Range 350- 400 ng/ml aminobutyric acid (GABA) Half Life 17-40 hrs  Used for partial seizures, adjunctive therapy drowsiness, blurred vision, (means taking other medications or monotherapy) Toxic Effects memory loss, seizure, cardiac  Administered orally; it is unbound to plasma arrhythmia proteins Major metabolite Desipramine & Nortriptyline  Excreted unchanged in urine, not metabolized by humans FLUOXENTINE (PROZAC)  Therapeutic Levels: 2-15 ug/ml  Blocks the reuptake of serotonin in central  Half Life: 5-9hrs serotonergic pathways.  Adverse Effects: Dizziness, ataxia, fatigue and  Also used for treatment of obsessive- nystagmus (involuntary eye movement) compulsive disorders  Therapeutic Level: 90-300 ng/ml FELBAMATE (ex: FELBATOL)  Toxic effects (>300ng/ml): attempted suicide,  Indicated for use in severe epilepsies → mixed decreased libido and sexual function seizure disorder, Lennox-Gastaut Syndrome, adults with refractory epilepsy CLOZAPINE (ex: CLOZARIL, FAZACLO)  Administered orally – complete absorption by GIT  Antipsychotic – tx refractory schizophrenia (type of  Eliminated by renal and hepatic metabolism illnesses in which the condition is treatment  Therapeutic dose: 30-60 ug/ml resistant; does not respond to previous tx)  Half Life: 14-22 hrs (may change depending on the  Therapeutic dose: 350-420ng/ml other AED taken by patient aside from Felbamate)  Half Life: 8-16hrs  Phenobarbital, primidone, phenytoin, carbamazepine = enzyme inducers which OLANZAPINE (ZYPREXA) cause ↓ half life  Thienobenzodiazepine derivative  Toxic effects: fatal aplastic anemia & hepatic failure  Tx for schizophrenia, acute manic episodes, and recurrence of bipolar disorders Other Anti-epileptic Drugs  Can be administered as fast-acting IM injection but - used for partial and generalized seizures it is more commonly administered orally  Therapeutic range: 200-50ng/ml  Half Life: 21-54hrs  Adverse effects: tachycardia, decreased consciousness, possible coma IMMUNOSUPPRESSIVE DRUGS  Of clinical significance for patients who have undergone organ transplant  No therapeutic dose because the therapeutic range for immunosuppressive drugs depend on the organ which is transplanted and the time after transplantation. PSYCHOACTIVE DRUG CYCLOSPORINE Ex: Gengraf, Neoral, Sandimmune LITHIUM  Inhibits cellular immune response by blocking  Used for treatment of manic depressive illness production of IL-2 which is responsible for (bipolar disorder) regulating immunity and WBC activity  Drug of choice for the prevention of chronic cluster  Used to prevent rejection of allogeneic organ headache. transplants and for suppression of GVHD  cationic metal that does not bind to proteins  Orally administered and eliminated by hepatic  Inhibits thyroid hormone synthesis & release metabolism (inhibits Iodine uptake)  Heart, liver and pancreas require high dosage (300  Orally administered; complete,rapid GIT absorption ng/ml)  Eliminated thru renal filtration  Specimen of Choice: Whole blood  Therapeutic range : 0.8 - 1.2 mmol/L  Toxic Range: 350-400 ng/ml  Half Life: 10-35 hrs  Half Life: 12hrs  Toxic level:  Toxic Effects: Renal tubular and glomerular  1.2–2.0 mmol/L= apathy, lethargy, speech dysfunction → hypertension difficulties  >2 mmol/L = seizures, muscle rigidity, TACROLIMUS coma, renal impairment, and Ex: Astragaf, Envarsus, Necoria, Progaf hypothyroidism  It is 100x more powerful than cyclosporine. TRICYCLIC ANTIDEPRESSANTS (TCA)  Orally administered but GIT uptake is variable Ex: Imipramine, amitriptyline, doxepin,  Eliminated by hepatic metabolism nortriptyline, trazadone  Half Life: 10-12hrs  Elevated levels are seen in cholestasis  1st three are the most relevant TCA  High levels is associated with thrombus formation  Used for the treatment of depression, insomnia, extreme apathy and loss of libido.  Adverse effect: anemia, leukopenia,  orally administered with 5-50% absorption thrombocytopenia and hyperlipidemia 5  RAPAMYCIN (SIROLIMUS) ANTI INFLAMMATORY DRUGS  Antifungal agent with immunosuppressive activity →  Belongs to a group called Non-Steroidal anti- used to prevent graft rejections → kidney inflammatory drugs (NSAIDS) which as the term transplants implies prevent/retard the inflammatory process  Similar to tacrolimus  Commonly administered with cyclosporine and ANTI-INFLAMMATORY AND ANALGESIC DRUGS tacrolimus 1.SALICYLATES/ ASPIRIN (ACETYLSALICYLIC  Eliminated by hepatic metabolism ACID)  Half Life: 62hrs  common used analgesic, antipyretic and anti-  Major side effects: lipid abnormalities, inflammatory drug. thrombocytopenia, anemia, leukopenia, & infections  has an anticoagulant property – antiplatelet activity. MYCOPHENOLATE MOFETIL (ex: Myfortic)  It is a direct stimulator of the respiratory system  Rapidly converted in the liver to Mycophenolic and inhibitor of the Krebs cycle. acid Therapeutic lvl 5 mg/dL  Supplemental therapy with cyclosporine and Decreases thromboxane and tacrolimus Function prostaglandin formation thru inhibition  Decreases renal allograft rejection of cyclooxygenase  Half Life: 17hrs Side effects GI disturbances, interference with LEFLUNAMIDE platelet aggregation  Inhibits lymphocyte proliferation; for treatment of Mixed acid base disturbance rheumatoid arthritis Toxic effects (metabolic acidosis and respiratory (>30mg/dL) alkalosis), hypoglycemia, and Reye ANTI-NEOPLASTIC Syndrome  Drugs to prevent/inhibit the development of  Trinder assay (using ferric nitrate neoplasm or tumor (+) colored complex)  The assessment of therapeutic benefit and toxicity Method for  Enzymatic assay using salicylate of majority of anti-neoplastic drugs is not readily testing hydroxylase aided by therapeutic monitoring because the  HPLC correlation between the plasma concentration and  EMIT therapeutic benefits is hard to establish. Because, it  Reye Syndrome – w/ unknown origin affecting the will vary acc. to the type of neoplasm the patient liver causing the body to produce very high has. ammonia level. Patients with this syndrome had METHOTREXATE (ex: Otrexup, Rasuvo) viral infection during childhood such as mumps and  Also an immunosuppressive agent measles treated with aspirin.  Inhibits DNA synthesis in all cells by blocking ACETAMINOPHEN (ex: Tylenol) dihydrofolate reductase  commonly used as analgesic and antipyretic drug  Leucovorin is used to reverse action of which is used to treat fever, headache and mild to methotrexate moderate myalgia and athralgia.  Methotrexate dose followed by Leucovorin  Overdosage of this drug leads to hepatoxicity bc the neoplastic cell proliferate rapidly. (Acetaminophen is the most potent) What should happen? Reference method HPLC  The DNA synthesis will be most affecting Maximum dose 4gms daily the anti-neoplastic cell and after inhibition Metabolite of of DNA synthesis, we will be reversing the Glucoronide and Sulfate acetaminophen action thru Leucovorin conjugates produced by the liver:  Half Life: 5-9hrs within 2-3 hrs after  Therapeutic range for trough specimen: 20 mg/ml Half Life 3-8 hrs Insomnia, tachycardia, seizures, Adverse Effects arrhythmias, cardiorespiratory arrest 6  NEUROLEPTICS (ANTIPSYCHOTIC MAJOR TRANQUILIZER) Ex: Risperdal, Olonzapine ( Zyprexa), Quetiapine ( seroquel), Aripiprazole (abilify)  Neuroleptics – block the action of dopamine and serotonin in the limbic system.  2 classes:  Phenothiazines (chlorpromazine)  Butyrophenones (haloperidol)  Toxic effects: cholestasis, orthostatic hypotension, aplastic anemia, muscle rigidity Sample Collection  Serum or plasma – specimen of choice  Timing of Specimen collection: the single most important factor in TDM  Trough concentrations are drawn right before the next dose.  Peak concentration is drawn one hour after an orally administered dose (except digoxin). Methods 1. Immunochemical Methods/Immunoassays  Provides rapid analyses of blood and urine samples.  It can detect drug levels in the nanomolar ranges: sensitive and specific  Examples: EMIT and Flourescence Polarization Immunoassay (FPIA) 2. TLC 3. HPLC 4. GC-MS – gold standard for quantitation of many drugs 7