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CCHM322- Finals LEC - Lecture notes
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Clinical Chemistry 2 (MDT 3122L)
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Our Lady of Fatima University
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WEEK 13 | ENDOCRINOLOGY V
Reproductive Hormones and Other Miscellaneous Hormones Testosterone
- It is considered as the principal and the most potent androgen hormone.
- It is considered as the Principal and the most potent androgen hormone.
- Synthesized by the Leydig Cells of the testis of the male, derived from hormone progesterone.
- Controlled by gonadotropin (it pertains to the FSH and LH and luteinizing hormone). → this are the hormones produce from the pituitary gland.
- Function: o It is very important from the growth and development of the reproductive system (prostate and external genetalia, just like with the other hormones. o Testosterone also exhibits circadian rhythm.
- Levels demonstrate a circadian pattern and peak at (8am) and fall to their lowest level at 8pm.
- There is gradual reduction of testosterone after age 30 with an average decline of 110ng/dL every decade of life.
- Test for male infertility: Includes the seminalysis, FSH and LH measurement.
- Reference Values: 3.9-7 ng/mL (serum)
- Transport proteins
- Sex hormone binding globulin (SHBG) – 60% of the testosterone.
- Albumin – 40% of the testosterone.
- Concentration determines the level of testosterone into the circulation. Types of Testicular Infertility
- Pretesticular Infertility (Secondary Hypogonadism)
- Due to hypothalamus or the pituitary
- Testosterone, FSH, LH – normal or decrease in this condition.
- Testicular Infertility (Primary Hypogonadism)
- Problem is in the testicles
- May be congenital (cryptorchidism, Klinefelter’s syndrome and 5-a-reductase deficiency) or acquired (varicocele, tumor, orchitis). o Cryptorchidism – the absence of one or both of the testis from the scrotum. o Klinefelter’s syndrome (XXY syndrome) – the male develops a female features like weaker muscle, greater height, poor coordination, less body hair, small genitals, and breast growth/development. o 5 - a-reducatse deficiency – male have a genetalia that appears female. o Varicocele – the enlargement of the vein into a scrotum o Orchitis – the inflammation of the testicles.
- Decreased testosterone levels and increase FSH and LH
- Posttesticular Infertility
- Due to disorders of sperm transport and function.
- Testosterone, FSH, and LH – normal. Other Disorders of Sexual Development Testicular Feminization Syndrome
- Most severe form of androgen resistance syndrome, resulting in lack of testosterone action in the target tissue.
- Physical development pursues the female phenotype, with fully developed breast and female distribution of fat and hair.
- Patient has also utility or response to the administration of synthetic/exogenous testosterone.
- Lab tests: Normal levels of testosterone with elevated level FSH and LH. Sertoli Cell – Only Syndrome
- Characterized by lack of germ cells or sperm cells.
- Men present with small testes, high FSH levels, azoospermia (semen that lacks the sperm cell), and normal testosterone level.
- Testicular biopsy is the only procedure to confirm this diagnosis. Kallmann’s Syndrome
- A result of an inherited, X-linked recessive trait that manifests as hypogonadism during puberty and the impaired sense of smell. Dehydroepiandrosterone DHEA
- The principal androgen formed by the adrenal cortex of the adrenal gland.
- It is not produced by the gonads.
- Valuable in the assessment of adrenal cortical hormones. Estrogen
- Arises through structural alteration of the hormone testosterone molecule.
- Is arise from the male hormone
- Function:
- In conjunction with progesterone, they function in uterine growth and regulation of menstrual cycle and maintenance of pregnancy.
- Deficiency: Irregular and incomplete development of the endometrium (is the area for the implantation of the fertilized egg).
- Precursor: Cholesterol, acetate, progesterone and testosterone.
- Forms: Estrone E1, Estradiol E2, Estriol E A. Estrone (E1)
- It is the most abundant estrogen in postmenopausal women. B. Estradiol (E2)
- The most potent and the major estrogen secreted from the ovary.
- Synthesized from testosterone, then diffuses out of the thecal cells of the ovaries of the female.
- Precursor of both E1 and E3 – serves as negative feedback for Follicle Stimulating Hormone (FSH). → an increase with E2 will cause the inhibition from secretion of the FSH.
- Used to assess ovarian function.
WEEK 13 | ENDOCRINOLOGY V
- Transport proteins: o Albumin – 60 % of the E2 are bound to it. o SHBG – 3 8% of the E2 is bound to it. o Free form – 2% (remaining) C. Estriol (E3)
- Estrogen found in the Estradiol (E2)
- Major estrogen secreted by the placenta during pregnancy
- It is also the form of the estrogen that is found in maternal urine.
- Its formation in the pregnant women is dependent on the fetal and placental function.
- Used to assess the fetoplacental unit (________), postdate gestations and intrauterine retardation.
- Used as marker for Down Syndrome together with the HCG, Inhibin A, Alpha-fetoprotein (AFP)
- Preferred specimen: Plasma Progesterone
- Produced by the granulose (lutein) cells of the corpus luteum in the female.
- Dominant hormone responsible for the luteal phase cycle among females.
- It is considered as the single best hormones to determine whether the ovulation has occurred or the female is fertile.
- Primarily for the evaluation of fertility in female.
- Deficiency: Failure of implantation of the embryo.
- Metabolites: Pregnanediols, Pregnanediones, Pregnanelones Test for Menstrual Cycle Dysfunction and Anovulation
- Estrogen
- Progesterone
- Follicle Stimulating Hormone (FSH)
- Luteinizing hormone Test for Female Infertility
- HCG
- PRL
- FT
- TSH
- FSH
- LH
- Estradiol
- Progesterone Pancreas
- A digestive gland in the gastrointestinal system.
- Considered both as an exocrine and endocrine gland
- Functions:
- Exocrine: o Responsible for the synthesis of digestive enzymes (amylase and lipase). o Acinus: functional secretory unit as an excrone gland.
- Endocrine: o Responsible for the synthesis o Alpha cells (20-30%) – glucagon o Beta cells (60-70%) – insulin o Delta cells (2-8%) – somatostatin o All of the is in the islets of Langerhans Human Chorionic Gonadotropin
- Produced by the trophoblast cells of the placenta.
- Serves to maintain progesterone production by the corpus luteum in the early pregnancy.
- Can be detected 2 - 3 days after ovulation.
- Qualitative test for urine samples has detection limit about 50 mIU/mL (used as a basis for pregnancy test kits)
- Method: Immunometric (sandwich) method Human Placental Lactogen
- Functionally, structurally and immunologically similar to growth hormone and prolactin.
- Stimulates the development of the mammary glands specially during lactation.
- Increases maternal plasma glucose level and promotes positive nitrogen balance.
- Important in the diagnosis of intrauterine growth retardation. Gastrin
- A peptide secreted by the stomach.
- Released in response to Beagle stimulation (or the stimulation to the Vagus nerve) and presence of food in the stomach.
- Causes secretion of the hydrochloric acid (HCL by the parietal cells into the stomach.
- Diagnostic marker for Zollinger-Ellison Syndrome (ZES) → is a disease in which tumors causes the stomach to produce too much acid resulting to peptic ulcer.
- Major stimulus: Presence of amino acids.
- Increased levels: ZES, Achlorhydria (the absence of the stomach acid), Chronic Renal Failure (gastrin is basically secreted into the urine also). Gastric Fluid Acidity
- G Cells – produces the gastrin which stimulates the parietal cell
- Parietal Cells – produces the Hydrochloric acid (HCL) and the intrinsic factor (it is needed for the B absorptions.
- Chief Cells – produces the pepsinogen (Pepsinogen is converted to pepsin by gastric acid. Pepsin is very important for the breakdown of protein into smaller peptides). Serotonin (5 hydroxytryptamine)
- An amine derived from hydroxylation and decarboxylation of amino acid tryptophan.
- Synthesized by argentaffin cells, primarily in GI tract.
- Also found in high concentration in pineal gland and CNS.
WEEK 14 | TOXICOLOGY
Toxicology
- Study of the toxic substances or poisons.
- Study of the adverse effects (bad effects) of xenobiotics in humans.
- Xenobiotics – are substances that are not producing the body but may enter into a biochemical reaction that happening in the body. (chemicals, drugs) Five Major Disciplines of Toxicology
- Mechanistic Toxicology
- Cellular and biochemical effects of toxins.
- Mechanism it is also the study of the specific mechanism on how a toxin causes damage to the body.
- Provide a basis for rational therapy design and the development of tests to assess the degree of exposure of poisoned individuals.
- Descriptive Toxicology
- Uses the results from animal experiments to predict what level of exposure will cause harm in humans (risk assessment).
- Regulatory Toxicology
- Both the principle of Mechanistic and Descriptive Toxicology is used in the regulatory toxicology.
- Involves the interpretation of the combined data from mechanistic and descriptive studies.
- Is used to establish standards that define the level of exposure that will not pose a risk to public health or safety.
- Ex: agency of the government which uses the principle of the regulatory toxicology is the Food and Drug Administration (FDA) – this agency is the one that tell us what is the allowable level of certain chemicals or substance into a commodity that meant for human used or consumption.
- Forensic Toxicology
- Primarily concerned with the medicolegal consequences of toxin exposure.
- The result in forensic toxicology when we used as a evidence in a trial court.
- Focuses on establishing and validating the analytic performance of the methods used to generate evidence in legal situations, including the cause of death.
- Suspecting heavy metal poisoning.
- Used this to know the exact cause of death.
- SOCO – used this type of toxicology
- Clinical Toxicology
- Specific perform in the laboratory.
- The study of interrelationships between toxin exposure (lead) and disease state (Microcytic hypochromic anemia, basophilic stippling).
- Emphasizes not only diagnostic testing but also therapeutic intervention. Environmental Toxicology
- It is the study of the pollutants to the air, soil, water.
- DENR – used this type of toxicology
- Includes the evaluation of environmental chemical pollutants and their impact on human health. Exposure to Toxins
- 50% - intentional suicidal attempt
- 30% of cases – accidental exposure
- 20% - homicide or occupational exposure (industrial company, agricultural) Routes of Exposure
- Toxins can enter the body via several routes: o Ingestion o Inhalation o Transdermal absorption
- Mechanism of Absorption of toxins from the gastrointestinal tract o Taken up by processes intended for dietary nutrients. o Absorbed by passive diffusion. Terminologies
- Acute toxicity - single, short-term exposure to toxins. (Accidental exposure)
- Chronic toxicity - repeated exposure for extended period of time. (Occupational exposure)
- Toxic Dose 50 (TD50) - the dose that would be predicted to produce a toxic response in 50% of the population
- Lethal Dose 50 (LD50) - the dose that would predict death in 50% of the population
- Effectivity Dose 50 (ED59) - the dose that would be predicted to be effective or have therapeutic benefit in 50% of the population Dose-Response Relationship Table 30 - 1 Toxicity Rating System Toxicity Rating Lethal Oral Dose in Average Adult Super toxic <5 mg/kg Extremely toxic 5 - 50 mg/kg Very toxic 50 - 500 mg/kg Moderately toxic 0-5 g/kg Slightly toxic 5 - 15 g/kg Practically toxic >15 g/kg Adapted with permission from Klaassen CD. Principles of toxicology. In Klaassen CD, Amdur MO, Doull J, eds. Toxicology: the basic science of poisons. 3 rd ed. New York: Macmillan, 1986: Analysis of Toxic Agents
- Select the best specimen for selected test o You cannot measure mercury to used urine o You cannot detect arsenic through the blood o Anticoagulant used: Royal Blue top tube and Tan Top tube (used for the lead determination)
- Specimen collection, handling, and storage
- Two-step analysis of toxic agents analysis
- Screening Test
- Rapid, simple, and qualitative test
- Very sensitive, it is not specific
- Immunoassays, TLC
- Confirmatory Method
- GC-MS
WEEK 14 | TOXICOLOGY
• ICP-MS
• AAS
- Sample: saliva, urine, hair, nail and blood Toxic Agents 1. Alcohol
- One of the commonly abuse toxic agent
- Alcohol absorption is 3x slower in full stomach
- Expressed in proof – pertains to the amount of alcohol into a solution. (Ex: 80 proofs → it contains 40% alcohol; divided by 2) a. Ethanol (Grain Alcohol) b. Methanol (Wood Alcohol) c. Isopropanol (Rubbing Alcohol) d. Ethylene glycol (1,2-ethabediol)
- CNS depressant - > 50 mg/dL Blood alcohol level
- Causes: Disorientation, confusion, and euphoria, which can progress to unconsciousness, paralysis, and, with high-level exposure, even death.
- Symptoms of intoxication begin when the concentration is > 0% w/v. Alcohol 𝐴𝑙𝑐𝑜 → ℎ𝑜𝑙 𝑑𝑒ℎ𝑦𝑑𝑟𝑜𝑔𝑒𝑛𝑎𝑠𝑒 Aldehyde 𝐴𝑙𝑑𝑒 → ℎ𝑦𝑑𝑒 𝑑𝑒ℎ𝑦𝑑𝑟𝑜𝑔𝑒𝑛𝑎𝑠𝑒 Acid Table 31 - 2 Common Indicators of Ethanol Abuse Test Comments GGT Gamma-glutamyl transferase
- Marker for occult alcoholism
- Increases can be seen before the onset of pathologic consequences.
- Sensitive GGT
- Increases in serum, activity can occur in many non-ethanol- related conditions
- Non-specific, sensitive AST Aspartate Aminotransferase
- Increases in serum activity can occur in many non-ethanol- related conditions
- Non-specific AST/ALT ratio Aspartate Aminotransferase/Alanine Transaminase
- A ratio of greater than 2 is highly specific for ethanol- related liver disease
- De ritis ratio >2 → indicates alcoholic hepatitis HDL High-density Lipoprotein High serum HDL is specific for ethanol consumption MCV Mean cell Volume Increased erythrocyte MCV is commonly seen with excessive ethanol consumption Increases are not related to folate or vitamin 𝐵 12 deficiency GGT, γ-glutamyl transferase; AST, aspartate aminotransferase; ALT, alanine aminotransferase; HDL, high-density lipoprotein; MCV, mean cell Volume.
- Ethanol/Grain Alcohol
- Used to make alcoholic beverages
- Most common substance of abuse (to the entire toxic agent)
- Ethanol is considered a toxic agent
- Ethanol abuse causes acidosis – accumulation of ketones and lactate
- Causes diuresis → suppressed ADH
- Hangover symptoms are due to the effect of acetaldehyde.
- 80 mg/dL – is the statutory limit for the operation of the motor vehicle
- 50 g/day for 10 years – will lead to accumulation to the hepatocytes, which may lead to alcohol hepatitis. Ethanol 𝐴 →𝑙𝑐𝑜 ℎ𝑜𝑙 𝐷𝑒ℎ𝑦𝑑𝑟𝑜𝑔𝑒𝑛𝑎𝑠𝑒Acetaldehyde𝐴𝑙𝑑𝑒 → ℎ𝑦𝑑𝑒 𝐷𝑒ℎ𝑦𝑑𝑟𝑜𝑔𝑒𝑛𝑎𝑠𝑒 Acetic Acid
- Methanol/Wood Alcohol
- Commonly used solvent and a contaminant of homemade liquors.
- Ex: Lambanog
- Fatal Dose: 60 - 250 mL
- Formic Acid – is very toxic, cause severe acidosis (lead to death), causes optic neuropathy (blindness) Methanol 𝐴𝑙𝑐𝑜 → ℎ𝑜𝑙 𝐷𝑒ℎ𝑦𝑑𝑟𝑜𝑔𝑒𝑛𝑎𝑠𝑒 Formaldehyde →? Formic Acid
- Isopropanol/Rubbing Alcohol
- Metabolized by hepatic ADH to acetone, which is its primary metabolic end product.
- Intoxication with isopropanol, may result in severe acute-phase ethanol-like symptoms that may persist for an extended period.
- Fatal Dose: 250 mL
- Ethylene Glycol
- Common component of hydraulic fluid and antifreeze agent of automobile colling system.
- Sweet taste
- Final product leads to deposition of CaOx in renal tubules (Appearance: envelope shape)
- Fatal Dose: 100 g Ethylene glycol → Oxalic and Glycolic Acid Ethanol Determination
- Laboratory Analysis o Specimen – serum, plasma and whole blood o SpSealed specimens can be refrigerated or stored at room temperature for up to 14 days without loss of ethanol. o Nonsterile specimens – should be preserved with sodium fluoride/oxalate. o Lab Test – elevated GGT, AST, AST/ALT ratio, HDL and MCV ▪ GGT ▪ AST – liver enzyme ▪ AST/ALT ratio – De ritis ratio ▪ HDL and MCV - increased o Method: Ethanol + NAD → Acetaldehyde + NADH ▪ Enzymatic (uses non-human ADH which oxidizes ethanol to acetaldehyde with reduction of NAD to NADH @340 nm)
WEEK 14 | TOXICOLOGY
o Lead poisoning can also cause basophilic stippling and microcytic hypochromic anemia.
- It has characteristic “wrist drop or foot drop” manifestation → affect nerve conduction
- Effects of Lead o Acute Exposure – Abdominal or neurological symptoms manifest. o Neurological symptoms – encephalopathy characterized by a cerebral edema and ischemia. o Severe lead poisoning can result in stupor, convulsions, and coma. o CDC cut-off for normal level of lead in children: <10 ug/dL. o Hard tissue – half-life is 20 years o Soft tissues – half-life is 120 days
- Treatment: EDTA and Dimercaptosuccinic acid binds to lead
- Toxicity Dose: > 0 mg/day
- Fatal Dose: 0 g
- Toxic Blood Levels: >70 ug/dL (definitive)
- Samples: Whole blood (used for quantitative testing), urine (used for recent lead poisoning) and hair
- Serum and plasma – are not advisable
- Indicators of Lead Toxicity o Urinary D-ALA o Free RBC porphyrin o Presence of Basophilic Stippling in RBC (also seen in arsenic poisoning)
- Tests o Graphite Furnace AAS o Inductively Coupled Plasma Emission Spectrophotometry (ICPS) o Anodic Stripping Voltammetry o Zinc protoporphyrin or free RBC protoporphyrin test Mercury
- Found in glass thermometer
- Have the ability to amalgamate – merge to other substance
- Dental amalgam – made up of mercury
- Binds with protein and also an enzyme inhibitor
- Exists in three forms: o Elemental (liquid) o Inorganic salts o Component of organic compounds
- Inorganic mercury – tachycardia, tremors, thyroiditis, and, most significant, a disruption of renal function
- Organic mercury – neurologic symptoms o Low levels of exposure cause tremors, behavioral changes, mumbling speech, and loss of balance. Higher levels of exposure result in hyporeflexia, hypotension, bradycardia, renal dysfunction, and death. o There is a mercury in predatory fish
- Sample for Testing: o Whole blood (organic mercury) – AAS o Urine (inorganic mercury) – anodal stripping voltammetry
- Method for Testing: o Reinsch Test – also used for arsenic
- Significant Exposure: >50 ug/dL (whole blood) Pesticides
- Organophosphates and carbamates function by inhibition of acetylcholinesterase – is a neurotransmitter into the CNS and PNS which is very important for the movement and muscle contraction.
- Also include insecticides and rodenticides
- Low levels of exposure are associated with salivation, lacrimation, and involuntary urination and defection
- Higher levels of exposure result in bradycardia, muscular twitching, cramps, apathy, slurred speech, and behavioral changes. Death due to respiratory failure may also occur.
- Method: o Evaluation or erythrocytic acetylcholinesterase activity o Measurement of serum pseudocholinesterase (markers or insecticide and pesticide poisoning).
WEEK 15 | DRUGS OF ABUSE
Drugs of Abuse
- In drug will become a drug of abuse when is used in consistently with its medical purpose.
- Example: The drug is meant to be used as a treatment for insomnia.
- The problem of the drug of abuse it can cause addiction and it cause dependence (physical and psychological dependence).
- When you try stop using these drugs, tendency you will experience withdrawal syndrome and it may also cause physiologic changes. Physical Dependence
- Those are the changes that occur in the body after repeated used of the dangerous drugs. Factors Affecting the Withdrawal Syndrome
- The drug being used (it will depend upon the drug that you are using)
- The dose and route of administration (depends on how you administer the drug into the body; different route of administration by inhalation, smoking, intravenous, or ingestion)
- Concurrent use of other drug (with highly addictive individuals they are not contented in one drug; they combine it with other drugs; and it is toxic)
- Frequency and duration of drug use (the symptoms the adverse effects are proportional to the duration of the drug used)
- The age, sex, health and genetic make - up of the user (tolerance of the person into that drug; how to absorbed the drugs into his body)
- Symptoms: you cannot sleep if you don’t intake the drugs, sudden weight or weight/loss gain, irritability Psychological Dependence
- Much last longer
- Primary reason of relapse
- Cause of addiction
- Among the drug addicts one of the most important activities in their day is taking drugs. “I never knew I was addicted until I tried to stop” - unknown Five Classes of Drugs
- Narcotics
- Depressants
- Stimulants
- Hallucinogens
- Anabolic Steroids
- Some of the effects of the dangerous drugs: Some of these drugs will change your mood, thought, feelings. Some will alleviate your pain, anxiety, and even depression. Some will induce sleep or even some will energize you. “Drugs take you to hell, disguised as heaven”
- Donald Lynn Frost
- Narcotics
- Also known as opioids same with opiates.
- Refers to opium, opium derivatives and their synthetic substitute
- Examples: o Heroin o Oxycontin o Vicodin o Codeine – anti-tussive drug o Morphine – powerful analgesic; pain reliever o Methadone – used as a treatment for migraine, and pain reliver Poppy or Papaver somniferum
- Natural source of opiods
- Source of all the natural opium Opiates
- Capable of analgesic (responsible to insensibility pain), sedation (make you relax of calm) and anesthesia (it will cause of loss of sensation)
- Derived chemically from opium poppy.
- Naturally Occurring Opiates: opium, morphine and codeine
- Chemically Modified Opiates/semi-synthetic opiates: heroin, hydromorphone and oxycodone (Percodan)
- Common Synthetic Opiates: meperidine (Demerol), methadone (Dolophine), propoxyphene (Darvon), pentazocine (Talwin)
- Morphine and meperidine increase liver and pancreatic enzyme. (They affect the functioning of two organs)
- Major cause of drug related death intake of Darvon and Alcohol.
- Major metabolites of heroin: N-acetylmorphine and morphine
- Antagonist for opiate overdose: Naloxone or Narcan.
- Toxic effects: respiratory acidosis, myoglobinuria, cardiopulmonary failure and constriction of pupils
- Withdrawal effects: tremor, muscle cramp, nausea, vomiting and diarrhea Heroin
- Highly addicted drug and it is the most rapid acting of its.
- It is the metabolites of morphine
- Common names – Big H, Black Tar, Chiva, Hell Dust, Horse, Negra, Smack and Thunder Effects on the Mind Effects on the Body Overdose Effects
WEEK 15 | DRUGS OF ABUSE
Easing Powder, God’s Medicine, Hops, Midnight oil, Joy plant, Zero, Toys and Toxy
- In China, they had opium war, start in the trading of China and Great Britain. China exported tea. Introduce the opium to China in exchange for the tea. Effects on the Mind Effects on the Body Overdose Effects
- Euphoria
- Relaxation
- Relief of pain
- Constipation
- Dry mouth and mucus membrane
- Slow breathing
- Seizure
- Dizziness
- Weakness
- Loss of consciousness
- Coma
- Death Oxycodone
- Common names - Hillbily heroin, Kicker, Oc, Ox, Roxy, Perc, Oxy
- Origin o Synthesize from thebaine, a constituent of the poppy plant (is a minor constituent of the opium and it has a stimulatory effect)
- Is a semi-synthetic narcotic Effects on the Mind Effects on the Body Overdose Effects
- Euphoria • Pain relief
- Sedation
- Respiratory Depression
- Constipation
- Pupillary constriction
- Cough suppression
- Can cause liver damage with Acetaminophen
- Extreme drowsiness
- Muscle weakness Confusion
- Cold and clammy skin
- Pinpoint pupils
- Shallow breathing
- Slow heart rate
- Fainting
- Coma
- Death
- Stimulants/Uppers
- Will increase your alternes and energy
- Amphetamines
- Methylpenidate
- Diet aid
- Methamphetamines
- Cocaine
- Methcathion Amphetamines
- Common names - Bennies, Black beauties, Crank, Ice, Speed and Uppers
- Origin o First marketed as Benzedrine (is a nasal decongestant)
- Acacia berlandieri - source of amphetamines
- Used for treating nasal congestion, sleeping disorder, narcolepsy, ADHD
- Manifestation: heighten mental and physical activity, euphoria
- Low level intake: dryness of the mouth, dizziness, blurred vision, excessive speech, insomnia
- Excessive intake: dilusion, hallucination, panic state and psychosis (detachment from the reality)
- Withdrawal: depression, parasomnias abnormal disruption of sleep), extreme appetite
- Method: Immunoassay and Gas chromatography
- It can be passed by breastfeeding/breast milk Effects on the Mind Effects on the Body Overdose Effects
- Similar to cocaine
- Psychosis similar to Schizophrenia
- Paranoia
- Auditory and visual hallucination
- Increased blood pressure and pulse rate
- Insomia‘
- Loss of appetite
- Physical exhaustion
- Agitation
- Increased body temperature
- Hallucination
- Convulsion
- Death Cocaine
- Common names - Coca, Coke, Crack, Flake, Snow and Sod Cot
- Is a CNS stimulant, that may cause excitement and euphoria
- It is also used as local anesthetic
- Erythroxylon Coca - natural source of Cocaine
- Before, the coke they really have Cocaine. They really include Cocaine as one of the main ingredients.
WEEK 15 | DRUGS OF ABUSE
- Can cause sudden death due to direct toxicity on myocardium (muscle part of the heart and it is the thickest heart of the heart that may lead to Acute myocardial infraction)
- Overdosage may result to violent behavior
- Inhibitor: Prozac – is an anti-depressant drug
- Treatment: Benzodiazepine
- Toxic Effects: hypertension, arrythmia, seizure, and myocardial infarction
- Urine metabolites: Benzoylecgonine
- For single use, it can be detected in urine for 3 days, up to 20 days for chronic users Effects on the Mind Effects on the Body Overdose Effects
- Euphoria
- Alertness
- Excitation
- Irritability
- Anxiety
- Paranoia
- Physical and mental exhaustion
- Addiction
- Increased blood pressure and heart rate
- Dilated pupils
- Insomnia
- Loss of appetite
- Cardiac arrhythmia
- Ischemic heart condition
- Sudden cardiac arrest
- Convulsion
- Stroke
- Death Khat
- Common names - Abyssinian Tea, African Salad, Catha, Chat, Kat, Oat
- Origin o From flowering evergreen shrub (sources of the Khat) o East Africa o Arabian Peninsula
- Active components of the Khat o Cathine o Cathinone Effects on the Mind Effects on the Body Overdose Effects
- Hallucination
- Paranoia
- Nightmares
- Hyperactivity
- Increased blood pressure and heart rate
- Brown staining of teeth
- Gastric disorder
- Physical exhaustion
- Delusion
- Loss of appetite
- Difficulty with breathing
- Increased blood pressure and heart rate Flakka
- Common names – Zombie drugs, gravel
- The word Flakka came from the Spanish language of “La flaca” which means “skinny girls with charms all she needs”
- It affects dopamine and norepinephrine
- Chemical name: alpha-pyrrolidinopentiophenone
- Short-term effects: (Excited Delirium) – Combative and Violent behavior o Euphoric sensation o Rapid heart rate and palpitation o Increase in blood pressure o Alertness o Aggressive behavior
- At high doses: Increases body temp → muscle breakdown and kidney damage Methamphetamine
- Most known drug in our country like the marijuana.
- Common names – Shabu, Meth, Ice, Crank, Chalk, Crystal, Fire, go fast and Speed
- Is a stimulant and it also increase libido
- It is used to address impotence and erectile dysfunctions
- Recreational drug
- Neurotoxic - used as aphrodisiac and euphoriant
- Low doses: Elevate mood, increase alertness, reduce appetite and promote weight loss
- High doses: Psychosis, skeletal muscle breakdown, seizure, bleeding in the brain
- Chronic high dose: Rapid mood swings, delusion, violent behavior
- It may damage serotonin neurons Effects on the Mind Effects on the Body Overdose Effects
- Highly addictive
- Violent behavior
- Anxiety
- Confusion
- Insomnia
- Paranoia
- Aggression
- Visual and auditory hallucination
- Mood swings
- Increased wakefulness
- Increased physical activity
- Decreased appetite
- Rapid breathing and heart rate
- Irregular heartbeat
- Hyperthermia
- Stroke
- Heart attack
- Multiple organ problem
- Sedative Hypnotics
- Used to reduced tension, reduce anxiety even for seizure and also convulsion
- They have therapeutic roles and CNS depressants
- Examples: Tranquilizer
- Commonly Abused Barbiturates: Secobarbital, pentobarbital, phenobarbital
- Commonly Abused benzodiazepine: Diazepam (Valium), Chlordiazepoxide (Librium), and Lozeparam (Ativan) Sedative Hypnotics
WEEK 15 | DRUGS OF ABUSE
Effects on the Mind Effects on the Body Overdose Effects
- Drowsines s
- Sleep
- Decreased anxiety
- Amnesia
- Impaired mental functionin g
- Confusion
- Aggressio n
- Excitabilit y
- Slurred Speech
- Loss of motor Coordinatio n
- Weakness
- Headache
- Respiratory Depression
- Severe sedation
- Unconsciousne ss
- Slow Heart rate
- Respiratory Suppression
- Death Methaqualone
- A 2,3-disubstitute quinazoline with anesthetic, antihistamine, and anti-tussive property
- Has a sedative hypnotic property
- Has a similar symptom of toxicity to barbiturates
- Hallucinogen
- Drugs that may induced hallucination (sensory perception such as visual, sound that occurs in the absence of an actual stimuli.
- Mostly found in plants and fungi
- Known to alter human perception and mood
- Examples: o Ecstacy / MDMA o K2/Spice o Ketamine o LSD Ecstacy / MDMA
- Common names – Adams, Beans, Clarity, Disco Biscuits, E, Eve, Go, Hug Drug, Lover’s Speed, Peace, STP, X, Party drug and XTC 55
- Stimulant ecstacy is a stimulant
- Popular recreational drug 3,4 Methylenedioxymethampetamine
- MDMA or Ecstacy
- Route: orally, inhalation, ingestion, smoking
- Signs of acute intoxication: hyperpyrexia
- Toxic effect: hypertension, cardiac arrythmias and convulsion, pancytopenia
- Half-life: 8 - 9 hours
- Effect: euphoria, heightened sexual drive, expand consciousness
- Effect at increased dose: hyperthermia, tachycardia, seizure, DIC
- 20% of the MDMA is unchanged into the urine and it onset of effect is 30-60 minutes after the intake of the drug. Effects on the Mind Effects on the Body Overdose Effects
- Confusion
- Anxiety
- Depressio n
- Paranoia
- Sleep Problems
- Drug craving
- Affects Serotonin (mood)
- Same with amphetamine s
- Affects motor activity, alertness, heartrate and blood pressure
- Muscle tension
- Tremor
- Involuntary teeth clenching
- Muscle cramps
- Nausea, sweating
- Faintness, chills
- Blurred vision
- Hypertheermi a
- Liver, kidney and cardiovascula r system failure
- Interfere with metabolism
- Pancytopenia
- DIC Lysergic Acid Diethylamide/LSD
- Common names – Acid, Blotter Acids, Dots, Mellow Yellow and Window Pane
- A semisynthetic indolalkylamine and hallucinogen
- Most potent pharmacological material known
- Produces effects at low doses – 20 μg
- Causes blurred or undulating vision
- Even in a very slow amount of LSD it will already have its effect both to the mind and body.
- Most common adverse reaction: panic reactions
- Antidote: Diazepam Effects on the Mind Effects on the Body Overdose Effects
- Hallucination
- Distorted perception of shape and size of the object, movement, color, sound, touch and the user’s own body image
- Anxiety
- Depression
- Dilated pupils
- Higher body temperature
- Increased heartrate and blood pressure
- Sweating
- Loss of appetite
- Sleeplessness
- Dry mouth
- Tremors
- Psychosis
- Death
WEEK 15 | DRUGS OF ABUSE
Marijuana/ Cannabis
- Also, one of the known drugs in our country
- Common names – Aunt Mary, BC Bud, Blunts, Boom, Dope, Gangster, Ganja, Grass, Hash, Hash-ish, Herb, Kif, Joint, Mary Jane, Pot, Reefer, Sinsemilla, Skunk, Smoke, Weed and Yerba
- Cannabis sativa – is the natural source
- Cannabis will have a good effect to Parkinson’s disease, seizure, convulsion, and even extreme pain cause by the cancer. Cannabinoids
- Naturally occurring cannabinoids: Marijuana and Hashish
- Tetrahydrocannabinol (THC) is the most potent component or the psychoactive substance of marijuana (induces euphoria)
- Associated with impairment of short-term memory and intellectual functions
- After a single use, THC-COOH can be detected in urine for 1 day; up to 3 - 5 days for chronic users
- Urinary metabolites: 11 - nor - deltatetrahydrocannabinol or the tetrahydrocannabinol carboxylic acid
- Physiologic Effects: reddening of the conjunctiva and tachycardia Effects on the Mind Effects on the Body Overdose Effects
- Influences:
- Pleasure
- Memory
- Thought
- Sensory and time perception
- Coordinated movement
- Sedation
- Blood shot eyes
- Increased heart rate
- Coughing
- Increased appetitie
- Decreased blood pressure
- Restlessness
- Irritability
- Sleep difficulty
- No death Phencyclidine
- Also called as Angel dust or Angel hair
- A depressant, stimulant, and has hallucinogenic and anesthetic properties
- Can be ingested or inhaled by smoking
- About 10-15% is unchanged when excreted in urine
- Major metabolite: Phencyclidine HCl
- Low dose: sense of dissociation, euphoria and numbness
- High dose: loss of feeling in lower extremities, disorganize thoughts and disconnection to reality
- Overdose: sense of super human strength
- Toxic effects: Stupor and coma
- Detected after 7-30 days of abstinence Steroid
- Naturally produced from the male hormone testosterone.
- Promote muscle growth
- It enhanced physical performance and appearance
- Increased the mass stamina and mass stamina vigor and strength of the muscle
- Common names Arnolds (Arnolds Schwarnegger), Juice, Pumpers, Roids, Stackers, and Weight Gainers
- It also used to treat hypogonadism and cryptorchidism
- Annabolic Steroid
- Chemically associated with male hormone testosterone
- Improves athletic performance by increasing muscle mass
- Toxic effects: chronic hepatitis, atherosclerosis, abnormal platelet aggregation and cardiomegaly
- Effect by continued uptake: o In male: testicular atrophy, infertility, gynecomastia o In female: masculine traits, breast reduction, nd sterility
- For the measurement urine is used and the screening test is the Radioimmunoassay (RIA) and Ratio of the testosterone and Epitestosterone
- Confirmatory method - GCMS Effects on the Mind Effects on the Body Overdose Effects
- Mood swings
- Increased feeling of hostility
- Impaired judgment
- Increased level of aggression
- Addiction
- Suicide
- Early sexual development
- Acne
- Stunted growth
- Physical changes
- Sterility
- Increased risk of prostate cancer
- Adverse effects Methods for Identifying and Measuring Drugs of Abuse Specimen for Drug Testing
WEEK 16 | THERAPEUTIC DRUG MONITORING
Therapeutic Drug Monitoring
- It is the analysis, assessment and evaluation of drugs into the circulation, specially of the drugs which are called Narrow Therapeutic Index (NTI).
- NTI – this are the drugs that in there is small dose difference they may cause dependence, serious therapeutic failure or even adverse drug reactions.
- Example of adverse effects: gall dependence (drugs of abuse), serious therapeutic failure, disability or even death of the person.
- What are the roles of the Medtech in TDM? o The Medtech are the one who collect the sample (in able for us to determine the concentration of the drugs; and is also important to consider the timing of the blood collection). There are some drugs that is measured during their peak concentration, there are some other drugs which are measured during their trough concentration. o We are the one who measures the drugs and also the reporting of the data. o Interpretation and for other intervention that is the duty of the doctors. Purpose of TDM
- To ensures that the drugs produce maximal therapeutic index for the patient.
- To minimize or eradicate side effects; maximize that therapeutic benefit to the patient eradicate or minimize side effects.
- Ensure that a given drug dosage is within a range that produces maximal therapeutic benefit.
- Identify when the drug is above or below a therapeutic range which may lead to either inefficacy or toxicity.
- Our drugs are within the therapeutic range.
- Sometimes individual have a different response to the drugs and that is because of the variation.
- There are factors that may affect the drug level and efficacy to the body. (age, gender, genetics, even the food that we eat prior to the intake of the drug, and also the interaction with the other drugs. Routes of Administration
- Basis for TDM
- By oral/by ingestion (in the form of capsules, tablets)
- Introduction to the circulation or by intravenous
- By intramuscular/by to the muscles.
- Under the skin/Intradermal it is different from the absorption to the skin (applying medication in the skin)
- Rectal administration/Rectum (suppository)
- The unchanged fraction of the administered dose as it enters systemic circulation defines its bioavailability.
- Some portion of the capsules will not go the circulation. There are some part of it that is part in the feces, eliminate by pooping. Five Pharmacological Parameters
- Liberation – the release of the drugs
- Absorption – transport of drugs from the site of administration to the blood.
- Distribution – it refers to delivery of the drugs to different tissues.
- Metabolism – it refers to the chemical modification of drugs by the cell. (Mixed Function Oxidase System – present in the liver). Liver – is the chief metabolic organ of the body.
- Excretion – the illumination of the drugs from the body; the process by which the drugs and its metabolites are excreted in the body.
- Absorption
- Factors affecting the efficiency of drug absorption from the gastrointestinal tract to its bioavailability in the bloodstream. o Intestinal motility - (peristalsis - affect the transformation, the movement of the drug in the GIT) o pH – there are some drugs which lab acidic pH, there are also drugs which lab basic pH. Acidic drug they absorbed in the stomach, while the basic drug they are absorbed in the intestine. o Presence of inflammation – there is a problem with the GIT and the absorption is also affected. o Presence of other food and other drugs – interfere with the absorption of the drugs.
- Dissociation - from its administered form
- Solubility - in gastrointestinal fluids
- Diffusion - across gastrointestinal membranes
- Tablets and capsules require dissolution before being absorbed.
- Liquid solution have a tendency to be more rapidly absorbed.
- Most drugs are absorbed by passive diffusion.
- Weak acid are absorbed in the stomach while weak basic are absorbed by in the intestine.
- Acidic drugs primarily bind to albumin.
- Basic drugs primarily bind 𝐀𝟏- acid glycoprotein
- Some drugs bind to both
- Drug Distribution
- Hydrophobic Drugs can easily traverse cellular membranes and partition into lipid compartments, such as adipose and nerve cells.
- Hydrophobic drugs – is a water fearing drugs or the drugs which fail to mixed with water.
- Volume of distribution (Vd) index – is the ratio of the injected dose of drugs through IV over the concentration of drugs into the plasma.
- D – injected dose of drugs through IV (mg or g)
- C – concentration of drugs into the plasma (mg/L or g/L) 𝐕𝐃 =
𝐃
𝐂
- Free Vs. Bound Drug o Bound drug – this are the drugs that is attached to their serum-binding proteins (albumin, alpha- 1 - acid glycoprotein) o Free drug – not attached or bind in the serum- binding proteins o Changes in serum-binding proteins may occur during inflammation, malignancies, pregnancy,
WEEK 16 | THERAPEUTIC DRUG MONITORING
hepatic disease, nephrotic syndrome, malnutrition, and acid–base disturbances. o Increases in serum alpha- 1 - acid glycoprotein during acute phase reactions will lead to increased binding of drugs such as propranolol, quinidine, chlorpromazine, cocaine, and benzodiazepines o The action of the drugs can also be interfere with the presence of other drugs and other endogenous substances like urea, bilirubin and hormones. 3. Metabolism
- The liver is the chief metabolic organ in the body – its primary organ that metabolize every drugs that we take.
- Biotransformation – from the inactive form of the drugs through enzymatic reactions it will convert to its active component.
- Biotransformation – the enzymatic processes involved in metabolizing drugs thru metabolic process generating a therapeutically active metabolite
- Most drugs are xenobiotics
- Xenobiotics – this are exogenous substances; when they enter the body they can participate in biochemical pathways that is intended for endogenous substances. That is meant for prostaglandin.
- Fatty liver or liver cirrhosis – may reduced capacity to metabolize drugs
- Metabolic Clearance o Mixed Function Oxidase System – the biochemical pathway responsible for the greatest portion of drug metabolism. o It is present in the liver
- Drug Elimination o Hepatic Metabolism or Renal Filtration – or a combination of the two, eliminates most drugs. o Organs that is primarily affected during the drug intake. (They are eliminated, excreted in the body by the processing of this organs).
- Excretion
- Liberation Causes of Drug Toxicity
- Elevated concentration of free drugs (The drug regimen)
- Abnormal response to drug administration (The allergic response)
- Presence of active drug metabolites First Order Elimination
- Represents the linear relationship between the drug eliminated per hour and the blood level of drug
- The longer the drug stay in the circulation, the more chance that will be eliminated in the body.
- It is important that the drug is go into its target tissue.
- First Pass Metabolism – every substances that is absorbed in the GIT it will passed through into the hepatic portal system before it reach the genital circulation. Pharmacodynamics
- Concentration of drugs vs. response
- Pharmacodynamics – it will tell us what the drug does to the body. (Ingested it) Pharmacokinetics
- It tell us what the body does to the drug; how the body changes or affect a drugs.
- Drug dose and drug blood level
- The activity of a drug (s) in the body as influenced by absorption, distribution, metabolism, and excretion. Therapeutic Index
- Ratio between the minimum toxic dose and the maximum therapeutic serum concentration.
- The larger the TI, the safer the trough. 𝐓𝐈 =
𝐓𝐃𝟓𝟎
𝐄𝐃𝟓𝟎
Therapeutic Range
- Difference between the highest and the lowest effective dosages. Pharmacokinetics
- Assists in establishing or modifying a dosage regimen.
- Serum concentrations rise when the rate of absorption exceeds distribution and elimination.
- The concentration declines as the rate of elimination and distribution exceeds absorption.
- Most drugs are not administered as a single bolus but are delivered on a scheduled basis
- After the first oral dose, absorption and distribution occur, followed only by elimination.
- Before the concentration of drug drops significantly, the next dose is given.
- The peak of the second dose is additive to what remained from the first dose.
- Sample Collection o Timing of Specimen Collection ▪ There are drugs that is measured during their peak concentration and there are drugs that is measured during their trough concentration. ▪ Serum or plasma is the specimen of choice for the determination of circulating concentrations of most drugs. ▪ Certain drugs have a tendency to be absorbed into the gel of certain serum separator collection tubes ▪ Gel separator is not recommendable ▪ Heparinized plasma is suitable for most drug analysis. Pharmacogenomics
- Science concerned with the ways to compensate for the genetic difference in patients which cause varied response.
- There are different factors which affect the response to the drugs (genetic makeup).
- Categories of Patients
WEEK 16 | THERAPEUTIC DRUG MONITORING
Amiodarone (Cordarone)
- Blocks potassium channel in the cardiac muscle, used for treating ventricular arrhythmia
- An Iodine containing drug which can cause Hyperthyroidism
- Toxic range: 1 to 2 ug/mL
- Toxic effects: bradycardia, hepatitis, photodermatitis Verapamil
- Used to treat angina, hypertension and supraventricular arrhythmias
- Therapeutic range: 80 - 400 ng/mL
- Toxic effects: hypotension, peripheral edema (effect of having a cardiac problem), ventricular fibrillation
- Edema is also a manifestation of problem in the liver, problem in the kidney.
- Antibiotics
- Meant for killing microorganisms Aminoglycosides
- For the treatment of gram-negative bacterial infection
- Administered IM or IV
- Eliminated by renal filtration
- Cause damage to the 8th cranial nerve at toxic level
- 8 th cranial nerve - __ ocular nerve (important for hearing, balance, and also eye movement)
- It is a nephrotoxic and hepatotoxic
- Toxic range: o >30 ug/mL (Amikacin and Kanamycin) o >15 ug/mL (Gentamicin and Tobramycin)
- Requires measurement of the peak and trough concentration
- Impairs the function of the Proximal Convoluted Tubule (PCT) (reversible)
- Method: Chromatograph and Immunoassays Vancomycin
- Effective against gram-positive bacteria
- Administered IV
- Only requires trough concentration
- Eliminated through renal filtration and excretion
- Toxicity occurs in therapeutic range (5 to 10 ug/mL)
- Toxicity side effects: red man’s syndrome (allergic response to vancomycin), nephrotoxicity (> 10 ug/mL) and ototoxicity (the hearing is affected; tinnitus – ringing sound into the ears) (>40 ug/mL) Chlorampenicol
- Protein synthesis inhibitor
- Cause abnormality in blood forming cells
- Distributes to all tissues and it concentrates in the CSF
- 50 % are protein bound, rapidly absorbed in the GIT
- Toxic level: >25 ug/mL
- Toxic effects: Blood dyscrasia, cytoplasmic vacuolation (erythroid and myeloid cells)
- Antiepileptic Drugs
- These drugs are meant for treating epilepsy episode
- 1 st Generation – first drug that is used for treating epilepsy o Phenobarbital o Phenytoin o Valproic acid o Carbamazepine o Ethosuximide
- 2 nd Generation – latest drugs for treating epilepsy o Felbamate o Gabapentin o Lamotrigine o Levetiracetam o Oxcarbazpine o Tiagabine o Zonisamide Epilepsy
- Epilepsy is a brain disorder that happens when certain nerve cells in your brain misfire. It causes seizures, which can affect your behavior or the way you see things around you for a short time. Two Types of Seizure ➢ Focal Seizure/Partial Seizure
- Only causes mild seizure
- Only a particular part of the brain has abnormality ➢ Generalized Seizure
- These happen when nerve cells on both sides or your brain misfire. They can make you have muscle spasms, black out, or fall. Six Types of Generalized Seizure ➢ Tonic-clonic Seizures/Grand Mal Seizure
- These are the most noticeable
- When you have this type, your body stiffens, jerks, and shakes, and you lose consciousness.
- Sometimes you lose control of your bladder or bowels
- They usually last 1 - 3 minutes
- Can lead to breathing problems or make you bite your longer tongue or cheek. ➢ Clonic Seizures
- Your muscles have spasms, which often make your face, neck, and arm muscles jerk rhythmically.
- They may last several minutes. ➢ Tonic Seizures
- The muscles in your arms, legs, or trunk tense up.
- These usually last less than 20 seconds and often happen when sleep.
- If you’re standing up at the time, you can lose your balance and fall.
- These are more common in people who have a type of epilepsy known as Lennox-Gastaut Syndrome ➢ Atonic Seizures
- Your muscles suddenly go limp, and your head may lean forward.
WEEK 16 | THERAPEUTIC DRUG MONITORING
- If you’re holding something, you might drop it, and if you’re standing, you might fall.
- These usually last less 15 seconds but some people have several in a row.
- Patients are advised to wear helmet.
- Associated with patients with Lennox-Gastaut Syndrome and Dravet Syndrome. ➢ Myoclonic Seizures
- Your muscles suddenly jerk as if you’ve been shocked.
- They may start in the same part of the brain as an atonic seizure, and some people have both myoclonic and atonic seizures. ➢ Absence Seizures/Petit Mal Seizure
- You seem disconnected from others around you and don’t respond to them.
- You may stare blankly into space, and your eyes might roll back in your head.
- They usually last only a few seconds, and you may not remember having one.
- They’re most common in children under 14 years old. Lennox-Gastaut Syndrome (LGS)
- Or childhood epilepsy/epileptic encephalopathy, is a pediatric epilepsy syndrome characterized by multiple seizure types; mental retardation or regression; and abnormal findings on electroencephalography (EEG) Dravet Syndrome
- Previously know as severe myoclonic epilepsy of infancy (SMEI), is a type of epilepsy with seizures that are often triggered by half temperature or even fever. Refractory Epilepsy
- Patient who does not response to their anti-epileptic drugs.
- Means that medicine isn't bringing your seizure under control. You might hear the condition called by some other names, such as uncontrolled, intractable, or drug- resistant epilepsy. Phenobarbital
- Anti-seizure and anti-convulsant drug
- Is a drug that enhance bilirubin metabolism
- Long-acting barbiturates that controls the tonic clonic seizure and focal epileptics
- Used for treating withdrawal symptoms in infants born to ?/barbiturates addicted mothers
- Used to treat cases of congenital Hyperbilirubinemia
- Absorption is slow and complete, 50 % protein bound
- Eliminated by hepatic metabolism and renal filtration
- Only trough level is evaluated (is used for the TDM of the Phenobarbital)
- Inactive proform: Primidone (Mysoline)
- Half-life: 70 - 100 hours
- Peak serum level: 10 hours after an oral dose
- Therapeutic range: o 20 - 40 ug/mL (phenobarbital) o 5 - 12 ug/mL (primidone)
- Toxic effects: drowsiness, fatigue, depression and reduced metal capacity Phenytoin (Dilantin)
- It controls seizures and short-term prophylactic agent in the brain injury.
- It decreases sodium and calcium influx into hyperexcitable neurons
- Administered IV , GIT absorption is incomplete
- 87 - 97 % protein bound
- Elliminated through hepatic metabolis
- Toxicity may be seen at the level of therapeutic range
- Major toxicity: initiation of seizures; teratogen (it can cause birth defects – cleft lip or cleft palate) and nystagmus (involuntary eye movement)
- Other toxic effects: hirsutism (female), gingival hyperplasia, vitamin D deficiency, and folate deficiency
- Therapeutic range: 10 to 20 ug/mL (total); 1 to 2 μg/mL (free)
- Toxic range: > 20 ug/mL
- Injectable proform: Fosphenytoin Valproic Acid (Depakene)
- Used for the treatment of Petit Mal Seizure and Grand Mal Seizure
- Administered orally
- Highly protein bound (93%)
- Eliminated by hepatic metabolism
- Therapeutic level: 50 - 120 ug/mL
- Toxic effects: nausea, lethargy, weight gain, pancreatitic, hallucination
- Toxic levels: o 120 ug/mL (nausea, lethargy, weight gain) o 200 ug/mL (pancreatitis, hallucination) Carbamazepine (Tegretol)
- Effective for Grand Mal Seizure and seizures accompanied by pain
- Grand Mal Seizure – the loss of full control of the body movement
- A tricyclic compound related to imipramine (TCA)
- 70 - 80% protein bound
- Eliminated by hepatic metabolism
- Has a serious toxic effects and not frequently used
- Hematologic dyscrasia and aplastic anemia.
- Idiosyncratic effects: rashes, leukopenia , nausea, vertigo, febrile reactions
- Therapeutic levels: 4 - 12 ug/mL
- Toxic levels: > 15 ug/mL hematologic dyscrasias, and aplastic anemia
- Also used an analgesic for trigeminal neuralgia
- Trigeminal nerve is the 5th cranial nerve used as a treatment for pain of the trigeminal nerve. Ethosuximide
- Drug of choice for controlling Petit Mal Seizure
- Free in serum and not protein bound
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CCHM322- Finals LEC - Lecture notes
Course: Clinical Chemistry 2 (MDT 3122L)
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WEEK 13 | ENDOCRINOLOGY V
FINALS | CCHM322 LECTURE |K.BAGANG
Reproductive Hormones and Other Miscellaneous
Hormones
Testosterone
• It is considered as the principal and the most potent
androgen hormone.
• It is considered as the Principal and the most potent
androgen hormone.
• Synthesized by the Leydig Cells of the testis of the male,
derived from hormone progesterone.
• Controlled by gonadotropin (it pertains to the FSH and
LH and luteinizing hormone). → this are the hormones
produce from the pituitary gland.
• Function:
o It is very important from the growth and
development of the reproductive system (prostate
and external genetalia, just like with the other
hormones.
o Testosterone also exhibits circadian rhythm.
• Levels demonstrate a circadian pattern and peak at (8am)
and fall to their lowest level at 8pm.
• There is gradual reduction of testosterone after age 30
with an average decline of 110ng/dL every decade of life.
• Test for male infertility: Includes the seminalysis, FSH
and LH measurement.
• Reference Values: 3.9-7.9 ng/mL (serum)
• Transport proteins
• Sex hormone binding globulin (SHBG) – 60% of the
testosterone.
• Albumin – 40% of the testosterone.
• Concentration determines the level of testosterone into
the circulation.
Types of Testicular Infertility
1. Pretesticular Infertility (Secondary Hypogonadism)
• Due to hypothalamus or the pituitary
• Testosterone, FSH, LH – normal or decrease in this
condition.
2. Testicular Infertility (Primary Hypogonadism)
• Problem is in the testicles
• May be congenital (cryptorchidism, Klinefelter’s
syndrome and 5-a-reductase deficiency) or acquired
(varicocele, tumor, orchitis).
o Cryptorchidism – the absence of one or both of
the testis from the scrotum.
o Klinefelter’s syndrome (XXY syndrome) – the
male develops a female features like weaker
muscle, greater height, poor coordination, less
body hair, small genitals, and breast
growth/development.
o 5-a-reducatse deficiency – male have a
genetalia that appears female.
o Varicocele – the enlargement of the vein into a
scrotum
o Orchitis – the inflammation of the testicles.
• Decreased testosterone levels and increase FSH and
LH
3. Posttesticular Infertility
• Due to disorders of sperm transport and function.
• Testosterone, FSH, and LH – normal.
Other Disorders of Sexual Development
Testicular Feminization Syndrome
• Most severe form of androgen resistance syndrome,
resulting in lack of testosterone action in the target tissue.
• Physical development pursues the female phenotype,
with fully developed breast and female distribution of fat
and hair.
• Patient has also utility or response to the administration
of synthetic/exogenous testosterone.
• Lab tests: Normal levels of testosterone with elevated
level FSH and LH.
Sertoli Cell – Only Syndrome
• Characterized by lack of germ cells or sperm cells.
• Men present with small testes, high FSH levels,
azoospermia (semen that lacks the sperm cell), and
normal testosterone level.
• Testicular biopsy is the only procedure to confirm this
diagnosis.
Kallmann’s Syndrome
• A result of an inherited, X-linked recessive trait that
manifests as hypogonadism during puberty and the
impaired sense of smell.
Dehydroepiandrosterone DHEA
• The principal androgen formed by the adrenal cortex of
the adrenal gland.
• It is not produced by the gonads.
• Valuable in the assessment of adrenal cortical hormones.
Estrogen
• Arises through structural alteration of the hormone
testosterone molecule.
• Is arise from the male hormone
• Function:
• In conjunction with progesterone, they function in
uterine growth and regulation of menstrual cycle and
maintenance of pregnancy.
• Deficiency: Irregular and incomplete development of the
endometrium (is the area for the implantation of the
fertilized egg).
• Precursor: Cholesterol, acetate, progesterone and
testosterone.
• Forms: Estrone E1, Estradiol E2, Estriol E3
A. Estrone (E1)
• It is the most abundant estrogen in
postmenopausal women.
B. Estradiol (E2)
• The most potent and the major estrogen
secreted from the ovary.
• Synthesized from testosterone, then diffuses out
of the thecal cells of the ovaries of the female.
• Precursor of both E1 and E3 – serves as
negative feedback for Follicle Stimulating
Hormone (FSH). → an increase with E2 will
cause the inhibition from secretion of the FSH.
• Used to assess ovarian function.
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