Biochem II post midterm(s) content

What type of protein do not require a carrier molecule? What are some examples?

Peptides & proteins

examples include TSH FSH LH hCG

What is the master endocrine gland??

pituitary gland

It is attached to the hypothalamus and is responsible for releasing stimulating hormones

Describe the hypothalamic-Pituitary axis feedback loop

Hypothalamus releases releasing hormones which act on the pituitary to release stimulating hormones. target endocrine organs release target hormones in response

target hormones act on the hypothalamus to reduce release of releasing hormones

Diseases that affect the pituitary are called ____ disorders

Diseases that affect the hypothalamus are called ___ disorders

Diseases that affect the target organ are called ____ disorders

Diseases that affect the pituitary are called secondary disorders

Diseases that affect the hypothalamus are called tertiary disorders

Diseases that affect the target organ are called primary disorders

What is the principle method used for analyzing hormone levels? What issues are associated with this method of analysis?

Immunoassays

Affected by high dose hook effect and HAMA

What are dynamic function tests? What are the three main types ?

Involves stimulating or suppressing a hormone axis and observing the hormone response

Includes;

--Stimulation tests: designed to stimulate release of a hormone to investigate hypofunction via injection of synthetic stimulating hormone

--Suppression tests : designed to suppress the release of a hormone to investigate hyperfunction via injection of synthetic target hormone.

--Stress tests: designed to monitor a hormone's response to physiological stress on the body

What is an example of a dynamic function stress test?

Insulin tolerance test

What are the 2 cells of the thyroid and what do they produce?

Follicular cells produce thyroid hormones

Parafollicular cells produce calcitonin

What thyroid hormone is more metabolically potent?

FT3 is more potent than FT4

T/F: Goiter is the enlargement of the thyroid and is seen only in hyperthyroidism

false

can be seen in both hypothyroidism an hyperthyroidism

What is exophthalmos? What is it a symptom of?

Bulging eyes caused by build up of adipose behind eyes

symptom of hyperthyroidism

What is cretinism?

congenital hypothyroidism

babies are often screened for this using a heel prick capillary puncture

What is the most common form of hypothyroidism in devloped countries?

Hashimoto's disease

autoimmune disease that cases antibodies against thyroid tissue and diffusion of lymphocytes into the thyroid

Describe primary and secondary hypothyroidism

Primary hypothyroidism: thyroid is affected

increases TSH, decreases FT4, decreases FT3

Secondary Hypothyroidism: pituitary is affected

decreased TSH, decreased FT4, decreased FT3

What is Grave's disease?

The most common cause of hyperthyroidism. It is an autoimmune disease that causes diffuse toxic goiter.

Can lead to thyrotoxic crisis which is life threatening. stat thyroid may be ordered

What is Hashimoto's disease?

autoimmune hypothyroidism

Describe primary hyperthyroidism vs secondary hyperthyroidism

Primary hyperthyroidism: thyroid affected

Decreased TSH, Increased FT4, Increased FT3

Secondary Hyperthyroidism: pituitary affected

Increased TSH, Increased FT4, Increased FT3

What test screens for thyroid status?

TSH

What are the 3 generations of thyroid test?

1st Generation: 5-10 mU/L

2nd Generation: detection down to 0.1 mU/L

3rd Generation: 0.010.02 mU/l

Thyroglobulin tests are used to detect

thyroid cancer

What are the three thyroid antibodies

TPOAbs (thyroid peroxidase antibodies): destroys enzyme needed for thyroid hormone production and leads to hypothyroidism. Seen in Hashimoto's

TgAbs(thyroglobulin Abs): destroys thyroglobulin and leads to low thyroid hormones

TRAbs(thyroid receptor antibodies): binds to thyroid receptors and causes hyperthyroidism. seen in Grave's disease

What is sick euthyroid syndrome?

Critically ill patients producing a pattern of low FT3/FT4 and TSH

Pregnancy causes a ___ in FT3/FT4

Increase

If sTSH is normal, patients are considered ___. Is further testing required?

euthyroid, no further testing required

If TSH is high or low, what is the next test to be performed?

FT4

TSH is low.

FT4 is Low

describe the disorder

secondary pituitary hypothyroidism

TSH is low

FT4 is high

describe the disorder

Primary hyperthyroidism

TSH is low

FT4 is normal

FT3 is normal/decreased

describe the disorder

Euthyroid

TSH is low

FT4 is normal

FT3 is elevated

describe the disorder

T3 thyrotoxicosis

TSH is high

FT4 is low

describe the disorder

primary hypothyroidism

TSH is high

FT4 is high

describe the disorder

secondary pituitary hyperthyroidism

What is chain of custody and what is it a requirement for?

formal and legal way of identifying the persons who handled and stored a patients specimen

Chronological documentation for sample handling and methodologies used needed for WORKPLACE DRUG TESTING

tamper proof seal is used

What are two of the confirmatory testing done for toxicology?

Immunoassay

Gas chromatography-Mass spectrophotometry

What are the two arterial blood gas assays that fall under toxicology

CoHb

SulfHb

Clinical syndromes essential for the recognition of poisoning patterns are known as

toxidromes

Describe the following:

ED50

TD50

LD50

Therapeutic index

ED50: Effective dose for 50% of people

TD50: Toxic dose for 50% of people

LD50: Lethal dose for 50% of people

Therapeutic index: TD50/ED50

What are the two screening tests used for drugs of abuse?

Spot tests: colorimetric qualitative assay

Lateral flow devices: uses immunoassay/chromatography principles

What is the confirmatory toxicology testing done for legal cases?

Gas Chromatography - mass spectrophotometry

T/F: If a line is present on a lateral flow chromatography DOA test, that means there is no evidence of the drug being tested in the system of the person

False

the drug is not detected and is below the cut-off range, but there can still be trace amounts that are below the cut off range

this isnt really clinically significant but this question is just to engrain the theory in my head

Workplace drug testing is regulated by

SAMHSA

What are the three main ways a sample can be adulterated?

Substitution of urine

Drinking detox products

Adding an adulterant to the urine

How can we tell if a patient has diluted their urine sample?

SG is >1.005

What everyday product can cause false negatives in a DOA test and SG >1.035

Bleach

What sample can we test to determine if any drugs were used in the last two trimesters of a woman's pregnancy?

Meconium DoA testing

What sample can we test to detect drug usage over a course of several months?

Hair

giving aspirin to children during a viral infection increases the risk of

Reye's syndrome

rapidly worsening brain disease

What is aspirin metabolized to? What are symptoms of toxicity?

salicylic acid

Toxicity symptoms include TINNITUS, nausea, vomiting, coma, seizures,

HYPERVENTILATION that can lead to respiratory alkalosis

salicylic acid can also cause metabolic acidosis, so patients can have mixed acid base disorders

What are the two methods of analysis for salicylates

Trinders manual reaction

Enzymatic vitros assay

What is the most common drug ingested in overdose?

Acetaminophen "tylenol"

What happens during an acetaminophen overdose?

Glutathione is depleted and causes toxic metabolite acetamidoquinone to build up in liver hepatocytes

What is the half life if acetaminophen in an overdose?

12h

What is the antidote for acetaminophen? What determines whether it is to be administered or not

Antidote for acetaminophen is N-acetylcysteine

causes anaphylactic reaction in many patients

only administered if the acetaminophen dose is considered hepatically toxic. this is determined using the Rumack Matthew Nomogram

What is the Rumack-Matthew Nomogram?

It is a chart used to assist in the degree of toxicity after acetaminophen ingestion

it is used to determine whether the antidote N-acetylcysteine should be used as it can cause anaphylaxis

What are the primary ingredient in the following substances:

Windshield wiper fluid

Antifreeze

Rubbing alcohol

Windshield wiper fluid: Methanol

Antifreeze: Ethylene glycol

Rubbing alcohol : isopropanol

What is the legal blood alcohol concentration in canada?

17 mmol/L

What are the following substances metabolized into?

Ethanol

Methanol

Isopropanol

Ethylene glycol

Ethanol metabolized into acetic acid

Methanol metabolized into formaldehyde and formic acid

Isopropanol metabolized into acetone

Ethylene glycol metabolized into glycolic, oxalic and hippuric acid

What is considered the biochemical marker for chronic alcohol use?

Elevated GGT

What happens in methanol poisoning? What is the antidote?

formic acid metabolite accumulates

causes metabolic acidosis, hi GAP, Blindness, drowsiness, confusion, seizures, coma, hypotension

antidote is ethanol - inhibits methanol metabolism by saturating Alcohol dehydrogenase

administer sodium bicarbonate, folate and do dialysis

Ingestion of antifreeze can cause ____ crystals to appear in the urine

calcium oxalate

If a police officer asks for a sample, what must we ask to see before giving the samples requested

Search and seize warrant

What is the formula for calculated osmolality

Nax2 + glucose + urea

Albumin binds to __ drugs

A1-acid glycoprotein binds to __ drugs

Albumin binds to acidic drugs

A1-acid glycoprotein binds to basic drugs

What is through and peak in therapeutic drug monitoring?

Through: lowest concentration of drug

Peak: highest concentration of drug

Describe therapeutic ranges

consists of minimum effective concentration (lower limit) and minimum toxic concentration (upper limit)

Pharmacodynamics vs pharmacokinetics

Pharmacodynamics: what the drugs do to the body - action on target site

pharmacokinetic: what the body does to the drugs - elimination

Pharmacokinetics involves what 4 phases

Absorption

Distribution

Metabolism

Elimination

What method of administration skips the absorption step

IV

What is bioavailability?

amount of drug absorbed relative to quantity given

What enzyme is involved in drug metabolism ? What does it do

CYP450

Converts drug to water soluble metabolites

What is the first pass effect?

initial rapid metabolism of drug in the liver

First order vs Zero order pharmacokinetics

First order: Enzyme > Drug - concentration is reduce in half at a distinct contact time

Zero order: Drug > E - drug decreases by a constant amount

Steady state is achieved after _ doses

5 doses

When is a sample for trough collected?

immediately prior to next dose

When is a sample for peak collected?

2h after oral ingestion

30 minutes after IV ingestion

1h after IM injection

What is digoxin? What is the antidote?

cardiac glycoside that is used to treat heart failure

enhanced by low K+ levels and increases K+ levels

Antidote is digibind

What is Procainamide?

Antiarrythmic that is metabolized into N-acetyl procainamide which also is arrhythmic so it is important to do Proc and NAPA panel during TDM

What is carbamazepine?

Anticonvulsant often used in combination with Phenytoin

When combined, the therapeutic range is lowered and the toxic effects can occur at lower doses

How is phenytoin the most common cause of OD in children?

the drug concentrates at the bottom of the bottle and can be in toxic amounts for children

it is important to mix the bottle before use

What commonly used anticoagulant interferes with gentamycin assays? How does it impact the results?

Heparin inactivates gentamicin and causes falsely decreased results

What test can be performed to determine what tricyclic antidepressant should be prescribed for a patient

Urine MHPG

What is cyclosporine A?

Immunosuppressant used to prevent host-graft rejection

What is tacrolimus?

Immunosuppressant that is 100x more potent than Cyclosporine

What are the DOA drug classes?

Amphetamines

Cocaine

Phencyclidine

THC

Barbiturates

Opiates

Benzodiazepines

What can cause a false positive amphetamine result

Vick's inhalers

Eldepryl

Didrex

ADHD medications like Adderall and vyvanse

What does the DOA cocaine assay test for?

Metabolite benzolecgonine

What is the antidote used for phencyclidine?

Diazepam

What are barbiturates?

drugs that depress central nervous system activity and are used as anticonvulsants and sedative

T/F: Poppy seeds can cause a falsely positive Opiate test

true

What is the antidote for opiate overdoses

Naloxone (Narcan)

How are AMI's treated?

Administer thrombolytics within 4 hours

perform angioplasty within 60-90 minutes

What is the Q wave?

first downward deflection of the QRS complex indicative of an AMI

What are some ECG tracings that can be seen in an AMI?

ST segment elevation: complete coronary blockage

ST depression: partial blockage

T inversion: partial blockage

Q wave

What three enzymes are biomarkers for AMI

AST, LD, CK

What CK isoenzyme is most specific for the heart?

CK-MB

What is the CKWMB index?

CKMB/total CK

>0.04 is indicative of AMI

What two cardiac proteins can replace enzyme testing?

Myoglobin and Troponin

Myoglobin is a __ cardiac marker

early

lack of myoglobin rules out AMI

What is considered the definitive gold standard marker or cardiac injury

Troponin

Troponin is a __ cardiac marker

late

used to rule in AMI

Troponin is not found in healthy people

What are the three types of troponin?

Troponin I - inhiitory

Troponin T - Tropomyosin binding

Troponin C - Calcium binding