Part 3 Flashcards
Precision/personalized medicine
Drug therapy specifically targeted to an individual’s genetic content
Essential nutrient and examples
Must be obtained externally because the body cannot produce it, water, carb, protein, lipids, vitamins, minerals
Ghrelin
Hormone released by the stomach upon lack of distension to stimulate appetite in the hypothalamus
Leptin
Hormone released by adipose tissues upon filling to decrease appetite in the hypothalamus, increase glucose uptake in muscle, decrease gluconeogenesis by liver
How much water do we need and why?
50% of weight in floz, Universal solvent, transport medium, heat regulation, lubrication
RDA’s
Recommended daily allowance, levels of intake of essential nutrients considered to be the general basis to meet the requirements of almost all healthy people
1 lb of body weight = how many calories
3500 Calories
definition of a calorie
Energy required to raise one gram of water one degree celcius
Fat soluble vitamins
A,D,E,K… remaining are water soluble
BMI calculation
Weight in kg/height in m^2
Adipose tissue as an organ releases what hormones?
-TNF-a, leptin, adiponectin
Adiponectin function
Acts on the muscle to encourage glucose uptake, acts on liver to decrease gluconeogenesis
Parts of the small intestine absorption
Duodenum - iron, ca2+, magnesium
Jejeunum - simple sugars and water soluble vitamins
Ileum - amino acids, fatty acids, B12, sodium, cholesterol, alcohol ***most important, if removed will need supplemental nutrition for life
Ox phos ATP yield
32, + 4 from glycolysis and TCA gives 36-40
RBC’s lack mitochondria and therefore…
…cannot create ATP, must get it from the blood stream
Hormones that increase blood sugar
- glucagon
- epinephrine
- growth hormone
Cori cycle/lactic acid cycle
Liver uses lactate from muscle to make glucose, takes 3 times the energy to perform than energy that is produced
B1 name and what deficiency can cause
Thiamine, deficiency causes eye paralysis, congestive heart failure (wet beriberi), hyporeflexia, neuropathy (dry beriberi) and wernike korsakoff syndrome
B6 name and what deficiency can cause
Pyroxidine, peripheral neuropathy
B12 name and what defiency can cause
Cyanocobolamine, optic neuritis and loss of proprioception and vibration sensitivity, megaloblastic anemia
B2 name and deficiency canc
Riboflavin, angular stomatitis cheilosis
what does Vitamin A deficiency cause
Dry conjunctiva (bidots spots), corneal uceration, dry skin, poor night vision
what does vVitamin C deficiency cause
Gingivial hypertrophy and bleeding
Vitamin D
Osteomalacia, musclular hypotonia
B3 Niacin deficiency can cause the 3 d’s
(pellagra) Dermatitis, diarrhea, dementia,
Sinemet (carbidopa and levodopa) interaction with this common OTC supplement
Iron, inactivates it
marfan syndrome diagnostic criteria
Presence of family history and 1 of the cardinal features, or genetic testing in the setting of family history, or in the absence of family history 2 cardinal features (aortic root dilation and ectopia lentis)
Beighton score
Test for ehlers danlos involving scoring of right and left extremities in tests of hypermobility with a 1 being positive and 0 negative, includes hyperextension of pinky >90 degrees, apposition of thumb to flexor aspect of forearm, hyperextension of elbow >10 degrees, and knees, and touching palms of hands to floor without bending knees
Which arm forearm bone rotates?
The radius, the head of the radius is rounded and allows for spinning over the ulna
Bones that are particularly susceptible to injury in the wrist
- Carpal navicular/scaphoid is prone to fracture, blood supply becomes compromised resulting in long healing periods
- Lunate disloation is easy
Most likely spot for a clavicle break and most common mechanism to cause a clavicular fracture?
S bend, FOOSH (fall on outstretched hands)
PIP joint
Proximal interphalangeal joint between proximal and intermediate phalanges
IP joint
Interphalangeal joint, between proximal and distal phalanges on digit 1
DIP joint
Distal interphalangeal joint, between intermediate and distal phalanges
Cephalic vein pathway and similarities to lower limb
Travels up the anterior face of the arm in the superficial fascia, up the deltopectoral groove and empties into the subclavian or axillary vein, pretty much identical to great saphenous in lower limb
Basilic vein pathway
Travels up the medial face of the arm in the superficial fascia before diving deep and emptying into the axillary vein
Median cubital vein
Junction between cephalic and basilic, used in phlebotomy
Trace the aortic arch and its branches
Aorta
- brachiocephalic artery (right common carotid and right subclavian)
- left common carotid
- Left subclavian
- Subclavian becomes axillary
- Axillary becomes brachial
- brachial becomes radial and ulnar
- Radial becomes deep palmar arch
- ulnar becomes superficial palmar arch
- Anastamoses
Thoracoacromial trunk pathway
-Comes off axillary artery briefly after changing from subbclavian artery, sends blood vessels forward (pectoral branch) and backward (acromial branch)
Posterior and anterior humoral circumflex arteries
Surround the surgical and anatomical neck of the humerus
Lateral thoracic artery
Comes off the axillary artery to travel the chest wall and eventually dipping into latissimus dorsi muscle, sometimes shares a trunk with subscapular artery
Subscapular artery
Comes off the axillary artery distal to the lateral thoracic artery to supply the scapular muscles, sometimes shares a trunk with the lateral thoracic artery
What nerve follows profunda brachii artery?
radial nerve after the whole brachial plexus debacle
TAN acronym for contents of the cubital fossa
Biceps brachii tendon, brachial artery, median nerve
Common flexor tendon
Shared tendon between 3 forearm muscles on the medial epicondyle of the humerus, flexor carpi ulnaris, palmaris longus, flexor carpi radialis
Trigger finger syndrome
Because the tendons of flexor digitorum superficialis bifurcate at the middle phalanges and flexor digitorum profundus slides underneath, a lesion on profundus could cause an inability to unflex the finger, most commonly affecting the 4th digit and the thumb
Common extensor tendon
Shared tendon between 3 forearm muscles on the lateral epicondyle of the humerus, extensor carpi ulnaris, extensor digitorum, extensor digiti minimi
Extensor aponeurosis
The opposing side of the flexor retinaculum, features 6 tunnels for things to pass through
Tunnel 1 contents
abductor pollocis longus and extensor pollucis brevis
Tunnel 2 contents
extensor carpi radialis longus and extensor carpi radialis brevis
Tunnel 3 contents
extensor pollocis longus
Tunnel 4 contents
extensor indices and extensor digitorum
Tunnel 5 contents
Extensor digiti minimi
Tunnel 6 contents
Extensor carpi ulnaris
3 things that travel under the coracoacromial arch
Supraspinatus muscle, biceps brachii long head tendon, and bursa
3 Borders of the thoracic outlet
Anterior scalenes muscle, clavicle, first rib
Warfarin and VKORC1 gene and CYP2C9
Can be tested for to see if pt is especially sensitive to warfarin because they influence metabolism, however this is not routinely or widely recommended at this time
Herbal medicinal and dietary supplements differ from traditional medicine in that…
…they are assumed safe unless disproven by the FDA, cannot put labels making medical claims - restricted to general statements about how the product affects people
4 main processes of pharmacokinetic events
1) absorption - entrance of drug into blood stream
2) distribution - moving from blood stream into tissues of body
3) metabolism - physical and chemical alterations that a substance undergoes in the body
4) excretion - eliminating waste products of drug metabolism
Characteristics of drugs that make them easier to absorb
-More lipid soluble
-Nonpolar
Common sites of absorption of drugs
1) mucosa of stomach, mouth, small intestine, or rectum
2) Blood vessels in muscles or subcutaneous tissues
3) dermal layer
Most common mechanism of drug absorption
passive diffusion
Ficks law
Law of passive diffusion from higher concentration to lower concentration until equilibrium achieved, speed of which directly proportional to different concentration levels and inversely proportional to the thickness of the membrane
Facilitated transport
Passive process to carry drug molecules passively down a conc. gradient facilitated through a carrier molecule
Active transport
Requires ATP and carrier molecules to move a drug from a low to high conc area in an active process
Oral administration
Used whenever possible, safest and most convenient route, onset of action is 30-60 min, most absorption occurs in small intestine, drug enters liver and can be metabolized
First pass effect
Occurs when a drug is largely metabolized by the liver before reaching systemic circulation, often requires administration of higher dose as a result or can be dodged if drug is administered in other ways
Sublingual administration
Used whenever rapid effects are needed, absorption directly through oral mucosa into blood stream, few minute onset of action, avoids first pass
Rectal administration
Often used when a localized effect is needed or another route is not feasible (unconscious or vomiting), onset is 15-30 min, retention varies by patient
Disadvantages of alimentary administration (3)
-Rate of absorption varies, can be a problem if small range in blood levels separates desired therapeutic and toxic effects
-patient compliance is not ensured
-first pass effect
Intravenous administration
Bypasses absorption barrier, onset in several minutes, insoluble drugs cannot be delivered via IV
Subcutaneous administration
Often done for drugs inactivated by stomach, action is several minutes
Intramuscular administration
Onset of several minutes, provide sustained drug injection over period of time
Disadvantages of parenteral administration (4)
-Rapid absorption can lead to adverse effects,
-sterile formulation and aseptic technique.
-local irritation at site of injection
-not suitable for insoluble substances
Topical administration
Most oitments, gels, creams are applied to skin, eye or ear for local effects with onset of 1 hour, systemic absorption is relatively minimal
If serum TSH is normal, then ____. If serum TSH is high, then order ____, if serum TSH is low, then order ____
no further work up, FREE T4, FREE T4 and T3
Biotin (b7), commonly used in OTC advertised anti hair loss products, can interfere lab assay of what hormone?
Thyroid hormones
Inhalation administration
Lungs have large surface for absorption with onset within 1 min, effects can be local or systemic
Intranasal administration
DRug absorption can cause either local or systemic effects
Vaginal administration
Local effects with onset of 15 minutes
Weak acid type drug medications are more likely to be absorbed where and why?
In the stomach, because it has a very low pH (think aspirin and ulcers)
Weak base type drug medications are more likely to be absorbed where and why?
The duodenum because it has a neutral pH 5-7
Bioavailibility and how is this determined?
Amount of drug dose that reaches the systemic circulation ex) if 100mg administered and 50mg reaches blood stream, 50% bioavailable. Determined by comparing plasma levels of a drug via different routes of administration compared to injection (which has bioavailablility of 100%)
A rated drug vs AB vs B rated drug
A rated means FDA has named generic as therapeutically equivalent to brand name, AB means there were bioequivalent problems that have been resolved with further studies, B rated means the generic is not bioavailability equivalent
Prodrugs
Compounds pharmacologically inactive as administered then undergoes conversion into active form while in the body
Phase 1 vs phase 2 metabolism
Phase one is nonsynthetic metabolism involves making the drug polar to be excreted such as via oxidation, phase 2 is synthetic metabolism involves combining a drug with a substrate to conjugate it and increase its polarity for excretion
Metabolic induction and example
When some drugs are taken repeatedly, they stimulate the drug microsomal meetabolizing syndrome, increasing the amount of enzymes and faster rate of drug metabolism, duration of action is decreased for all drugs metabolized by cytochrome P-450, formulates tolerance
Metabolic inhibition
Some drugs inhibit rather than induce production of microsomal enzymes, excess drug may accumulate in the body and the dose requirement may need to be reduced to avoid toxicity
1st order kinetics
For most drugs is proportional to the plasma concentration, conc. of drug diminishes logarithmically with time
zero order kinetics
Occurs when drug elimination does not change with time
Pharmacodynamics
Study of how drugs produce their effect on the body
Signal transduction
Process by which a receptor binding a ligand leads to a cascade of biochemical events that results in physiological effect
4 basic mechanisms of transmembrane signaling
1) Lipid soluble ligand crosses the membrane and acts on the intracellular receptor
2) Transmembrane receptor proteins that upon binding a ligand intracellular enzymatic activity is activated
3) Ligand gated ion channels opening or closing in result of binding
4) Transmembrane receptor stimulates a G protein that generates a 2ndary messenger (often use cAMP)
Example of drug that is less selective resulting in having multiple unintended consequences
Propranolol acts as a B blocker used to act on B1 and B2 receptors and inhibit effect of norepi on heart, but it is non specific and also has an impact on the lungs as well causing bronchoconstriction and therefore isn’t good to use in patients with asthma or COPD (except is it tho? Because some of the modern studies we’ve seen said B blocker benefit outweighs asthma COPD risk)
Agonist
Drug that interacts with a receptor and produces a pharmacologic response, once inserted to a suitable receptor drug acts same way normal hormone would, has affinity and efficacy
Antagonist
Drug that interacts with a receptor and produces no response, in presence of an antagonist drug, normal response reduced or completely prevented, antagonists have affinity for receptor but lack efficacy
Partial agonist
Do not evoke maximal response compared to a strong agonist, efficacy somewhere between a full agonist and full antagonist, have affinity for receptor but often do not activate receptor resulting in decreased efficacy
Chirality/sterioisomerism
Chemical structures that contain an assymetric carbon with all 4 valences utilized by different groups resulting in nonsuperimposible mirror images of each other
Determining R or S chirality
Rank the valence groups off the central carbon from highest atomic number to lowest, if it goes clockwise then it is R, if it goes counter it is S
Example of how isomers matter
Despite having the same chemical equation, the chirality of S-citalopram and R-citalopram result in S-citalopram being the most selective SSRI to have a therapeutic response while R has no clinical benefits and is not therapeutically active
Therepeutic index
Describes relative safety of a drug expressed in a radion LD50/ED50
LD50
Lethal dose that will kill 50% of animals given drug
ED50
Effective dose that will produce therapeutic effect in 50% of animals given the drug
The greater the Therapeutic index, the _____. The closer the TI is to 1, the ______
the safer the drug, greater potential danger to the patient
Down regulation
Desensitization - if receptors are continually stimulated as is the case with chronic use of certain drugs, their responsiveness may decrease as a result of decrease in # of receptors or changing responsiveness to existing receptors
Up regulation
Supersensitivity - prolonged decrease in stimulation of receptors can result in functional increase in receptor sensitivity, may occur with chronic use of receptor antagonist drugs, results increased production of receptors
Placebo
Preparation that is devoid of intrinsic pharmacologic activity, any response is solely the patient’s psychologic reaction and not to direct physiologic or biochemical action of the placebo itself
List the essential amino acids (think of the acronym)
PVT TIM HALL
1) Histidine
2) isoleucine
3) leucine
4) lysine
5) methionine
6) phenylalanine
7) threonine
8) tryptophan
9) valine
10) arginine
B9 folate deficiency can cause
megaloblastic anemia
Development pathway of an RBC
Pluripotential hematopoietic stem cell -> CFU-S (committed to the myeloid line) -> CFU-B -> CFU-E -> proerythrocyte -> reticulocyte -> erythrocyte
Ferritin function, where is it found, and what is the precursor called before it binds iron
The storage form of iron in all types of cells, found in serum as well used to measure iron deficiency, in the liver is majority of stores, before binds iron is apoferritin
Apotransferrin and transferrin. What is suggested if transferrin is high?
The transporter molecule of iron in the blood stream, apotransferrin lacks bound Fe and becomes transferrin upon binding Fe. Iron defiency anemia.
Pernicious anemia
Anemia brought on by conditions such as gastric bypass which prohibit a patient from being able to absorb enough B12 and thus are deficient
D antigen
The most immunogenic antigen on the surface of certain people’s RBC’s, form the basis of the rhesus factor Rh with individuals being Rh positive (they have the D antigen and thus no antibodies against it) or Rh negative (they lack the D antigen and thus have antibodies against it)
Sensitivity
Measure of a test’s ability to pick up a positive value (regardless of false positives), a sensitive test with a negative diagnosis rules out a condition (snout)
Specificity
Measure of a test’s ability to determine negative values (regardless of false negatives), a specific test with a positive diagnosis rules in a condition (Spin)
Positive predictive value
Proportion of patients with a positve test who truly have the disease
List 3 mandatory questions to ask every time you order a medication
Any prior drug allergies or reactions to meds in the past?
Any chance you could be pregnant or are breastfeeding?
Any other medications you are taking?
