Group 8/21/19 Flashcards
Learning objectives
- Pharmacokinetics: the dynamics of drug metabolism, excretion, and clearance (finished Goodman and Gilman’s Ch2)
- Anatomy of the upper limb and chest (muscles, tendons, nerves, bone)
- Anatomy of brachial plexus
what polarity class must drugs be before elimination and why?
drugs must be metabolized into more hydrophilic metabolites in order to be eliminated from the renal system; lipophilic elements will not pass readily into the urine
Drug-metabolizing reactions generally transform the drugs into polar, inactive metabolites before they’re excreted
what are the phase 1 reactions of biotransformation that can happen in the liver?*
oxidation, reduction, or hydrolytic reactions with cytochrome P-450. Usually yield slightly polar, water-soluble metabolites, that are often still active.
Geriatric patients will lose this phase first.
what are the phase 2 reactions of biotransformation that can happen in the liver?*
conjugations (Methylation, Glucuronidation, Acetylation, Sulfation) of the phase 1 product with a second molecule. Usually yields very polar, inactive metabolites (renally excreted)
Geriatric patients have More GAS, more phase 2 reactions
Patients who are slow acetylators have increased side effects from drugs because their metabolism is lower
prodrugs definition
pharmacologically inactive compounds that are converted to their active forms by metabolism. Usually requires an ester hydrolysis reaction or amide linkage.
what is the most important organ for excreting drugs and their metabolites?
kidneys
what are the 3 processes of excretion of drugs and metabolites in the urine?
glomerular filtration, active tubular secretion, and passive tubular resorption
where do drugs enter during glomerular filtration, what influences how quickly they are filtered?
- drug enters the tubular lumen to be filtered
- only unbound drug is filtered, so filtration rate depends on extent of plasma binding of drug and glomerular filtration rate
where do drugs enter during active tubular secretion, what happens in this process?
- drug enters proximal renal tubule
- adds the drug to the tubular fluid from the peritubular network
what happens during passive tubular resorption?
- drugs from tubular lumen are resorbed back into systemic circuation
- nonionized forms (more permeable) of weak acids and bases undergo passive resorption, especially on distal tubule
how does the pH of the tubular urine influence excretion of the drugs?
when tubular urine is basic, weak acids are ionized and excreted faster
when tubular urine is acidic, less weak acids are ionized and less acids are excreted
opposite effect for basic drugs (basic drugs excreted slow with basic urine; fast with acidic urine)
what is enterohepatic recycling, and what is its effect?
transporters in the hepatocyte will secrete drugs and metabolites into bile, released into GI tract, reabsorbed into body
can prolong the effects of a drug or toxin
excretion by other routes
drugs can be excreted into sweat, saliva, and tears
how does the pH of milk influence what kind of drugs congregate in it?
milk is more acidic than plasma
basic compounds are more congregated there, does not influence entry of nonelectrolytes
excretion/elimination definition
elimination is a measurement of the amount of a substance removed from systemic circulation per unit time (e.g., mg/min, μg/min, etc.).
clearance definition
clearance is the volume of plasma in systemic circulation from which a substance is completely removed per unit time, measured in L/h or mL/min
equation rate of elimination/C takes into account the concentration of unbound drug
hepatic clearance
drug has a near unity extraction ratio from the liver to the bile, and it has a low concentration.
Elimination rate is limited by the rate the drug can be transported by blood in liver.
how does the drug metabolizing capacity of an eliminating organ relate to how quickly it extracts a drug?
If the organ can metabolize the drug quickly, clearance relates to the organ’s blood flow. If the drug is metabolized slowly, it’s cleared proportionally to the unbound fraction of the drug in the blood and the drug’s intrinsic clearance
renal clearance and factors that affect it
extracts the drug to the urine. Filtration rate of the drug depends on volume of fluid passing through, unbound drug concentration, drug’s intrinsic clearance. Reabsorption depends on protein binding, blood flow, and the state of the nephrons
rates of distribution
the drug starts in the central volume, which includes plasma and tissue reservoirs
These are in equilibrium, and the drug distributes to a final volume
concentrations in the plasma decrease in a log-linear fashion
if blood flow to an organ is affected, it affects the rate of distribution to that organ
compartments in the multicompartment model of drug disposition
central compartment includes highly perfused lean organs like heart, brain, liver, lung, kidneys
final compartment are slowly perfused tissues such as muscle, skin, fat and bone
terminal half life
can occur in drugs that have had prolonged dose or have a high concentration
drug goes beyond the central compartment to deep compartments, and equilibrate slowly from there. Once drug from central compartment gets cleared, then this will start to equilibrate and diffuse out, prolonging half life
what are nonlinear pharmacokinetics and what are they caused by?
nonlinear caused by changes in the parameters, like the clearance, volume of distribution, or half life, depending on the dose or concentration of the drug
can be caused by saturation of protein binding, hepatic metabolism, or active renal transport of the drug
saturable protein binding, and how organs with a low vs high clearance-extraction ratio are affected
drug concentration may increase so that binding sites are occupied and unbound drug concentration increases
organs with low clearance-extraction ratio (eg liver) will cause V and CL to increase as drug concentration increases
organs with high clearance-extraction ratio will increase V and therefore increase the half life
what are the effects of saturable equilibrium?
the rate of drug entry into the systemic circulation exceeds the maximum possible rate of drug metabolism, and elimination becomes zero order
saturation of metabolism may decrease clearance
what are the effects of saturation of metabolism?
decreased clearance and relative rate of drug elimination, though no effect on volume of distribution. Half live does not stay constant
therapeutic index, equation and meaning*
a dosage range that can safely and effectively treat disease
TI= TD50/ED50; TD50 is the median toxic dose, ED50 is the median effective dose
safer drugs have a higher TI value, drugs with lower TI values frequently require monitoring
disadvantages of loading lose
a sensitive person may be exposed to toxic concentrations of a drug, and they can take a long time to decrease
how can you adjust the dosing rate based on a particular patient?
measure the concentration of the drug in the patient during supposed steady state, try to get the minimal and maximal concentration.
calculate new dose by using C(measured)/C(predicted)= dose(previous)/dose(new)
actions of the pectoralis major muscle
adducts and medially rotates humerous
draws scapula anteriorly and inferiorly
flexes and extends the humerus
actions of the pectoralis minor muscle
stabilizes the scapula by drawing it inferiorly and anteriorly
actions of the subclavius muscle
anchors and depresses the clavicle
actions of the serratus anterior muscle
protracts and rotates scapula
actions of the trapezius
descending part elevates
ascending part depresses
middle part retracts scapula
rotates the glenoid cavity superiorly
actions of the latissimus dorsi
extends, adducts, and medially rotates the humerus; raises body toward arms during climbing
actions of the levator scapulae
elevates scapula and rotates its glenoid cavity inferiorly by rotating scapula
actions of the rhomboid minor and major
retract scapula and rotate its glenoid cavity inferiorly; fix scapula to thoracic wall
actions of the deltoid
clavicular part: flexes and medially rotates arm
acromial part: abducts arm
spinal part: extends and laterally rotates arm
actions of the supraspinatus
helps complete adbuction of arm with rotator cuff muscles
actions of the infraspinatus
laterally rotates arm with rotator cuff muscles
actions of the teres minor
laterally rotates arm with rotator cuff muscles
actions of the teres major
adducts and medially rotates arm
actions of the subscapularis
medially rotates arm with rotator cuff muscles; helps hold humerus in the glenoid cavity
brachial plexus definition and roots
a major nerve network that supplies the upper limb
brachial plexus is formed by the union of the anterior rami of the last four cervical (C5-C8) and first thoracic (T1) nerves
what structures does the dorsal scapular nerve innervate?
rhomboids, occasionally supplies levator scapulae
what structures does the long thoracic nerve innervate?
serratus anterior
what structures does the suprascapular nerve innervate?
supraspinatus and infraspinatus muscles; glenohumeral joint
what structures does the subclavian nerve innervate?
subclavius and sternoclavicular joint
what structures does the lateral pectoral nerve innervate?
primarily pectoralis major, sometimes pectoralis minor
what structures does the musculocutaneous nerve innervate?
coracobrachialis, biceps brachii, brachialis); skin of lateral aspect of forearm
what structures does the median nerve innervate?
muscles of anterior forearm compartment (except flexor carpi ulnaris and ulnar half of flexor digitorum profundus); five intrinsic muscles in thenar half of palm
what structures does the medial pectoral nerve innervate?
pectoralis minor and sternocostal part of pectoralis major
what structures does the medial cutaneous nerve of arm innervate?
skin of medial side of arm, as far distal as the medial epicondyle of humerus and olecranon of ulna
what structures does the medial cutaneous nerve of forearm innervate?
skin of medial side of forearm, as far distal as wrist
what structures does the ulnar nerve innervate?
flexor carpi ulnaris and ulnar half of flexor digitorum profundus (forearm); most intrinsic muscles of hand; skin of hand medial to axial line digit 4
what structures does the upper subscapular nerve innervate?
superior portion of subscapularis
what structures does the lower subscapular nerve innervate?
inferior portion of subscapularis and teres major
what structures does the thoracordorsal nerve innervate?
latissimus dorsi
what structures does the axillary nerve innervate?
glenohumeral (shoulder) joint, teres minor, deltoid muscles, skin of superolateral arm (over inferior deltoid)
what structures does the radial nerve innervate?
all muscles of posterior compartment of the arm and forearm; skin of posterior and inferolateral arm, posterior forearm, and dorsum of hand lateral to axial line of digit 4
which nerves does the lateral cord of the brachial plexus connect to?
musculocutaneous, median
which nerves does the posterior cord of the brachial plexus connect to?
axillary and radial
which nerves does the medial cord of the brachial plexus connect to?
median and ulnar
what are the 3 trunks of the brachial plexus, and what nerves are they supplied by?
superior trunk- c5 and c6 roots
middle trunk- c7 root
inferior trunk- c8 and t1 roots
what do the trunks of the brachial plexus divide into, and what muscles do these areas generally innervate?
each trunk divides into an anterior and posterior division
anterior division supplies anterior (flexors and protonators) compartments of upper limb
posterior division supplies posterior (extensors and supinators) compartments
what are the three cords of the brachial plexus?
lateral, medial and posterior
which divisions of which trunks make up the lateral cord of the brachial plexus?
anterior divisions of the superior and middle trunks
which divisions of which trunks make up the medial cord of the brachial plexus?
anterior division of the inferior trunk
which divisions of which trunks make up the posterior cord of the brachial plexus?
posterior divisions of all 3 trunks
what is the action of the biceps branchii muscle?
supinates forearm, flexes while supinated, resists dislocation of the shoulder
what is the action of the coracobrachialis muscle?
helps flex and adduct arm; resists dislocation of shoulder
what is the action of the brachialis muscle?
flexes forearm in all positions
what is the action of the triceps brachii muscle?
extends forearm, resists dislocation of the humerus, important for adduction
what is the action of the aconeous muscle?
helps to extend forearm; stabilizes elbow joint
thorax
part of the body between the neck and the abdomen
intercostal space
space between the nerves that are connected
which ribs are floating?
11-12
which ribs are false/ vertebrochondral
8-10
which ribs are true/ veretebrosternal
1-7
what are the actions and innervations of the serratus posterior superior muscle?
2nd-5th intercostal nerves
proprioception (elevate ribs)
what are the actions and innervations of the serratus posterior inferior muscle?
anterior rami to t9-t12 thoracic spinal nerves
proprioception (depress ribs)
what are the actions and innervations of the levator costarum muscle?
posterior primary rami of c8-t11 nerves
elevate ribs
what are the actions and innervations of the external intercostal muscle?
intercostal nerve
elevate ribs during forced inspiration
what are the actions and innervations of the internal intercostal (including innermost intercostal) muscle?
intercostal nerve
interosseous part depresses ribs; interchondral part elevates ribs; during active/forced respiration
what are the actions and innervations of the subcostal muscle?
intercostal nerve
same as intercostal muscles
what are the actions and innervations of the transverse thoracis muscle?
intercostal nerve
weakly depresses ribs and may be involved in proprioception
which ramus/rami form the intercostal nerves?
anterior rami of nerves t1-t11
which ramus/rami form the subcostal nerve?
anterior ramus of t12
what innervates the breasts?
anterior and lateral cutaneous branches of the 4th-6th intercostal nerves
what are the names for the divisions of the lungs?
right main bronchus and left main bronchus
each main primary bronchus divides into lobar branchi
each lobular branchus divides into several tertiary segmental bronchi
what do the tertiary segmental bronchi divide into?
conducting branchioles
what do the conducting branchioles end in?
terminal branchioles
what is the role of conducting bronchioles?
transport air but lack glands or alveoli
what do the terminal bronchioles give rise to?
respiratory bronchioles
what is the basic structural unit of gas exchange in the lung?
pulmonary alveolus
what is the role of the respiratory bronchioles?
air transportation and gas exchange
what do the respiratory bronchioles give rise to?
2-11 alveolar ducts, which give rise to 5-6 alveolar sacs
where are the nerves of the lungs and visceral pleura derived from?
pulmonary plexuses
which vertebrae does the axillary nerve come from?*
c5-c6
which vertebrae does the musculocutaneous nerve come from?*
c5-c7
which vertebrae does the radial nerve come from?*
c5-t1
which vertebrae does the median nerve come from?*
c5-t1
which vertebrae does the ulnar nerve come from?*
c8-t1
how can the axillary nerve be injured?*
fractured surgical neck of humerus
anterior dislocation of humerus
how can the musculocutaneous nerve be injured?*
upper trunk compression
how can the radial nerve be injured?*
compression of axilla, eg due to crutches or sleeping with an arm over chair
midshaft fracture of humerus
repetitive pronation/supination of forearm, e.g. due to screwdriver use
how can the median nerve be injured?*
supracondylar fracture of humerus (proximal lesion)
carpal tunnel syndrome and wrist laceration (distal lesion)
how can the ulnar nerve be injured?*
fracture of medial epicondyle of humerus “funny bone” (proximal lesion)
fractured hook of hamate (distal lesion) from FOOSH
how can the recurrent branch of median nerve be injured?*
superficial laceration of palm
which nerve does a humerus fracture affect, depending on its location up the arm?*
proximally to distally, “ARM”- axillary, radial, median
how will a patient present with an axillary nerve injury?*
flattened deltoid
loss of arm abduction at shoulder, less than 15 degrees
loss of sensation over deltoid muscle and lateral arm
how will a patient present with an musculocutaneous nerve injury?*
loss of forearm flexion and supination
loss of sensation over lateral forearm
how will a patient present with an radial nerve injury?*
wrist drop: loss of elbow, wrist, and finger extension
decreased grip strength, need to extend wrist
loss of sensation over posterior arm/forearm and dorsal hand
how will a patient present with an median nerve injury?*
ape hand (can't move thumb away/abduct from hand) and pope's blessing loss of wrist flexion, flexion of lateral fingers, thumb opposition, lumbricals of 2nd and 3rd digits loss of sensation over thenar eminence and dorsal and palmar aspects of lateral 3.5 fingers with proximal lesion
how will a patient present with an ulnar nerve injury?*
“ulnar claw” on digit extension
radial deviation of wrist upon flexion (proximal lesion)
loss of wrist flexion, flexion of medial fingers, abduction and adduction of fingers (interossei), actions of medial 2 lumbrical muscles
loss of sensation over medial 1.5 fingers including hypothenar eminence
how will a patient present with a recurrent branch of median nerve injury?*
“ape hand”
loss of thenar muscle group: opposition, abduction, and flexion of thumb
no loss of sensation
what will a lesion in the upper trunk of the brachial plexus cause?*
erb palsy
what will a lesion in the lower trunk of the brachial plexus cause?*
klumpke palsy (claw hand)
what will a lesion in the posterior cord of the brachial plexus cause?*
wrist drop
what will a lesion in the long thoracic nerve in the roots of the brachial plexus cause?*
winged scapula
what will a lesion in the axillary branch of the brachial plexus cause?*
deltoid paralysis
what will a lesion in the radial branch of the brachial plexus cause?*
saturday night palsy (wrist drop)
what will a lesion in the musculocutaneous branch of the brachial plexus cause?*
difficulty flexing elbow, variable sensory loss
what will a lesion in the median branch of the brachial plexus cause?*
decreased thumb function, pope’s blessing
what will a lesion in the ulnar branch of the brachial plexus cause?*
intrinsic muscles of hand, claw hand
how can you remember the sections of the brachial plexus?*
Randy Travis Drinks Cold Beer: Roots, Trunks, Divisions, Cords, Branches
what is the injury and cause of Erb palsy (waiter’s tip)?*
injury: traction or tear of the upper trunk, c5-c6 roots
cause: lateral traction on neck during delivery of infants, trauma in adults
what are the muscle deficits associated with Erb palsy, and the presentation?*
deltoid, supraspinatus, infraspinatus, biceps brachii
waiter’s tip: arm hangs by side, arm medially rotated, arm extended and pronated
what is the injury and cause of Klumpke palsy?*
injury: traction or tear of lower trunk, c8-t1 root
cause: upward force on infants during delivery, trauma to adults, like grabbing a tree branch while falling
what are the muscle deficits associated with Klumpke palsy, and the presentation?*
intrinsic hand muscles: lumbricals, interossei, thenar and hypothenar
total claw hand
what is the injury and cause of thoracic outlet syndrome?*
injury: compression of lower trunk and subclavian muscles
causes: cervical rib, pancoast tumor
what are the muscle deficits associated with thoracic outlet syndrome, and the presentation?*
intrinsic hand muscles: lumbricals, interossei, thenar and hypothenar
atrophy of intrinsic hand muscles, ischemia, pain, and edema due to vascular compression
what is the injury and cause of winged scapula?*
injury: lesion of long thoracic nerve, roots c5-c7 (“wings of heaven”)
causes: axillary node dissection after mastectomy, stab wounds
what are the muscle deficits associated with winged scapula, and the presentation?*
serratus anterior
inability to anchor scapula to thoracic cage, cannot abduct arm over horizontal position
