Week 8 (Anesthetics, Transplant, Cardiac Life Support) Flashcards

Question

Cocaine as topical anesthetic

Answer 1

Cocaine is **vasoconstrictive** (less bleeding in surgical area) ENT uses cocaine for endoscopy of nose/sinuses (can **anesthetize mucous membrane**) Only **ester** that is metabolized in the **liver**

Answer 2

Local anesthetic Disadvantages are that it has **short** **duration**, systemic toxicity, allergic reactions

Answer 3

Most widely used cocaine derivative Inhibits membrane depolarization by blocking conductance of Na+ into cell (reversibly binds and **inactivates Na+ channels**) Blocks conduction in **peripheral nerves** Action ends when concentration falls below critical minimal level **Rapid** **onset** of action, **2 hr duration** (4 hr with epinephrine)

Answer 4

**Small C fibers (unmyelinated)** and **small/medium sized A delta fibers (myelinated)** are more sensitive to action of local anesthetics than larger fibers, so patients may be able to feel sensations such as pressure and vibration but not pain A alpha: muscle spindle A beta: muscle spindle, touch A gamma: touch, pressure **A delta: pain** B: preganglionic autonomic **C: pain**

Answer 5

**Amine** end is **hydro**philic **Aromatic** end is **lipo**philic **Linked** by intermediate chain: **amino amides** have amide link and **amino esters** have ester link

Answer 6

Amides have **"i"** in first part of word **Lidocaine** **Mepivacaine** Prilocaine **Bupivacaine** Etidocaine Dibucaine Metabolized by **liver** and allergic reaction less likely

Answer 7

Esters have **no "i"** in first part of word Tetracaine **Procaine** Chloroprocaine **Cocaine** **Benzocaine** Metabolized by **pseudocholinesterase** (a plasma enzyme) and more likely to have **allergic reaction**

Answer 8

**Lipid solubility** determines potency (increased lipid solubility leads to faster blockade of Na+ channels) **Diffusibility** influences speed of action **Protein binding** related to duration of action Percent ionization at physiologic pH: **nonionized** form **diffuses** across nerve membrane so means **faster** **onset** of action; **decreased pH** shifts equilibrium toward ionized form which **delays** onset of action (slower onset of action and less efficetiveness in presence of inflammation which has acidic environment) **Vasodilating** properties

Answer 9

**Bicarbonate**: to speed onset of action by increasing pH **Epinephrine**: vasoconstrictor so washout of anesthetic slower so longer duration of local anesthetic **Opioids**: analgesic so can use less local anesthetic, less motor blockade but same sensory blockade **Hyaluronidase**: enzyme that breaks collagen so better tissue penetration of local anesthetic; only used in ophtho cases for retrobulbar block

Answer 10

**Esters** metabolized by plasma enzyme **pseudocholinesterase** and **excreted in urine** Exception is **cocaine** which undergoes metabolism in the **liver** **PABA** is an **allergen** and a metabolite of hydrolysis by pseudocholinesterase (?) **Amides** metabolized in **liver** and should be used with caution in pts with liver disease

Answer 11

Due to the anesthetic solution: **Systemic toxicity** (cardiovascular and CNS) Allergy (**hypersensitivity** reaction; hives, swelling) **Neurotoxicity** **Tissue irritation** **Cardiovascular** toxicity: **decrease depol** of cardiac tissue, **decrease conduction velocity**; vasodilation leading to **hypotension**; negative inotropic effect leading to **bradycardia**, **v-fib,** **asystole** **CNS** toxicity: **light** **headedness**, **tinnitus**, circumoral numbness, **metallic** taste, **double** **vision**, **drowsiness**, **slurred speech**, **nystagmus**, **seizures** leading to hypoxia, acidosis, hyperkalemia, respiratory arest

Answer 12

**Numbness of tongue** **Lightneadedness** **Visual disturbance** **Muscular twitching** **Unconsciousness** **Convulsions** **Coma** **Respiratory arrest** **CVS depression**

Answer 13

**Benzocaine: methemoglobinemia** **2-chloroprocaine**: **back pain** when large doses used and is related to **EDTA** in preparation **Bupivacaine**: CVS toxicity at serum concentration slightly above seizure threshold, **cardiac arrest** that is resistant to resuscitation (pt needs to be on bypass until bupivacaine wears off)

Answer 14

**Topical** anesthesia **Local infiltration** **IV regional** anesthesia: Bier block **Peripheral nerve block:** brachial plexus, median nerve **Spinal** anesthesia **Epidural** anesthesia **Caudal block**

Answer 15

**Somatic** nervous system: **Ach** acts on **nicotinic** receptors of motor neurons of **skeletal muscle** **ANS** **sympathetic** nervous system (thoracolumbar region with ganglia near spinal cord): **Ach** is preganglionic but **NE** is primary postganglionic (**Epi** for adrenal glands and **Ach** for sweat and salivary glands though) **ANS parasympathetic** nervous system (cervicosacral region with ganglia near innervated tissue): **Ach** only!

Answer 16

**Ach** is NT for: **All preganglionic parasymp** and **symp** ANS fibers **All postganglionic parasymp** ANS fibers **Postganglionic symp** fibers to **sweat** and **salivary** glands **All somatic motor neurons** released at **NMJ**

Answer 17

Receptor is **ligand-gated ion channel** **2 Ach** molecules required to bind 2 alpha subunits to **open Na/K ion channel**

Answer 18

**G protein coupled receptor** **Ach** is ligand

Answer 19

**Nicotinic** receptors use **ion gated** mechanism for signaling; sufficient ligands cause ion channel to open; diffusion of Na and K across receptor causes **depolarization**, the end-plate potential, that opens **voltage-gated Na+ channels** which allows for firing of AP and potentially muscular contraction; primary receptors of **autonomic** ganglia and sole Ach receptors at **NMJ** **Muscarinic** receptors use intracellular **G proteins** as signaling mechanism; ligand (Ach) binds receptor which has 7 transmembrane regions; receptor bound to intracellular G proteins which activate other **ionic channels** via **second messenger cascade**; found at some **autonomic** ganglia and **effector organs**

Answer 20

Degrades **synaptobrevin** (SNARE protein) preventing Ach containing vesicles from **fusing** with **presynaptic** plasma membrane --\> blockade of Ach release --\> flaccidity (**"floppy baby"**) In case of poisoning, treatment is **antitoxin** and **supportive** care (mechanical ventilation) Medical therapies include treatment of migraines, spasticity, cosmetics, etc

Answer 21

Ach released from presynaptic nerve terminal into synaptic cleft after nerve impulse Ach then binds **2 alpha subunits** of **nAchR** opening the **ion channel** to Na+ and K+ When sufficient nAchRs are activated, transmembrane potential **increases from -90 mv to -45 mv** and **AP** is propagated over skeletal muscle surface causing **contraction**

Answer 22

NMB used daily by anesthesiologists to facilitate **endotracheal intubation**, provide muscle **relaxation** as needed for intraabdominal, orthopedic, laparoscopic and delicate surgeries

Answer 23

**Depolarizing** neuromuscular blocker Structurally similar to **Ach** (**competitive agonist**) and binds 2 alpha subunits of nicotinic receptor to open the channel Rapid (**\<60 sec**) depolarization of muscle cells causes **fasciculations** followed by **flaccid paralysis** Use when **rapid** and/or **brief** paralysis desired (rapid **endotracheal** **intubation** for patients at risk for pulmonary aspiration, for pts with potentially difficult ET intubation, relaxation for very short procedures such as direct larygoscopy/biopsy) Remains **bound for several minutes** because NOT broken down by acetylcholinesterase; **diffuses away** from motor end plate and quickly degraded into acetic acid and choline by **pseudocholinesterase** (which is NOT found at NMJ) Muscle function usually returns after 5-10 min Side effects: **hyperkalemia** due to depolarization (more in pts with recent burns, renal failure, neuro/muscular disorders), **myalgias**, increased **ICP**, intragastric pressure, ophthalmic pressure; may cause prolonged paralysis if pt has atypical pseudocholinesterase; **malignant hyperthermia**

Answer 24

**Everything else** other than succinylcholine!! Quarternary ammonium compounds with structures similar to Ach Bind selective alpha subunits of nicotinic receptors Bulky molecules bind nAchR and act as **competitive antagonists** to **prevent depolarization** Reversal due to slow release into NMJ and then hepatic/biliary and/or renal **metabolism**

Answer 25

**Benzylisoquinolines**: curare derivatives including d-tubocurare, atracurium, cisatracurium **Aminosteroids**: pancuronium, vecuronium, **rocuronium**

Answer 26

**No** evidence of NM blockade when even **70%** of nAchR are blocked! Once **80-90% of nAchRs are blocked** then **NM transmission fails** This margin of safety essential in modern anesthesia and is basis for monitoring NM blockade in OR

Answer 27

**Mivacurium**: duration 12-20 min; like succinylcholine metabolized by **pseudocholinesterase**; but discontinued by manufacturer

Answer 28

**Cisatracurium**: duration 40-75 min; metabolized by **Hofman** **elimination** (pH and temp dependent enzymatic degradation **NOT organ dependent**; good for pts with liver and kidney disease) **Vecuronium**: duration 45-90 min; **primarily hepatic/biliary** but some renal excretion **Rocuronium**: like succinylcholine, rapid onset makes appropriate for **rapid** intubation; duration 35-75 min; **primarily hepatic/biliary** but some renal excretion

Answer 29

**Pancuronium**: duration 60-120 min; atypically increases HR by **vagal** **antagonism** at cardiac receptors; long-acting NDMBs with primarily **renal excretion**

Answer 30

**Histamine** release by **atracurium, pancuronium, mivacurium** (and **morphine**!) can cause **bronchospasm**, **flushing**, peripheral **vasodilation** (avoid in severe asthmatics, septic and other susceptible pts) Allergic reactions can cause **anaphylaxis**

Answer 31

Problem: **residual** **weakness** at end of surgery may prevent adequate spontaneous ventilation Solution: reverse the paralysis by **increasing** amount of **Ach at NMJ (neostigmine)** to competitively beat out NDMB and cause muscle contractions

Answer 32

**AchEIs** reversibly bind and inactivate AchE in NM junction Used to **increase level of Ach in NMJ** to compete with NDMBs for binding sites, thereby reversing NDMB paralysis

Answer 33

Ach is also increased at **MUSCARINIC** receptors! **SLUDGE** **Antimuscarinic** (**atropine**) agents must be used to block effects of Ach and avoid cholinergic effects!

Answer 34

**Reversibly inhibits AchE** to allow Ach to remain elevated to stimulate nicotinic and muscarinic receptors Most commonly used **reversal agent** in OR Weak nAchR agonist so excess dosing can itself cause weakness Also **inhibits pseudocholinesterase** activity, so NEVER give succinylcholine after administering neostigmine

Answer 35

Reversible AchEI Rapid onset only 1-2 min, lasts \>1hr only at higher doses Less than 10% as potent as neostignime Used to **diagnose myasthenia gravis**: if strength improves after giving edrophonium it means Ach levels got high enough to overcome Ach receptor antibodies, leading to resumption of stimulation at NMJ

Answer 36

Reversible AchEI 20% as potent at neostigmine Limited inhibition of pseudocholinesterase Used to **treat myasthenia gravis**

Answer 37

Tertiary amine Only AchEI that **crosses BBB** Used to treat CNS anticholinergic toxicity and for antagonism of volatile anesthetic effects especially in patients with **Alzheimer's disease**

Answer 38

**Organophosphates** Form very stable bonds to enzyme AchE --\> increased Ach Used in ophthalmology to induce miosis and thereby decrease intraocular pressure Key ingredient in pesticides Acute **treatment** of **organophosphate** **poisoning** is with anticholinergic agent **atropine** but definitive treatment is **pralidoxime** (must be given before "aging" occurs though)

Answer 39

**Inhibition of AchE** causes increased Ach which causes increased muscle contractility but ALSO **cholinergic crisis** (**SLUDGE** = salivation, lacrimation, urination, defecation, GI upset/hypermotility, emesis) and **bradycardia** Excessive dosing can **exacerbate weakness**

Answer 40

**Pretreat** with an **anticholinergic** agent to act at muscarinic receptors Ex: **glycopyrrolate, atropine**

Answer 41

**Atropine**: fast onset, shorter duration, crosses BBB, used in tx of bradycardia and as part of **ACLS** **Glycopyrrolate**: intermediate onset, longer duration, does NOT cross BBB, may also be used to counteract bradycardia (induced by surgical stimulation of parasymp nervous system)

Answer 42

**Antidote** for AchEIs because **reactivates inhibited AchE** **Treat organophosphate exposure** Helps **prevent phosphorylation by organophosphate** and helps **reactivate AchE** Also used to treat patients exposed to **nerve gas** or with OD of **pyridostigmine** (cholinergic crisis) in **myasthenia gravis**

Answer 43

Safe and effective reversal is based on speed of onset and duration of action fo drugs used **Neostigmine/glycopyrrolate** **Edrophonium/atropine** **Pyridiostigmine/glycopyrrolate** Physostigmine/not applicable

Answer 44

**Novel NMB reversal agent** Negatively charged cyclodextrin molecule that reverses NMB by electrostatically **binding aminosteroid nondepolarizing agents** Most avidly encapsulates **Rocuronium**, less avidly binds vecuronium and no binding of benzylisoquinolines Binding creates concentration gradient favoring **release of rocuronium fron nAchR** Equal or faster recovery time after rocuronium compared with succinylcholine Overcomes problem of inability to achieve timely/complete NMB reversal and complications by relying on Ach

Answer 45

Because living donor kidneys are healthier--they're alive! NOT because of matching

Answer 46

Transplant doubles anticipated lifespan of patient waiting for transplant Life-prolonging, and quality-of-life-enhancing

Answer 47

Diabetes mellitus glomerulonephritis Hypertension Other Annual death rate overall is 6.3%

Answer 48

**Hyperacute** rejection (antibody-mediated) **Acute** rejection (cell-mediated, antibody-mediated, vascular rejection) **Chronic** rejection Chronic allograft nephropathy (CAN)

Answer 49

Signal 1: **APC** presents antigen to T cell receptor ("kiss") Signal 2: **Costimulation** by B7 on APC to CD28 on T cell ("hug"); after 2 signals, **calcineurin** (phosphatase enzyme) dephosphorylates NFAT so **NFAT** can now get into the nucleus and cause transcription of **IL-2** and **CD25** --\> Signal 3: **self-proliferation** signal

Answer 50

**Calcineurin inhibitors** Block the dephosphorylation of NFAT so **NFAT** cannot get into the nucleus to cause transcription of **IL-2** and **CD25** --\> **no signal 3** to cause **proliferation** of T cell Slow down process of responding to foreign antigen Note: don't have to tweak immune system THAT much, just cut calcineurin activity by **50%** and this is enough

Answer 51

**CTLA-4 Ig** Like **abatacept** in RA **Blocks costimulatory molecule** (B7) from interacting with counterpart on T cell

Answer 52

**Mab to CD25** receptor (the receptor for **IL-2**) on T cells Blocks signal 3 so T cell cannot proliferate

Answer 53

AKA **Rapamycin** **Blocks mTOR** so cannot do **cell division**

Answer 54

Prolonged DGF Acute reversible **decrease in GFR** (due to **vasoconstriction** caused by calcineurin) Post-transplant **TTP** Chronic CI toxicity Electrolyte disturbance

Answer 55

Because any transplant causes **fibrosis** in some way 20% of non-renal transplant recipients become candidates for renal transplant

Answer 56

**Intractable** angina **Refractory** heart failure **Uncontrolled** ventricular arrhythmias

Answer 57

Baseline 5-year survival is 40% but with these meds, can raise that to 75% **ACEI** **Beta blocker** **Aldosterone antagonist** **ICD**

Answer 58

Absolute contraindications: Active malignancy Active infection Obesity with BMI \> 35 Active substance abuse Noncompliance Lack of social support Relative contraindication: Diabetes with end-organ dz Pulmonary HTN Age \> 70 Renal failure Cerebrovascular/peripheral vascular disease Cirrhosis Pulmonary disease

Answer 59

**Status 1A** (days): PA cath + 2 drips; VAD \< 30d; IABP or ventilator, exceptions **Status 1B** (weeks): 1 inotrope; VAD \> 30d **Status 2** (months): everyone else **Longer** wait time for **larger** people and **blood type O** because just harder to find

Answer 60

Biggest mortality in first year is infection and rejection (only 10% of pts) After that, conditional half life is 15 years Cardiac allograft vasculopathy and malignancy more common in year 2 and beyond

Answer 61

No afferents so no angina No efferents so no vaual input so higher resting HR and rely on circulating epi and NE from adrenal during exercise More exaggerated orthostatic response because loss of feedback regulation (baroreceptor reflex, RAAS) Increased receptor density so more sensitive to circulating epi, NE

Answer 62

No effect: **atropine**, **digoxin** (because no vagus nerve) Exaggerated effect: **adenosine, beta agonists, beta blockers** (because more alpha and beta receptors)

Answer 63

Looking for **cellular** and **humoral rejection** Only care about **moderate** and **severe** to treat Treatment of rejection depends on whether pt is **asymptomatic**, **reduced EF** or in **heart failure/shock**

Answer 64

**Asymptomatic** (denervation), **fagitue**, **reduced EF** Panvascular disease, distal pruning Rapid progression Concentric lesions Generally lipid poor, fibrointimal proliferation

Answer 65

Diagnosis: surveillance angiograms, IVUS (not standard) Prevention: **aspirin**, **pravastatin** (doesn't interact with tacrolimus), **vitamin C and E, sirolimus** Treatment: PCI but doesn't work that well and pts usually need **second** **transplant** (TCAD is most common indication for second transplant)

Answer 66

**10-15 years**

Answer 67

**CF** **Idiopathic pulmonary fibrosis (IPF)** **COPD** **Alpha 1 antitrypsin deficiency** **PPH**

Answer 68

No evidence that it makes any difference in terms of survival, but we do it at UCLA anyway

Answer 69

**Infection** biggest problem in **first 30 days** (lung exposed to outside environment...) **Hypertension** **Renal dysfunction** **Hyperlipidemia** **Diabetes** **Bronchiolitis obliterans syndrome** (chronic rejection after transplant; is **progressive** **obstructive** just like emphysema and is biggest cause of death **more than 1 year after transplant**; at 5 years, 50% of pts have this) Skin cancer (**squamous cell carcinoma**) is problem!

Week 8 (Anesthetics, Transplant, Cardiac Life Support) Flashcards

(94 cards)