Anesthetics and Analgesics

Question 1

General CNS Pharmacology

Answer 1

 Drugs Act on Specific Receptors that Modulate Synaptic Transmission
 Mechanisms:
 Act Directly on Receptor
 2nd Messenger Coupling
 Affecting Ion Channels
 Agonists or Antagonists
 Either Excite or Inhibit Neural Function

Question 2

Neurotransmitters of CNS

Answer 2

 Glutamate – Excitatory
 GABA/Glycine – Inhibitory
 Acetylcholine – Excitatory or Inhibitory –
Muscarinic Receptors mainly in CNS
 Dopamine – slow inhibitory action
 Norepinephrine – Excitatory
 Serotonin - Excitatory or Inhibitory

Question 3

Blood brain barrier

Answer 3

 Unique to CNS & created by combination of
different tissues
 “Tight junctions” between endothelial cells
 astrocytes (CNS supporting cells)
 impermeable basement membrane in CNS

Question 4

What is the only thing that can penetrate the blood brain barrier

Answer 4

lipid soluble chemicals and molecules transported by specific active transport systems
 most chemical enter brain by simple diffusion

Question 5

What are anesthetics

Answer 5

implies loss of consciousness
 loss of memory of event or pain
 ideal for longer surgery/procedures
 local versus general (systemic)

Question 6

What are analgesics

Answer 6

implies relief of pain
 conscious and aware
 no memory loss

Question 7

An ideal anesthetic must:

Answer 7

1. Produce LOC with rapid onset
2. Amnesia (especially in orthopedic Sx)
3. Skeletal muscle relaxation
4. Inhibition of sensory & autonomic reflexes
5. Minimum of toxic side effects
6. Rapid onset of anesthesia, easy adjustment, and rapid recovery of consciousness

Question 8

Stage I of anesthesia

Answer 8

Analgesia: Conscious, but with loss of somatic pain/sensation

Question 9

Stage II of anesthesia

Answer 9

Excitement (Delirium): conscious & amnesiac, but agitated/restless

Question 10

Stage III of anesthesia

Answer 10

Surgical anesthesia: begins with onset of regular, deep respiration, progresses to hypoventilation and bradynpea
** this is where they keep you during surgery

Question 11

Stage IV of Anesthesia

Answer 11

Medullary paralysis: cessation of spontaneous breathing decreased ability to self regulate BP, HR, etc
** this real bad

Question 12

In general, how are anesthetics administrated?

Answer 12

combination of inhaled and IV

Question 13

Inhaled anesthetic Agents

Answer 13

 Halothane (Fluothane)
 Nitrous Oxide (laughing gas)

Question 14

IV Anesthetics: Barbituates

Answer 14

fast acting, relatively safe
 Increase time Cl channels are open
 Thiopental (Pentothal), Methohexital

Question 15

What are adverse effects of Barbiturates?

Answer 15

long 1/2 life = greater general sedation, potential for OD

Question 16

IV Anesthetics: Benzodiazepines

Answer 16

 Suffixes commonly pam or lam
 Diazepam (Valium), Lorazepam, Midazolam
 adverse effects: similar to barbiturates, but milder due to being more selective
 Increases frequency of CL channel openings

Question 17

IV Anesthetics: Propofol (Diprivan)

Answer 17

most used anesthesia drug in surgery and for drug induced comas
 Faster clearance that older drugs
 Less of a “hangover: effect

Question 18

IV Anesthetics: Katamine (this is on test)

Answer 18

“dissociative anesthesia”- is a cardiovascular stimulant

Question 19

IV Anesthetics: Etomidate

Answer 19

produces hypnotic anesthesia w/o CV adverse effects

Question 20

IV Anesthetics: Opioids

Answer 20

Fentanyl & Morphine – Used more post-operatively for pain control

Question 21

Pharmacokinestics of general anesthetics

Answer 21

These agents are lipid soluble & cross BBB
 and become widely distributed throughout
body
 stored in fat tissue and released slowly  prolonged recovery/hangover-like effect
 confusion, disorientation, lethargy, stage II anesthesia
 worse in patients with larger adipose stores

Question 22

3 things that affect drug metabolism

Answer 22

age, pulmonary, and hepatic function

Question 23

Preoperative medications

Answer 23

 Barbiturates: anti-anxiety & amnesia
 Benzodiazepines: anti-anxiety, amnesia,
relaxation
 Antihistamines: sedation & inhibit vomiting
 Antacids: decrease risk of aspiration damage

Question 24

Neuromuscular Blockers pre op

Answer 24

skeletal muscle paralysis
 anticholinergics at NMJ: Curare (Tubocurarine)
 depolarizing blockers: Succinylcholin

Question 25

Goal of local anesthetic

Answer 25

block afferent neurotransmission
 peripheral nerve (nerve block)
 spinal cord (spinal block)

Question 26

advantages of local anesthetics

Answer 26

 rapid recovery
 absence of cognitive problems after surgery (no
amnesia)
 minimal effects on CV, respiratory or renal function

Question 27

disadvantages of local anesthetics

Answer 27

not as complete loss of sensation

Question 28

suffix of local anesthetics

Answer 28

“caine”

Question 29

Common Local Anesthetic:

Answer 29

• Lidocaine
• Onset: slow
• Duration: short
• Uses: Infiltration, peripheral nerve block, spinal

Question 30

Mechanisms of action of local anesthetics

Answer 30

• Inhibit Na+ channel opening

Question 31

Clinical uses of local anesthetics:

Answer 31

 Topical: applied to skin & mucous membranes  Transdermal: drive in w/ iontophoresis or
phonophoresis
 Infiltrate: applied to broken skin or sub-q
 Peripheral nerve block: inject close to nerve
trunk
 Central nerve block (epidural or spinal): inject
into (epidural) space surrounding the spinal cord
or within the subarachnoid (intrathecal) space
 Usually L3-4 or L4-5, indwelling catheter
 Ganglionic block: inject sympathetic ganglion

Question 32

What is ganglion block commonly used for?

Answer 32

chronic regional pain syndrome

Question 33

“Differential” Nerve block

Answer 33

 Smaller diameter (C-fibers) and unmyelinated
fibers are more sensitive to the anesthetic
 Peripheral pain is carried by C-fibers –> good pain relief can be achieved at doses that do not causes paralysis
 Sympathetic nervous system carried by C-fibers –> affecting vasomotor tone (vasoconstriction/ dilation)
 But, depends on the dose (high concentration, larger fibers affected)

Question 34

Systemic Effects of Local Anesthetics

Answer 34

anesthetic diffuses throughout body

Question 35

CNS Effects of Local Anesthetics

Answer 35

 initial excitation (agitation, confusion, seizures)
 latent effects: CNS depression (somnolence)

Question 36

Cardiovascular Effects of Local Anesthetics

Answer 36

cardiovascular depression: decreased HR, BP

Question 37

Local anesthetics may be useful when…

Answer 37

applied transdermally with ionto or phonophoresis

Question 38

Patients with complex regional pain syndrome:

Answer 38

 schedule PT after pt receives ganglionic or nerve block, when maximally effective
 maximize use of the involved extremity

Question 39

Patients w/ indwelling cath for severe/chronic pain

Answer 39

Caution: possible loss of sensation/temperature

Question 40

What does the term opiod refer to?

Answer 40

all compounds mimicking the effect of morphine (an opium derivative)

Question 41

How to Opioids work?

Answer 41

 All utilize the endogenous neurotransmitters
pathways involved in descending pain modulation
 Receptors for opioids are primarily in periaqueductal gray and raphe magnus, but also in the SC and periphery
 Descending fibers carry pain modulating signals through the lateral fasciculus to the SC, where it modulates pain through interneurons
 Both central and peripheral effects of opioids

Question 42

Endogenous opioids

Answer 42

 Enkephalins
 Dynorphins
 Endorphins
(-endorphin: most potent for analgesia)

Question 43

Endogenous opioid receptors

Answer 43

Primarily mu, but also kappa R’s are most important for analgesia

Question 44

opiod receptors and their strength

Answer 44

• Mu: most potent for pain relief and in highest concentration in the periaqueductal gray (also the most side effects)
• Gamma: brainstem and other locations in CNS
• Kappa: Widely distributed, importance unknown

Question 45

Strong (binding with Mu) Opioids

Answer 45

• Meperidine: given oral, IM, IV, SQ (2-4hr)
• Morphine: Given IM, IV, SQ, Epi (4-5 hr)

Question 46

Mild to moderate (bind with kappa and/or delta) Opioids

Answer 46

• Codine: Oral, IM, SQ (4 hr)
• Oxycodone: Oral (3-4 hr)

Question 47

Mixed (both agonist and antagonist effects) Opioids

Answer 47

Butorphanol: IM, IV (3-4 hr)

Question 48

Effects of strong opioids

Answer 48

 Binds primarily at mu Rs
 greatest analgesia, but greatest potential for OD
 administration: oral, IM, SQ, IV or intrathecal (pump)

Question 49

Effects of mild-moderate opioids

Answer 49

 tend to bind kappa and delta more than mu Rs

Question 50

Effects of Mixed opioids

Answer 50

 antagonists at mu, but agonists at kappa & delta R
 adequate analgesia, but less euphoria & sedation

Question 51

Opioid Antagonist

Answer 51

• Naloxone
• Block all opioid R
• Reverse analgesia, euphoria, and respiratory depression

Question 52

Mechanism of Opioid Analgesia

Answer 52

• 1st order afferents for peripheral pain reception move in
• Endogenous or exogenous opioids inhibit transmission of substance P or other pain neurotransmitter from getting to descending pain modulators

Question 53

Other effects of opioids

Answer 53

 Acting at central brain areas, opioids also
produce central pain inhibition and euphoria
 Thalamus, hypothalamus, limbic system
 Alters “perception of pain” (pain doesn’t hurt)
 Addiction
 Tolerance
 Respiratory and CV depression
 Acting on peripheral receptors (such as in skin
and joints), may cause local analgesia

Question 54

adverse/side effects of opioids

Answer 54

 Sedation, drowsiness & mental slowing
 Euphoria and confusion
 Respiratory depression
 rate and depth of respiration both decrease
 Orthostatic hypotension
 Nausea and vomiting
 Constipation
 Addiction: drug seeking behavior
 Dependence: withdrawal in absence of drug
 Tolerance: increased dose to achieve same effect

Question 55

Opioid Withdrawal symptoms

Answer 55

 Body aches
 Shivering
 Diarrhea
 Stomach cramps
 Fever
 Sweating
 Gooseflesh
 Tachycardia
 Insomnia
 Uncontrollable yawning
 Irritability
 Weakness/fatigue
 Loss of appetite
 Nausea & vomiting