Anesthetics and Analgesics Flashcards
General CNS Pharmacology
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
Neurotransmitters of CNS
Glutamate – Excitatory
GABA/Glycine – Inhibitory
Acetylcholine – Excitatory or Inhibitory –
Muscarinic Receptors mainly in CNS
Dopamine – slow inhibitory action
Norepinephrine – Excitatory
Serotonin - Excitatory or Inhibitory
Blood brain barrier
Unique to CNS & created by combination of
different tissues
“Tight junctions” between endothelial cells
astrocytes (CNS supporting cells)
impermeable basement membrane in CNS
What is the only thing that can penetrate the blood brain barrier
lipid soluble chemicals and molecules transported by specific active transport systems
most chemical enter brain by simple diffusion
What are anesthetics
implies loss of consciousness
loss of memory of event or pain
ideal for longer surgery/procedures
local versus general (systemic)
What are analgesics
implies relief of pain
conscious and aware
no memory loss
An ideal anesthetic must:
- Produce LOC with rapid onset
- Amnesia (especially in orthopedic Sx)
- Skeletal muscle relaxation
- Inhibition of sensory & autonomic reflexes
- Minimum of toxic side effects
- Rapid onset of anesthesia, easy adjustment, and rapid recovery of consciousness
Stage I of anesthesia
Analgesia: Conscious, but with loss of somatic pain/sensation
Stage II of anesthesia
Excitement (Delirium): conscious & amnesiac, but agitated/restless
Stage III of anesthesia
Surgical anesthesia: begins with onset of regular, deep respiration, progresses to hypoventilation and bradynpea
** this is where they keep you during surgery
Stage IV of Anesthesia
Medullary paralysis: cessation of spontaneous breathing decreased ability to self regulate BP, HR, etc
** this real bad
In general, how are anesthetics administrated?
combination of inhaled and IV
Inhaled anesthetic Agents
Halothane (Fluothane)
Nitrous Oxide (laughing gas)
IV Anesthetics: Barbituates
fast acting, relatively safe
Increase time Cl channels are open
Thiopental (Pentothal), Methohexital
What are adverse effects of Barbiturates?
long 1/2 life = greater general sedation, potential for OD
IV Anesthetics: Benzodiazepines
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
IV Anesthetics: Propofol (Diprivan)
most used anesthesia drug in surgery and for drug induced comas
Faster clearance that older drugs
Less of a “hangover: effect
IV Anesthetics: Katamine (this is on test)
“dissociative anesthesia”- is a cardiovascular stimulant
IV Anesthetics: Etomidate
produces hypnotic anesthesia w/o CV adverse effects
IV Anesthetics: Opioids
Fentanyl & Morphine – Used more post-operatively for pain control
Pharmacokinestics of general anesthetics
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
3 things that affect drug metabolism
age, pulmonary, and hepatic function
Preoperative medications
Barbiturates: anti-anxiety & amnesia
Benzodiazepines: anti-anxiety, amnesia,
relaxation
Antihistamines: sedation & inhibit vomiting
Antacids: decrease risk of aspiration damage
Neuromuscular Blockers pre op
skeletal muscle paralysis
anticholinergics at NMJ: Curare (Tubocurarine)
depolarizing blockers: Succinylcholin
Goal of local anesthetic
block afferent neurotransmission
peripheral nerve (nerve block)
spinal cord (spinal block)
advantages of local anesthetics
rapid recovery
absence of cognitive problems after surgery (no
amnesia)
minimal effects on CV, respiratory or renal function
disadvantages of local anesthetics
not as complete loss of sensation
suffix of local anesthetics
“caine”
Common Local Anesthetic:
- Lidocaine
- Onset: slow
- Duration: short
- Uses: Infiltration, peripheral nerve block, spinal
Mechanisms of action of local anesthetics
- Inhibit Na+ channel opening
Clinical uses of local anesthetics:
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
What is ganglion block commonly used for?
chronic regional pain syndrome
“Differential” Nerve block
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)
Systemic Effects of Local Anesthetics
anesthetic diffuses throughout body
CNS Effects of Local Anesthetics
initial excitation (agitation, confusion, seizures)
latent effects: CNS depression (somnolence)
Cardiovascular Effects of Local Anesthetics
cardiovascular depression: decreased HR, BP
Local anesthetics may be useful when…
applied transdermally with ionto or phonophoresis
Patients with complex regional pain syndrome:
schedule PT after pt receives ganglionic or nerve block, when maximally effective
maximize use of the involved extremity
Patients w/ indwelling cath for severe/chronic pain
Caution: possible loss of sensation/temperature
What does the term opiod refer to?
all compounds mimicking the effect of morphine (an opium derivative)
How to Opioids work?
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
Endogenous opioids
Enkephalins
Dynorphins
Endorphins
(-endorphin: most potent for analgesia)
Endogenous opioid receptors
Primarily mu, but also kappa R’s are most important for analgesia
opiod receptors and their strength
- 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
Strong (binding with Mu) Opioids
- Meperidine: given oral, IM, IV, SQ (2-4hr)
- Morphine: Given IM, IV, SQ, Epi (4-5 hr)
Mild to moderate (bind with kappa and/or delta) Opioids
- Codine: Oral, IM, SQ (4 hr)
- Oxycodone: Oral (3-4 hr)
Mixed (both agonist and antagonist effects) Opioids
Butorphanol: IM, IV (3-4 hr)
Effects of strong opioids
Binds primarily at mu Rs
greatest analgesia, but greatest potential for OD
administration: oral, IM, SQ, IV or intrathecal (pump)
Effects of mild-moderate opioids
tend to bind kappa and delta more than mu Rs
Effects of Mixed opioids
antagonists at mu, but agonists at kappa & delta R
adequate analgesia, but less euphoria & sedation
Opioid Antagonist
- Naloxone
- Block all opioid R
- Reverse analgesia, euphoria, and respiratory depression
Mechanism of Opioid Analgesia
- 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
Other effects of opioids
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
adverse/side effects of opioids
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
Opioid Withdrawal symptoms
Body aches
Shivering
Diarrhea
Stomach cramps
Fever
Sweating
Gooseflesh
Tachycardia
Insomnia
Uncontrollable yawning
Irritability
Weakness/fatigue
Loss of appetite
Nausea & vomiting
