Pharmacology Flashcards
Morphine
- produces analgesia
- activates opioid receptors on periaqueductal grey (PAG)
Naloxone
- antagonist
- blocks effects of morphine
- blocks placebo effect
- competitive antagonist
- short duration of action
- no oral availability
Cocaine
-blocks catecholamine reuptake
What confers most of key properties of local anesthetics?
-chemical structure
Local anesthetics are weak _______.
Bases
The intermediate chain of a local anesthetic is determinant for:
- onset speed
- duration
- potency
Aromatic Moiety of Local Anesthetic
- lipophilic
- allows cross of nerve cell membrane
Amino Group of Local Anesthetic
- hydrophlic
- can be protinated
Intermediate Chain of a Local Anesthetic can be either:
- an ester
- or an amide
- drugs with two “i”s are amides
Equation to determine ratio between cationic and neutral forms of local anesthetic:
neutral/cationic = 10^(pH-pKa)
-higher pKas and lower pHs cause dec. in fraction of neutral local anesthetic
Local Anesthetic MOA
- block Na channels-> thereby blocking action potentials
- LA passes through nerve cell membrane into nerve before blocking Na channel from inside
- LAs are use dependent
LAs preferentially block:
- pain sensation
- block small diameter neurons with less myelination
- ex. C fibers that modulate pain and temp
- LAs don’t block CNS
Faster onest, more potent, and longer lasting LAs have:
- lower pKa
- higher lipid solubility
- inc. protein binding (protects LA)
Ester Local Anesthetics
- hydrolyzed in plasma and in liver
- typically shorter duration
Amides Local Anesthetics
- metabolized only in liver
- longer duration
a1-acid-glycoprotein
- binds LAs and buffers them
- affected by age, contraceptive use, and smoking
Local Anesthetic Excretion
-via kidney
Topical Anesthesia
- tetracaine, lidocaine, cocaine
- EMLA cream
- benzocaine
Infiltration Anesthesia
- lidocaine
- procaine
- bupivacaine
Nerve Block Anesthesia
- lidocaine
- bupivacaine
IV Regional Anesthesia (Bier’s Block)
lidocaine
Spinal Anesthesia
- lidocaine
- bupivacaine
- tetracine
- injection into CSF bathing lumbar spinal cord
- loss toxicity and loss to plasma
- internal to dura placement
Epidural Anesthesia
- lidocaine
- bupivacaine
- injection just outside dural enclosed spinal canal
- can catheterize
- higher loss in plasma
- good for longer surgery
- external dura placement
Epinephrine
- coapplication of epi with LAs causes vasoconstriction and helps retain LA near injection site
- inc. duration of LA
- dec. peak plasma levels of LA
Local Anesthetic Toxicity
- can block channels in all nerve and muscle tissue
- convulsions
- autonomic nervous system
- cardiac arrhythmia
- local anesthetic hypersensitivity
- allergy
Tetrodotoxin and Saxitoxin
- block Na channels from outside of cell
- cause nerve block and paralysis
Migraine Abortive Treatment
- aspirin, acetaminophen, NSAIDs
- combo: ibuprofen/caffeine, aspirin, or similar
- triptans (sumatriptan) (5HT 1B/1D agonists)
- ergotamine derivative (dihydroergoatmine) (nonselective 5HT agonists)(also agonizes alpha1 receptors and causes vasoconstriction)
Migraine Prophylactic Treatment
- beta blockers (propanolol, metoprolol) (most efficacious)
- Ca channel blockers (verapamil) (do not give if already on beta blockers)
- ACE inhibitors (lisinopril)
- antidepressants (SSRIs and tricyclic)
- anti-convulsants (gabapentin)
- botox injections for chronic migraine
Tension Headache Treatment
Abortive: aspirin, acetaminophen, NSAID (enc. pt not to overuse)
Prophylactic: tricyclic antidepressants, SSRIs, physical therapy, psychotherapy
Cluster Headache Treatment
- aggressive tx
- abortive: O2, triptans inj, ergots
- transitional: steroids, nerve blocks
- preventive: CCB, lithium, antiepileptics
Trigeminal Neuralgia Treatment
- anti-epileptics
- surgery
Giant Cell Arteritis Treatment
-glucocorticoids
Target of NSAIDS (COX2 inhibitors) in Migraine Tx
-neuroinflammation
Target of Triptan-Ergots Alkaloids in Migraine Tx
-5HT 1B-1D agonists
Amide Drugs & Time Course
- Lidocaine- faster, more local
- Bupivocaine- longer acting
Opioid Analgesic Agonists
- morphine
- hydrocodone
- oxycodone
- codeine
- tramadol
- fentanyl
Opioid Analgesic Combinations with NSAIDS
- codeine-acetaminophen
- codeine-aspirin
- hydrocodone-acetaminophen
- hydrocodone-ibuprofen
- oxycodone-acetaminophen
Opioid Analgesic Partial Agonists
-buprenorphine
Opioid Analgesic Antagoinsts
-naloxone
Non-Selective COX1/COX2 Inhibitors
- naproxen (inc. risk bleeding)
- aspirin
COX2 Selective Inhibitors
-Celecoxib (inc. risk clotting)
COX2 Inhibitors (CNS)
-acetaminophen
NMDA Receptor Antagonist & Function
-ketamine (blocks central sensitization)
Antidepressants
- tricyclics
- SSRIs
- SNRIs
Anticonvulsants
-pregalin, gabapentin
Tx for Dementia
- cholinesterase inhibitors: donepezil
- NMDA-glutimate antagonists: memantine (Alzheimers tx)
Wernicke’s Encephalopathy Tx
-Thiamine
3 Classes of Opioid Receptors and Function
- mu
- delta
- kappa
- all are coupled to Gi/o G proteins
Mu Opioid Receptor
- pharm response
- endogenous agonists
- agonist drugs
- pharm: analgesia (central), respiratory depression
- endo agonists: b-endorphin
- agonist drugs: morphine
Delta Opioid Receptor
- pharm response
- endogenous agonists
- agonist drugs
- pharm: analgesia
- endo angonists: met/Leu-enkephalin, b-endorphin
- agonist drugs: no drugs in clinical use
Kappa Opioid Receptor
- pharm response
- endogenous agonists
- agonist drugs
- pharm: spinal analgesia
- endo agonists: dynorphin 1-17
- agonist drugs: pentazocine
Opioid Receptor Function
- dec. neuronal excitability
- inhibition of presynaptic VSCC
- activation of K channels leading to membrane hyperpolarization
- inhibition of cAMP synthesis
Analgesic Actions of Opioids
- inhibition of spinal cord/ascending pain pathway
- activation of descending pain pathway
- also reduce subjective response to pain
Side Effects of Opioids
- respiratory depression
- nausea, vomiting
- cough suppression
- pupillary constriction
- constipation
- histamine release
Fentanyl
- opioid mu receptor agonist
- short duration of action
- requires mechanical ventilation
Buprenoprhine
-partial mu agonist that can precipitate mild withdrawl
Clonidine
-used to treat withdrawl sx caused by opioid addiction
Opioid Mechanism of Action
- inhibiting asc. pain pathway
- activating dec. pain pathway (inhibits inhibitory gabaergic interuerons in PAG)
- modulate perception of pain
Enkephalin
-endogenous opioid
NMDA Receptor Role in Pain
- glutimate binds to AMPA and NMDA receptors
- ions that go through AMPA receptor
- NMDA must bind glutimate and require depolarization to open and allow Ca to enter cell
- Ca causes hyperphosphorylation of NMDA receptor to act like AMPA receptor making the cell depolarize more quickly
Adjuvant
- drug that was not intended to prevent pain but is added to tx neuropathic pain
- not combined with opioids
