Pharm 32 Flashcards
o MOA: agonize 5-HT1 receptors
○ Leads to vasoconstriction of painfully dilated meningeal, dural, cerebral, and pial vessels
○ Inhibits dural vasodilation and inflammation
○ Inhibits trigeminal nuclear excitability
triptan MOA
sumatriptan, frovatriptan, zolmitriptan
triptan drugs
sumatriptan, frovatriptan, zolmitriptan
o Minor differences in pharmacokinetic or receptor affinity exist across these drugs, but for most patients, the agents are interchangeable
o Choice is usually dictated by cost/formulary availability
When are triptan drugs most effective
○ Taken at onset of migraine
○ Combined with an NSAID
○ NOT overused
○ No opioid use recently
Sumatriptan
used most often - rapid and short acting
Frovatriptan
used for menstrual migraines
Ergot alkaloids use
acute migraine treatment
Potent vasoconstrictor MOA
ergot alkaloids
Formulations of ergot alkaloids
always include caffeine to improve bioavailability
○ DO NOT combo with other vasoconstrictors or use on anyone who cannot tolerate a vasoconstrictor
§ Such as in peripheral vascular disease
§ Individuals already on “triptans”
§ Must monitor BP and for angina/peripheral vascular ischemia
○ Cold fingers and toes!
Ergot alkaloids ADE
○ Dysphoria ○ Nausea ○ Vomiting ○ Cardiovascular effects ○ Greater cost of oral formulations
Ergot alkaloids ADE
Primary role of muscle relaxants in spasticity
pts with underlying spastic syndromes
muscle relaxants role in musculoskeletal pain
Adjunct to NSAIDs, and/or opioids for MSK pain
Peripheral GABA receptors
Baclofen
Alpha 2 adrenergic agonist MOA
tizanidine
GABA-A and GABA-B allosteric agonists (opens Cl- channels)
diazepam
general CNS depressant
methocarbamol
cyclobenzaprine
Interferes with the release of calcium ions from the sarcoplasmic reticulum
dantrolene
□ Administered via intrathecal route for severe spasticity
Reduces motor neuron excitability/spasticity; relieves clonus, flexor spasms, muscle rigidity
baclofen
Management of spasticity
Similar uses as baclofen
Common OFF LABEL use is for acute low back pain
tizanidine
Chronic spastic syndromes (usually oral) and malignant hyperthermia (IV)
Not a regular go-to for lower spastic back pain due to HEPATOTOXICITY
dantrolene
Acute, painful muscle spasms associated with musculoskeletal conditions
□ DO NOT combine with TCAs due to similar structure –> toxicity
□ STRONG anticholinergic
□ Sedation
cyclobenzaprine
Adjunctive treatment of muscle spams associated with acute painful musculoskeletal conditions
methocarbamol
§ Use: Muscle spasms, Spasticity
§ ADE: Tolerance, dependence, CNS depression, abuse
§ PKs: Unpredictable and undergo a variable duration of action; Accumulates in tissues
diazepam
Schedule 4 drug
§ ADE
□ Tolerance, dependence, CNS depression, abuse
□ MAX recommendation in therapy length: 2-3 weeks
□ Longer treatments are associated with withdrawal
carisoprodol
Activates peripheral nociceptors on primary sensory neurons to temporary increase release of substance P
Eventually leads to depletion of substance P in neurons to relieve neuronal firing
capsaicin
good for insect bites, minor burns/cuts/scrapes, poison oak/ivy/sumac, eczema, psoriasis, dry skin
menthol
Methyl salicylate
§ Combined with trolamine salicylate to form “Aspercreme”
□ Intraarticular salicylic acid concentrations can reach 60% of those provided by large systemic doses of ASA –> CHEAP
□ Useful for mild musculoskeletal and arthritic pain
NSAID that is topical and transdermal
diclofenac
§ VERY low doses of an NSAID, but still warned about the systemic effects of taking an NSAID
□ CV thrombotic events, GI effects (ulcers, bleeding, perfs), renal, HTN, CHF, pregnancy, liver warnings
□ PREGNANCY: may cause premature closure of ductus arteriosus
diclofenac
ASA triad
chronic rhinosinusitis, nasal polyps, severe bronchial asthma
local anesthetics MOA
blocks sodium channels to prevent the pain signal impulse from conducting along the afferent nerve
Suppresses the perception of the pain occurring
○ Why the anesthesia may fail
§ Pharmacokinetic reasons
□ Increased local blood flow/distribution away from site of injection
□ Local tissue acidosis/edema - like during infections
□ Patients with higher rates of metabolism
○ Why the anesthesia may fail
§ Pharmacodynamic reasons
□ Effects of inflammation on peripheral and central sensitization of nerves
□ Patients with less susceptible nerve fibers
ADE: cardiac of local anesthetics
□ AV block
□ Dysrhythmias
□ Bradycardia/Hypotension
□ Cardiac arrest
ADE: neurological of local anesthetics
□ CNS excitation followed by depression
□ Spinal HA
□ Autonomic blockades results in urinary/fecal incontinence
Lidocaine vs. ropivacaine
lidocaine: faster acting
ropivacaine: longer acting with half life >4hrs
benzocaine vs. tetracaine
benzocaine more prone to methemoglobinemia
Any history of CV disease, heart disease, or hepatic impairment, contraindicates this use
ergotamine/dihydroergotamine
Why is caffeine in ergotamine for migraine treatment?
Caffeine increases the bioavailability of ergotamines
Caffeine can help with the migraine
Factors that increase triptan effectiveness to treat migraine
a. Taken at very onset of migraine
b. Combined with an NSAID
c. Not overused
d. Opioid use not recent
Factors that decrease triptan effectiveness to treat migraine
a. Waiting to take the med
b. Not combined with an NSAID
c. Used frequently already
d. Have a contraindication
Rapid-acting, and therefore potentially more effective as migraine and cluster headache abortive therapies
sumatriptan
Longer-acting, and therefore potentially more useful for menstrual or other similarly timed recurring migraines
frovatriptan
Describe and compare contraindications of the ergot alkaloids and -triptans
A. Cardiovascular, coronary heart disease
B. HTN, uncontrolled
C. Hepatic impairment (as are liver metabolized!)
D. Peripheral vascular disease - ANY HISTORY, symptoms, or signs
E. Hypersensitivity to drug or components
ergotism from moderate ingestion
n/v
ergotism from higher ingestion levels
i. Distal vasoconstriction - check for peripheral vascular ischemia! (cold fingers and toes)
ii. Itching/burning limb pain
iii. Loss of limb sensation
iv. Gangrene/auto-amputation of charcoal-black limbs
ergotism from convulsive levels
i. Flexion of fingers/wrists/ankles
ii. Double vision
iii. Altered mental state/mania
iv. Hallucinations and diaphoresis
OTC analgesics for tension HA tx
i. 1,000mg acetaminophen
ii. Ibuprofen, ASA, naproxen
prevention of tension HA
i. can include amitriptyline, PT
ii. PT will strengthen muscle/reduce tension, address postural deficits
iii. Trigger management
prevention of cluster HA
first choice
i. Verapamil is first choice for prevention
1) Does not readily cross the BBB so much have larger doses
a) Do have to watch for BP dropping, swelling/edema
prevention of cluster HA
second choice
ii. Lithium is first or second choice
prevention of cluster HA
other choice
iii. Others:
1) Glucocorticoids, Warfarin, Melatonin
treatment of cluster HA
i. “Triptan” - rapid onset formulation –> sumatriptan
ii. Oxygen: 7 - 12 L/min by a non-rebreather mask
reduced HA incidence
HTN meds
Sources of pain relieved by Tylenol
a. Frequent episodic tension type HA (1,000mg) and other general Has
b. Osteoarthritis pain
i. NSAIDs are recommended as initial therapy for OA
1) Oral NSAIDs for hand, knee, hip OA
2) Topical NSAIDs for hand and knee OA and >75yrs
Source of pain NOT relieved by Tylenol
low back pain
A. Acute pain treatment for muscle relaxants
a. Methocarbamol
b. Diazepam - risk for tolerance, abuse, and dependence
c. Carisoprodol - risk for tolerance, abuse, and dependence
d. Tizanidine - off label
e. Diclofenac 1% gel for acute pain of strains, sprains, and contusions of 2-4 grams to skin of the affected areas
B. Chronic pain treatment for muscle relaxants
a. Baclofen
b. Dantrolene - watch hepatotoxicity
Capsaicin use
i. Post herpetic neuralgia
ii. Minor aches/pains of muscles/joints - arthritis, backache, sprains
menthol use
sore throats
MSK aches/pains
methyl salicylate use
arthritis
mild MSK pain
diclofenac use
upper/lower extremity joint arthritis
acute pain of strains/sprains/contusions
capsaicin SE
i. Dose must be titrated up and can produce a burning sensation for the first few days of application
ii. Lower doses produce less burning
diclofenac SE
i. All indications with NSAIDs
1) CV thrombotic events, CHF, renal, liver toxicities, GI effects (ulcers, perforations, bleeds), pregnancy (premature closure of ductus arteriosus)
2) Increased sun sensitivity
MOA of local anesthetics
Suppress pain by blocking the sodium channels on afferent nerves to suppress pain impulse conduction signals at the administration site to reduce the body’s awareness of the pain
local anesthetics clinical use
Suppresses pain without generalized depression of nervous system at correct doses and route/site of administration
Chronological onset of local anesthetic action (5 steps to know)
- anesthetic is injected near a nerve
- local anesthetic permeates axonal neuronal membranes
- binding of local anesthetic to sites on voltage-gated sodium channels
- period of time when only a few sodium channels are blocked -> results are insufficient for full anesthesia
- clinically observed rates of onset and recovery from blockade due to relatively slow diffusion of local anesthetic molecules into and out of the whole nerve.
ester-type anesthetics (4)
cocaine
procaine
tetracaine
benzocaine
amide-type anesthetics (5)
lidocaine mepivaciane articaine bupivacaine ropivacaine
Ester-type anesthetics metabolism
Very short plasma half-life:
Therefore only administered locally and are broken down quite quickly
1/2 life renders them ineffective for systemic / significant tissue distribution
Amide-type anesthetics metabolism
b. Has a much larger tissue distribution and can therefore be administered over a greater area
c. Metabolized by the liver
d. Great choice for wanting a longer duration of anesthetic
cross allergenic potential with ester and amide anesthetics
a. If allergic to a specific ester, cannot use other ester anesthetics
i. CAN use an amide-type however
ii. And vice-versa
b. Esters are metabolized to PABA and some individuals have a reaction to this
adverse effects of local anesthetics that are an extension of the MOA
a. Difficult to control toxicity of agents due to sodium channels being required for normal function of neurons
i. Blockage can result in…
1) Cardiac effects: potentially dysrhythmias
2) Central nervous system adverse effects
3) Induce seizures
4) Systemic effects when absorbed systemically/administered into highly perfused tissues
use of epi in local anesthetics
- a vasoconstrictor that helps to reduce the systemic effects and prolong the local effects
- helps with bleeding at the site
- decreases rate of vascular absorption
- increases anesthetic molecules at targeted nerve membrane
- deeper and longer duration of anesthesia achieved
- provides a marker for inadvertently entering a vascular vessel due to CV excitability
- May have ability to activate endogenous analgesic mechanisms and produce a deeper state of anesthesia through activation and binding of alpha2 adrenergic receptors
(Absorption of a vasoconstrictor itself can cause palpitations, tachycardia, nervousness, HTN)
