Pharm: Drugs for Pain Flashcards
(26 cards)
Morphine
- full agonist ** prototype
MOA: binds all opioid receptors, w/ highest affinity for mu
PK * high first pass metabolism - low oral ratio
CI: widely distributed, shouldn’t be used during labor d/t distribution to fetus
** high efficacy for analgesia w/ high abuse potential. highly addicitve!!!
Fentanyl
- full agonist
- 100x more potent than morphine
use: anesthesia**, chronic/severe pain
PK - highly lipophilic - slowly metabolized, but short acting b/c distributes to fatty tissues (this is good w/ anesthesia and surgery - acts right away)
Heroin
- full agonist: no legal medicinal use
- 3x more potent than morphine
** Greater lipid solubility; gets into brain more rapidly than morphine
** More exaggerated euphoria
Converted to morphine in the body but its effects last half as long
Codeine
- partial agonist (mu effects seen starting with low doses; kappa effects at high dose)
These drugs are often combined with NSAIDs to increase analgesic efficacy – These are the most widely prescribed outpatient analgesics:
ex. + tyelenol or aspirin
Hydrocodone
- partial agonist (relatively pure mu; probably misclassified [a DEA Schedule-III agent])
These drugs are often combined with NSAIDs to increase analgesic efficacy – These are the most widely prescribed outpatient analgesics:
- ex: Vicodin (+acetaminophen)
Oxycodone
- partial agonist (relatively pure mu)
These drugs are often combined with NSAIDs to increase analgesic efficacy –
+ acetaminophen = percocet
+ aspirin = percodan
Buprenorphine
- mixed agonist/antagonist
- acts differently at different receptor subtypes !
A partial agonist at mu receptors
Has high affinity for receptors so very slowly dissociates
*** USE: Major use is for opioid detoxification as a substitute for methadone
Less severe and shorter duration of withdrawal compared to methadone
naloxone
- opioiod antagonist
- USE: heroin/opioid overdose
- Administration of an antagonist to a patient who is dependent on opioids will precipitate a withdrawal syndrome
- useful in treating some drug-free addicts
reverses respiratory depression but causes w/drawal sx
short acting!
naltrexone
- opioid antagonist
- USE: heroin/opioid overdose
- Administration of an antagonist to a patient who is dependent on opioids will precipitate a withdrawal syndrome
- useful in treating some drug-free addicts
reverses respiratory depression but causes w/drawal sx
long acting!
which receptor is most imp. for opioid?
its a GPCR
** mu (μ) opioid receptors (m1, m2)
Endorphins>enkephalins>dynorphins
Supraspinal & spinal analgesia; sedation; inhibition of respiration; slowed GI transit; modulation of hormone & neurotransmitter release
Principle known signal mechanisms:
- Inhibit cyclic AMP production
- Open G-protein modulated K+ channels allowing K+ efflux from the cell and hyperpolarization, slow IPSP
- Reduce presynaptic Ca++ influx which inhibits neurotransmitter release, glutamate, Substance P (which mediates pain perception), and others
opioid receptor distribution?
Brain stem – opioid receptors influence respiration, cough, nausea, & vomiting, BP, pupillary diameter, stomach secretions
Medial thalamus – this area mediates deep pain that is poorly localized
Spinal cord – receptors here are involved with receipt and integration of incoming sensory information, activation of these receptors attenuates painful afferent stimuli.
Hypothalamus – receptors in this CNS area affect neuroendocrine secretion.
Limbic system – has a high density of opioid receptors in the amygdala. These receptors influence emotional behavior.
Periphery – peripheral sensory nerve fibers and nerve terminals, inhibit Ca++ influx and the release of excitatory (glutamate) and pro-inflammatory (Substance P) substances
Immune cells – have opioid receptors, function is largely unknown
effects of mu receptor activation?
analgesia
euphoria
** miosis (constriction - PS)
** respiratory depression : major cause death in OD
physiological dependence
reduced GI motility (constipation)
what does kappa receptors cause?
dysphoria - disorientation and depersonaliation
analgesia
OTC cough suppression?
dextromethophan and codeine
effects of opioids on the eye?
miosis “pin point pupils” - due to indirect parasympathetic actions (atropine blocks).
Little or no tolerance develops to this miosis, so all abusers show pinpoint pupils.
This is important diagnostically, because many other types of causes of coma and respiratory depression produce dilation of the pupil.
Mydriasis occurs in opiate overdose only if asphyxia develops - when respiration is dramatically depressed
CV effects of opioids?
No major effects on blood pressure or heart rate
Because of respiratory depression and carbon dioxide retention, cerebral vessels dilate and increase the cerebrospinal fluid (CSF) pressure.
**Therefore, use of opioids is usually contraindicated in individuals with severe brain injury.
GI effects of opioids?
** Constipation
decreased GI motility secondary to increased tone (due to effects both in the CNS and on the local enteric nervous system).
Constipation is a significant problem, especially for patients on chronic therapy
opioid effects on mast cells
= histamine release
causing urticaria, sweating, and vasodilation.
Because opioids can cause histamine-induced bronchoconstriction, asthmatics should not receive the drug.
clinical uses of morphine?
- Analgesia, best w/ severe/constant pain (pain is perceived, but dulled)
- Acute Pulmonary Edema:
relief from dyspnea assoc. w/ left ventricular failure is d/t:
- reduced perception of SOB
- decreased anxiety dt/ anxiolytic effects
- reduction in cardiac preload/afterload
- relieves pain - Myocardial Infarct: relieve pain and anxiety
- Cough suppression: Dextromethorphan and Codeine
- Nonspecific diarrhea: Loperamide, diphenoxylate (+ atropine), difenoxin (+ atropine)
methadone
(dolophine)
- orally effective as opioids
- Equally potent with morphine but induces less euphoria and has a longer duration of action
USE: ** for controlled withdrawal of dependent abusers of heroin and morphine**
- substituted for injected opioid
- pt. is slowsly weaned from methadone – causing milder withdrawal syndromes
which opioid is ok to use w/ obstetrics?
meperidine (Demerol) -
- note: this one DILATES pupils
- Less effects on smooth muscle so can be employed in obstetrics
- Toxic metabolite can accumulate at high doses and cause seizures so it should not be used for chronic treatment
drugs used for heroin w/drawal?
- methadone
2. buprenorphine
opioid tolerance
Receptors down-regulated and signal transduction pathways desensitized
- starts with first dose but doesn’t become clinically relevant for 2-3 weeks
Tolerance develops to these effects:
- Analgesia: takes more drug to get same pain relief, starts right away
- Respiratory depression
- Euphoria – key for addiction process
- Sedation
Tolerance does not develop to:
- Miosis
- Constipation – why chronic tx is not good
opioid w/drawal sx?
rhinorrhea lacrimation yawning chills piloerection hyperventilation hyperthermia mydriasis vomiting diarrhea anxiety
