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201 Cards in this Set
- Front
- Back
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Henderson-Hasslebach equation for bases
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[BH+]/[B] = 10 ^(pKa – pH)
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Local anesthetics produce a ___(A)_____ in a circumscribed region of the body without ______(B)________
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A. transient and reversible loss of sensation (analgesia)
B. without loss of consciousness |
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Local anesthetics are classified as either _______ or _______
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Amides or Esthers
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typical pK value of a local anesthetic?
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between 8 and 9 (weak base)
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At physiologic pH, local anesthetics are found in what form?
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ionized (weak base)
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What effect does inflammation have on local anesthetics?
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Descreases membrane permation and therefore descreases effectiveness of anesthetic
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Bupivacaine is more toxic than other Local Anesthetics due to _____________________
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increased binding to resting channels, broadening QRS
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Which Local Anesthetic increases sympathetic tone?
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Cocaine
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Which local anesthetic metabolite may produce methemoglobinemia?
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prilocaine
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Which of these local anesthetics is an amide?
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the one with two "I"s in its name.
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Which of these local anesthetics may produce an immune response?
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The one that is an ester. So the one that doesn't have two I's in its name.
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Procaine (Novocain)
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local anesthetic Ester of PABA
short duration of action. lacks topical activity. Minimal toxicity available with and without epinephrine |
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Tetracaine (Pontocaine)
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long-acting local anesthetic with a slow onset of action (> 10 minutes).
spinal anesthesia and for ophthalmological use. 10x more potent and toxic than procaine |
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Benzocaine (Americaine)
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used topically only to treat sunburn, minor burns and pruritus
OTC |
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Cocaine
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short-acting, naturally occurring alkaloid
only medical use is for the topical anesthesia of mucous membranes. blocks the uptake of catecholamines vasoconstriction can lead to HTN, but also decreases intraoperative mucous membrane bleeding, so this is both an effect and a toxicity use with caution in pts with HTN, CVD or thyrotoxicosis Schedule II controlled substance; highly abused |
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Lidocaine (Xylocaine)
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prototype amide local anesthetic; intermediate duration of action.
preferred for infiltration blocks and for epidural anesthesia. rapidly absorbed after parenteral administration metabolized in the liver by microsomal mixed-function oxidases (P450 system) greater potency and longer duration of action than procaine major clinical uses of lidocaine are as a local anesthetic and, intravenously, as an antiarrhythmic agent. |
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Prilocaine (Citanest)
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Local anesthtic with intermediate duration of action that is longer than that of lidocaine.
not used topically or for subarachnoid anesthesia. DO NOT USE in pts with cardiac or respiratory disease or in those with idiopathic or congenital METHEMOGLOBINEMIA Methemoglobinemia can be reversed by administration of methylene blue. |
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Bupivacaine (Marcaine, Sensorcaine)
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long duration of action.
generally preferred for infiltration blocks and epidural anesthesia. greater cardiotoxicity than other amide local anesthetics. |
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Ropivacaine (Naropin)
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long-acting local anesthetic
less arrhythmogenic than bupivacaine is the S-isomer form, whereas bupivacaine is racemic less lipid soluble and cleared via the liver more rapidly than bupivacaine, thus less likely for adverse events possible interactions with alfentanil, theophylline, fluvoxamin and cimetidine |
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There are four levels of general anesthesia. Which level of general anesthesia is considered "surgical anesthesia"
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Level Three
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Which anesthetic may produce a cataleptic state in which there is profound analgesia, no response to commands, and amnesia, but the patient’s eyes may be open, respiration is spontaneous, and limbs may move?
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This is a description of Dissociative anesthesia and it is caused by Ketamine.
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Which anesthesia term is incorrectly paired with its definition?
A. Unresponsiveness: loss of reaction to sensory stimuli B. Surgical anesthesia: state of unconsciousness, anxiolysis, amnesia, analgesia and muscle relaxation that allows surgery C. Induction: phase of anesthesia from beginning or administration of drugs until patient is unresponsive to desired level D. Emergence: process beginning when anesthesia is terminated until anesthetic is eliminated from the body |
D. That is the definition for Recovery. Not Emergence.
Although the two are similar, Emergence is a part of Recovery and its definiton is "stage of recovery in which patient is regaining consciousness". |
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Common side effect of inhaled anesthetics that may increase post-operative morbidity?
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Hypothermia
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What 5HT3 antagonist can be given post-operatively to reduce nausea and vomitting?
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Odansetron
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What inhaled anesthetic causes diffusion hypoxia and how do you counter it?
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N2O.
Give 100% O2 for a few minutes after discontinuing administration of anesthesia mixture. |
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What MAC do most anesthesiologists start out with? Why?
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Start with 0.8 MAC, because margin of safety is low and you can easily adjust concentration by increasing ventilation
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During metabolism, what toxic metabolites get removed from halothane? What do they do?
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Chlorine and Bromine
can lead to immune response and cause hepatitis |
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During metabolism, what toxic metabolite gets removed from enflurane and sevoflurane? What does it do?
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Flouride ions
Can cause kidney damage. |
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• Nitrous Oxide
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rapid induction; low potency
incapable of anesthetizing on its own used as second gas with other agents to speed up induction contraindicated in pts with hx of eye surgery in the past three months |
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• Halothane (Fluothane®)
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high potency; slow induction
highly toxic: immune response, hepatitis, malignant hyperthermia, cardiovascular problems, miscarriage, reduces renal function |
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• Isoflurane (Forane®)
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Widely used - good potentcy with rapid induction and low toxicity!
Useful in neurosurgery Low toxicity - hepatic and renal toxicity virtually nonexistent! |
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• Sevoflurane (Ultane®)
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Rapid effect
Least irritating to airway - widely used with kids Safest in cardio-vascular disease Compound A (haloalkene product produced when combined with CO2 absorbents. Has caused kidney toxicity in rats. Has not been seen in humans) |
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• Desflurane (Suprene®)
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Very rapid emergence and induction; may be used for outpatient surgery
Very pungent odor, irritates airways, so not used for induction Profound respiratory depression Heart rate tends to increase. Preserves cardiac output and flow to major organ beds. |
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During a long surgery, pt starts to become hypotensive. What part of most anesthesia mixtures could be increased to counter hypotension?
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N2O
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Besides losing his license, whatphysiologic effects might occur to a dentist who has been abusing nitrous oxide for a long time?
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Peripheral neuropathy
Megaloblastic anemia decreased bone marrow |
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N2O can be exchanged with trapped nitrogen in the body. Who can this cause problems for?
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Pts with occluded middle ear or Eustachian tube, pneumothorax, loop of intestine, lung or renal cysts, or recent hx of eye surgery. Will increase pressure in the abcessed area
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What effect does shock have on anesthesia?
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reduced cardiac output and increased ventilation will speed up induction of anesthesia
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• Thiopental (Pentothal®)
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barbituate
rapid induction and short duration can be combined with N2O for short procedures No analgesic effect Contraindicated in pts with porphyria |
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• Midazolam (Versed®)
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ultrashort-acting benzodiazepine.
causes sedation, anxiety relief and anterograde amnesia. Widely used as a pre-anesthetic medication and during induction. must be given intravenously, and has a very rapid onset of action. Frequently used for minor surgical procedures, combined with an opioid such as fentanyl. can be reversed if necessary with flumazenil |
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• Propofol (Diprivan®)
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• drug of choice for most anesthetic procedures. It is the most widely used anesthetic in the US.
• facilitates GABAergic transmission • contains albumin, may cause allergic reactions • painful when injected. • used both for induction and maintenance of anesthesia • It is also used for prolonged anesthesia in critical care settings • Causes vasodilation, overdose may decrease blood pressure. Blunts baroreceptor reflex; heart rate does not increase in response to decreased blood pressure. • Propofol is a severe respiratory depressant, and respiration must be monitored • Decreases cerebral blood flow, metabolism and intracranial pressure, useful in neurosurgery • Postoperative nausea and vomiting are much less than that seen with most other anesthetics • Propofol is safe for use in pregnancy |
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• Ketamine (Ketalar®)
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Dissociative anesthetic - respiration maintained
Sympathomimetic, bronchodilation Emergence delirium in adults Drug of abuse |
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• Fentanyl (Sublimaze®)
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• strong opioid agonist
•Given by IV injection, rapid onset of action, good analgesia. • Fentanyl lollipops given to children pre-operatively to minimize anxiety and pain. • Awareness and conscious recall may occur, for this reason they are frequently combined with midazolam for short procedures • Naloxone can be used as an antagonist if necessary to reverse effects |
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• Glycopyrrolate
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muscarinic anticholinergic
can be used as a preoperative medication in order to reduce salivary, tracheobronchial, and pharyngeal secretions, as well as decreasing the acidity of gastric secretion. It is also used in conjunction with neostigmine, a neuromuscular blocking reversal agent, to prevent neostigmine's muscarinic effects such as bradycardia. |
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Neuromuscular blocking agent used in surgical anesthesia that can cause malignant hyperthermia reaction?
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succinyl choline
Give dantrolene to counter MH |
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Strong Opioid Agonists
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• Morphine
• Hydromorphone (Dilaudid) • Heroin • Methadone (Dolophine) • Meperidine (Demerol) • Fentanyl (Sublimaze) • Alfentanil (Alfenta) • Sufentanil (Sufenta) • Remifentanil (Ultiva) |
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• Morphine
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prototype strong opioid agonist; binds to and stimulates all of the opiate receptors
administered orally, parenterally, intrathecally, epidurally, and rectally high first pass metabolism, so it is less effective orally than when injected elimination half-life of morphine is about 1.5-2 hours; analgesia can be maintained for 3-7 hours following immediate release of morphine administration metabolism occurs primarily in the liver but also may occur in the brain and kidneys via cytochrome P450 (CYP2D6) enzymes morphine is conjugated with glucuronic acid to form 3-glucuronide (50%), 6-glucuronide (5—15%), 3,6-glucuronide and other minor metabolites morphine 6-glucuronide is a more potent analgesic than morphine and may significantly contribute to morphine's activity. It may accumulate significantly when morphine is given chronically morphine 3-glucuronide may cause hyperalgesia, excitement, and myoclonus during high dose morphine therapy excretion is primarily in the urine as the morphine- 3-glucuronide metabolite |
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Hydromorphone (Dilaudid)
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morphine derivative, very strong analgesic, more potent than morphine and as effective
Advantages over morphine: useful in patients with renal dysfunction, as metabolites do not accumulate; less likely to produce itching than morphine Disadvantage compared to morphine: duration of action slightly shorter than morphine |
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Heroin
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schedule I drug, not available for medical use in the USA
easily passes the blood brain barrier and metabolized to morphine more potent than morphine (10 times) high abuse potential |
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Methadone (Dolophine)
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longer duration of activity than morphine t1/2 = 15 - 60 hours
potent μ agonist that also blocks NMDA receptors and inhibits reuptake of monoamines useful in hard-to-treat pain (neuropathic pain, cancer) tolerance and dependence occur more slowly than with morphine has also been used in maintenance therapy of heroin addicts, and to decrease withdrawal symptoms when stopping other opioids withdrawal from methadone may be milder, although it is more prolonged that that from other opioids |
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Meperidine (Demerol)
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recommended only for use for very brief courses in patients who are healthy and/or have problems with other opiate agonists (e.g. short painful procedures)
causes seizures with long-term use, large doses or in pts with renal failure dilates pupils; does not suppress cough blocks reuptake of seratonin DO NOT USE in pts on MAOIs - seratonin syndrome! |
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Fentanyl (Sublimaze)
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highly lipid soluble; 100 times more potent than morphine
very widely used for short surgical procedures used to aid induction and maintenance of general anesthesia and to supplement regional and spinal analgesia fentanyl is preferred to morphine in anesthesia due to its ability to attenuate hemodynamic responses and maintain cardiac stability transdermal fentanyl is indicated for the treatment of chronic pain in patients requiring opioid analgesia. fentanyl lozenges (Oralet) are indicated for use in a hospital setting as an analgesic used for premedication or to induce conscious sedation prior to diagnostic or therapeutic procedures extensively metabolized by CYP3A4, significant drug interactions may occur if inhibitors or inducers of this enzyme are administered concurrently |
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Alfentanil (Alfenta)
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synthetic opiate agonists that are used primarily in anesthesia
faster onset and shorter durations of action than fentanyl administered intravenously or epidurally Alfentanil undergoes liver biotransformation via CYP3A4. Clinically significant drug interactions have been reported between alfentanil and agents that inhibit this isoenzyme |
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Moderate-to-Strong Opioid Agonists
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Hydrocodone (Codan)
Oxycodone (OxyContin) |
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Hydrocodone (Codan)
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semisynthetic codeine derivative, used for moderate to moderate-to-severe pain
frequently combined with other agents as an analgesic (e.g., Vicodin) homatropine, an anticholinergic agent, is included in subtherapeutic amounts in some hydrocodone antitussive products (e.g., Hycodan) to discourage deliberate overdosage administered orally; well absorbed from the GI tract hydrocodone undergoes complex hepatic metabolism via O-demethylation, Ndemethylation, and 6-keto reduction to the corresponding 6-alpha- and 6-beta-hydroxy active metabolites. o a small portion of hydrocodone is converted to hydromorphone by the cytochrome P450 isoenzyme 2D6 (CYP2D6); this metabolite is responsible for some of the analgesic effect o patients who are receiving agents that inhibit CYP2D6 or who genetically have low levels of CYP2D6 may be have less analgesia from hydrocodone o nevertheless, hydrocodone itself does have a direct action on μ receptors, so there will be some effect elimination half-life is about 3.8 hours Schedule II alone; schedule III with acetominophen |
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Oxycodone (OxyContin)
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similar to hydrocodone and morphine
widely used to control moderate to severe pain, including cancer pain, postoperative, postextractional and postpartum pain also used in non-pain syndromes such as restless leg and Tourette’s syndrome administered orally as immediate-release or controlled-release tablets, or as an oral solution frequently combined with aspirin(Percodan) or acetaminophen (Percoset) distributed to skeletal muscle, liver, intestinal tract, lungs, spleen, and the CNS oxycodone has been found in breast milk metabolism of oxycodone occurs in the liver with excretion principally in the urine although oxycodone has a direct receptor effect, some of the analgesia activity requires metabolism by CYP2D6 (as with hydrocodone), so the effectiveness will be reduced in people taking SSRIs or with low CYP2D6 activity elimination half-life is 3-5 hours; duration of analgesia is 3-4 hours unless extended release product is used, when it is 12 hours Schedule II |
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Moderate Opioid Agonists
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Codeine
Propoxyphene (Darvon; off market) Tramadol (Ultram) |
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Codeine
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widely used as an antitussive agent- more cough suppressant activity than morphine
commonly used analgesic for mild to moderate pain- much less effective than morphine has analgesic and addictive properties at doses higher than those used to reduce cough codeine itself does not bind to the mu receptor, so will not compete with strong agonists it is partially metabolized to morphine by CYP2D6, which is responsible for the analgesic action abuse potential is low it is frequently combined with aspirin or acetaminophen (e.g. Tylenol 3) deaths of children under 2 from codeine-containing cough suppressants has led the FDA to issue a warning about using any cough or cold medications in small children codeine alone is a Schedule II drug, with aspirin or acetaminophen it is a Schedule III, and when combined with other products in a liquid cough suppressant, it is Schedule V |
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Tramadol (Ultram)
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approved for use in mild to moderate pain
weak mu agonist inhibits reuptake of norepinephrine and serotonin, similar to tricyclic antidepressants naloxone does not completely inhibit its analgesic effect equivalent in analgesic relief to codeine produces good analgesia, with only mild side effects the side effects resemble those of other opioids (dizziness, sedation, nausea, constipation) dosage adjustments of tramadol are required in patients with renal or hepatic dysfunction combination with antidepressants may result in seizures should not be combined with TCAs, SSRIs or MAOIs, as this may cause serotonin syndrome non-scheduled drug |
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Mixed Opioid Agonist-Antagonists
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Buprenorphine (Buprenex)
Pentazocine (Talwin) |
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Buprenorphine (Buprenex)
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partial agonist at mu-receptors and possibly kappa-receptors.
although its analgesic effects may be slightly less than that of morphine, its abuse potential is reported to be much lower reduces drug craving in heroin addicts and is used in the treatment of heroin addiction usually given by injection, but also effective sublingually or intranasally tablets are formulated together with naloxone (Suboxone), which is not absorbed sublingually; prevents dissolving the tablets in water and injecting the solution IV |
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Pentazocine (Talwin)
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agonist at kappa-receptors; partial agonist at mu receptors
useful for moderate pain; administered orally or parenterally less sedation, respiratory depression and GI effects than other opioids dysphoria, CNS stimulation, and hallucinations may occur can precipitate withdrawal syndrome in opioid addicts (partial agonist will behave as an antagonist!); combination with strong agonists is contraindicated Schedule IV |
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Opioid Antagonists
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Naloxone (Narcan)
Naltrexone (ReVia) Nalmefene (Revex) |
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Naloxone (Narcan)
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pure opioid antagonist
drug of choice for opioid overdose not effective orally, because of first pass metabolism, must be given parenterally can reverse the respiratory depressant effects of opioids relatively short duration of action (i.e. only about 2 hours) o repeated dosing may be required in overdose with long acting opioids o patient may appear normal and then go back into coma if naloxone wears off before the agonist does sometimes included in combinations with oral narcotic analgesics (e.g. Talwin NX) to prevent abuse (i.e. injection of the drug) can precipitate withdrawal in addicts low doses sometimes titrated to prevent adverse effects of intravenous or epidural opioids (nausea, vomiting, itching), while allowing the analgesic effect |
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Naltrexone (ReVia)
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orally effective, long acting opioid antagonist (24 hours)
used to prevent recovering addicts from getting an effect ‘high’ if they abuse an agonist keep in mind that an opioid addict must first be detoxified (i.e. brought through withdrawal) before naltrexone therapy can be initiated. patient compliance is a major problem decreases craving for alcohol in recovering alcoholics, and now approved for use in the treatment of alcoholism risk of hepatotoxicity is a serious drawback |
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Dextromethorphan (with guafenisin; Robitussin DM)
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good cough suppressant with no analgesic effect
produces less constipation than codeine ingredient in many OTC products blocks NMDA receptors; may potentiate analgesic effect of morphine can block neuronal uptake of serotonin; combination with MAOIs may cause serotonin syndrome has become a significant drug of abuse in teenagers available over the counter in cough syrups, and on the internet in concentrated form The ingestion of pure dextromethorphan in powdered form and in excessive dose can cause death as well as other serious adverse events such as brain damage, seizures, loss of consciousness, and irregular heart beat |
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What are the three opioid receptors?
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mu, kappa and delta
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Opioid receptors are all on the presynaptic terminal, but only one is also found on post-synaptic terminals. Therefore it produces the most effects and side-effects. Which one is it?
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mu
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what are the descending neuronal pathways which modulate pain transmission
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rostral ventral medulla, locus coeruleus, midbrain periaqueductal gray
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which receptors cause some people to have a dysphoric reaction to opioids?
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kappa and delta
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which opioids are commonly used to supress cough? Which one cannot suppress cough?
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Codeine and dextromethorphan used to supress
meperidine does not suppress |
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why should you not give mophine to a pt with head trauma?
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increases intracranial pressure
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which opioid will not constrict pupils?
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meperidine
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opioids cause respiratory depression. This can be good in pts with ____________.
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pulmonary edema
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what causes the itching associated with morphine and other opioids?
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release of histamine.
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which effects of opioids will not develop tolerance?
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miosis and constipation
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What drug interactions should you expect in a pt on SSRIs who starts taking codeine
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hydrocodone wont work. SSRI's inhibit CYP2D6, which is a necessary enzyme to convert codeine to morphine
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which strong opioid agonist is not a Schedule II drug?
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heroin. Schedule 1 drug. No approved medical use.
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Behavioral and physical symptoms occur when a drug that was taken chronically is abruptly withdrawn or its action terminated by an antagonist.
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Physical dependance
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What has happened if a drug produces satisfaction and a drive to use it to avoid discomfort?
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Psychological dependance
Dysphoria and intense craving occur following the withdrawal of an abused drug |
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An increased amount of a drug is required to produce the same effect.
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Tolerance
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genetic lack of sensitivity to the effects of a drug
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Innate tolerance
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occurs with increased metabolism of a drug, usually due to induced enzymes or receptors
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Pharmacokinetic tolerance
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receptor changes that decrease the effects of the drug
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Pharmacodynamic tolerance
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adaptation to the degree of intoxication or impairment
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Learned tolerance
Thus the "functional alcoholic" has learned to tolerate the impairments of alcohol and can still go about his day |
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loss of effect when the drug is given in the same setting- the person “expects” the effect-, but enhancement if given in a novel way or environment (i.e. cocaine sniffers moving towards crack smokers)
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conditioned tolerance
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may occur with “binges” in which a drug,
like cocaine, is used repeatedly over a short period of time, the effect will wear off. |
Acute tolerance
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when use of one drug produces tolerance to other drugs in the class, common with opioids.
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cross-tolerance
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An increase in responsiveness following multiple exposures to stimulants on a daily basis. The dose-response curve is shifted to the left and the response in the brain is increased. This may involve a conditioned response and may contribute to craving and environmental cues which lead to relapse.
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Sensitization
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Define Addiction
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Generally involves both physical and psychological dependence, and there may be tolerance. It is characterized by chronic, compulsive or uncontrollable use of the drug in spite of adverse consequences, loss of control in limiting intake, and emergence of negative emotional states when access to the drug is prevented.
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neurotransmitter for reward pathway. Contributes to pyschological dependance
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Dopamine
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pathway fro dopamine
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projects from the ventral tegmental area to the nucleus accumbens, caudate, amygdale and frontal cortex.
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how do opioids stimulate reward pathway?
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By inhibiting the inhibitors. Inhibits GABA neurons that would normally inhibit reward pathway.
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neurotransmitter with an important role in appetite, impulsivity and craving.
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serotonin
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three components responsible for addiction?
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genetics of individual
properties of the drug environmental influence |
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Sympathomimetic.
Promotes release of newly synthesized catecholamines (norepinephrine and dopamine) from storage vesicles in presynaptic nerve terminals. |
amphetamine
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Amphetamine Effects:
Side Effects: Toxicities: |
Effects: Behavioral stimulation, increased psychomotor activity, stimulates reward pathway, alertness, reduced fatigue, increased energy, decreased appetite
Side effects: anxiety, insomnia, and irritability Toxicities: Amphetamine psychosis, cardiotoxic (cause of associated fatalities via pulmonary edema or heart failure) |
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why is smoking meth or crack so much more addicting than taking oral amphetamines or snorting cocaine?
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inhalation produces rapid onset of peak effect (i.e. faster, more intense high) similar to IV injection
gets in the blood faster; gets to the brain faster |
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why does smoking meth rot the teeth?
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acids involved in converting amphetamine to crystal meth
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What contributes to addiction of amphetamines and crystal meth?
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Physical dependance and rapid tolerance create perpetuating cycle. Need more drug to get high. Creates increased physcial dependance on drug.
Strong cravings during abstinence Withdrawal symptoms are strong but mostly psychological: decreased energy, increased appetitie, severe depression, possible suicidal ideation, possible paranoia/psychosis. |
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How are cocaine and amphetamine different?
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Cocaine inhibits reuptake of DA and NE
Amphetamine stimulates their release |
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Adverse effects of cocaine?
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• Strong psychological dependance
• strong vasoconstrictor (HTN, tachycardia, sweat) • damages nasal membranes when snorted; damages oral mucosa when smoked • formification • lethal effects of OD or long term abuse (MI, stroke, hyperthermia, seizures) • fetal toxicity (68% of mothers in NY without prenatal care test positive for cocaine) |
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Happy effects of smoking (Why people do it)
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Activates nicotinic receptors in the CNS and periphery.
Increases blood pressure and heart rate, increases epinephrine release, and increases tone and activity of the GI tract (i.e. appetitie suppresant- why models and movie stars smoke so much) Activation of nicotinic receptors in the CNS facilitates serotonin and dopamine release, which causes reinforcing and antidepressant actions. Elevation of DA release may involve activation of endogenous opioid pathways. Effects on memory and learning are mediated through nicotinic receptors.(note: nicotine temporarily stimulates memory and learning, but lack of oxygen via cigarette smoke, impairs memory) |
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Nicotine Tolerance, Dependence and Withdrawal
(why it's so hard to quit) |
Nicotine causes psychological and physical dependence.
Withdrawal symptoms are craving, irritability, anxiety, anger, difficulty concentrating, restlessness, impatience, increased appetite, insomnia. This can last months. |
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What drugs can be given to treat nicotine withdrawal
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nicotine patch and nicotine pills help taper off; i.e. reduce withdrawal symptoms
bupropion (Xyban®) appears to reduce craving for nicotine. Varenecline (Chantix) is a partial agonist at nicotine receptors that decreases craving and blocks the effects of nicotine if a person smokes. |
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Most commonly abused illegal drug in US?
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marijuana
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Drug of abuse that causes rapid mood changes, alters perception, impairs memory, has mild withdrawal symptoms and does not cause physical dependance
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marijuana
also accurate for LSD |
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medical uses of marijuana
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anti-emetic – dronabinol (Marinol®), reduces nausea and vomiting, used in chemotherapy
analgesia – reduces muscle spasms and pain in patients with multiple sclerosis appetite enhancement for AIDS patients was thought to reduce intraocular pressure in glaucoma, but no longer considered effective |
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what receptors does LSD act on?
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5HT (serotonin)
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may increase heart rate and blood pressure
fatalities due to dehydration, hyperthermia, and heart or kidney failure has been shown to cause degeneration of serotonin neurons in rats- may cause persistent memory problems |
MDMA (Ecstasy)
MDMA stands for 3,4-methylenedioxymethamphetamine |
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dissociative anesthetic that promotes physical aggression and hallucinations?
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PCP
Causes amnesia – so individuals are later unaware of violent acts |
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Why do cops hate PCP so much?
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Causes physical aggression combined with analgesic
So they're raging and they don't feel the nightstick. Gotta taze 'em to bring 'em down |
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Four most popular rave drugs?
All but one also fit which other category? |
MDMA (Ecstasy)
flunitrazepam (Rohypnol; “roofies”) GammaHydroxyButyrate (GHB; “soap”) Ketamine (Special K) Ecstasy is only one that does not cause retrograde amnesia. Amnesia effects of other three make them popular "date rape" drugs Ecstacy just makes you easy. But I guess you'll remember it the next day |
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Primary effects of Prostaglandins?
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Strong vasodilator; increases vascular permeability; increases chemotaxis; increases pain
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So prostaglandin inhibitors will have what effect?
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1. vasoconstrict
2. descrease vascular permeability 3. decrease chemotaxis 4. decrease pain Hence anti-inflammatory (2 & 3) and analgesic (4) effects that come with inhibiting PG synthesis |
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most important precursor for prostaglandin synthesis?
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arachadonic acid
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Arachadonic acid is mobilized from ______________ by _______________
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membrane phospholipids by phospholipase A2
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prostaglandin precursor that is widely distributed and has ‘housekeeping functions’
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COX-1
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prostaglandin precursor that is an immediate early response gene product whose expression is stimulated by growth factors, tumor promoters, and cytokines
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COX-2
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Which prostaglandin precursor is mainly responsible for the synthesis of prostacyclin in endothelial cells
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COX-2
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Effects of TXA1 (thromboxane)
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Clotting factor (needed for platelet aggregation). Causes vasoconstriction. Contracts bronchial muscles. Activates GI muscles. Need COX1 to synthesize
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Effects of PGI2 (prostacyclin)
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Iinhibits platelet activation. Causes vasodilation. Relaxes bronchioles. Activates GI-tract. Increases GFR in kidneys (due to vasodilation).
Need COX-2 to synthesize. used to produce vasodilation in primary pulmonary hypertension |
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Effects of PGE2 (dinoprostone)
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Vasodilates, relaxes bronchials, activates GI
PG's are ecreted by seminal vesicles in men and are associated with high fertility Has abortive effects in first and second trimester on women. Contracts uterus Administered vaginally for first trimester abortions. Softens cervix and contracts uterus. Produces fever |
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PGF2
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Contracts bronchial muscles. Contracts uterus.
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PGE1 (alprostadil)
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Relaxes bronchial muscles. Activates GI. Increases GFR in kidney
Relaxes smooth muscles in corpus cavernosum to promotes erection when injected into penis or given as urethral suppository used in pediatrics to keep a patent ductus arteriosus open before surgery because neonates are highly sensitive to vasodilation by PGE1 misoprostol (PGE1 analog) reduces gastric acid secretion in ulcers |
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Primary beneficial effects of Aspirin?
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Analgesic (Pain relief)
Anti-pyretic (reduce fever) Anti-inflammatory (acute and chronic) |
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Secondary benficial effect of Aspirin?
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anticoagulant for pts prone to blood clots
this is a side-effect that has proven beneficial in select population |
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How does aspirin releive pain?
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inhibiting prostaglandin synthesis, which is responsible for pain and local inflammation and swelling.
Aspirin also prevents the sensitization of pain receptors to mechanical as well as chemical stimuli.(makes swollen owies hurt less when you bump them) Centrally, aspirin acts at the hypothalamic area and reduces fever and malaise (when you feel better, pain doesn't bother you as much). Aspirin is generally not very effective as an analgesic in non-inflamed painful conditions. |
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how does aspirin reduce fever?
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Aspirin lowers the body temperature only in febrile patients but not in normal patients. In other words, aspirin is antipyretic and not hypothermic.
Aspirin and related drugs reduce fever by "resetting" the "thermostat" to normal body temperature. It should be clearly understood that aspirin like drugs lower the elevated body temperature only when the fever results from such conditions that raise the hypothalamic "thermostat" to a "higher set point" (as in infection, graft, rejection) So aspirin won't help in MH, heat stroke, heat exhaustion, etc. |
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Causes Irreversible inhibition of both cyclooxygenase enzymes, COX-1 and COX-2.
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Aspirin (acetylsalicylic acid, ASA)
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what effect does aspirin have on uric acid?
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biphasic and dose dependant
at low doses, aspirin decreases uric acid excretion and increases plasma urate concentration at high doses, aspiring increases uric acid excretion and decreases urate plasma levels |
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Why is aspirin not a good choice for Gout therapy?
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In doses high enough to increase uric acid excretion, aspirin would cause stomach irritation and ulcer bleeding
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All of the following are symptoms of aspirin intoxication except:
A. Hyperventiliation B. Fever C. GI bleeding D. K+ loss E. Renal failure |
C. GI bleeding is a common side effect of aspirin use and does not require toxic levels to initiate.
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Why is aspirin so hard on the GI tract?
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concentration of unbuffered salicylate in the mucosal cell may reach a value 20 times that in the lumen of the stomach. This concentration difference may be a cause of mucosal damage and ulceration in some patients
aspirin, related agents (NSAIDs), and cortical steroids, etc.. all have in common, ONE effect on stomach - that is increased acid production leading to ulceration and/or bleeding. prostaglandin(s) physiologically protect the stomach against the onslaught of gastric acid secretion through a negative feed back mechanism which consists of lowering acid production. |
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how does aspirin sometimes induce asthma attacks?
What can you do about this? |
inhibiting COX pathways means more arachadonic acid gets moved to leukotriene synthesis. High luekotriene levels can induce asthma.
Stop taking aspirin or take zileuton (lipoxygenase inhibitor) and/or zafirlukast and montelukast (leukotriene receptor inhibitor). Effective prophylaxis against asthma |
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why is aspirin hard on the kidneys?
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Not b/c it's excreted via kidney. Although aspirin OD could overwork kidneys to an extent.
Primary kidney damage comes from inhibition of prostaglandins which are important vasodilators to the kidney. Without the, kidneys vasoconstrict and descrease oxygen flow |
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what effect does aspirin have on male fertility?
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descreased prostaglandins means decreased fertility
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aspirin can readily pass placental barrier. Is this a problem?
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Not really. No known teratogenic effects.
Still, recommended that pregnant women use tylenol instead, which doesn't cross barrier Also, in pregnant women who need to stay on aspirin therapy, it is recommended that they stop taking it several days prior to delivery to decrease bleeding |
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approximate fatal dose of aspirin?
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20 grams (but range is wide +/- 10 grams)
10 - 30 grams |
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Celecoxib
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COX-2 inhibitor. Reversible. no inhibitory effect on platelet aggregation, but may increase platelet aggregation through increasing prostcyclin
- have the potential to cause less gastropathy and risk of GI bleeding than nonspecific COX inhibitors - FDA currently requires warnings in their labeling for the risk of GI ulceration, bleeding and perforation - administered orally Adverse reactions: GI disturbances including ulceration and bleeding, hypersensitivity, increased risk of cardiovascular diseases Contraindications: GI disease, asthma, breast feeding, pregnancy, renal failure, sulfonamide hypersensitivity |
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NSAID drug of choice
Best side effects profile |
Ibuprofen
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most common reversible, nonspecific cox inhibitors
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Indomethacin
Sulindac (Clinoril) Diclofenac (Voltaren) Ketorolac (Toradol) Ibuprofen (Motrin, Rufen) Naproxen (Anaprox, Naprosyn) Piroxicam (Feldene) Meloxicam (Mobic) Nabumetone (Relafen) Arthrotec (Diclofenac & Misoprostol) Acetaminophen (Tylenol) |
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NSAID with worst side effects profile (but very potent)
CNS disturbances common |
indomethacin
phenylbutazone (not marketed in US) |
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Diflunisal (Dolobid)
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Aspirin derivative
Less GI irritation than aspirin No significant antipyretic effects (probably due to poor penetration into the CNS) |
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why are prionic acids like ibuprofen and naproxen a better choice than aspirin for primary effects?
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Lower toxicity and fewer side effects in most patients
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Indomethacin (Indocin)
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reduce PMN migration
inhibit phospholipase A very potent AI AR agent, high incidence of side effects used for patent ductus arteriosus (others work too) |
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Sulindac (Clinoril)
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less nephrotoxic than other NSAIDS
severe GI adverse effects including pancreatitis longer half-life permits daily or twice-daily dosing |
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Diclofenac (Voltaren)
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potent COX inhibitor
decreases arachidonic acid bioavailability oral absorption, liver metabolism, t1/2 = 1.2 - 2 hours mostly GI side effects combined with misoprostol (Arthrotec) to decrease GI side effects |
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Ketorolac (Toradol)
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used mostly as an analgesic in postsurgical pain
oral, IV IM administration, t1/2 = 4-8 hours after 5 days of use frequent GI side ; not for long term use may be combined with opiates also used IM to treat acute migraine headaches |
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Naproxen (naprosen)
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• useful in the treatment of rheumatoid arthritis, osteoarthritis and ankylosing spondylitis
• a 500 mg dose of naproxen is equivalent to 3.6-4.8 g daily dose of aspirin in rheumatoid arthritis. Its effectiveness is equal to or greater than that of ibuprofen, fenoprofen and indomethacin • mean plasma t1/2 = 13 hours - significantly longer than aspirin or ibuprofen • crosses the placenta readily, therefore, should not be given to pregnant women |
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Piroxicam (Feldene)
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• inhibits PMN migration, lymphocyte function
• decreases oxygen radical production • long half life, high incidence of GI side effects |
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Nabumetone (Relafen)
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non-specific COX inhibitor with long half-life
• requires conversion to an active metabolite • half-life long enough to support once daily administration • may cause fewer adverse GI effects than do other anti-inflammatory drugs in clinical use • oral administration, liver metabolism, renal excretion, 99% plasma protein binding |
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Phenylbutazone
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very potent NSAID, serious side effects (GI, bone marrow)
not marketed in the USA |
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This drug is an alternative to aspirin for analgesic and antipyretic effects.. (no antiinflammatory effects)
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Acetaminophen (Tylenol)
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Acetaminophen is often preferred to aspirin because:
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It is tolerated better.
It lacks several undesirable side effects of aspirin, namely ulcerogenics, blood clotting defects, acid-base imbalance, auditory toxicity, etc.. It should be emphasized, however, that acetaminophen is not completely innocuous or safe. It's overdose causes fatal hepatic necrosis. Therefore, acetaminophen should be handled with great care, especially in children. |
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the most serious toxic
action of acetaminophen. |
dose-dependent fatal hepatic necrosis
o in adults, hepatotoxicity occurs after ingestion of 10-15 grams of acetaminophen at once. 25 grams may be fatal (hepatic necrosis). o the hepatotoxicity may progress into encephalopathy, coma and death. |
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DOC for children with fever or pain?
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Acetaminophen (Tylenol)
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Treatment of acetaminophen intoxication
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• gastric emptying
• forced diuresis • hemodialysis • specific antidote is N-acetylcysteine (Mucomyst) • N-acetylcysteine must be administered parenterally, as soon as possible, within 10-12 hours after intoxication |
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how do cortical steroids aid treatment of chronic inflammation?
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inhibit AA release
inhibit immune response |
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how do gold salts aid treatment of chronic inflammation?
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• Inhibition of phagocytosis.
• Uncouple oxidative phosphorylation and inhibit cellular respiration. • mStabilize lysosomal membranes and inhibit actions of lysosomal enzymes. • React with proteins (e.g., sulfhydryl groups). • Inhibit proteolytic enzymes of leukocytes. • Prevent prostaglandin synthesis. • Suppress cellular immunity. |
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Gold salt Toxicity:
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bone marrow damage, dermatitis, enterocolitis, jaundice, peripheral neuropathy
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a chelating drug that is effective in rheumatoid arthritis (also in Wilson's disease).
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Penicillamine (Cuprimine)
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Infliximab (Remicade)
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• chimeric IgG1k monoclonal antibody targeted against tumor necrosis factor-alpha (TNFalpha).
• composed of human constant and murine variable regions • approved for Crohn's disease and rheumatoid arthritis • combined with methotrexate • administered intravenously Adverse reactions: headache and infusion reactions Contraindications: pregnancy, breast feeding, children, infections |
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Hydroxychloroquine (Plaquenil)
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• Possesses antihistaminic, anticholinesterase, and antiprotease properties.
• Inhibits prostaglandin synthesis. • Inhibits biosynthesis of mucopolysaccharide. • Inhibits responses to chemotactic stimuli and phagocytosis. • Stabilizes lysosomes. • Reacts with nucleic acids and tissue proteins. • Toxicity: pruritus, hemolysis (G6PD deficient), ototoxicity, retinopathy, peripheral neuropathy |
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Sulfasalazine (Azulfidine)
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• treatment of inflammatory bowel disease and Rheumatoid Arthritis (RA).
• equi-effective with injectable Gold Compounds and is better tolerated • as effective as Penicillamine and less toxic. Toxicities of Sulfasalazine • GI disturbances, rash, etc... • Hepatitis and blood dyscrasias are rare • Monitoring for hepatitis & marrow suppression is recommended for 2-3 weeks during first three months of treatment and less frequently thereafter |
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Adverse effects of pain:
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◦ Increased cardiac workload.
◦ Massive neuroendocrine response. ◦ Hypertension. ◦ Hypercoagulation. ◦ Hypoventilation & resulting pneumonia. ◦ Paralytic ileus, nausea, vomiting. ◦ Immunosuppression. ◦ Prolonged and poor recovery. ◦ Fear, anxiety, helplessness. |
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which nerve fibers are associated with chronic pain?
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Slower conduction C-fibers (nonmyelinated).
Responding to Persistent chemical, thermal, mechanical injury. This slow pain is the cause of chronic suffering. |
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Tylenol should not exceed _____ per day or _______ per day in a chronic alcohol drinker
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4 grams
2 grams |
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why should alcoholics take only half normal amount of Tylenol?
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lack of glutathione
glutathione helps protect against hepatotoxicity of tylenol metabolite |
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hepatotoxic metabolite of tylenol
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N-acetyl-p-benzoquinone
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Aspirin & Ketorolac are both contraindicated in asthma patients or AIA. Why?
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NSAIDs inhibit conversion of arachidonic acid to prostaglandins.
This tilts the process toward the lipoxygenase pathway resulting in production of leukotrienes. Leukotrienes promote bronchoconstriction. |
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Capsaicin
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functional substance in chili peppers (what makes 'em hot)
Analgesia originally attributed exclusively to depletion of substance P. Now combined with the idea of 'defunctionalization' of nociceptors via loss of membrane potential (inhibits signal transmission). Commonly used in localized peripheral neuropathy. |
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how are Antiepileptics used to treat pain
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Decreased CNS sensitization.
Uses: Postherpetic neuralgia, diabetic neuropathy, peripheral neuropathy, fibromyalgia. |
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first-line in neuropathic pain
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Gabapentin (Neurontin) & Pregabalin (Lyrica)
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tricyclic antidepressant used to treat chronic pain?
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Amitriptyline (Elavil)
Duloxetine (Cymbalta) |
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Common opioids for mild to moderate pain?
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Tramadol, oxycodone, and codeine
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examples of opioids used in severe pain
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Morphine, methadone, fentanyl, and hydromorphone (Dilaudid)
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opioid supplied as a confection for children?
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fentanyl (pre-surgical lollipops decrease anxiety and pain)
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Why was morphine combined with the opioid antagonist, naltrexone? Seems counterproductive
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Attempt to reduce tampering & abuse.
If taken as directed, opioid bound first and naltrexone passed through with little to no effect. If crushed, the naltrexone is released decreasing the subjective effects of morphine (euphoria). |
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What is PCA?
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Patient Controlled Analgesia - the short-term morphine button given post-surgical. Helps keep pain under control so adverse effects of pain don't complicate recovery. Less addiction potential because pain never gets out of control so reward center isn't stimulated as much as it would be if you went from out of control pain to controlled pain. keeping it controlled means less reward stimulation.
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Primary causes of hyperuricemia (gout)
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overproduction or underexcretion of uric acid
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secondary cause of gout?
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accumulation of uric acid due to another disease such as leukemia
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mechanisms to control/treat gout?
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inhibit urate crystal synthesis (prophylactic control)
inhibit PMN, macrophage and IL responses (acute) |
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Colchicine
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unique anti-inflammatory agent, effective only against gouty arthritis
has no analgesic effect, no effect on COX enzymes has no effect on urate excretion binds to tubulin; inhibits the assembly of microtubules (cause of side effects) produces its anti-inflammatory effect by inhibiting leukocyte migration and phagocytosis inhibits the formation of leukotriene B4 used to reduce the pain and inflammation of an acute attack of gouty arthritis used prophylactically at initiation of therapy with uricosuric agents |
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NSAIDs in gout treatment
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antiinflammatory and analgesic effects. Indomethacin and naproxen mostly.
Aspirin is contraindicated. Inhibits uric acid excretion. Makes gout worse. |
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indomethacin (Indocin)
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primary NSAID used in the treatment of gout
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Uricosuric agents
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• increase the urinary excretion of uric acid by blocking the active reabsorption of uric acid in the proximal tubule
• Keeps urine alkaline to promote acid excretion • Drink lots of fluid to avoid kidney stones • initial administration may trigger gouty attack, prophylactic colchicine therapy may be needed • inneffective against acute attacks and may aggravate symptoms. Cease taking during acute attacks. |
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How do acidic foods and medications affect gout?
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Acids compete for uric acid excretion so more uric acid will be reabsorbed and available in plasma to form crystals
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probenecid (Benemid)
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• Decreases tubular resorption of uric acid
• therapy should not be started until 2-3 weeks after an acute attack • will decrease excretion of other acidic compound or metabolites (most important: penicillin, others: methotrexate, clofibrate, glucuronides of NSAIDs, etc.) |
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allopurinol (Zyloprim)
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• inhibit xanthine oxidase and thus inhibits the synthesis of uric acid
• is effective in both primary and secondary forms of gout • serious side effects can occur, including vasculitis, agranulocytosis and hypersensitivity reactions • initial therapy may provoke acute gouty attack, colchicine prophylaxis may be necessary |
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How does xanthine oxidase contribute to hyperuricemia?
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critical enzyme in metabolism of hypoxanthine and xanthine (oxypurines) to uric acid. Without it, they don't break down and uric acid is not formed
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rasburicase (Fasturtec)
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Rasburicase is a recombinant form of urate oxidase not endogenous in humans; normally, uric acid, the end product of human purine metabolism is excreted by the kidneys.
But rasburicase catalyzes enzymatic oxidation of uric acid into a readily excreted metabolite, allantoin, thus lowering high serum uric acid levels. |
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Rasburicase sounds like the perfect gout drug. Why is it not used more?
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In addition to normal adverse reactions such as nausea/vomiting, fever, headache, abdominal pain, constipation, diarrhea, remember that this is not a natural human enzyme so severe hypersensitivity reactions can develop including anaphylactic shock and anaphylactoid reactions. Ideally, give this drug one time to pediatric patients with severe malignancies that contribute to gout. After that, antibodies develop and it shouldn't be used again.
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what causes migraine pain?
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extracranial and intracranial arterial dilation and release of neuroactive molecules such as substance P
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what are the two phases of migraines?
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First phase is (prodromal phase) that of vasoconstriction of intracranial arteries resulting in a reduction of blood flow, followed by ischemic changes associated with the prodrome of the attack (aura).
Second phase (headache phase) is that of vasodilation primarily of the extracranial arteries during which headache occurs. Vasodilation as such, is not uncomfortable, but the mediators of arterial inflammation or the release of vasoactive materials around the pain-dilated arteries seem to cause the pain. |
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Drugs for symptomatic treatment of migraine
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Sumatriptan (Imitrex)
Ergotamine tartrate (Ergomar, Ergostat) Analgesics - aspirin, tylenol, codeine NSAIDs - naproxen, ibuprofen, ketorolac |
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Drugs for prophylaxis of migraines
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Ergot alkaloid - Methysergide (Sansert)
Beta-Blockers - Propranolol (Inderal) Calcium Channel Blockers - Verapamil (Calan, Isoptin) Antidepressants - Amitriptyline (Elavil, Endep) Clonidine (Catapres) Valproic Acid (Depakene) Topiramate (Topamax) Botulinum toxin (Botox) Angiotensin II receptor blockers |
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Sumatriptan (Imitrex)
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Treats acute migraine attacks
• 5-HT1D agonist on intracranial vessels and small peripheral nerves • probably suppresses release of sensory neuropeptides • given PO or SC, half-life: 2 hours • headache recurs within 24-48 hours, 2nd dose is required • expensive, reserved for cases when nothing else works Toxicities are mild to moderate and associated with functions of vasoconstriction (vasospasm, arrythmia, ischemia, cramp, hemorrage, etc. Severe effects include MI and stroke) Contraindications: breast-feeding, cardiac disease, cerebrovascular disease, HTN, DM, pregnancy, renal impariment and smoking |
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Ergotamine tartrate (Gynergen, Ergomar, Ergostat)
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• It is one of the most effective and specific agent for migraine (acute attacks)
• Stimulates alpha1 receptors, vasoconstriction • It should be administered in adequate doses early in the attack, Most effective when given in prodrome phase • It may also be useful in cluster headache when given over a short period of time (10-14 days) • During acute attack, simultaneous use of sedatives and antianxiety agents may help relieve apprehension and pain and cause sleep. Antiemetics may help alleviate nausea and vomiting. Adverse reactions • side effects: due to vasoconstriction • acute: diarrhea, nausea, vomiting, cardiovascular toxicity (similar to sumatriptan) • chronic: ergotism - vasoconstriction + CNS |
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visual disturbances that precede headache?
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"Aura"
occurs during prodromal phase of migraine attack |
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mechanism of action for ergotamine tartrate?
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partial agonist on 5-HT receptors in certain blood vessels; antagonist in various smooth muscles; poor agonist/antagonist in CNS
partial agonist on alpha receptors mechanism is similar to the -triptans, however, not as specific ergotamine can be administered orally or by inhalation, sublingual, and/or by parenteral routes. |
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Contraindications of ergotamine tartrate?
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Being a powerful vasoconstrictor, ergotamine should be avoided in patients with peripheral vascular disease (thromboangiitis obliterans, CVD, HTN, atherosclerosis, Reynaud's, etc).
Avoid ergotamine also in the following situations: allergy (to ergot alkaloids), renal and hepatic diseases, malnutrition, peptic ulcers, during pregnancy |
