pharm quiz 2

Subdecks (1)

Cards (108)

  • Nicotinic Acetylcholine Receptor (nAch)
    Receptor for the neurotransmitter acetylcholine that is found on skeletal muscle
  • Skeletal Muscle Blocking Drugs block the effects of acetylcholine at the nicotinic-muscle (Nm) receptor
  • Nondepolarizing blockers
    One of the two basic types of skeletal muscle blocking drugs
  • Order of Muscle Paralysis
    1. 1st - small muscles of face, eyes, head, neck
    2. 2nd - muscles of limbs, then trunk
    3. 3rd - respiratory muscles (intercostals) with the diaphragm last
  • Recovery from Muscle Paralysis
    Recovery is in the reverse order of paralysis
  • Nondepolarizing blockers
    • Block nAch receptor sites
    • Also block prejunctional Na channel
    • Effects can be reversed by acetylcholinesterase inhibitors (e.g. neostigmine, pyridostigmine)
  • Tubocurarine
    • Prototype nondepolarizing blocker, less used today
    • Quaternary N, charged, requires IV administration, eliminated unchanged in urine
    • Also binds to ganglionic receptors to cause ganglionic blockade, hypotension
    • Causes histamine release > bronchospasm, hypotension, increased salivary/GI secretions, hives
  • Atracurium

    • Nondepolarizing blocker at nAch receptor sites
    • Intermediate duration, < 1 hour; minimizes muscle pain during surgery
    • Little histamine release and no cardiac effects, minimal hypotension
    • Inactivated in plasma and undergoes spontaneous decomposition, a degradation reaction
    • Breakdown to laudanosine which may cause seizures with high blood concentration, should be avoided prolonged infusion of atracurium in ICU
  • Cisatracurium
    Stereoisomer of atracurium, forms less laudanosine, less side effects, used more clinically
  • Pancuronium
    • Nondepolarizing blocker, more widely used than tubocurarine
    • Little ganglionic blockade and less histamine release compared to tubocurarine
    • Possesses antimuscarinic (anticholinergic) effect to block receptors, causes increased heart rate; also increases release of norepinephrine to increase heart rate
    • Approximately 25% is metabolized to an active metabolite 3-OH pancuronium; long-acting (2-3 hrs.)
  • Vecuronium
    Intermediate-acting nondepolarizing blocker (1 hr.), used more than pancuronium as adjunct to general surgery
  • Succinylcholine
    • Short-acting depolarizing drug, up to 15 mins
    • Induces phase I (depolarizing) and phase II (desensitizing) neuromuscular blockade
    • Used for short procedures like setting fractures, intubation, electroshock therapy
    • Rapidly metabolized by plasma or pseudocholinesterase, forms active metabolite; due to a genetic variation of an enzyme, the effect may last for hours
  • Succinylcholine
    • Initial fasciculations before paralysis (this effect is suppressed with atracurium given prior to succinylcholine)
    • Myalgias (muscle pain) occurs in some patients (more pronounced in heavily muscled people)
    • May cause malignant hyperthermia
    • Increases K+ in blood in burn, head trauma, spinal cord injuries and neuromuscular disease patients; can lead to cardiac arrest
  • Antidotes for Reversal of Muscle Paralysis
    Nondepolarizing drugs - acetylcholinesterase inhibitors like neostigmine, act competitively
  • Malignant Hyperthermia

    • Genetic defect with Ca release from sarcoplasmic reticulum
    • Certain gas anesthetics and succinylcholine cause the massive release of Ca inside skeletal muscle
    • Causes rigor mortis type rigidity, increased body temperature, tachycardia, acidosis, and rapid death if not immediately treated
    • Antidote is dantrolene (interferes with Ca release in sarcoplasmic reticulum of skeletal muscle, more so than cardiac muscle)
  • Muscle Spasticity
    • Upper motor neuron syndrome characterized by increases in tonic stretch reflexes
    • In addition to (+) signs of flexor spasm/clonus/hyperreflexia; (-) signs of fatigue, weakness, & paralysis (motor neuron damage)
    • Causes include head injury, cerebral palsy, stroke, multiple sclerosis
    • Treated with exercise/physical therapy, analgesics to reduce pain and antispastic drug treatment
  • Antispastic Drugs
    • Diazepam - central action
    • Baclofen - central action
    • Dantrolene - direct action on skeletal muscle
    • Tizanidine - central action on alpha-2 receptors, agonist
  • Dantrolene
    • Interferes with the intracellular release of Ca ions from skeletal muscle sarcoplasmic reticulum (minimal effect on cardiac SR)
    • Most effective in spasticity of cerebral origin; also used in multiple sclerosis, cerebral palsy, stroke, spinal cord injuries
    • Benefits of decreased muscle stiffness must be weighed against the disadvantage of reduction of muscle strength
    • In malignant hyperthermia, administered IV
    • Adverse reactions include muscle weakness, GI disturbances, increased liver enzymes/hepatitis/hepatotoxicity
  • Baclofen
    • Chemical analog of GABA, stimulates (i.e. agonist) presynaptic GABAB receptors (found mainly in spinal cord) to open K channels (increase K out of cell to cause hyperpolarization), attenuates depolarization and is inhibitory
    • More effective in conditions that affect the spinal cord (spinal cord injuries, multiple sclerosis)
    • Adverse reactions include drowsiness, confusion, GI disturbances (nausea, diarrhea, or constipation), allergic skin reactions
  • Tizanidine
    • Reduces excitatory neurotransmitter release (i.e., glutamate) via presynaptic and postsynaptic alpha-2 receptor stimulation in the spinal cord (inhibits intracellular Ca)
    • Reduces muscle spasticity associated with cerebral and spinal disorders
    • Adverse reactions include dry mouth, drowsiness, asthenia (muscle weakness), hypotension
  • Benzodiazepines
    • Main sites of action: Limbic system - antianxiety effect, Reticular formation - sedation/hypnosis, Cortex - anticonvulsant effect, Spinal cord - skeletal muscle relaxation
    • Effect is through interaction with GABAA receptors which causes presynaptic inhibition via increased Cl influx
  • Spinal cord injuries, multiple sclerosis
    Conditions that affect the spinal cord
  • Adverse effects
    • Drowsiness
    • Confusion
    • GI disturbances (nausea, diarrhea, or constipation)
    • Allergic skin reactions
  • Mechanism of action, clinical indication, adverse reactions
    1. Tizanidine
    2. Reduces excitatory neurotransmitter release (i.e., glutamate) via presynaptic and postsynaptic alpha-2 receptor stimulation in the spinal cord (inhibits intracellular Ca)
    3. Reduces muscle spasticity associated with cerebral and spinal disorders
    4. Adverse reactions - dry mouth, drowsiness, asthenia (muscle weakness), hypotension
  • Benzodiazepines
    • Bind to a specific receptor, the benzodiazepine receptor that is part of the GABA-A receptor complex
    • GABA is an inhibitory transmitter that hyperpolarizes neurons by allowing the influx of negatively charged Cl ions
    • Benzos increase the inhibitory effect of GABA by increasing frequency of channel opening & greater Cl ion influx; only work if GABA is present
  • Diazepam
    • Benzodiazepine that binds to GABA-A receptors that increase influx of Cl ions to hyperpolarize neurons which results in inhibition of neuronal activity. In the spinal cord this causes muscle relaxation
    • Used in muscle spasticity and muscle spasms
    • Also has sedative, antianxiety, and anticonvulsive/seizure effects
  • Skeletal muscle relaxants
    • Neuromuscular blockers
    • Spasmolytics
    • Nondepolarizing
    • Depolarizing (succinylcholine)
    • Muscle action (dantrolene)
    • Short acting (mivacurium)
    • Long acting (tubocurarine)
    • Chronic use (cyclobenzaprine)
    • CNS action (baclofen, diazepam, tizanidine)
  • Succinylcholine
    • Causes muscle fasciculations in the later stages of block
    • Reversibility by pyridostigmine
    • Well-sustained tension during a period of tetanic stimulation
  • Nondepolarizing neuromuscular blockade
    • Block of post-tetanic potentiation
    • Effects can be reversed by cholinesterase inhibitor
    • No significant muscle fasciculations during onset of block
  • Neostigmine does not cause skeletal muscle contractions or twitching
  • Malignant hyperthermia
    Dantrolene is most effective in the management
  • Prolonged neuromuscular blockade can be due to genetic variation in drug metabolism
  • Tubocurarine
    • Associated with hypotension caused by histamine release
  • Baclofen acts on neurons in the spinal cord to increase chloride ion conductance
  • Dantrolene has little effect on calcium release in cardiac muscle
  • Diazepam causes sedation at most doses required to reduce muscle spasms
  • Intrathecal use of baclofen is effective in some refractory cases of muscle spasticity
  • Tizanidine acts on alpha 2 adrenergic receptors to inhibit neurotransmitter release
  • Atracurium
    • Inactivated by spontaneous breakdown
    • Laudanosine metabolites possess skeletal muscle relaxing effect
  • Baclofen, dantrolene, diazepam, tizanidine
    Drugs with spasmolytic activity that could also be used in the management of seizures caused by overdose of a local anesthetic