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306 Cards in this Set
- Front
- Back
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when does premonitory phase of migraine occur
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hours to days before HA
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describe premonitory phase of migraine
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-Nonspecific Sx (mood, taste, temp, fatigue)
-Sensitivity to light, smell, and sound |
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when does aura phase of migraine occur
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5-20 minutes prior to HA, lasts <60 minutes
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describe aura phase of migraine
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o Aura is most commonly visual
o Zigzag lines, scintillating images o Parathesia, vertigo, tinnitus |
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when does HA phase of migraine occur
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4-72 hours in duration, if 72+ hours = Status Migrainous
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describe HA phase of migraine
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o Usually starts in AM
o Throbbing unilateral pain o N/V/photophobia/phonophobia o Aggravated by physical activity |
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describe postdrome phase of migraine
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lethargic, irritable, hangover-like symptoms
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vascular theory of migraines
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• Vasoconstriction by 5-HT/neuropeptide release = aura
• Vasodilation by NO = migraine • Inflammation caused by trigeminal nerve |
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Grading scale for migraines
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• Migraine Disability Assessment Scale (MIDAS)
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6 Migraine Treatment Goals
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• Treat attacks rapidly and consistently without recurrence
• Restore the patients ability to function • Minimize the use of rescue meds • Optimize self-care and reduce subsequent use of healthcare resources • Cost effective management • Minimal or no adverse effects |
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3 nonpharm tx for migraine
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o Ice
o Rest/sleep (regular) o Quit environment |
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4 nonpharm Px for migraine
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o Avoid triggers
o HA diary o Wellness program o Relaxation therapy |
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describe Step Care Within migraine Attacks
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o 0 hours – NSAID or Simple Analgesic
o 2 hours – if unsuccessful, try triptan or ergot o Then try NSAID or simple analgesic again |
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describe Step Care across migraine Attacks
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o NSAID or Simple Analgesic
o if unsuccessful, try triptan or ergot |
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describe Stratified Care for migraine Attacks
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o Mild-Moderate: NSAID or Simple Analgesic
o Moderate-Severe: triptan or ergot |
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indications for simple analgesics (ASA/APAP) for migraines
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MILD TO MODERATE
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purpose of butalbital in combo products with simple analgesics for migraines
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induces sleep
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purpose of narcotics in combo products with simple analgesics for migraines
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pain relief
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purpose of caffeine in combo products with simple analgesics for migraines
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improve GI absorption (synergy w/ ASA/APAP)
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4 adverse effects of using simple analgesics for migraines
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Dizziness,
lightheadedness drowsiness “hangover” effect |
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precautions with using simple analgesics for migraines
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Can lead to rebound HA with overuse (>2x per week)
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MOA of NSAIDs in migraines
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reduces inflammation in the trigeminovascular system by inhibiting PG synthesis
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indication for NSAID us in migraines
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MILD TO MODERATE
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3 pearls for NSAID use in migraines
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o As effective as ASA or APAP
o Use rapid acting NSAIDs only o Quite effective in menstrual migraines |
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MOA of triptans
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o Vasoconstriction of intracranial vessels (5-HT1B)
o Inhibition of vasoactive neuropeptide release from trigeminal perivascular nerves (5-HT1D) o Interruption of pain signal transmission within the brain stem trigeminal nuclei (5-HT1D) |
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indication for triptans
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MODERATE TO SEVERE
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3 pearls for triptan use in migraines
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o More effective if given early in attack
o Onset of action is quickest from SC > IN > PO o BBB penetrated more easily with 2nd generation triptans |
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7 adverse effects of triptans
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bad taste
N/V malaise fatigue dizziness vertigo chest tightness/pressure |
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2 renally cleared triptans
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o naratriptan
o frovatriptan |
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contraindications with triptan use
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CVD or those with 2+ risk factors: angina, MI, strokes, TIA, peripheral, ischemic bowel disease
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MOA of ergotamine
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-direct vasoconstrictor of smooth muscle in cranial blood vessels
-alpha adrenergic blocker -nonselective 5-HT agonist |
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indications for ergotamine use
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MODERATE TO SEVERE
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3 pearls for ergotamine use
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o More effective if given early in attack
o Available in a variety of dosage forms o Bioavailability (IV = IM = 100%, IN = 40%) |
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7 adverse effects with ergotamine use
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↑BP
**peripheral ischemia ergotism **N/V/D (ergotamine > DHE) thirst pruritis vertigo |
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precautions for use with ergots
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Excessive use (>2 days/week) can result in medication overuse headaches (MOH)
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4 narcotics used in migraines
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butorphanol nasal spray
meperidine oxycodone hydromorphone |
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indications for narcotics and migraines
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Rescue medication for failed non-opioid therapy or severe migraine
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3 pearls for use with narcotics for migraines
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o Consider only when non-opioid meds ineffective
o Only use if sedation would not harm patient o Establish risk of overuse/dependence |
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2 antiemetics used with migraines
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metoclopramide
phenothiazines |
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indications for antiemetics with migraines
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N/V ASSOCIATED W/ MIGRAINE
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1 pearl for antiemetics used with migraines
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Metoclopramide
• Antiemetic of choice, can increase absorption of oral abortive meds (e.g. triptans) |
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adverse effects of metoclopramide
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EPS, sedation, restlessness
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adverse effects of phenothiazines
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EPS, sedation, dizziness
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7 indications for prophylaxis treatment of migraines
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• HA related disability occurs 3+ days per month
• MH duration greater than 48 hours • Acute migraine meds are ineffective, contraindicated, or overused • Attacks produce profound disability, prolonged aura, or migrainous infarction • Attacks occur 2-4 times per month despite acute care treatment • Patient asks for prophylactic treatment |
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2 goals of prophylaxis treatment for migraines
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• Reduction in frequency of 50% per HA diary
• Reduction in use of abortive meds per HA diary |
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indication for NSAIDs in migraine prophylaxis
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1ST LINE MENSTRUAL MIGRAINE PROPHYLAXIS
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2 pearls for use of NSAIDs in migraine prophylaxis
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o Menstrual migraine – initiate 1-2 days prior to anticipated HA onset and continue 3 days post menses
o Usefulness in refractory prophylactic cases |
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indications for beta blockers in migraine prophylaxis
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1ST LINE MIGRAINE PROPHYLAXIS
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3 pearls for use of BBs in migraine prophylaxis
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propranolol
o 75% of patients have >50% reduction in HAs o BBs with ISA (intrinsic sympathomimetic activity) are not effective o Useful in co-morbidities: anxiety, HTN, angina, s/p MI |
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MOA of valproate
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o GABA-mediated
o Interacts with central 5-HT system by reducing firing rate of midbrain 5-HT neurons |
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indications for valproate use in migraine Px
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• 1ST LINE MIGRIANE PROPHYLAXIS
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2 pearls for valproate use in migraine Px
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o Check baseline LFTs, CBC, amylase
o Useful in pts with comorbid seizure disorders, mania, and anxiety |
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adverse effects of valproate
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sedation
N/V thrombocytopenia hepatotoxicity pancreatitis ***weight gain hair loss |
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2 contraindications to valproate use
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Liver disease
bleeding disorders |
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MOA of TCAs
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downregulation of central 5-HT2 adrenergic receptors
independent of antidepressant activity |
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indications of TCAs in migraine Px
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1ST LINE MIGRAINE PROPHYLAXIS
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pearls of TCA use in migraine Px
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o Amitriptyline most widely studied antidepressant
o Less effective than propranolol in patients with migraine alone, but superior in mixed migraine o Useful in comorbidities: anxiety, depression, sleep disturbances |
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indications of topiramate in migraine Px
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1ST OR 2ND LINE MIGRAINE PROPHYLAXIS
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adverse effects of topiramate
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**Weight loss
cognitive dysfunction **paresthesia metallic taste |
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contraindications of topiramate
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kidney stones
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indication of SSRIs in migraine Px
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2ND LINE MIGRAINE PROPHYLAXIS
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3 pearls for SSRI use in migraine Px
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o Useful in comorbidities: anxiety, depression, neuropathic pain, panic disorder
o Less effective than TCAs o Fluoxetine most studied SSRI |
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contraindications for SSRI use
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mania
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indication of CCBs in migraine Px
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3RD or 4TH LINE MIGRAINE PROPHYLAXIS
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3 pearls for CCB use in migraine Px
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o Verapamil is most commonly used
o Often used when BBS are contraindidcated o Useful in comorbidities: prolonged aura, HTN, angina |
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adverse effects of CCBs
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**constipation
hypotension edema |
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indications for ACEIs in migraine Px
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3RD OR 4TH LINE MIGRAINE PROPHYLAXIS
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1 pearl for ACEI use in migraine Px
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Useful in comorbidities: HTN, CAD
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4 1st line agents for migraine Px
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NSAIDs
propranolol valproate TCAs |
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2 2nd line agents for migraine Px
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topiramate
SSRI |
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2 3rd line agents for migraine Px
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CCBs
RAAS blockers |
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describe cluster headaches
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• Short, severe, episodic, unilateral pain over eyes and forehead
• Clustering of HAs is predominant feature • Rare, M>F |
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episodic cluster HAs
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HA for a year with remissions of 14 days
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chronic cluster HAs
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HA throughout year with remissions <14 days
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acute Tx for cluster HAs
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• Oxygen is DOC
• Sumatriptan SC __________________ • Ergotamine • DHE • Lidocaine • Capsaicin |
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goal for prophylaxis of cluster HAs
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o Shorten duration of cluster
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3 indications for prophylaxis of cluster HA
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o Chronic cluster HA
o Seasonal cluster HA o Refractory |
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3 prophylaxis options for cluster HAs
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o Verapamil 360-480 mg: DOC prophylaxis
o Lithium DOC for chronic CH o Prednisone: 1st line episodic CH |
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6 symptoms of tension type headaches
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o Bilateral
o Pressing/tightening (non-pulsating) quality o Mild or moderate intensity o Not aggravated by routine physical activity o No N/V o Either photophobia or phonophobia, or neither |
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infrequent episodic TTH
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<1 attack/months
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frequent episodic TTH
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1-14 attacks/month
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chronic TTHs
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>15 attacks/month
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pathophysiology of TTH
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o Abnormal CNS sensitivity, pain generation, and facilitation
o Activation of trigeminal nerve |
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3 acute Tx of TTHs
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o Analgesics (ASA/APAP)
o NSAIDs (naproxen, esp) o Combo analgesics +/- caffeine |
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when to use prophylaxis of TTH
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o Initiated for patients experiencing >2 attacks per week, duration >4 hours, patient at risk for MOH, or if severity leads to significant disability
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4 Px treatments of TTH
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o TCAs
o SSRIs o Muscle relaxants o Botox |
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cause of transient insomnia
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brief adjustment reaction, rotating shifts, international travel
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duration of transient insomnia
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few days
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cause of short-term insomnia
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significant life stressor (e.g., illness, job change, bereavement, dissolution of a relationship)
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duration of short-term insomnia
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4-28 days
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cause of chronic insomnia
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primary insomnia, circadian rhythm sleep disorder, chronic medical condition, psychiatric illness
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duration of chronic insomnia
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1 month to several years
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describe insomnia epidemiology
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• Incidence increases with age
• F > M o But older male patients have more sleep awakenings • Increased in o Low SES o Divorced, widowed, or separated o Recent stress o Depression o Drug or EtOH abuse |
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how is the sleep cycle altered in primary insomnia
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may be normal
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how is the sleep cycle altered in the elderly
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o Stage 1 and 2 increased
o Stage 3 and 4 decreased (2% per decade) o % REM sleep decreased o suprachiasmatic nucleus deteriorates with age o decreased secretion of endogenous melatonin o Missing or wea external cues |
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DSM-IV criteria for insomnia
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• Difficulty initiating or maintaining sleep for at least 1 month
• Causes significant disress or impairment • Others |
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5 goals of treatment for insomnia
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-Determine the type of insomnia present
-Improve/resolve insomnia symptoms -Optimize effectiveness of medications -----Target specific symptoms -----Address underlying problem -----Combine with nonpharmacologic measures -Minimize side effects of medications -Improve QOL |
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5 nonpharmacologic treatment for insomnia
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• Stimulus control
• Relaxation therapy • Paradoxical intention • Sleep restriction • CBT |
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2 OTC treatments for insomnia
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diphenhydramine
doxylamine |
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what type of ion channel are BZD receptors?
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• Pump chloride into the cell
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4 GABA subunits on the BZD receptor
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alpha 1, 2, 3, 5
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alpha 1 subunits responsible for
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• Mediate sedation
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alpha 2 and 3 subunits responsible for
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• Mediate anxiolytic and myorelaxation effects
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alpha 5 subunits responsible for
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• Mediate cognition and processing
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which BZDs are used for sleep maintenance?
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LOT
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which BZD is used for sleep onset?
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triazolam
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dependence of BZDs
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• Chronic use (stopping causes rebound insomnia)
• Taper by 25% per week and then lower doses every other day |
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tolerance of BZDs
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• Shorter acting quicker to develop tolerance
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6 side effects of BZDs in elderly
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• Memory impairment
• Over sedation • Psychomotor retardation (increased risk of falls) • Withdrawal symptoms • Paradoxical disinhibition • depression |
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2 categories of non-BZD sedative hypnotics
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BZD receptor agonists
melatonin receptor agonists |
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3 BZD receptor agonists
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eszopiclone
zolpidem zaleplon |
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1 melatonin receptor agonist
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ramelteon
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all NSH's work for both SM and SO, except
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eszopiclone (SM only)
ramelteon (SO only) |
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2 ADRs of eszipoclone
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unpleasant taste
dry mouth |
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ADR of zolpidem
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difficulty with coordination
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ADR of zaleplon
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lightheadedness
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ADR of ramelteon
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nausea
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MOA of trazodone
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Triazolopyridine which is a specific inhibitor of serotonin. Antagonist of 5-HT1A, 5-HT1c, and 5-HT2 receptors
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MOA of TCAs
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inhibit the reuptake of 5-HT and N
block H1 receptors block alpha receptors |
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3 strongly sedating TCAs
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Amitriptyline
doxepin clomipramine |
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3 moderately sedating TCAs
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Imipramine
desipramine nortriptyline |
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definition of restless leg syndrome
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The symptomatic urge to move the legs that is usually accompanied or caused by uncomfortable or unpleasant sensations deep within the legs
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4 risk factors for RLS
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o Iron Deficiency
o Pregnancy o ESKD (uremia) o Anemia |
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Dopaminergic hypothesis of RLS
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• Dopaminergic mechanisms involved in spinal flexor reflex control
• Dopamine agonists provide symptomatic relief of RLS • Lack of dopamine or the presence of dopamine antagonists causes or worsens symptoms of RLS |
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Iron deficiency hypothesis
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• Therapeutic benefit of iron administration
• Lower iron levels in substantia nigra • Lower iron and ferritin in CSF with normal serum iron |
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define intermittent RLS
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• Less than daily frequency of symptoms
• Troublesome enough to require treatment |
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Tx for intermittent RLS
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BZD
low potency opioid levodopa/carbidopa DA agonist |
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describe daily RLS
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• Daily frequency of symptoms
• Troublesome enough to require daily treatment |
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Tx for daily RLS
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• Tx 1) DA agonist > Gabapentin > low potency opioid
• Tx 2) then DA agonist |
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describe refractory RLS
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• Daily frequency with worsening symptoms
• Failed daily monotherapy treatment |
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Tx for refractory RLS
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o Δ to gabapentin or another DA agonist
o Add a BZD, opioid or gabapentin o Δ to a high-potency opioid |
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6 goals of RLS Tx
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• Decrease nights with RLS symptoms
• Decrease symptom severity • Decrease nighttime awakenings • Decrease day time sleepiness • Improve quality of sleep • Improve overall QOL |
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4 nonpharm Tx of RLS
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• Regular exercise
• Good sleep hygiene • Recommend mental alertness activities • Discontinue drugs that may precipitate or aggravate RLS |
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7 drugs that may aggravate RLS
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o Nicotine
o Caffeine o Alcohol o SSRIs/TCAs o Metoclopramide, prochlorperazine o DA antagonists o Diphenhydramine |
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indication of Dopamine Agonists in RLS
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DOC – INTERMITTENT OR DAILY RLS
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use of DA agonists in RLS
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• Onset is 90-120 minutes
• Can cause augmentation • Longer half lives reduce rebound |
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ADRs of DA agonists
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N/V, constipation, insomnia, fluid retention, hallucinations, sleep attacks
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indications for Sinemet
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INTERMITTENT OR DAILY RLS
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use of Sinemet
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• Avoid taking with high-protein foods
• Can cause augmentation or rebound |
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ADRs of Sinemet
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N/V
insomnia hallucinations |
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indications of opioids for RLS
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INTERMITTENT OR DAILY RLS
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use of opioids for RLS
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• Short-acting for intermittent symptoms
• Long-acting for daily symptoms |
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indications of BZDs for RLS
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INTERMITTENT RLS
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3 anticonvulsants for RLS
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gabapentin
CBZ VAL |
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indications for anticonvulsants for RLS
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DAILY OR REFRACTORY (adjuvant) RLS
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use of antivonculsants for RLS
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• Consider for patients with neuropathy, documented failure or intolerance to dopaminergic medications
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3 Strategies to resolve Augmentation
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• Dosage reduction or D/C dopaminergic medication
• Abrupt D/C of dopaminergic medication may result in severe rebound of RLS causing 48-72 hours of insomnia • Addition of opioids to dopaminergic treatment may improve augmentation |
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classes for intermittent RLS
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Sinemet
DA agonists Opioids BZDs |
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classes for daily RLS
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Sinemet
DA agonists Opioids anticonvulsants |
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classes for refractory RLS
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anticonvulsants
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define narcolepsy
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• Excessive daytime sleepiness
• Cataplexy – when a person suddenly feels week and collapses at moments of strong emtion such as laughter, anger, fear, or surprise • Hypnagogic hallucinations • Sleep paralysis |
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epidemiology of narcolepsy
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• FH
• F = M • Onset <25 years old most common • Cataplexy occurs in 60-90% |
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pathophysiology of narcolepsy
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• Loss of neurons containing hypocretin (orexin) in CNS
• Hypocretin produced in posterior and lateral hypothalamus and is thought to regulate the maintenance of wakefulness and REM sleep suppression • Hypocretin is maximally released during wakefulness, causing increased muscle tone |
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2 diagnostic tests for narcolepsy
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• Polysomnography
• Multiple sleep latency test (MSLT) |
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4 goals of Tx for narcolepsy
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• Restore normal daily functioning by eliminating daytime sleepiness
• Reduce frequency of hypnagogic hallucinations • Reduce frequency of sleep paralysis • Reduce frequency of cataplexy |
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4 nonpharm Tx for narcolepsy
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• Education on therapeutic expectations of management
• Avoidance of sleep loss or circadian rhythm disturbances • Good sleep hygiene • Planned naps to provide temporary alertness |
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drug Tx for narcolepsy
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• Dextroamphetamine
• Methylphenidate • Modafinil • Sodium oxybate |
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4 drug Tx for cataplexy ass'd with narcolepsy
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Sodium oxybate
TCAs SSRIs MAOIs |
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only pharmacologic treatments for obstructive sleep apnea
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MODAFINIL in CPAP patients who have continued excessive daytime sleepiness
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5 Cs of Addiction
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• Chronicity
• Control (impaired) over drug use • Compulsive use • Continue use despite harm • Craving |
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Most common DSM-IV criteria met for substance abuse
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• Recurrent substance-related legal problems
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Questionnaire for Adolescent Substance Abuse
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• CRAFFT
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Age at which heavy alcohol use and DUIs peaks
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• 21-25
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Kinetics of alcohol
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• zero order
• about 1 drink cleared per hours |
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Metabolite of alcohol responsible for flushing, nausea, thirst, palpitations, CP, vertigo, and HTN
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• acetaldehyde
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S/Sx of alcohol withdrawal
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• tremor
• tachycardia • diaphoresis • labile BP • anxiety • N/V • Hallucinations • Seizures • Hyperthermia • Delirium |
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describe Wernicke's encephalopathy
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Acute life-threatening neurologic disorder due to Chronic EtOH consumption
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Chronic EtOH consumption leads to
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o Inadequate thiamine intake
o Decreased absorption of thiamine from the GIT o Impaired thiamine utilization in cells |
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Sx of WE
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o Mental confusion
o Oculomotor disturbance o Ataxia |
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80-90% of alcoholics with WE develop Korsakoff’s psychosis
describe KP |
o KP is a chronic neuropsychiatric syndrome characterized by behavioral abnormalities and memory impairments
o Can have both retrograde and anterograde amnesia |
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mgmt of acute alcohol intoxication
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• Time
• CV and respiratory support • IV fluids – banana bag especially if malnourished/chronic alcoholic in order to prevent WE / KP • Assess for other drug use, especially BZDs or opioids, to see if antagonists can be used • Monitor until withdrawal begins and then start treatment |
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3 goals of alcoholism treatment
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• Prevention and treatment of withdrawal symptoms
• Long-term abstinence after detoxification • Entry into ongoing medical and alcohol-dependence treatment |
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3 alcoholism assessments
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• CIWA-Ar is scored every 2 hours and determines Tx with either chlordiazepoxide or lorazepam
• CAGE • AUDIT |
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FDA-Approved medications for Alcohol Dependence
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disulfiram
naltrexone acamprosate |
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serious effect of disulfiram
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liver failure
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CIs of naltrexone
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current opiate use
severe liver disease (black box warnings) |
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CI of acamprosate
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severe renal impairment
hypersensitivity |
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3 treatable symptoms of MDMA intoxication
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hyperthermia
serotonin syndrome dehydration |
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Tx for MDMA intoxication
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hyperthermia
-Symptomatic -rapid cooling (cooling blankets) -dantrolene serotonin syndrome -DI with TCAs and/orSSRIs -Dehydration -IV fluids -Electrolyte replacement |
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Tx of acute cocaine intoxication
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Most toxicity too brief to treat
Anxiety -BZD Hyperthermia -Rapid cooling Refractory HTN -Nitroprusside or labetolol MI -No metoprolol -Use labetolol (mixed alpha and beta blockade) |
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Treatment of Acute LSD/psilocybin Intoxication
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• Supportive (BZDs, haloperidol)
• Quiet, dark room |
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Treatment of Acute BZD Intoxication
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Flumazenil
Maximum total cumulative dose is 5 mg |
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Treatment of Acute Opiate Intoxication
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Naloxone
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antidepressants that can switch patients with BPD from depression into mania
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Venlafaxine > paroxetine, sertraline or bupropion
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3 theories regarding the pathophysiology of BPD
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• Monoamine dysfunction
• Permissive theory • Kindling/Behavioral Sensitization |
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describe monoamine dysfunction in BPD
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o Hyperfunction of NE and DA
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describe Permissive theory of BPD
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o Both mania and depression episodes have underlying 5HT deficiency
o Mania = excessive NE o Depression = decreased NE |
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describe BPD I
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• 1+ manic or mixed episodes
• usually accompanied by major depressive episodes • M ≥ F |
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describe BPD II
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• 1+ major depressive episodes
• accompanied by 1+ hypomanic episodes • F > M |
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describe cyclothymic disorder
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• 2+ years of numerous periods of hypomanic and depressive symptoms
• Symptoms do not meet criteria for manic and depressive episodes |
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difference between mania and hypomania
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mania lasts 1+ week and is severe enough to interfere with normal functioning
hypomania lasts 4+ days, but doesn't interfere with normal functioning |
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describe mixed episode
|
• Criteria both for manic and for major depression episode are met (except for duration) nearly every day for at least 1 week
|
|
|
4 goals of BPD therapy
|
• Remission or reduction of symptoms
• Rapid control of aggression and agitation • Prevent recurrence o Subsequent episodes last longer and are more resistant to medication treatments • Improve quality of life between episodes o Improve social and occupational function |
|
|
3 nonpharm Tx for BPD
|
• Sleep hygiene
• ECT • Psychotherapy (lack of evidence) |
|
|
3 phases of BPD Tx
|
acute
continuation maintenance |
|
|
indications for lithium
|
mania
bipolar depression maintenance |
|
|
responses to lithium
|
acute phase > mixed phase > rapid cyclers
|
|
|
MOA of lithium
|
o Blocks NE and DA effects in the CNS
o Increases levels of GABA in the CNS o Inhibits inositol phosphatase - Mediates the actions of ACh and NE |
|
|
4 common ADRs of lithium
|
Dyspepsia
GI upset weight gain decreased cognition |
|
|
8 dose-related ADRs of lithium
|
Action tremor (1-2 hours after dose)
sedation lethargy polyuria polydipsia cognitive dulling GI upset weight gain |
|
|
toxic ADRs of lithium
|
above 1.5-2 mEq/L
Slurred speech, course active tremor/twitching, dizziness, vertigo, muscle weakness, confusion, ataxia, syncope, convulsions, ECG changes, stupid, coma, death |
|
|
rare ADRs of lithium
|
Acne
psoriasis alopecia arrhythmias diabetes insipidus (blocks ADH) |
|
|
cautions with lithium
|
Renal failure
CV disease Na depletion |
|
|
monitoring for lithium
|
o TSH, Chem7, pregnancy testing
o baseline ECG, weight, and CBC |
|
|
drugs that increase lithium
|
tetracycline
NSAIDs ACEI COX2 inhibitors diuretics (esp thiazides) |
|
|
drugs that decrease lithium
|
caffeine
theophylline |
|
|
drugs that increase risk of neurotoxicity with lithium
|
antipsychotics, SSRIs, TCAs, CCBs, carbamazepine
|
|
|
indications for valproate
|
o Acute mania
o Maintenance treatment of BPD o Preferred in mixed episodes, rapid cyclers |
|
|
advantages of valproate
|
o Less toxic than Li
o Rapid loading o QD formulation available |
|
|
disadvantages of valproate
|
o Drug-drug interactions (but still less than Li) – such as ASA increasing [VAL]
o Fetal abnormalities |
|
|
MOA of valproate
|
o Na channel blocker, decreases glutamate release
o Affects K channels, stabilizing membranes o Enhances GABA activity within the brain |
|
|
dose related ADRs of valproate
|
GI upset (anorexia, nausea, dyspepsia)
elevated LFTs resting tremor (v. Li’s active tremor), sedation weight gain somnolence weakness HA TCP |
|
|
Mgmt of GI Sx with valproate
|
• 1) take with food
• 2) reduce dose • 3) H2RA • 4) enteric coated |
|
|
toxic ADRs of valproate
|
• Tremor, ataxia, nystagmus, visual hallucinations, coma
• Tx: hemodialysis |
|
|
rare ADRs of valproate
|
hepatic dysfunction, pancreatitis, hyperammonemia, alopecia
|
|
|
monitoring with valproate
|
o Baseline CBC and LFTs, q 1 month x 2, then q 3-6 months
o Weight o Pregnancy test |
|
|
MOA of CBZ
|
augmentation of gaba
|
|
|
indications for CBZ
|
o 2nd line agent for acute and prophylactic treatment of mania
o Carbamazepine ER (Equetro) – acute mania and mixed episodes • May be better than Li with rapid cycling, mixed episodes, or atypical presentation |
|
|
disadvantages of CBZ
|
o Drug interactions
o Lab monitoring o Adverse events o Most formulations not FDA approved for mania |
|
|
dose-related ADRs of CBZ that occur within the 1st month and are transient if dose is titrated
|
Dizziness, drowsiness, HA, diplopia, nystagmus, ataxia, blurred vision, nausea, weight gain, hepatotoxicity
|
|
|
rare and serious ADRs of CBZ
|
• Aplastic anemia, agranulocytosis (report unexplained fever), TCP, leukopenia
• Stevens Johnson Syndrome |
|
|
monitoring of CBZ
|
o CBZ level Q3M
o CBC w/ diff Q2-4W x 2 months, then Q 3-6 months o LFTs Q 6 months |
|
|
CBZ metabolism
|
o 3A4 inducer and substrate (autoinduction)
|
|
|
CBZ is increased by
|
3A4 inhibitors
• Azole antifungals, macrolides, fluoxetine, fluvoxamine, cimetidine, protease inhibitors |
|
|
indication for oxcarbazepine
|
2nd line for acute treatment of mania
|
|
|
metabolism of oxcarbazepine
|
induces 3A4 metabolism
|
|
|
MOA of lamotrigine
|
o inhibits Na channels
o inhibits release of glutamate |
|
|
indications for lamotrigine
|
o Bipolar depression and rapid cycling
o maintenance therapy only |
|
|
common ADRs for lamotrigine
|
• Dizziness, tremor, somnolence, HA, nausea, ataxia, diplopia
|
|
|
rare, serious ADRs for lamotrigine
|
SJS
|
|
|
dosing for lamotrigine
|
very slow titration, can take months
|
|
|
Li v. Lamotrigine at preventing relapses in general
|
equal
|
|
|
Li v. Lamotrigine at preventing depression relapses
|
lamotrigine > Li
|
|
|
Li v. Lamotrigine at preventing manic relapses
|
Li
|
|
|
Atypical antipsychotics used to treat BPD
|
• Aripiprazole
• OLANZAPINE • Quetiapine • Risperidone • Ziprasidone |
|
|
Black box warning on atypical antipsychotics
|
• Increased risk of hyperglycemia, DM, dyslipidemia, weight gain
|
|
|
Antidepressants that have HIGH risk of switching from depression to mania while on mood stabilizers
|
• TCAs, venlafaxine, MAOIs
|
|
|
Antidepressants that have LOW risk of switching from depression to mania while on mood stabilizers
|
• Bupropion, SSRIs
|
|
|
BPD Therapies that are teratogenic
|
Li
CBZ VAL lamotrigine (no human data) |
|
|
Treatment for moderate acute mania
|
o single agent
o Li, VAL, CBZ, or OX |
|
|
Treatment for severe acute mania
|
o (Li or VAL) + Antipsychotic
o Add CBZ, OX, or ECT |
|
|
Treatment for Maintenance of Mania
|
• Li, VAL, or LAM
|
|
|
Treatment for Acute Depression
|
• Li or LAM
• Then antipsychotic + antidepressant |
|
|
Treatment for Mixed Phase
|
• VAL
• Then, CBZ, OX, or ECT |
|
|
Definition of Rapid Cycler
|
• 4+ episodes within 1 year
• remission for 2+ months or a switch to an episode of opposite polarity |
|
|
Treatment for rapid cycling
|
• valproic acid
• lamotrigine • treat hypothyroidism • treat drug or alcohol abuse • D/C antidepressants |
|
|
Parasympathetic innervation of the eye orginates
|
• Innervates ciliary muscle and sphincter pupillae muscle
|
|
|
Parasympathetic innervation of the eye innervates
|
constriction of the pupil
|
|
|
Parasympathomimetics = _____ and cause ______
|
cholinergics
• Miosis (contraction/constriction) |
|
|
Parasympatholytics = _____ and cause ______
|
anticholinergics
• Mydriasis (dilation) • Cytoplegia • Paralysis of ciliary muscle decreases accomodation • Belladonna |
|
|
Sympathetic innervation of the eye originates...
|
from superior cervical ganglion in spinal cord
|
|
|
Sympathetic innervation of the eye innervates
|
• Innervates the dilator pupillae muscle, blood vessels of ciliary body, episclera, and extraocular muscles
|
|
|
Sympathomimetics causes
|
dilation
|
|
|
Sympatholytics causes
|
constriction
|
|
|
S/Sx of Ocular HTN
|
• IOP 21+ mmHg (normal is 10-20)
• Normal visual fields • Normal optic discs • Open angles |
|
|
Only Tx Ocular HTN if 1+ of the following
|
• IOP > 30 mmHg
• FH of glaucoma • Black ethnicity • High myopia • Patients with one eye |
|
|
Goal of treating ocular HTN
|
• Lower IOP by 25-30% (may not reach “normal”)
|
|
|
1st line Tx for ocular HTN
|
o BBs
o PG analogs |
|
|
adjunctive agents for ocular HTN
|
o Carbonic anhydrase inhibitors
o Alpha 2 adrenergic agonists |
|
|
drugs that can cause open angle glaucoma
|
• Anticholinergics
• Vasodilators • corticosteroids |
|
|
3 goals for Tx POAG
|
• Reduce IOP by 25-30% initially
• Ultimate goal for IOP is <21 mmHg • Primary outcome = preserve vision |
|
|
1st line Tx of POAG
|
o BBs
o PG analogs |
|
|
adjuncts for Tx POAG
|
o Brimonidine
o Topical carbonic anhydrase inhibitors |
|
|
2nd line Tx of POAG
|
o pilocarpine
o diprivefrin or EPI o apraclonidine |
|
|
Treatment approach for POAG
|
• start with 1 eye and then increase to 2 eyes if tolerated
• monitor IOP and optic disc after 2-4 weeks, then every 1-6 months until stabilized • Monitor visual fields every 3-12 months or after changes in drug therapy • If single agent is not tolerated, switch to alternative agents • If single agent is not effective, then switch or use a combo |
|
|
3 drug classes that decrease aqueous production
|
• BBs
• Alpha 2 adrenergic agonists • Carbonic anhydrase inhibitors |
|
|
3 drug classes that increase aqueous outflow
|
• PG analogs
• Parasympathomimetics • Sympathomimetics |
|
|
MOA of beta blockers
|
decrease aqueous production
|
|
|
nonspecific BBs
|
• Timolol
• Levobunolol • Metipranolol |
|
|
Relatively B1 specific BBs
|
betaxolol
|
|
|
Nonspecific BBs with intrinsic sympathomimetic activity
|
carteolol
|
|
|
Efficacy of BBs
|
• Lower IOP by 20-30%
• Timolol and levobunolol > betaxolol • Choice depends on side effects, response, and cost • Betaxolol and carteolol have lower risk of systemic side effects |
|
|
local ADRs of BBs
|
o Stinging (betaxolol and metipranolol)
|
|
|
2 alpha2-adrenergic agonists
|
• Brimonidine (most common)
• Apraclonidine |
|
|
MOA of alpha-2 adrenergic agents
|
• Decrease aqueous production
|
|
|
alpha-2 adrenergic agents used as
|
• Monotherapy
• Adjunctive therapy with BBs, PG analogs, and CAIs |
|
|
Local effects of alpha-2 adrenergic agents
|
• Allergic type reactions, esp with apraclonidine – must D/C drug
|
|
|
Systemic effects of alpha-2 adrenergic agents
|
• Dizziness, somnolence, dry mouth, decreased BP, decreased pulse
• Esp with brimonidine over apraclonidine |
|
|
Cautions with using alpha-2 adrenergic agents
|
• CV disease, renal compromise, cerevrovascular disease
• Patients taking antihypertensives, CAD drugs, MAOIs, TCAs |
|
|
2 carbonic anhydrase inhibitors
|
• Brinzolamide
• Dorzolamide (w/ timolol = Cosopt) |
|
|
MOA of carbonic anhydrase inhibitors
|
• Decrease aqueous humor production
|
|
|
Efficacy of carbonic anhydrase inhibitors
|
• Reduces IOP by 15-26%
• Monotherapy or adjunctive therapy • Rarely used 1st • Generally well tolerated with few side effects • Comparable efficacy to BBs |
|
|
Local side effects of carbonic anhydrase inhibitors
|
• Ocular burning, stinging, discomfort, allergic reactions, bitter taste, superficial punctate keratitis
|
|
|
Cautions with carbonic anhydrase inhibitors
|
• Sulfa allergy esp. w/ anaphylaxis
• Renal impairment • Hepatic impairment |
|
|
4 prostaglandin analogs
|
• Latanoprost (most used, but must be refrigerated)
• Bimatoprost • Travoprost • Unoprostone (multiple daily doses) |
|
|
MOA of prostaglandin analogs
|
• Increase aqueous humor outflow
|
|
|
Efficacy of prostaglandin analogs
|
• Reduces IOP by 25-35%
• Similar efficacy to BBs • Lower risk of systemic side effects than BBs • Once daily administration (best QHS) • Monotherapy or adjunctive therapy |
|
|
Local side effects of prostaglandin analogs
|
• Iris pigmentation
• Ocular irritation • Uveitis (caution in pts with ocular inflammatory conditions) |
|
|
2 Parasympathomimetics
|
• Pilocarpine (QID dosing)
• carbachol |
|
|
MOA of parasympathomimetics
|
• increase outflow of aqueous humor
|
|
|
Efficacy of parasympathomimetics
|
• Reduces IOP by 20-30%
• Equivalent efficacy to BBs |
|
|
Local side effects of parasympathomimetics
|
• Miosis and decreased night vision (mostly in pts with cataracts)
• Frontal HA, browache, periorbital pain • Eyelid twitching, conjunctival irritation |
|
|
Systemic effects of parasympathomimetics
|
• Diaphoresis, N/V/D, cramping, urinary frequency, bronchospasm, heart block
• Seen more with higher doses, less when using NLO |
|
|
2 Sympathomimetics
|
• Diprivefrin (EPI prodrug that inc. absorption, last line, $$$)
• EPI |
|
|
MOA of sympathomimetics
|
• Increased outflow of aqueous humor
|
|
|
Efficacy of sympathomimetics
|
• Less effective than BBs
• Rarely used as monotherapy, used in combo with o PG analogs o CAIs o Parasympathetics o ***NOT BBs |
|
|
Local effects of sympathomimetics
|
• Tearing, burning, ocular discomfort, browache, conjunctival hyperemia, punctate keratopathy, allergic blepharoconjunctivitis
|
|
|
Systemic effects of sympathomimetics
|
• HA, faintness, increased BP, tachycardia, arrhythmia
|
|
|
Cautions with sympathomimetics
|
• Cardio/cerebrovascular diseases, CLOSED ANGLE GLAUCOMA, hyperthyroidism, DM
• Patients undergoing anesthesia with hydrogenated hydrocarbon anesthetics |
|
|
Local adverse effects of eye drop preservatives
|
• Superficial punctuate keratitis
• Corneal ulcers • Corneal cell dysfunction and lysis |
|
|
drugs that can closed-angle glaucoma
|
o Anticholinergics
o Sulfas o sympathomimetics |
|
|
S/Sx of closed angle glaucoma
|
• Cloudy, edematous cornea
• Ocular pain or discomfort • N/V/abdominal pain, diaphoresis • IOP as high as 40-90 mmHg |
|
|
Goals of CAG therapy
|
• Rapid reduction of IOP to preserve vision
|
|
|
Tx of CAG
|
• Pilocarpine 2-4% 1 gtt q 5 minutes x 4-6 times
• Hyperosmotic agents • Secretory inhibitor o BB, alpha 2 agonist, PG analog, or topical CAI |
|
|
5 drugs that have ocular side effects
|
• Amiodarone
• Phenytoin • Ethambutol • Viagras • Corticosteroids |
|
|
drug interactions with methylphenidate
|
CBZ, MAOIs, TCAs
|
