1
Q
Anticonvulsants
Phenytoin (Dilantin)
Indications and MOA
A
Indications: first-line treatment for tonic-clonic and partial complex seizures
MOA: inhibit and stabilize electrical discharges in the motor cortex of the brain by affecting the influx of sodium ions during generation of nerve impulses
2
Q
Anticonvulsants
Phenytoin (Dilantin)
Avoid, caution
A
- Avoid: sinus bradycardia, second and third degree AV block and Stocks-Adams syndrome (syncope with heart block)
- Caution: hypotension and myocardial insufficiency, elderly
3
Q
What is one significant effect of rapid withdrawal from anticonvulsants/seizure medications?
A
Rebound status epilepticus can occur with sudden withdrawal
4
Q
Anticonvulsants
Phenytoin (Dilantin)
Interactions
A
- Increase level of phenytoin: cimetidine, diazepam, alcohol intake, valproic acid, allopurinol
- Decrease level of phenytoin: barbiturates, antacids, calcium, chronic alcohol use
- Phenytoin decreases the effects of: carbamazepine, estrogens, acetaminophen, corticosteroids, levodopa, sulfonylureas, cardiac glycosides
5
Q
Anticonvulsants
Phenytoin (Dilantin)
Adverse fx (17)
A
- Most common: Nystagmus, dizziness, pruritus, paresthesia, headache, somnolence, ataxia, confusion
- Cardiovascular effects: hypotension, tachycardia
- Gastrointestinal (GI) effects: n/v, anorexia, constipation, dry mouth, gingival hyperplasia
- Genitourinary effects: urinary retention, urine discoloration
6
Q
Anticonvulsants
Phenytoin (Dilantin)
Monitoring
A
- baseline lab and plasma levels
- TSH
- drug levels
7
Q
What should patients with seizure disorders keep in mind in regards to driving?
A
avoid driving if not seizure free for more than 1 year
8
Q
Anticonvulsants
Phenytoin (Dilantin)
Patient education
A
- keep up good oral hygiene
- Monitor for phenytoin hypersensitivity syndrome = fever, skin rash, lymphadenopathy which occurs at 3-8 weeks of tx
9
Q
Anticonvulsants
Carbamazepine (Tegretol)
Indications & MOA
A
Indications: focal and generalized onset seizures, bipolar disorder
MOA: exact unclear but thought to affect the sodium channels, slowing influx of sodium in the cortical neurons, which slows the spread of abnormal activity
10
Q
Anticonvulsants
Carbamazepine (Tegretol)
Black box warning - in which population does this issue occur most frequently?
A
development of Stevens Johnson syndrome and toxic epidermal necrolysis in chinese patients - strong association with HLA-B 1202 allele variant in development of these conditions; blood dyscrasias; dermatologic toxicity
11
Q
Anticonvulsants
Carbamazepine (Tegretol)
Caution
A
Caution: elderly
12
Q
Anticonvulsants
Carbamazepine (Tegretol)
Drug interactions
A
- grapefruit juice
- Levels increased: propoxyphene, cimetidine, erythromycin, clarithromycin, verapamil, hydantoins
- Levels decreased: beta blockers, warfarin, doxycycline, succinimides, haloperidol
13
Q
Anticonvulsants
Carbamazepine (Tegretol)
Adverse fx (10)
A
- Depression of bone marrow
- Liver damage, impairs thyroid function
- Drowsiness, dizziness, blurred vision, n/v, dry mouth, diplopia, headache (HA)
14
Q
Anticonvulsants
Carbamazepine (Tegretol)
Symptoms of toxicity
A
- hypertension
- tachycardia
- stupor
- agitation
- respiratory depression
- nystagmus
- urinary retention
- seizures
- coma
15
Q
Anticonvulsants
Lamotrigine (Lamictal)
Indications & MOA
A
- Indications: adjunctive treatment of partial seizures, primary generalized tonic-clonic seizures in adults and children 2+
- Use with valproic acid and phenytoin
- MOA: affects voltage-sensitive sodium channels and inhibits presynaptic release of glutamate and aspartate in the neuron
16
Q
Anticonvulsants
Lamotrigine (Lamictal)
Interactions
A
Levels decreased: barbiturates, estrogens, phenytoin, mefloquine
Levels increased: alcohol, carbamazepine, CNS depressants, valproic acid
17
Q
Anticonvulsants
Lamotrigine (Lamictal)
Black box warning
A
serious skin reactions
18
Q
Anticonvulsants
Lamotrigine (Lamictal)
Adverse fx (13)
A
- GI: n/v, constipation
- cardiovascular: chest pain, peripheral edema
- CNS: somnolence, fatigue, dizziness, anxiety, insomnia, headache, amblyopia, nystagmus
- dermatological: rashes
19
Q
Anticonvulsants
Lamotrigine (Lamictal)
Patient education
A
- report any new onset of rash
- avoid alcohol & OTC drugs
- stay well hydrated
20
Q
Anticonvulsants
Zonisamide (Zonegran)
Indications & MOA
A
Indications: partial seizures
MOA: blocks voltage-dependent sodium and chloride channels
21
Q
Anticonvulsants
Zonisamide (Zonegran)
Avoid
A
Avoid: allergy to sulfa drugs
22
Q
Anticonvulsants
Pregnancy/lactation and pediatric considerations
A
- Pregnancy/lactation
- Avoid – Phenytoin, Carbamazepine, Lamotrigine, zonisamide, valproic acid
- Succinimides: Pregnancy ok with close monitoring, avoid in lactation
- Gabapentin: Pregnancy/lactation: if benefits outweigh risks
- Topiramate: Pregnancy: avoid; lactation: only if benefits outweigh the risks
- Levetiracetam: Pregnancy: caution; lactation: avoid
- Peds
- All ages – phenytoin, carbamazepine
- 1month+: levetiracetam
- 3months+: topiramate
- 2+: lamotrigine, valproic acid
- 3+: succinimides, gabapentin
- 16+: zonisamide
23
Q
Anticonvulsants
Succinimides: Ethosuximide, Methsuximide
Indication & MOA
A
Indication: absence seizures
MOA: delays calcium influx into neurons; decrease nerve impulses and transmission in the motor cortex
24
Q
Anticonvulsants
Succinimides: Ethosuximide, Methsuximide
Other considerations, symptoms of toxicity
A
- Other considerations: Do not take with alcohol, decreases effectiveness of birth control
- Narrow TI - toxicity = CNS depression, respiratory depression, acute nausea/vomiting
25
Which anticonvulsants should you be cautious of with patients with renal & hepatic impairment?
Renal impairment only?
* phenytoin
* carbamazepine
* lamotrigine
* zonisamide
* succinimides
* topiramate
* **Renal only:** levetiracetam & gabapentin
26
Anticonvulsants
Succinimides: Ethosuximide, Methsuximide
Adverse fx (5)
GI most common
CNS: somnolence, fatigue, ataxia
Blood dyscrasias
27
Anticonvulsants
Valproic Acid (Depakote)
Indications & MOA
Indications: focal (partial) onset seizures, generalized onset seizures, focal onset impaired awareness and absence seizures
MOA: increases GABA availability, enhances the action of GABA, mimics its action at postsynaptic sites, blocks voltage gated sodium channels - results in suppression of high-frequency repetitive neuronal firing
28
Anticonvulsants
Valproic Acid (Depakote)
Caution, black box warning, sx of toxicity
* Caution: elderly - BEERS
* BBW: hepatotoxicity in severe pancreatitis
* toxicity = CNS depression, confusion, jaundice
29
Anticonvulsants
Valproic Acid (Depakote)
Adverse fx
* CNS fx: headache, drowsiness, dizziness, tremor, visual disturbance, behavioral changes, SI, brain atrophy
* GI fx: nausea, vomiting, weight gain,
* Other: hypersensitivity reactions
30
Anticonvulsants
Gabapentin
Indications & MOA
Indications: focal seizures
MOA: GABA analogue that binds to unknown receptors in the brain
31
Anticonvulsants
Gabapentin
Pharmacokinetics, caution
* Food increases absorption, not metabolized by the liver, excreted in the urine
* Caution: elderly (BEERS), patients with substance abuse history
32
Anticonvulsants
Gabapentin
Adverse fx
* CNS fx: ataxia, paresthesia, dizziness, somnolence, difficulty concentrating, mood changes, SI
* Other: weight loss, decreased sweating & hyperthermia
33
Anticonvulsants
Levetiracetam (Keppra)
Indications & MOA
Indications: adjunct for partial onset seizures in children and adults
MOA: may inhibit burst firing without affecting normal neuronal excitability
34
Anticonvulsants
Levetiracetam (Keppra)
What is a benefit of keppra over other anticonvulsants?
Caution, patient education
* Fewer drug interactions
* Caution: elderly
* Patient education: somnolence, dizziness or balance issues when starting
35
Anticonvulsants
Levetiracetam (Keppra)
Adverse fx
* CNS fx:somnolence, dizziness, nervousness, mood disturbances, SI
* Other: dermatologic reactions, blood dyscrasias
36
Dopaminergics
Carbidopa-Levodopa (Sinemet)
Indication & MOA
Indication: Parkinson Disease
MOA
Levodopa: circulates in the plasma to the BBB where it crosses to be converted by enzymes to dopamine
Carbidopa: inhibits peripheral plasma breakdown of levodopa, thereby increasing the availability of levodopa at the BBB
37
Dopaminergics
Carbidopa-Levodopa (Sinemet)
Avoid, caution, interactions, other considerations
* Avoid: narrow-angle glaucoma, major psych dx, malignant melanoma
* Caution: CVD, elderly - more sensitive to CNS fx
* Interactions: TCAs decrease fx; may increase fx of HTN drugs; avoid with antacids
* Other considerations: Risk for neuroleptic malignant syndrome if abruptly stopped; should be taken on a schedule without food
38
Dopaminergics
Carbidopa-Levodopa (Sinemet)
Adverse fx
* CNS fx: somnolence, dizziness, HA, depression, dyskinesia, insomnia, abnormal dreams, neuroleptic malignant syndrome, peripheral neuropathy
* CV fx: orthostatic hypotension, HTN
* GI fx: nausea, constipation, hepatocellular injury
39
Muscle relaxants - general considerations
* short term use, may be habit forming and sedating
* may consider long-term use for MS or ALS; avoid alcohol use
* Not for pregnant women - will relax the uterus
* Use baclofen in caution with lactating women
40
Muscle relaxants
Baclofen
Indications & MOA
Indications: severe muscle spasms with pain
MOA: inhibits transmission of both monosynaptic and polysynaptic reflex reflexes at the spinal cord level, possibly by hyperpolarization of primary afferent fiber terminals, which results in the relief of muscle spasticity
41
Muscle relaxants
Baclofen
Caution, interaction, adverse fx
* Caution: renal impairment, elderly (BEERS), seizure disorder
* Interaction: additive sedation with CNS depressants
* Adverse fx: drowsiness, confusion, HA, NV, hypotension, seizures
42
Muscle relaxants
Cyclobenzaprine (Flexeril)
MOA
MOA: acts on monosynaptic and polysynaptic spinal reflexes; inhibits synaptic reflex arcs affecting the messages that are producing and maintaining the skeletal muscle spasm
43
Muscle relaxants
Cyclobenzaprine (Flexeril)
Avoid, caution, peds, interaction
* Avoid: hyperthyroidism, heart failure, arrythmias, heart block or conduction disturbances, acute recovery phase of MI
* Caution: urinary retention, angle closure glaucoma, increased ocular pressure, hepatic impairment. elderly
* Peds: 12+
* Interaction: additive sedation with CNS depressants
44
Muscle relaxants
Cyclobenzaprine (Flexeril)
Adverse fx
* Anticholinergic fx: dry mouth, constipation, blurred vision
* drowsiness, fatigue, N/V, hallucinations, serotonin syndrome
45
Muscle relaxants
Tizanadine
MOA
MOA: centrally acting alpha-2 adrenergic agonist; presynaptic inhibition of motor neurons
46
Muscle relaxants
Tizanadine
Avoid, caution, other considerations
* Avoid: hepatic impairment
* Caution: renal impairment, elderly
* Other considerations: Do not abruptly stop - may cause rebound tachycardia; P450 drug
47
Muscle relaxants
Tizanadine
Adverse fx
* Anticholinergic fx: dry mouth,constipation
* CV fx: hypotension, bradycardia
* hepatotoxicity, anaphylaxis, angioedema, weakness, fatigue
48
Cholinesterase inhibitors
Donepezil (Aricept), Rivastigmine (Exelon)
Indications & MOA
Indication: Alzheimers disease
MOA: reversibly and noncompetitively inhibits centrally active acetylcholinesterase which results in increased levels of acetylcholine available for synaptic transmission in the CNS - indirect cholinergic agonists
49
Cholinesterase inhibitors
Donepezil (Aricept), Rivastigmine (Exelon)
S/s of toxicity, caution, Donepezil specific considerations
* S/S of toxicity = constricted pupils, excessive salivation, diarrheaAvoid: with anticholinergic drugs
* Caution: renal and hepatic impairment, seizure disorders
* Donepezil - metabolized by the P450 system. risk of QT prolongation
50
Cholinesterase inhibitors
Donepezil (Aricept), Rivastigmine (Exelon)
Adverse fx
* CNS fx: dizziness, HA, agitation, insomnia, tremor, exacerbation of extrapyramidal side fx if patient has parkinson's
* GI fx: wt loss, N/V, diarrhea
* Other: falls
51
Cholinesterase inhibitors
Memantine (Namenda)
Indications & MOA
* Indications: Often used in combo with aricept or exelon when alzheimers behavioral symptoms becomes more moderate to severe
* MOA: noncompetitive antagonist at NMDA receptors
52
Cholinesterase inhibitors
Memantine (Namenda)
Caution, adverse fx
* Caution: CVD, renal impairment, seizure disorder
* Adverse fx
* CNS fx: confusion, dizziness, HA, somnolence
* GI fx: constipation, diarrhea
* CV fx: HTN
* Other: hypersensitivity reaction
53
Alpha-1 selective antagonists
Zosins - doxazosin, tamsulosin, terazosin
Indications & MOA
* Indication: HTN, BPH, raynaud's disease, migraines
* MOA
* HTN: competitively inhibits postsynaptic alpha-1 receptors which results in vasodilation
* BPH: competitively inhibits postsynaptic alpha-1 receptors in prostatic stromal and bladder neck tissues - reduces sympathetic tone-induced urethral stricture causing BPH symptoms; relieve outflow obstruction
54
Alpha-1 selective antagonists
Zosins - doxazosin, tamsulosin, terazosin
Avoid, caution, pregnancy/lactation, peds, patient education
* Avoid: presence of volume depletion
* Caution: heart failure, angina, recent MI, renal & hepatic impairment, elderly (BEERS)
* Tamsulosin is an option that does not cause orthostatic hypotension
* Pregnancy/lactation: avoid
* Peds: limited data
* Patient education: Risk for first-dose or reinitiation orthostatic hypotension - take at night
55
Alpha-1 selective antagonists
Zosins - doxazosin, tamsulosin, terazosin
Adverse fx
* Anticholinergic fx: fluid retention, blurred vision, dry mouth, constipation
* CNS fx: HA, dizziness, fatigue
* GU fx: impotence, urinary frequency, priapism
* Other: allergic reactions, nasal congestion
56
Alpha 2 agonists
Clonidine (Catapres)
Indications & MOA
* Indications: HTN, ADHD
* MOA
* HTN: stimulates alpha-2 receptors in the brain stem, activating the inhibitory neuron, resulting in reduced sympathetic outflow from the CNS, decreasing peripheral resistance, heart rate, blood pressure and renal vascular resistance
* ADHD: possibly regulates activity in the prefrontal cortex responsible for emotions, attention and behaviors
57
Alpha 2 agonists
Clonidine (Catapres)
Avoid, caution, pregnancy, peds, patient education
* Avoid: at risk or hx of bradycardia
* Caution: renal impairment, cerebrovascular disease, severe coronary insufficiency, elderly (BEERS orthostatic hypotension, bradycardia)
* Pregnancy: caution; lactation: avoid
* Peds: approved
* Patient education: do not stop abruptly - can lead to severe increase in blood pressure
58
Alpha 2 agonists
Clonidine (Catapres)
Adverse fx
CNS fx: drowsiness, HA, fatigue, dizziness, nightmares
skin rash, dry mouth, bradycardia, constipation, impotence
59
Alpha 2 agonists
Methyldopa
Indications & MOA
Indications: HTN
MOA: stimulates central alpha-2 receptors by methyldopa's metabolite alpha-methylnorepinephrine which produces a decrease in sympathetic outflow to the heart kidneys and blood vessels
60
Alpha 2 agonists
Methyldopa
Avoid, caution, pregnancy, peds, interactions
* Avoid: at risk or history of bradycardia, active liver disease
* Caution: severe coronary insufficiency, renal impairment, cerebrovascular disease, elderly
* Pregnancy: compatible; lactation avoid
* Peds: not recommended
* Interactions: avoid with beta-blockers, clonidine
61
Alpha 2 agonists
Methyldopa
Adverse fx
* CV fx: edema, bradycardia, hypotension
* GI: elevated LFTs, hemolytic anemia, hepatotoxicity
* Other: sedation, skin rash, myalgias
62
Beta-adrenergic antagonists (beta blockers)
Selective beta-blockers: metoprolol, atenolol
Indications & MOA
Indications: heart failure, HTN, a fib, angina, treatment post-acute MI
MOA: block beta-1 receptors at the SA node to decrease heart rate, decrease contractility in the atria and ventricles and conduction velocity and slow conduction at the AV node
63
Beta-adrenergic antagonists (beta blockers) & combined alpha & beta adrenergic agonists and antagonists
Selective beta-blockers: metoprolol, atenolol, Non-selective beta blockers: Propranolol (Inderal), Carvedilol & Labetalol
Avoid, caution, pregnancy/lactation, peds, patient education
* Avoid: bronchospasms, second or third degree AV block
* Carvedilol, Labetolol: also severe hepatic impairment, NYHA Class IV HF
* Caution: peripheral vascular disease, diabetes - will mask hypoglycemia s/s except diaphoresis, hyperlipidemia, elderly - bradycardia & orthostatic hypotension
* Pregnancy/lactation: others preferred, contraindicated in first trimester
* Labetolol: compatible after first trimester; caution in lactation
* Peds: propranolol approved
* Patient education: Do not abruptly withdraw
64
Beta-adrenergic antagonists (beta blockers)
Selective beta-blockers: metoprolol, atenolol & Non-selective beta blockers: Propranolol (Inderal)
Adverse fx
* CNS fx: fatigue, insomnia, depression, dizziness
* CV fx: HTN, bradycardia
* GU fx: impotence, decreased libido
* Other: anaphylaxis, pruritis
65
Beta-adrenergic antagonists (beta blockers)
Non-selective beta blockers: Propranolol (Inderal)
Indications & MOA
Indications: a. fib, essential tremor, migraine prophylaxis, HTN, stable angina, thyroid storm, anxiety
MOA: competitively block response to beta-1 and beta-2 stimulation resulting in decreased HR, myocardial contractility, BP and myocardial O2 demand
66
Combined alpha & beta adrenergic agonists and antagonists
Carvedilol
Indications & MOA
Indications: HTN, HF with reduced EF, left ventricular dysfunction following MI
MOA: nonselective beta receptor blocker and alpha-1 receptor blocker - decreases BP and peripheral resistance to decrease myocardial O2 demand and lower cardiac workload
67
Epinephrine
Indications & MOA
Indications: emergency treatment of type 1 allergic reaction, including anaphylaxis
MOA: decreases vasodilation and vascular permeability that occur during anaphylaxis; relaxes smooth muscles, relieves bronchospasm, wheezing, dyspnea, pruritis, angioedema, urticaria
68
Epinephrine
Caution, pregnancy/lactation, peds
Caution: cardiac disease
Pregnancy/lactation: compatible
Peds: approved
69
Epinephrine
Adverse fx
* CNS fx: apprehensiveness, tremor, anxiety, HA, disorientation, weakness
* CV fx: palpitations, angina, HTN
* Other: alterations in blood sugar
