Pharm Flashcards

Question

Amantadine

Answer 1

Antiviral agent: Mechanism is unclear -all proposed enhance action of dopamine Benefits short-lived, but may favorably influence bradykinesia, rigidity and tremor; it also has antidyskinetic properties • Can be used as initial therapy of mild PD and as adjunct therapy in patients on levodopa with dose-dependent fluctuations and dyskinesias.

Answer 2

1. In the beginning if only mild symptoms (tremor mostly), use anticholinergics 2. Then maybe use selegiline/rasagiline which are possibly - neuroprotective. 3. If younger <65 use dopamine agonist, can add on carbidopa to help later 4. If older than 65, use levodopa since life expectancy is too low to develop complications 5. in the end you develop motor and psychiatric complications.

Answer 3

The peripheral metabolite of Levodopa by COMT - catechol-O-methyltransferase. This product will compete with dopamine transport to the brain.

Answer 4

Trihexyphenidyl Biperiden Benztropine Orphenadrine Procyclidine

Answer 5

Primary Mechanism of Action: Na+ Channel inhibition  Indications: 1) Simple Partial 2) Complex Partial 3) Secondarily Generalized and 4) Primary Generalized tonic-clonic seizures  Contraindications: May exacerbate myoclonic seizures and absences, esp in Lennox-Gastaut syndrome Therapeutic dose for most patients is 10-20µg/mL 2. ~90% bound to plasma protein  • Only free, unbound phenytoin molecules can penetrate the blood- brain barrier and exert pharmacological effects • Conditions such as hypoalbuminemia and uremia can significantly impact plasma levels since it is heavily bound to plasma protein -other protein binding ASDs, like valproate can compete also 3. Hepatic elimination by conversion to inactive metabolites - as saturation of hepatic enzymes occurs, enters zero-order kinetics (exponential) **phenytoin induces hepatic enzymes which impact metabolism of a number of drugs (like contraceptives) Small increments in phenytoin dosage can have large impact on plasma levels and could result in toxic plasma doses i.e. toxicity may occur with only small increments in dosage. • The phenytoin dosage should be increased each time by only 25–30 mg in adults, and ample time should be allowed for the new steady state to be achieved before further increasing the dosage.

Answer 6

- nystagmus - diplopia - ataxia - drowsiness - hirsutism & coarsening of facial features - gingival hyperplasia - decreased serum folic acid (B9), thyroxine, vitK - osteomalacia - vitD deficiency - megaloblastic anemia - rash (Stevens Johnson Syndrome) - teratogen

Answer 7

``` Fosphenytoin is a prodrug of phenytoin designed for parenteral use (first choice for status epilepticus) ```

Answer 8

May exacerbate absence or myoclonic (rapid brief jerks) seizures. • Blood disorders • Liver disorders Primary Mechanism of Action: Na+ Channel inhibition • Slows the rate of recovery of voltage-activated Na+ channels from inactivation. 75% protein-bound The t½ of the drug falls significantly over the first few weeks of therapy due to the induction of hepatic enzymes (CYP) that metabolize itself (autoinduction). CYP-inducing drugs such as phenytoin may increase the metabolism of carbamazepine  Important consideration for combination therapy. • Similarly, co-administration of carbamazepine with other drugs that are CYP substrates (such as hormonal contraceptives, theophylline, warfarin and phenytoin) can lower their concentrations.

Answer 9

-Drowsiness -blurred vision -diplopia, -headache, dizziness, ataxia, nausea and vomiting.  Cognitive effects can interfere with learning.  Hyponatremia is common.  Leukopenia can be as high as 10% but can be transient  Aplastic anemia and agranulocytosis  Teratogen: Pregnancy Category D Rash, particularly with high starting doses or rapid dose escalation. Carbamazepine-induced Stevens- Johnson syndrome (SJS) incidence is highest in Asian populations.

Answer 10

1) Na+ channel inhibition Other Mechanisms of Action: 2) Inhibition of T-type Ca2+ channels. 3) Increases GABA production (stimulate GABA synthetic enzyme, glutamic acid decarboxylase), and decreases GABA metabolism (inhibit GABA degradative enzymes, GABA transaminase and succinic semialdehyde dehydrogenase) Indications: • 1) Simple Partial 2) Complex Partial 3) Secondarily Generalized and 4) Primary Generalized tonic-clonic seizures 5) Absence 6) myoclonic, and 7) atonic seizures ("dropattack, sudden loss in muscle tone). • Highly effective for photosensitive epilepsy and juvenile myoclonic epilepsy. **contraindicated in liver disease.  Highly protein-bound, but the binding is saturable  Elimination through hepatic metabolism at least one metabolite implicated for the hepatotoxicity associated with valproate  Crosses the placenta and concentrations in cord serum blood may be 5-X higher than the mother **inhibits CYP enzymes, unlike phenytoin and carbamazepine

Answer 11

1. Transient GI symptoms, including anorexia, nausea, and vomiting 2. Dose-related tremor, sedation, ataxia 3. Temporary alopecia 4. Significant weight gain with chronic valproate treatment for some patients 5. Decreased platelet function and thrombocytopenia 6. *Hepatotoxicity-A rare complication is a fulminant hepatitis that is frequently fatal. Children below 2 years of age with other medical conditions were especially likely to suffer fatal hepatic injury. 7. *Acute pancreatitis and hyperammonemia 8. *Teratogenic effects such as neural tube defects (upto 20-fold higher risk than the general population), particularly spina bifida While the FDA still classifies valproate in Pregnancy Category D for epilepsy treatment, valproate was moved to Pregnancy Category X for migraine treatment in 2013. 9. *SIADH

Answer 12

Multiple mechanisms of action: 1) Na+ channel inhibition by prolonging the inactive state of the channel Other Mechanisms of Action 2) Inhibit synaptic release of glutamate 3) Inhibition of voltage-gated Ca2+ channels reported While lamotrigine has not been shown to affect the efficacy of oral contraceptives (OCs), it has been reported that OCs can reduce effective concentrations of lamotrigine, and so women taking OCs may require higher lamotrigine doses – Co-administration with valproate can double the plasma concentration of lamotrigine, while co-administration with phenytoin or carbamezapine can reduce plasma concentrations of lamotrigine  consideration for polytherapy

Answer 13

Dizziness, ataxia, somnolence, headache, diplopia, nausea, insomnia 2. Rash (10%) – especially in children • Rare progression to serious systemic illness (Stevens Johnson Syndrome* (only side effect listed in FA)

Answer 14

Indications: • Specifically used for absence seizures 2. Mechanism of Action • Inhibits T-type Ca2+ currents.

Answer 15

Adverse Effects • Most common is *gastric distress, including pain, nausea, and vomiting. *• Transient lethargy or fatigue *• Urticaria and other skin reactions, including Stevens-Johnson syndrome • Leukopenia, thrombocytopenia, pancytopenia, and aplastic anemia

Answer 16

Indications  Virtually every seizure type, especially when attacks are difficult to control  Status epilepticus  Relatively low toxicity and low cost. Binds GABAa receptor prolongs opening. Good oral absorption  Metabolized by hepatic microsomal enzymes (CYP).  Phenobarbital also induces* hepatic enzymes, both CYP and Drugs metabolized by hepatic enzymes (e.g. oral contraceptives ) can be more rapidly degraded when co-administered with phenobarbital.

Answer 17

Sedation and dizziness  Cognitive impairment, decreased coordination, mental confusion, behavioral alterations  Phenobarbital can produce irritability and hyperactivity in children, and agitation and confusion in the elderly.  Rash, possibly with other manifestations of drug allergy, occurs in 1-2% of patients.  Megaloblastic anemia that responds to folate, and osteomalacia that responds to high doses of vitamin D, occur during chronic phenobarbital therapy of epilepsy.  CNS depression, risk of *cardiorespiratory depression

Answer 18

``` Lennox-Gastaut Syndrome, • Myoclonic • Atonic • Absence seizures resistant to other ASDs (less effective than valproate and ethosuximide). ``` Tolerance develops after about 6 months

Answer 19

First line for treatment of status epileticus. ``` • Intermittent use for control of seizure clusters (diazepam) ```

Answer 20

Adverse Effects: • *Sedation and Dependence • Hypotonia, Dysarthria, Muscle incoordination • CNS depression • Behavioral disturbances (especially in children) • Aggression, Hyperactivity, Irritability and difficulty concentrating *tolerance and sedation are limiting effects.

Answer 21

inhibits GABA reuptake, used for partial seizures as adjunct -renal clearance Mechanism of Action: Inhibition of GABA transporter (GAT-1) – reduces reuptake of GABA by neurons and glial cells. Indications: • Adjunct therapy for partial seizures. Adverse effects: • GI and CNS distress

Answer 22

``` Mechanism of Action: Inhibit the breakdown of GABA by irreversibly inhibiting enzyme GABA transaminase (GABA-T) Indications: • Monotherapy for infantile spasms • Adjunct therapy for complex partial seizures refractory to other ASDs. -renal clearance ``` ``` Adverse effects: • Only available through a restricted distribution program due to concerns about retinal toxicity and permanent **visual field loss • Weight gain ```

Answer 23

Mechanism of Action: • Originally designed to be GABA analogs. • Selective inhibition of voltage-gated Ca2+ Indications: • Adjunct therapy for PARTIAL secondarily generalized seizures -*renal clearance Adverse Effects: • Weight Gain (5%) with edema • Somnolence, dizziness, blurred channels containing the α2δ1 subunit. vision, ataxia, confusion ``` Garbapentin: Effective as monotherapy for focal seizures. • Can exacerbate myoclonic & absence seizures. • Behavioral problems in children (6%) ``` ``` Pregabalin: only effective as adjunct for focal seizures Not effective for absence, myoclonic, or primary generalized tonic-clonic seizures ```

Answer 24

Mechanism of Action: • Binds to Synaptic Vesicle Protein 2A (SVP2A) protein (and Indications: • Adjunct therapy of partial seizures, Lennox-Gastaut syndrome presumably inhibits neurotransmittor release?) and primary generalized tonic-clonic seizures • Monotherapy for partial seizures Contraindications: • Renal dysfunction (majority cleared renally) Adverse Effects: • Relatively mild • Agitation/irritability/lethargy

Answer 25

Lennox-Gastaut syndrome is a form of severe epilepsy that begins in childhood. It is characterized by multiple types of seizures and intellectual disability. People with Lennox-Gastaut syndrome begin having frequent seizures in early childhood, usually between ages 3 and 5

Answer 26

Binds to AMPA receptor • Non-competitive antagonist of glutamate Indications: • Adjunct therapy for adults with partial seizures and generalized tonic-clonic seizures • July 2017: approved for monotherapy for partial seizures Adverse Effects: • The drug label has a black box warning that the drug cause may cause “serious or life-threatening psychiatric and behavioral adverse reactions, including homicidal or suicidal thoughts. • Dizziness, somnolence, vertigo, aggression, anger, loss of coordination, blurred vision, irritability, and slurred speech.

Answer 27

``` Carbamazepine Phenytoin Primidone Phenobarbital -high CYP inducers- decrease efficacy of oral contraceptives. ``` Lamotrigine - oral contraceptives will decrease efficacy of lamotrigine CPPPL

Answer 28

- Carbamezapine - Clobazam/Clonazepam (benzodiazepines) - Perampanel - Phenobarbital - Phenytoin - Tiagabine - Valproate

Answer 29

Abortive – 100%, oxygen, sumatriptan  Preventive – verapamil (not available in US), melatonin,  Transitional - occipital nerve block, steroids

Answer 30

Anti-depressants: tricyclics - amitriptyline & SNRI Anti-convulsants: valproate, divalproex, -topiramate (the most extensively studied) Beta-blockers - metaprolol, timolol, propanolol, NSAIDS and Triptans  Useful for the prevention of migraine headaches that occur in a predictable pattern, such as menstrual migraine.  Medications should be taken at the time of vulnerability, commencing 1 to 2 days prior to the expected onset of headache and continued during the period of vulnerability.

Answer 31

- Although not first-line treatment for hypertension or anxiety, -blockers may be useful along with other therapy in patients with comorbid hypertension or angina.  Mechanism of Action:  Unclear, but thought to raise migraine threshold by modulating adrenergic and serotonergic transmission in cortical and subcortical pathways.  Adverse effects can include drowsiness, fatigue, sleep disturbances, vivid dreams, memory disturbance, depression, impotence, bradycardia, and hypotension.  Should be used with caution in patients with congestive heart failure, peripheral vascular disease, asthma, depression, and diabetes.

Answer 32

May be particularly useful in patients with comorbid depression or insomnia.  Mechanism of Action:  Independent of antidepressant activity.  Thought to be related to downregulation of central 5-HT2 receptors, increased levels of synaptic norepinephrine, and enhanced endogenous opioid receptor actions. ____________________________  Adverse Effects and Cautions: ________________________________________  Anticholinergic side effects are common with amitriptyline, and limit the use of this agent in patients with benign prostatic hyperplasia and glaucoma.  Increased appetite and weight gain can also occur.  Most common adverse effects with venlafaxine are nausea, vomiting, and drowsiness.

Answer 33

May be particularly useful in patients with comorbid seizure disorder or bipolar illness.  To minimize adverse effects, anticonvulsants should be initiated at low doses and slowly titrated upward.  Topiramate is the most extensively studied medication for migraine prophylaxis.  The benefits of topiramate are observed as early as two weeks after initiation of therapy, with significant reductions in migraine frequency within the first month.  Approximately 50% of patients treated with target doses of topiramate are responders. _________________________________________  Mechanism of Action:  Beneficial effects are thought to be related to multiple mechanisms of action that include: 1. Enhancement of (GABA)-mediated inhibition. 2. Modulation of the excitatory neurotransmitter glutamate. 3. Inhibition of sodium and calcium ion channel activity.  Adverse Effects and Contraindications:  Nausea and vomiting are the most common side effects of valproate and divalproex, but these effects are self-limited and are less common with titration of doses.  Other adverse effects associated with valproate and divalproex include alopecia, tremor, asthenia, somnolence, and weight gain.  The most serious side effect of valproate therapy is hepatotoxicity, but the risk appears to be low in migraineurs.  Baseline liver functions tests should be obtained, but follow up studies are unnecessary in asymptomatic adults on monotherapy.  Valproate is contraindicated in pregnant women (potential for teratogenicity) and patients with a history of pancreatitis or chronic liver disease.  Paresthesia is the most common adverse effect of topiramate, occurring in about half of patients at target doses.  Other adverse effects of topiramate include fatigue, anorexia, diarrhea, weight loss, hypesthesia, difficulty with memory, language problems, taste perversion, and nausea.  Topiramate should be used with caution or avoided in patients with a history of kidney stones or cognitive impairment.

Answer 34

Simple analgesics and NSAIDS are effective medications for the management of many acute migraine attacks.  They offer a reasonable first-line choice for treatment of mild-to-moderate migraine attacks.  Suppository preparations are an option when migraine-associated nausea and vomiting are severe. the most consistent evidence of efficacy include: _________________________________  Mechanism of Action:  Appear to prevent neurogenically-mediated inflammation in the trigeminovascular system by inhibiting cyclooxygenase (COX)-mediated prostaglandin synthesis. ___________________________________  Adverse Effects and Contraindications:  GI effects that include dyspepsia, nausea, vomiting, and diarrhea.  CNS effects that include dizziness and somnolence.  Should be avoided or used cautiously in patients with previous ulcer disease, renal disease, or hypersensitivity to aspirin.

Answer 35

The triptans are migraine-specific medications, and their introduction represented a major advance in migraine pharmacotherapy.  They are appropriate first-line therapy for patients with mild-to-severe migraine, and are used for rescue therapy when non-specific medications (e.g., analgesics and NSAIDS) are ineffective.  Selection of a triptan is based on the characteristics of the headache, convenience of dosing, and patient’s preference.  At all marketed doses, the oral triptans are effective and well tolerated.  Selective agonists at serotonin 5-HT1B and 5-HT1D receptors.  Relief of migraine is the result of three key actions: 1) Normalization of dilated intracranial arteries through enhanced vasoconstriction. 2) Inhibition of vasoactive peptide release from perivascular trigeminal neurons. 3) Inhibition of transmission through second-order neurons ascending to the thalamus.

Answer 36

Adverse Effects and Contraindications:  Adverse effects are common, but typically mild in nature and of short duration.  These include paresthesias, dizziness, fatigue, flushing, and somnolence.  Up to 25% of patients receiving triptans report tightness, pressure, heaviness, or pain in the chest, neck, or throat.  The triptans are partial agonists at 5-HT coronary artery receptors, and are therefore contraindicated in patients with a history of ischemic heart disease, uncontrolled hypertension, and cerebrovascular disease.  The triptans should not be given to patients receiving selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs), as 5-HT syndrome may occur.

Answer 37

Ergotamine tartrate and dihydroergotamine can be considered for the treatment of moderate-to- severe migraine attacks.  Their use, however, is limited by issues of efficacy and side effects.  Ergotamine is available in oral, sublingual, and rectal preparations, with dihydroergotamine being available for intranasal and parenteral administration. Mechanism of Action:  Non-selective agonists at serotonin 5-HT1 receptors.  Cause constriction of intracranial blood vessels and inhibit the development of neurogenic inflammation in the trigeminovascular system.  Central inhibition of the trigeminovascular pathway has also been reported. Adverse Effects and Contraindications:  Nausea and vomiting are among the most common adverse effects.  Pretreatment with an antiemetic should be considered.  Other common side effects include abdominal pain, weakness, fatigue, paresthesias, muscle pain, diarrhea, and chest tightness.  Contraindicated in patients with renal or hepatic failure; coronary, cerebral, or peripheral vascular disease; uncontrolled hypertension, and sepsis.  Also contraindicated in women who are pregnant or nursing.

Answer 38

1. Patient meets criteria - headaches reoccur in predictable pattern (menstrual migraine) - NSAID or triptan - healthy or cormorbid hypertension or angina - beta adrenergic antagonist (verapmil) -comorbid depression or insomnia, tricyclic antidepressant - comorbid seizure or bipolar - anticonvulsants, if ineffective use beta adrenergic antagonist. then consider combination therapy

Answer 39

Conscious Sedation: Minimal amounts of amnestic and opioid; patient still able to converse, respond to stimuli and commands; able to protect airway and maintain ventilation Continuum to general anesthesia -decreases in responsiveness to painful stimuli and commands, decrease in ability to protect airway and maintain normal ventilation - *once patient has lost ability to protect the airway, it is considered general anesthesia - most operators desire such a hiogh degree of immobility and unresponsiveness for their patients and that request for sedation is actually general anesthesia

Answer 40

- increased partial pressure (alveolar fraction) of anesthetic (turn up the vaporizer) - increased alveolar ventilation, how fast you run the vent (more gas gets into blood) **insoluble agents have faster onset solubility N2O < Des < Sevo < Iso so nitrous is the fastest onset and isoflurane is the slowest No dans see iris

Answer 41

ONset in reverse, except F1 is zero Alveolar ventilation is the most important factor in emergence metabolism is a minor factor Sevo > Iso > Des > N2O

Answer 42

Minimal Alveolar Concentration - measure of potency - partial pressure of inhalational anesthetic in the alveoli which 50% of a population of non-relaxed patients remain immobile at skin incision

Answer 43

Cardiovascular: decrease in BP Respiratory: increased RR, decrease tidal volume so overall decrease in minute volume -opiod depress respiratory rate but tidal volume increases, overall also decrease in minute volume. Hepatic" decreases portal vein flow - halothane (discontinued) Uterine smooth muscle: decrease in uterine tone (helpful for delivery but it can lead to increase in uterine bleeding and vomitting)

Answer 44

rare life threatening condition in which inhaled anesthetics or succinylcholine induce fever and SEVERE muscle contractions. Susceptibility is often inherited as autosomal dominant with variable penetrance. Mutations in voltage sensitive ryanodine receptor Prolonged muscle contraction leads to hyperthermia, hypercapnia, hypoxia, hyperkalemia FA: Mutations in voltage-sensitive ryanodine receptor cause increase Ca2+ release from sarcoplasmic reticulum. Reuptake of the calcium leads to increased AMP expenditure leading to hyperthermia. Treatment: dantrolene (a ryanodine receptor antagonist).

Answer 45

Dantrolene (inhibits release of calcium from sarcoplasmic reticulum)

Answer 46

Milk of amnesia _anterograde, -gaba agonist -non-analgesic CV: vasodilatory and negatively inotropic -decrease in Vt, RR and minute ventilation -antiemetic FA: used for ICU sedation, rapid anesthesia induction, short procedures rapid redistribution from highly perfused tissues into lean tissues for quick offset of action. -liver metabolism is rapid as well Good context sensitive 1/2 time: the elimination 1/2 time after a continuous infusion, this is the important factor in a drugs suitability for maintenance sedation

Answer 47

IV GA - used for induction and short sedation, aka vomidate - minimal hemodynamic effects: HR, BP, GABA agonist - nonanalgesic - respiratory depressant - burns on injection rapid redistribution from highly perfused tissues into lean tissues for quick offset of action. -liver metabolism is rapid as well Good context sensitive 1/2 time: the elimination 1/2 time after a continuous infusion, this is the important factor in a drugs suitability for maintenance sedation

Answer 48

IV GA *Dissociative anesthesia w/ nystagmus NMDA receptor antagonist, **analgesic! increases in HR, BP and CO - can't give it to older patients -no respiratory depression rapid redistribution from highly perfused tissues into lean tissues for quick offset of action. airway reflexes are preserved mostly -hallucinations and unpleasant emergence so you coadminister benzos * lacrimation and secretions are increased - subanalgesic doses may help in limiting opiod tolerance

Answer 49

used for sedation or adjunct to general anesthetic alpha 2 agonist both sedative and analgesic receptors are in the locus coeruleus and spinal cord preserves respiratory drive -significant decreases in BP and HR can be seen -context sensitive half time is signficantly increased after 8 hrs

Answer 50

indicated to treat - paroxysmal hemicrania : severe, unilateral, orbital, supraorbital, temporal, <30 min (otherwise cluster), 1-40 attacks, sharp throbbing - cough induced - ice pick - V1, SUNCT - moderate to severe unilateral lasting <600 seconds and occuring as single or series of stabs, can be up to 200 times a day

Pharm Flashcards

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