Pharm 2 Flashcards

Question

Bile acid sequestrants (resins)

Answer 1

Cholestyramine Reduces LDL; may increase HDL Prevents bile acids from being absorbed and returned to liver, leading to fecal elimination Side effect profile discourages use

Answer 2

Available OTC, Rx Lowers VLDL, which ↓ production of LDL May also increase HDL ADE: flushing, tingling, itching, Hepatic toxicities reported interactions: statins

Answer 3

Bronchodilators SABA: albuterol/levalbuterol (rescue, onset ~15 min) LABA: formeterol/salmeterol (maintenance), used in conjunction w corticosteroids ADE: tachycardia, tremor, hyperglycemia, hypokalemia Indications: sympathomimetics, MAOI More effective to use corticosteroid + Beta 2 agonist than higher doses of corticosteroids alone Can see tolerance develop over time

Answer 4

MOA: SM relaxation from PDE inhibition, preventing breakdown of cAMP ADE: convulsions, arrhythmias, CNS stimulation, N/V insomina, aggravation of reflux/ulcers VERY NARROW TI (5-15) Decreased metabolism: erythromycin, cimetidine, liver failure, heart failure, elderly Increased metabolism: smokers, oral contraceptives, phenytoin Not recommended for exacerbations

Answer 5

MOA: prevents increase of cGMP and antagonizes action of Ach, resulting in bronchial SM relaxation SAMA=ipratropium LAMA=tiotropium

Answer 6

oral: prednisone, methylprednisolone. Short term, gain control of inadeuately controlled persistent asthma (3-10 days) inhaled: beclomethasone, flunisolide. Long term for prevention MOA: antiinflammatory, reduces airway hyperresponsiveness. inhibits cytokine production, inflamm cell migration and activation 1st line Tx starting at step 2 but not for acute attacks ADE: candidiasis, cough, dysophonia, HA, reversible glucose increases, fluid retention, peptic ulcer *adrenal axis suppression @ high doses Growth issues in long term use? If concern replace w/ mast cell stabilizers

Answer 7

MOA: anti-inflammatory; stabilizes mast cell membranes, inhibiting activation and release of mediators from eosinophils and epithelial cells Indication: most useful in younger, allergic asthmatics with mild persistent asthma, also useful in exercise induced asthma May take some time to see effects. Weak drug compared to corticosteroids ADE: (Rare) cough, congestion No risk growth suppression

Answer 8

MOA: Block leukotriene receptors on inflammatory cells and SM (montelukast), Stop synth of leukotrienes via lipoxygenase inhibition Well tolerated, minimal ADE, less effective than corticosteroids Enzyme inhibition of CYP450: decrease metabolism of warfarin and theophylline Watch LFTs

Answer 9

MOA: Forms complexes with IgE and prevents binding to receptors limiting inflammatory mediator release Indication: >12 y/o moderate-severe asthma and failed traditional agents

Answer 10

CNS: analgesia, sedation, euphoria, resp/cough suppression, N/V, pupil constriction GI: delayed gastric emptying, increased intrabiliary pressure, constipation Other: histamine release from mast cells, immune suppression, hypotension/bradycardia, osteoporosis, hyperalgesia

Answer 11

MOA: Activation of m, k, and d opioid receptors, activation of Gi --> K+ channels hyperpolarize and depress neuron function Metabolism: Primarily in gut wall and hepatocyte, conversion to M6G (active) and M3G (neurotoxic). ~10% excreted unchanged (renal) ADE: resp depression, sedation, N/V, mental clouding, urinary retention, constipation, pruritis, hypotension Contraindications: (relative) liver/heart failure, resp failure, asthma, hypotension

Answer 12

Weak opioid, analgesic properties related to conversion to morphine by CYP2D6 (watch polymorphisms)

Answer 13

Low levels of active metabolites, so preferred in renal failure ADE: CP

Answer 14

Low propensity to release histamine

Answer 15

Phenylpiperidine opioid w/ relatively short half life Less constipating than morphine ADE: CNS excitation (tremors, muscle twitches, seizures) Not for Tx of chronic pain d/t metabolite toxicity, not to be taken w/ MAOI, not for pt w tachycardia

Answer 16

Highly lipophilic, highly potent opioid that can be given transdermal/transmucosal Very short half life, no active metabolites (preferred in renal insufficiency) TD fentanyl is less constipating than morphine Not for opioid naive pt, not for acute, intermittent, mild pain

Answer 17

Long acting u, k, d opioid agonist and NMDA antagonist Half life: 20-35 hours (4-10 days to reach Css). Metabolism highly variable btwn individuals (portion of drug that is free vs. protein bound and metabolic activity towards CYPS) No active metabolites Primarily metabolized by CYP3A4, induces CYP3A4 QTc prolongation Less prone to developing tolerance, best opioid for tx neuropathic pain

Answer 18

Progressive loss of effect with sustained administration of an opioid receptor agonist Progressive decrease in drug efficacy Increased dosing decreases pain May develop adverse effects with increased dosing

Answer 19

Paradoxical increase in sensitivity to painful stimuli Increased dosing increases pain Same pain or different pain Increased sensitivity to pain

Answer 20

Nociceptor stimulation in injured tissue causes release of bradykinin, 5HT, K+, histamine, prostaglandins, Substance P that further sensitize/activate other nociceptors (decreasing pain threshold) Nociceptor activation produces action potentials that are transmitted to the spinal cord along myelinated A-delta fibers (sharp, fast) and unmyelinated C-fibers (slow, dull, burning) Pain signals transmitted via spinal cord to thalamus and project to cortical regions where pain is received Modulation of pain through: endogenous opioids (endorphins), descending pain pathway (5HT, NE @ dorsal horn)

Answer 21

Effects: antiinflammatory, analgesic, antipyretic Most are highly protein bound ADE: bleeding, gastric ulceration, renal impairment COX 1 inhibition: Gastric ulceration/bleeding/renal impairmnt MI/CVA protection COX 2 inhibition: Decrease pain/fever/inflammation MI/CVA risk

Answer 22

COX-inhibitor w/ no anti-inflammatory action Indication: mild-moderate nociceptive pain (lacks efficacy in neuropathic/functional pain) Very little protein bound (unlike other NSAIDS) Metabolism: extensive liver metabolism through conjugation w/ glucoronic acid, small portion CYP mediated

Answer 23

Liver: extensive through conjugation with glucuronic acid (60%), sulfuric acid (35%), and cysteine (3%). A small proportion undergoes CYP-mediated N-hydroxylation (CYP2E1). Major metabolism pathway--> nontoxic metabolites Minor pathway (mediated by CYP450) -->Toxic metabolite (NAPQI) ---> glutathione --> nontoxic metabolite P450 induced by alcohol Glutathione inhibited by alcohol AND tylenol OD

Answer 24

Irreversible COX1 and COX2 inhibitor Indication: inflammatory disorders mild-moderate pain, menorrhagia Vd: highly protein bound Metabolism: Plasma esterase to yield salicylate which is 90% eliminated through hepatic metabolism Half life of ASA very short, but salicylate 2-3 hr (and up to 30 hr if hepatic mechanisms become saturated)

Answer 25

Reversible inhibitors of COX 1 and COX 2 Risk of MI/CVA d/t TXA2/PGI1 imbalance Inhibit TXA2 (COX1) vasoconstrictor/promote plt agg Inhibit PGI2 (COX2) vasodilator/inhibit plt agg Nonselective COX inhibitors have bias towards COX2 inhibition

Answer 26

Selective COX 2 inhibitors Just as effective as traditional NSAIDs in suppressing inflammation and pain Somewhat lower risk for GI side effects Can impair renal function and cause hypertension and edema Increased risk of MI and stroke

Answer 27

In GI mucosa Protective @ stomach lining (increase mucous production, bicarb, mucosal blood flow) Inhibiting=peptic ulcers and GI bleeding

Answer 28

Indications: epilepsy (1st line for partial and tonic clonic), trigeminal neuralgia, bipolar mania Action @ voltage gated Na channels (stabilize in inactive state) Advantages: less sedating than other AEDs, mood stabilizing effects, no cognitive deficits High (75-90% protein bound) Metabolized by CYP3A4, induces CYP1A2, 2CP, 3A4. Initially high half life, decreases w/ multiple doses because it induces its own metabolism *also decreases concentration of other CYP mediated AEDs ADE: acute intox, resp depression, ataxia, drowsiness, blurred vision BBW for severe hemolytic anemia and derm rxns (HLH allele) Preg category D

Answer 29

Indication: partial and tonic clonic seizures, during and after NSGY MOA: Stabilizes inactive state of volt-gated Na channels High variability in oral bioavailability (20-90%) High protein binding, low Vd *drug interactions mainly related to protein binding Metabolism via CYP2C9, induces other CYP enzymes Zero order kinetics: elimination rate increases with higher concentrations (saturable) ADE: ataxia, diplopia, drowsiness/sedation, gingival hyperplasia, anemia, lymphadenopathy, osteoporosis Preg category D

Answer 30

Indication: partial seizures, postherpetic neuralgia **no efficacy for tonic-clonic seizures MOA: likely inhibits Ca channel activity Insignificant protein binding, excreted unchanged in urine/no hepatic enzymes (fewer drug interactions) ADE: somnolence, dizziness, ataxia, fatigue, HA, tremor (generally well tolerated) Pregnancy category C--safer than other AEDs

Answer 31

Reduces glutamate, NE, and Substance P levels (analgesic properties, neuropathic pain management) *abuse liability

Answer 32

Indication: Epilepsy, sedation MOA: barbiturate, action @ GABA receptors Drug of choice for infant/neonatal seizures ADE: resp depression, sedation, physical dependence, hyperactivity, cognitive impairment

Answer 33

Indication: partial, tonic-clonic seizures Can exacerbate neuropsych disorders and aggression

Answer 34

Indication: generalized seizures (beyond just tonic clonic), BPD, migraine prophylaxis MOA: Na channel inactivation, reduction in T type Ca currents, increase GABA signaling 90% protein bound Metabolism via CYP2C9, inhibits 2C9 and UGT ADE: A/N/V, sedation, ataxia, tremor, rash, alopecia, weight gain Rare risk of fulminant hepatitis which may be fatal BBW for hepatic toxicity and teratogenicity Preg Category D *worst AED Interactions: inhibits metabolism of CYP2C9 substrates (phenytoin, phenobarbital, ethosuximide)

Answer 35

Indication: Partial, tonic clonic seizures, BPD MOA: Na channel inactivation Insignificant protein binding Extensive hepatic metabolism, induces UGT Half life reduced by phenytoin, carbamazepine, phenobarbital. Increased by valproate Toxicity: weight gain, ataxia, nervousness, dizziness, blurred vision Risk of SJS and DIC (more common in peds)

Answer 36

Indication: absence seizures MOA: Decreases low threshold Ca currents in thalamic neurons Insignificant protein binding 75% hepatic metabolism via CYP3A4, no enzyme induction ADE: N/V/A, drowsiness/lethargy/dizziness, urticaria, SLE, eosiniphilia Preg category D

Answer 37

Citalopram, escitalopram, fluoxetine, paroxetine, sertraline MOA: highly specific in inhibiting SERT, efficacy attributed to subsequent actions of elevated 5-HT at postsynaptic 5-HT1A receptors ADE: nausea (5-HT3), agitation, insomnia, sexual dysfunction (5-HT2), serotonin syndrome= tremor, hyperthermia, CV collapse Inhibit CYP enzymes (esp Paroxetine and fluoxetine inhibit 2D6 and should not be used w TCAs) Highly protein bound Fluoxetine and sertraline have active metabolites with long half lives. Need washout period before starting TCA Mostly category C in pregnancy (Paroxetine category D)

Answer 38

Risk when SSRIs/SNRIs used in combo w/ TCAs or OD of TCA Tremor, hyperthermia, CV collapse

Answer 39

Venlafaxine, Desvenlafaxine, Duloxetine MOA: Inhibit SERT and NET ADE: Similar to SSRIs + b-adrenergic effects (HTN, tachy, CNS activation) Low risk OD but must not use with MAOIs No CYP metabolism (elimination by conjugation) so no high profile drug interactions Lower protein binding (exception = duloxetine is highly protein bound) Overall shorter T1/2 than SSRIs Also for anxiety disorders and pain

Answer 40

Amitryptiline, imipramine MOA: Inhibit both 5-HT and NE reuptake, major metabolites also have activity (antagonism at muscarinic Ach, H1, alpha-adrenergic receptors) ADE: muscarinic- dry mouth, blurred vision, constipation, urinary retention, delayed gastric emptying H1: sedation alpha-adrenergic: postural hypotension Risk of overdose: ventricular arrhythmias, confusion, mania (narrow TI) Interactions: CYP substrates, SSRI/SNRIs, potentiate alcohol/anesthetic agents, anti-HTNs Most are long acting w/ active metabolites, highly protein bound

Answer 41

Mirtazapine, trazadone Fewer sexual side effects than SSRI/SNRIs Very sedating

Answer 42

Inhibits MAO mediated degradation of monoamines (irreversible inhibition of MAO-A and MAO-B) Risk of triggering HTN crisis if pt eats food rich in tyramine ADE: CNS stimulation, orthostatic hypotension

Answer 43

Stimulant Also for smoking cessation, appetite suppression Inhibits NE/DA reuptake Lowers seizure threshold

Answer 44

NMDA receptor antagonist: increases glutamate levels in the brain and produces rapid antidepressant effect (10-15 min), normally for seizures/sedation/analgesia At high doses, may cause sedation and out of body experiences ADE: sedation, inattention, dissociation, abuse potential, SI

Answer 45

Allopregnalone=neuroactive metabolite of progesterone, peaks during 3rd trimester and falls after delivery (+allosteric modulator of GABA channels) Cont. infusion over 60 hours approved for tx of postpartum depression ADE: sedation--> LOC, HA, dizziness, dry mouth, hot flashes

Answer 46

Anxiolytic-GABA receptor actions alpha 1 subunit: sedation alpha 2/3: anxiolysis anticonvulsant, hypnosis, anterograde amnesia Advantages: high TI, rapid onset of action, little induction of liver enzymes ADE: rebound anxiety, withdrawal

Answer 47

MOA: blockade of 5-HT1A autoreceptors but stimulation of 5-HT1A postsynaptic receptors (partial agonist) Anxiolytic w/ lower abuse potential than Benzos Time to onset similar to SSRIss, slower and less effective than benzos

Answer 48

Tremor Rigidity Akinesia/bradykinesia Postural instability/abnormal gait Sleep disturbances Other (N/V, pain, fatigue) Autonomic (urinary, sweating, orthostasis) Psych (depression, anxiety, cognition)

Answer 49

Rasagaline, seligiline increase DA levels in the striatum For mld cases or as adjunct during Levodopa off periods Benefits rapidly decline ADE: nausea, hallucinations, confusion, depression, insomnia, orthostatic hypotension, HTN

Answer 50

Benzotropine Partially block cholinergic receptors to help balance cholinergic & DA activity Ind: mild disease < 60 years old without cognitive impairment

Answer 51

Promotes release of DA from terminals in dorsal striatum. May increase DA @ receptors by releasing intact striatal DA stores, may block neuronal DA reuptake Monotherapy for tremor or combo w/ Levodopa/Carbidopa to reduce Levodopa induced dyskinesia Need dose adjustment for renal insufficiency Decreases efficacy after few months (drug holiday can restore)

Answer 52

1st line for Parkinsons. Direct activation of DA2 R in striatum. Less effective than levodopa, but less likely to cause dyskinesias All can cause impulse control disorders d/t DA activation @ PFC Pramipaxole: sleep attacks unique, renal excretion Ropinirole: nausea more common, liver metabolism Rotigotine: TD (extensive 1st pass metabolism), for early/mild Sx Apomorphine: SQ. D2 and alpha 1/2 adrenergic receptors; increases NE. QT prolongation

Answer 53

Most effective therapy for Parkinson's but takes several months of tx before seeing full response Dyskinesia=most troubling ADE Off periods and weaning off occur Levodopa--increases DA synth in striatum and helps restore proper balance btwn DA and AcH=h Carbidopa--enhances effects of Levodopa by inhibition of decarboxylation in peripheral tissues

Answer 54

Selective, reversible inhibitor of COMT --> decreased peripheral levodopa metabolism, prolonging T1/2 and duration of levodopa. Increases duration of on phase, reduces weaning off phenomenon ADE: dyskinesia, N/D, hallucinations, ortho hypo, urine discoloration

Pharm 2 Flashcards

(78 cards)