Pulmonology Flashcards

Question

Nicotine

Answer 1

Lipid soluble, so can be absorbed across the skin and crosses the BBB ## Footnote Activates autonomic postganglionic neurons (sympathetic and parasympathetic) and somatic motor because of nicotinic receptors of skeletal muscle at neuromuscular junction NM: Skeletal muscle - Na+/K+ depolarizing ion channel NN: Postganglionic cell - Na+/K+ depolarizing ion channel

Answer 2

Parasympathomimetic alkaloid ## Footnote Muscarinic receptor agonist. Binds irreversibly to AChE Quaternary amine so it does not cross the BBB --\> has more peripheral effects. Tox: ↑ salivation, lacrimation, perspiration, abdominal pain, nausea, blurred vision First source of muscarine: Amanita muscaria (mushroom). Interestingly, effects mimic atropine poisoning more than muscarine excess.

Answer 3

Nicotinic Antagonist Uses: HTN (malignant HTN); induce hypotension during surgery Effects: NN/NG blockade (blocks opening; not Ach binding site); decrease BP; increases HR; arteriolar and venomotor tone largely under sympathetic control. decreased vagal tone causes tachycardia SE: postural hypotension, sympatho/parasympatho-plegia, sexual dysfunction, mydriasis, constipation, dry mouth Kinetics: Short acting; given IV only

Answer 4

Muscarinic Cholinergic Antagonist ## Footnote Tx: Antidote for organophosphate poisoning MOA: competitive (reversible) antagonist at all M receptors, thereby prevents release of IP3 & adenylyl cyclase Eye: dilation (mydriasis), cycloplegia (paralysis of ciliary muscle = loss of accommodation), reduced lacrimation, tachycardia (M2 receptors), bronchodilation Adv: Blind as a bat, mad as a hatter, red as a beet, hot as a hare, dry as a bone, the bowel and bladder lose their tone, and the heart runs alone --\> Total PNS block. Relatively safe for adults Rapidly cleared in urine \*be careful of closed angle glaucoma

Answer 5

Tertiary amine alkaloid (like atropine) ## Footnote Muscarinic Cholinergic Antagonist (can also block H1 receptor and cause sedation) Tx: Reduces vertigo, post-operative nausea, prevention of motion sickness (Transdermal patch) MOA: M1 receptor rapid onset and primarily CNS effects Adv: Same effects as atropine + CNS: delirium , drowsiness, amnesia, excitement, hallucinations, coma

Answer 6

Antimuscarinic Uses: asthma, COPD (more common) Effects: Synthetic analog of atropine; Bronchodilator ; decreases mucus production; blocks vagal activity in the lung when inhaled. SE: postural hypotension, sexual dysfunction, mydriasis, cough, Xerostomia, Inhaled; not as effective as beta agonists but can be used in combination

Answer 7

(α1=α2=β1=β2) Adrenergic Receptor agonist ## Footnote Effects: increases BP (α1), increases HR (β1 direct effect, β2 blocks vegal reflex), relative decrease in diastolic BP (β2 on skeletal muscle causing vasodilation) CI: acute angle glaucoma, pregnancy Kinetics: metabolize by COMT and MAO Epinephrine Reversal: Pretreatment with α antagonist converts an epinephrine infusion from a pressor response to a depressor response. (ie, β2 dilation predominates) Note: all direct adrenergic agonists can cause angina, MI, and arrhythmias; Released from adrenal medulla endogenously

Answer 8

(α1=α2=β1\>\>β2) Adrenergic Receptor agonist ## Footnote Uses: emergency hypotension; eg: to maintain coronary or cerebral flow (NOT C/I in closed angle glaucoma) Effects: increases BP (α1), decrease HR (net effect of β1and vagal reflex); increase contractility (β1) Kinetics: metabolized by COMT and MAO C/I: pregnancy α1: vascular SM (Gq; increase IP3/DAG, [Ca]i) α2: presynaptic and in CNS (Gi; decrease cAMP) β1: heart and juxtaglomerular cells (Gs; increase cAMP) β2: vascular SM (in skeletal muscle & heart) and bronchial SM (Gs; increase cAMP)

Answer 9

Beta-2 Selective Agonist Use: bronchodilator for asthma pts Effects: work through Gs to increase cAMP; smooth muscle relaxation; increase activity of cilia; inhibit mast cell degranulation Side Effects: tachycardia (inhibits vagus nerve presynaptically); decreases BP; skeletal muscle tremor; lowers PaO2 transiently due to pulmonary vasodilation of underventilated regions. Given as metered-dose inhaler or nebulizer Only the R isomer is active at the beta-2 receptor Bronchodilation: onset 15-30 minutes and DOA 3-4 hrs

Answer 10

Beta-2 Selective Agonist Use: bronchodilator for asthma pts; uterine relaxation (delay labor) Effects: work through Gs to increase cAMP; smooth muscle relaxation; increase activity of cilia; inhibit mast cell degranulation Side Effects: tachycardia (inhibits vagus nerve presynaptically); decrease BP; skeletal muscle tremor; lowers PaO2 transiently due to pulmonary vasodilation of underventilated regions. Given as metered-dose inhaler or nebulizer Only the R isomer is active at the beta-2 receptor Bronchodilation: onset 15-30 minutes and DOA 3-4 hrs

Answer 11

Monoamine oxidase inhibitors MAO normally metabolizes tyramine. If taking MAOIs, tyramine found in meat, cheese, and wine can build up and displace stored catecholamines Use: Tx depression

Answer 12

Amphetamine-like Indirect-Acting Sympathomimetic normal by product of tyrosine metabolism and produced from diets rich in proteins Readily metabolized by MAO in liver and inactive when taken orally due to first pass effect. MOA: causes release of stored catecholamines (similar to NE MOA) \*contraindicated with MAOIs

Answer 13

Adrenergic Neuron Blocker Uses: moderate HTN, but not used due to adverse effects ``` Effects: irreversible VMAT inhibitor; enters CNS and depletes NE, E, DA, 5-HT decreases BP (lowers CO/PVR but reflexes intact) ``` SE: sedation, mental depression, EPS, diarrhea, cramps, parkinsonism; depletion of cerebral amines Low doses: orthostatic hypotension CI: PUD, mental depression

Answer 14

Central Acting anti-HTN Uses: HTN Effects: Block NN inhibits NE release from SNS (Doesn’t enter CNS but causes sympathoplegia); decreases HR, CO, BP (from decreased CO at first; decreases PVR with prolonged use); compensatory Na+ and H2O retention SE: pharmacologic sympathectomy: postural hypotension, diarrhea, impaired ejaculation CI: cocaine, amphetamine, tricyclics, phenoxybenzamine

Answer 15

Indirect Acting sympathomimetic MOA: Displaces stored catecholamines TX: Narcolepsy, Enuresis, Idiopathic postural hypotension Side effects: low addiction liability; Compared to epinephrine: longer duration, orally active, low potency Not used for asthma

Answer 16

Mixed-Acting Sympathomimetic A B-receptor agonist Used in over the counter decongestant medicine and has been abused in the synthesis of methamphetamine

Answer 17

local anesthetic with peripheral sympathomimetic action via inhibition of transmitter reuptake at noradrenergic synapse amphetamine-like psychological effect that is shorter lasting and more intense than amphetamine Inhibits DA reuptake into neurons in the "pleasure centers" of the brain giving you a wild ride Cocaine is a hell of a drug Highly addictive (relative risk of 5/5). heated in an alkaline base to become "crack cocaine" which can be smoked producing an instant "rush" In PNS, inhibits voltage gated Na channels. In CNS, cocaine blocks reuptake of DA, NE, serotonin. The DAT block increases DA in nucleus accumbens is the rewarding aspect of the drug By blocking NET, causes increase in arterial pressure, tachycardia, ventricular arrhythmia Toxicities: intracranial hemorrhage, ischemic stroke, MI, seizures, coma, death

Answer 18

Indirect-Acting Sympathomimetic Displasces stored catecholamine transmitters. Important chiefly because of its use and misuse as a CNS stimulant Readily enters the CNS; effects mediated through the release of norepinephrine and dopamine

Answer 19

(β1\>\>β2) Adrenergic Receptor Antagonist Uses: HTN (intra-op/post-op or hypertensive emergency), SV arrythmia Effects: (-) inotropic, chronotropic, and dromotropic effects; decreases BP (no reflex tach); inhibits the renin/angiotensin/aldosterone system Kinetics: ultra-short acting; half-life about 10 minutes; rapidly metabolized by RBC esterases; given as IV SE: bradycardia; hypotension CI: asthma (bronchoconstriction); ok for COPD

Answer 20

Mixed antagonist for adrenoceptor alpha1-selective and B-antagonistic effects. Used for hypertensive emergencies and treating hypertension of pheochromacytoma Less tachycardia seen compared with phentolamine.

Answer 21

(α1=α2) Adrenergic Receptor Antagonist MOA: minor competitive antagonist of H1, H2, and M as well. Uses: Tx of ED, HTN secondary to pheochromocytoma Effects: decrease BP, increase HR (vagal reflex); α2 (located presynaptically) block enhances NE release [therefore, sympathetic cardiostimulation and enhanced baroresponse is observed]; minor inhibition of serotonin receptor and minor agonist at M SE: MI, tachycardia, arrhythmias, headache, nasal congestion CI: PUD

Answer 22

(α1\>α2) Adrenergic Receptor Antagonist MOA: Irreversible blockade (long duration; 14-48 hrs); H1, AchR, 5-HT receptor block; Indirect baroreflex activation (inhibition of NE reuptake) Effects: decreases BP (only when sympathetic tone is high [eg: low blood volume]); attenuates catecholamine induced vasoconstriction; increase HR from reflex. SE: Postural hypotension, tachycardia, nasal congestion, sedation, nausea, sexual SE; Uses: HTN secondary to pheochromocytoma Related to nitrogen mustard

Answer 23

(α1\>\>α2) Adrenergic Receptor Antagonist Uses: HTN (especially in combo w/ β blocker), benign prostatic hyperplasia Effects: decreases BP (dilation of resistance and capacitance vessels; more pronounced when in the upright position); some reflex tachycardia (less than nonselective α antagonists (phentolamine) because NE negative feedback on α2) SE: Orthostatic hypotension(less than nonselective α antagonists), increases HDLs, salt and water retention, dizziness, headache, ANA development Kinetics: half-life= 3 hours; extensive 1st pass hepatic metabolism; oral bioavailability = 50%

Answer 24

(α1\>\>α2) Adrenergic Receptor Antagonist Reversible blocker Uses: HTN, benign prostatic hyperplasia Effects: not much reflex tachycardia; decreases BP (dilation of resistance and capacitance vessels; more pronounced when in the upright position) SE: Orthostatic hypotension upon first dose Kinetics: half-life= longer than Prazosin; extensive 1st pass hepatic metabolism High bioavailability Half life 9-12 hrs

Answer 25

α1 antagonist selective for alpha-1a so primarily relaxes prostatic SM. Uses: benign prostatic hyperplasia

Answer 26

Propanolol (B1=B2), Metoprolol/ Atenolol (B1\>\>\>B2) (CI in asthmatics) Metoprolol is an inverse agonist. Metoprolol has shown a reduction in mortality in patients with stable severe heart failure. Propanolol is the prototype but comes with toxicities: sedation, vivid dreams, depression, worsening of asthma, bradycardia, fatigue, cold hands; has been replaced by Metoprolog and Atenolol Propanolol can treat Hypertension: less reflex tachycardia in comparison to direct vasodilators. MOA mainly from depression the renin-angiotensin-aldosterone system. Toxicity of propanolol: withdrawal causes nervousness, tachycardia, increase intensity of angina, increase BP. Metoprolol is as effective as propanolol in inhibiting beta 1, but way less potent in beta 2. Better agent in treating those with asthma, diabetes, peripheral vascular disease. Atenolol is less effective in treating hypertension due to the lack of maintaining adequate blood levels of the drug. Beta-Blockers reduce mortality following an MI

Answer 27

(β1=β2) Adrenergic Receptor Antagonist Uses: HTN (especially patients with PVD or bradyarrhythmias) Effects: partial agonists actually; less decrease HR/CO than other β blockers; lowers BP (TPR); potentiate antidepressants SE: fatigue, vivid dreams, cold hands CI: asthma (bronchoconstriction)

Answer 28

Nitric oxide drugs and drug classes NO (aka EDRF)– elevates cGMP in vascular smooth muscle; vasodilator; decreases pulm. resist. when inhaled; inhibits platelet aggregation; inhibits atheromatous plaque formation immune function: NO is a microbicide, excessive NO increases tissue injury Nervous system: synaptic plasticity (learning) in CNS; NANC neurons in PNS Uses: pulmonary HTN; hypoxic respiratory failure SE: methemoglobinemia. _Superoxide Dismutase_ – NO scavenger prolonging DOA by protecting against NO inactivation from superoxide. _Methylene Blue_ – soluble guanylate cyclase (sGC) inhibitor that prevents the action of NO and can reverse NO induced hypotension.

Answer 29

L-Arginine is substrate for NOS that forms NO and L-Citrulline. L-NMMA – comp. inhibitor binding to arginine-binding site in NO NOS requires cofactors: heme, tetrahydrobiopterin, FAD Cytosolic Ca binds Calmodulin which binds and activates eNOS or nNOS. iNOS is not Ca regulated and is purely transcriptionally regulated (induced by TNF and IL-1).

Answer 30

Very low blood:gas partition coefficient Rapid onset and recovery widely used for outpatient surgery can promote coughing due to irritiation of tracheobronchial tree, meaning they normally only use this for maintenance of anesthesia as opposed to induction. Marked increases in heart rate are occasionally seen.

Answer 31

Volatile anesthetic Relatively slow rate of onset and recovery Not really metabolized unlike halothane. Even though enflurane's solubility is lower, it's eliminated more slowly. adverse: more severe depression of normal cardiac contractility than others. Only inhaled anesthetic with frank clinical seizures Toxicities: metabolites are nephrotoxic Not used in patients with seizure disorders

Answer 32

Volatile anesthetic (has low vapor pressure and thus high boiling points so that liquid at room temperature/ sea-level pressure) The driving force for an inhaled anesthetic is the alveolar concentration. This concentration changes based on inspired concentration or partial pressure, and alveolar ventilation Relatively slow rate of onset and recovery Solubility is 2X and 10X more than nitrous oxide in brain tissue and blood, respectively. Therefore, elimiantion and recovery is less rapid. Hepatotoxicity (halothane hepatitis): adverse: more severe depression of normal cardiac contractility than others Still often used in children, as they seem to be more immune to adverse side effects 40% of halothane is metabolized so that elimination occurs more quickly than would be be expected based on tissue solubility.

Answer 33

Volatile anesthetic Relatively fast rate of onset and recovery Isoflurane, sevoflurane, halothane, enflurane produce initial activation of EEG at low doses and subsequent slowing when given doses of 1.0-1.5 MAC. Isoflurane EEG is silenced at 2.0-2.5 MAC. Pungency makes it less suitable for patients with active bronchospasm, usually used following induction of anesthesia with a different drug better choice for patients with impaired myocardial function/ischemic heart disease

Answer 34

Inhalation Anesthetic MAC 0.16 metabolism: \>70%(fluoride); High solubility renal insufficiency from hepatic metabolism to fluoride compound.

Answer 35

MAC \>100%; metabolism: none; only anesthetic that does not decrease VT and increase RR

Answer 36

Low solubility MAC 2.0% metabolism: 2-5% (flouride) Must make sure it is not used with an anesthesia machine in which the CO2 absorbent has been dried. The reaction of sevoflurane with desiccated CO2 absorbent can produce CO. Also, reaction with dessicated CO2 absorbent can cause fires and explosions. Bronchodilation (**good for induction** with obstructive dx pts); little increase in cranial pressure; decreases TPR; ideal inhalable anesthetic

Answer 37

Colorless, tasteless, odorless, nonirritating gas. Comes from incomplete combustion. Affinity for hemoglobin that is 220 times that of oxygen Signs: hypoxia in the following sequence 1) psychomotor impairment 2) headache and tightness in temporal area (15% CO-Hb) 3) loss of visual acuity and impairment 4) tachycardia, tachypnea, syncope, coma (40% CO-Hb) 5) convulsion, respiratory failure Tx: hyperbaric O2 reduces CO elimination half-life to 20 minutes from a normal of 320.

Answer 38

Colorless, irritant gas; comes from combustion of sulfur-containing fossil fuels and forms sulfurous acid on contact with moist membranes Bronchoconstriction upon inhalation mediated by Parasymppathetic Asthma pts are hypersensitive Signs: 1) acute asthma 2) delayed-onset pulmonary edema

Answer 39

Brownish, irritant gas associated with fires; found in silage (silofiller’s disease in farmers) Effects: pulmonary edema, eyes and nose irritation, dyspnea, fibrotic destruction of terminal bronchioles (bronchiolitis obliterans)

Answer 40

_Ozone:_ • bluish irritant gas; absorbs UV light • occurs around high voltage equipment Effect: irritates mucous membranes 1) moderate exposure: upper respiratory tract irritation 2) severe exposure: deep irritation and pulmonary edema Longterm exposure: fibrosis, bronchitis, and emphysematous changes _Solvent Vapors:_ Halogenated Aliphatic Hydrocarbons: • eg: chloroform, freon • carcinogenic but are still used in dry cleaning • Cause: CNS depression and liver, kidney, and heart damage. Aromatic Hydrocarbons: • Eg: benzene, toluene, Xylene • Components of gasoline • Acute effect: CNS depression • Chronic exposure to Benzen: bone marrow suppression and leukemia.

Answer 41

Tetraethylammonium, Hexamethonium, Mecamylamine, Trimethaphan. ## Footnote Trimethaphan and hexamethonium impair transmission by competing with ACh for nicotinic sites, or blocks channel. Use of ganglionic antagonists in treating hypertension/ autonomic hyperreflexia: Blood vessels have sympathetic innervation causing them to constric and cause a decrease in arteriolar and vasomotor tone. Using these drugs, this constriction is inhibited and so blood pressure will be lowered. Diminished contractility and b/c SA node is dominated by parasympathetic system, tachycardia.

Answer 42

Blood:gas Partition Coefficient – describes solubility of gas in blood. Low B:G implies Low solubility which means the partial pressure of gas in arterial blood (tension of the gas) rises quickly relative to the amount of dissolved gas particles. Rapid equilibration with brain tissue and fast onset of action characterized by anesthetics with low B:G. _Pulmonary Ventilation_: The rate of rise of anesthetic partial pressure in blood depends on minute ventilation. low B:G implies arterial tension of anesthetic is quickly maxed out and the rate of induction will hardly be modified by increased ventilation. Moderate to high B:G means is takes significant time for blood tension to reach adequate levels. Increasing ventilation substantially decreases the time it takes for this equilibration. _Arteriovenous gradient_: results from anesthetic uptake by tissues. The more uptake into tissues, the longer it takes for arterial blood (and brain tissue) partial pressure to reach equilibrium with alveolar. Tissue uptake is a function of the solubility (B:T) of the drug in various tissues, and the relative perfusion of each of these tissues. Brain, heart, liver, kidneys, and splanchnic bed are heavily perfused at rest (75% of CO) and account for most of the A-V gradient. Elimination: _Lung Clearance_ - anesthetics insoluble in blood and brain result in rapid recovery. For soluble anesthetics, recovery depends on length of exposure (due to slow accumulation and elimination from muscle, skin and adipose tissue) Hypercapnia releases catecholamines which attenuate the depression caused by the inhaled anesthetic. (usually observed by the arterial blood pressure slowly rising during the duration of a surgery to almost normal values). Arrhythmias from inhalable anesthetic occur in the setting of sympathomimetics. _Respiratory_: decreases tidal volume, increase respiratory rate, decrease ventilation; inhalable anesthetics are respiratory depressants (defined by decrease response to CO2 level changes)

Answer 43

_MAC:_ median concentration that results in immobility in 50% of patients exposed to a noxious stimulus. Corresponds to ED50 of quantal dose-response curve, but gives no information of slope of dose-response curve. Assume the response curve has a steep slope and 1.1 MAC achieves immobility in \>95% of pts. Changing MAC: MAC decrease with age and hypothermia and when used in conjunction with CNS depressants. MAC increases with pregnancy and tolerance from chronic use of CNS drugs or alcohol. MAC is additive with multiple anesthetics: nitrous oxide cannot achieve a 1 MAC dose at barometric pressure. Giving a gas mixture with 60% NO2 usually corrsesponds to 40% of a MAC (60% tension; 40% MAC) meaning this mixture must also contain a dose of another anesthetic corresponding to 70% MAC to get the total 1.1 MAC.

Answer 44

The platinum coordination complexes have broad antineoplastic activity and have become the foundation for treatment of ovarian, head and neck, bladder, esophagus, lung, and colon cancers. Do not form carbonium ion intermediates like other alkylating agents, but still covalently bind to nucleophilic sites on DNA to form inter- and intrastrand crosslinks (especially between guanines). These are recognized by p53, which halts growth. Both are divalent water soluble platinum containing complexes. They enter the cell through a copper channel and are pumped out through ABC copper transporters and by multidrug resistance protein 1 (MRP 1). Resistance may also be caused by loss of function of the MMR proteins which recognize platinum-DNA adducts and intiate apoptosis. Once in the cell, the chlorides/active groups are replaced by waters to become reactive compounds that can damage DNA. This is important because it explains why chloride diuresis helps prevent nephrotoxicity. The two drugs show cross-resistance Effects of cross linking are most pronounced during S phase, and are also associated with formation of a secondary leukemia.

Answer 45

Cisplatin penetrates CNS poorly, most is covalently bound to plasma proteins (in contrast to carboplatin). It is inactivated by aluminum, so must avoid contact with aluminum needles. Side effects: can cause nephrotoxicity if not treated with chloride diuresis. Causes ototoxicity that is not helped by chloride treatment (more pronounced in children). Nausea and vomitting occur in almost all patients. Also causes myelosuppression, peripheral motor and sensory neuropathy. Associated with development of AML Often used following surgical resection of Stage I and II non-small cell lung cancer

Answer 46

Relatively well tolerated, causing less nausea, neurotoxicity, ototoxicity, and nephrotoxicity than cisplatin. It also remains in its parent form in blood as it is less reactive than cisplatin. It's dose limiting toxicity is myelosuppression (thrombocytopenia) Used the same as cisplatin in cases of non-small cell lung cancer and extensive-stage small cell lung cancer

Answer 47

A folate analog that differs from methotrexate in its transport properties and sites of action. It has proven useful in treating **mesothelioma and non-small cell carcinomas of the lung**. It is a pyrrole-pyrimidine structure Exerts effects on both thymidilate synthase and early steps in purine biosynthesis (**TS**, DHFR, **ribonucleotide transformylase**). Unlike methotrexate, it produces little change in the pool of reduced folates. Enters cells mainly through the **reduced folate transporter**, which is upregulated in ALL cells Active against mesothelioma and non-small cell adenocarcinomas of the lung, especially non-squamous tumors. Main toxicity is myelosuppression, along with prominent erythematous and **pruritic rash (which can be treated with dexamethasone)**. Some patients have unexpected severe myelosuppression (treat with folate)

Answer 48

Like the anthracyclines, they form a ternary complex with topoisomerase II and DNA and prevent resealing of the break that normally follows topoisomerase binding to DNA. The enzyme remains bound to the free end of the broken DNA strand, leading to an accumulation of DNA breaks and cell death S and G2 hit the hardest Resistance: amplification of mdr-1 gene, mutation of topo II, or mutations of p53 Used to treat small cell carcinoma of the lung (in combination with cisplatin and ifosfamide) Can cause hypotension and bronchospasm if given too quickly. Dose-limiting toxicity is leukopenia. Also has side effects of nausea, vomiting, et c. Hepatic toxicity is evident after high-dose treatment (toxicity increases with decreasing serum albumin)

Answer 49

Irinotecan and Topotecan Potent, cytotoxic neoplastic agents that target topoisomerase I (allow single strand cleavage but prevent Topo I from coming unbound). Irinotecan is a pro-drug, topotecan is not. S phase–specific cytotoxic agents Resistance: Topotecan is a substrate for P-glycoprotein (mdr-1), but Irinotecan is not. Resistance can also result from mutated or decreased expression of Topo I.

Answer 50

Has relatively greater CNS penetration, and hepatic metabolism is not significant. Used to treat patients with small cell lung cancer and ovarian cancer (2nd line treatment for small cell behind cisplatin/carboplatin combined with etoposide) Dose-limiting toxicity is neutropenia (doesn't have diarrhea side effect).

Answer 51

Targets topoisomerase I Converted to active form SN-38 by carboxylesterases in the liver. Has a longer half-life than topotecan, but hepatic metabolism is significant (through glucuronidation). Dose limiting toxicity is delayed diarrhea (treat with loperamide). The second most common toxicity is myelosuppression. Can also lead to an anticholinergic syndrome with diarrhea, hypersalivation, lacrimation, et c. No longer used to treat non-small cell lung cancer due to difficulty in achieving proper blood levels.

Answer 52

Microtubule binding vinca alkaloid (like vincristine) Administered in normal saline IV. Used with cisplatin for treatment of small cell lung cancer. Primary toxicity is granulocytopenia (with less neurotoxicity as other vinca alkaloids) An oral formulation is active in small cell carcinoma

Answer 53

Vinca alkaloid that blocks cell mitosis by blocking polymerization of microtubules. Resistance: mdr-1, mutations in B-tubulin Has limited myelosuppression, which makes it useful for combination with other drugs with myelosuppression as a side effect. Metabolized by the liver and excreted in bile (as are all vinca alkaloids) Side effect is neurologic toxicity, seen more in adults than in children

Answer 54

Pyrimidine Analog Inhibits DNA synthesis by inhibition of DNA polymerase and ribonucleotide reductase, cell cycle-specific for the S-phase of the cycle (also blocks cellular progression at G1/S-phase). **It can also hit non-proliferating cells via inducing apoptosis** Gemcitabine is phosphorylated intracellularly by deoxycytidine kinase to gemcitabine monophosphate, which is further phosphorylated to active metabolites gemcitabine diphosphate and gemcitabine triphosphate. Gemcitabine diphosphate inhibits DNA synthesis by inhibiting ribonucleotide reductase; gemcitabine triphosphate incorporates into DNA and inhibits DNA polymerase (**chain terminator)**. Can be used to treat **non-small cell lung cancer** **Activity greatly enhanced by combination with cisplatin/carboplatin** Myelosuppression is generally the dose-limiting toxicity, **can't use with radiation therapy** Resistance is through increased deactivation by deoxycytidine deaminase or decreased activation by deoxycytidine kinase

Answer 55

Taxanes (docetaxel is synthetic congener of pacitaxel) albumin-bound nanoparticle solutions that bind to a different B-tubulin site as the vinca alkaloids and inhibit disassembly of microtublues (very limited water solubility, but docetaxel is more soluble) Resistance: mdr-1, B-tubulin mutations, an increase in survivin, alpha aurora kinase. Does not depend on p53 Dose limiting toxicity of paclitaxel is neutropenia (treat with filgrastim). Also causes hypersensivity reactions (**avoid by pre-treating with dexamethasone, diphenhydramine**). Also causes peripheral neuropathy Docetaxel causes more neutropenia but **less neuropathy**. Fluid retention is a problem here

Answer 56

Anthracycline Intercalater of DNA, Topo II inhibitior, free radical generator. Can be given with an iron chelator to prevent as much free radical formation to protect against dilated cardiomyopathy. p53 or caspase dependent Resistance: mdr-1, decreased activity/mutated Topo II, enhanced ability to repair strand breaks Given IV, does not cross the BBB Can turn urine red Myelosuppression is dose limiting toxicity.

Answer 57

EGFR Inhibitor Binds to the kinase domain and reversibly blocks enzymatic funtion of EGFR, killing EGFR cell lines Monitor warfarin (INR) while on these drugs Gefitinib: orally administered, used for non-small cell lung cancer. Most likely to be affective in nonsmokers, Asians, or women. Diarrhea and papular rash occur in 50% of patients. Intersitial lung disease occurs in 2%. **Higher response rate happens in patients in activating mutations in EGFR** Erlotinib: orally administered (should not be taken with food). Approved for second-line treatment of patients with locally advanced or metastatic non-small cell lung cancer. Side effects similar to Gefitinib, along with hepatic toxicity Resistance: secondary mutations that change binding site. Amplification of *met* oncogene which amplifies downstream of EGFR.

Answer 58

Monoclonal antibody that binds to the extra-cellular surface of EGFR to block receptor dimerization. Given IV Used for squamous cell carcinomas of the head and neck, colon cancer Side effects: acneform rash in majority of patients, along with pruritis, nail changes, headache and diarrhea. May cause anaphylactoid reactions during infusion, especially among patients in southern US.

Answer 59

An anti-VEGF-A humanized monoclonal antibody which serves to reverse the "leakiness" induced by VEGF. This "leakiness" prevents adequate drug delivery to tumors. When combined with carboplatin and paclitaxel increases survival in non-small cell lung cancer by 2 months (also for colon cancer, renal cell carcinoma) Given IV Contraindicated in patients with a history of hemoptysis, brain metastasis, or a bleeding diathesis. It also makes surgery more risky, and **can cause severe hypertension and proteinuria. Can occosionally cause strokes, MIs, and gastric perforation**. Contraindicated in patients with squamous cell tumors due to unacceptably high rates of life-threatening hemoptysis in early phase clinical trials

Answer 60

**Kallikrein:** located in plasma (creates bradykinin) and tissues (creates Kallidin); plasma prekallikrein activated by trypsin, Hageman factor, and kallikrein itself **Kininogens**: located in plasma (LMW and HMW), lymph, and interstitial fluid (LMW) **Kinins**: formed by Kallikreins or Kininogenases cleaving kininogens. (Bradykinin and Kallidin=Bradykinin+lysine) Effects: arteriodilator peptides (decrease BP briefly), Venoconstriction (increase capillary P) and Endo cell contraction (leaky capillaries). Rapidly produced after injury and result in 4 classic signs of inflammation. MOA: B1 and B2 receptors. B antag: anti-inflammatory; inhibit bronchoconstriction; pain mgmt.. Metabolism: Kininase I (made by liver) and Kininase II (ACE; found in lung) **Aprotinin**: Kallikrein inhibitor; inhibition reduces bradykinin formation **Aspirin**: prostaglandin mediates some actions of kinins **ACEinh or B agonist**: enhances bradykinin effects (anti-HTN)

Answer 61

Beta-2 Selective partial Agonist (new generation) Use: bronchodilator for asthma pts Effects: work through Gs to increase cAMP; smooth muscle relaxation; increase activity of cilia; inhibit mast cell degranulation Side Effects: tachycardia (inhibits vagus nerve presynaptically); decrease BP; skeletal muscle tremor; decrease PaO2 transiently due to pulmonary vasodilation of underventilated regions. Given as metered-dose inhaler or nebulizer Only the R isomer is active at the beta-2 receptor Bronchodilation: onset 15-30 minutes and DOA \>12 hrs (long acting don’t use for acute bronchospasm)

Answer 62

Antimuscarinic Uses: asthma, COPD Effects: Synthetic analog of atropine; Bronchodilator ; decreases mucus production; blocks vagal activity in the lung when inhaled. SE: postural hypotension, sexual dysfunction, mydriasis, cough, Xerostomia, Inhaled; not as effective as beta agonists but can be used in combination 24 hr DOA (long acting)

Answer 63

Allergens: antigens that provoke IgE; most commonly proteins from dust mite, cockroach, dander, pollen, molds. Mediators: 1) Early: (mast cells) histamine, LTC4, LTD4, PGD2, tryptase 2) Late: IL-5,9,13 results in  inflam cells and reactivity Triggers: viral infxn, cold air, etc. (usually not the antigen itself) Testing: decreased FEV1 during methacholine inhalation Note: Bronchoconstriction results from released mediators as well as from neural pathways (vagus nerve, NANC) Asthma Tx: Short-term(relievers): **β agonist (salmeterol, formoterol), Theophylline** Long-term(controllers): **inhaled corticosteroid, Leukotriene antagonists, cromolyn, nedocromil (inh mast cell degranulation)** when prescribing: first try β-agonist as needed only, if FEV1\<80% predicted then add low dose steroid; finally add long acting β-agonist if symptoms not controlled.

Answer 64

Chronic asthma: anti-IgE omalizumab, reduces lymphocytic, eosinophilic bronchial inflammation Acute asthma: Beta 2 agonist for mild attacks. Severe attacks require oxygen, albuterol, prednisone or methylprednisolone COPD: not reversible with bronchodilator. Relieve acute symptoms with albuterol or ipratropium bromide. For persistent symptoms: long acting salmeterol, long acting tiotroprium. Antibiotics and theophylline (improve ventilation)

Answer 65

Methylxanthine MOA: 1) PDE4 inhibitor, which increases cAMP (SM relaxation and decreased immune cell activation). **Bronchodilation** 2) **inhibit adenosine** receptors and therefore increases adenylyl cyclase activity. Adenosine normally causes bronchoconstriction, just like Acetylcholine does. 3) histone deacetylation: reduced transcription in immune cells. Effects: bronchodilation and anti-inflammatory in asthma; cortical arousal; increases HR, BP (catecholamine release); increases secretion of gastric enzymes; diuretic Well absored by GI tract Note: narrow therapeutic range Side effects: anorexia, nausea, vomiting, headache, anxiety, arrhythmia, death, insomnia **Roflumilast**: PDE4 inhibitor used for COPD but not asthma

Answer 66

Lungs dont have feedback inhibition of H2 histamine. Causes vasodilation, leakage of plasma mediators of acute inflammation, and antibodies. Attracts neutrophils, eosinophils, basophils, monocytes, lymphocytes Released from degranulation of mast cells and basophils via IgE stimulation and cross linking. Nervous system: H1 mediated. Urticarial response and neurons signaling inspiration and expiration, appetite and satiety. Cardio: decreases systolic and diastolic blood pressure and increases heart rate. Vasodilation via H1. H2 receptors cause increased contractility and pacemaker activity. Bronchiolar smooth muscle: bronchoconstriction by H1. **H1**: In the smooth muscle, endothelium, brain. Gq, increase IP3 and DAG. Histaprofiden is a partial agonist. Mepyramine, triprolidine, cetirizine are partial antagonists or inverse agonist. **H2**: Gastric mucosa, cardiac muscle, mast cells, brain. Gs increases cAMP. Amthamine is partial agonist. Cimetidine, rantidine, tiotidine are partial antagonists or inverse agonists.

Answer 67

H1 Antagonist 1st Generation: Readily enters the CNS Rapidly absorbed; peak blood at 1-2 hrs Other effects: slight sedation, anti-motion sickness Uses: Allergic Rhinitis (Hay Fever), urticaria (very effective when given before exposure); largely ineffective in bronchial asthma and involves many mediators other than Histamine. **Cyclizine**: DOA 4-6 hrs **Meclizine:** DOA 12-24 hrs **Hydroxyzine**: DOA 4-6 hrs **Carbanoxamine**: ethanolamine: DOA 12-24hrs **Chlorpheniramine, Brompheniramine**

Answer 68

Benadryl H1 Antagonist 1st Generation: Readily enters the CNS Rapidly absorbed; peak blood at 1-2 hrs; DOA 4-6 hrs Ethanolamine (like carbinoxamine) Other effects: anticholinergic (blurred vision), marked sedation, anti-motion sickness activity, suppresses EPS from antipsychotics; Na+ channel block (more potent than procaine) Uses: Allergic Rhinitis (Hay Fever), urticaria (very effective when given before exposure); largely ineffective in bronchial asthma and involves many mediators other than Histamine.

Answer 69

Dramamine H1 Antagonist 1st Generation: Readily enters the CNS Rapidly absorbed; peak blood at 1-2 hrs; DOA 4-6 hrs Ethanolamine Effects: anticholinergic, marked sedation, anti-motion sickness activity Uses: marketed almost exclusively for motion sickness (Note for Scopolamine and H1 antag’s: best motion sickness achieved when combined with ephedrine/amphetamine)

Answer 70

H1 Antagonist 1st Generation: Readily enters the CNS Rapidly absorbed; peak blood at 1-2 hrs; DOA 4-6 hrs Phenothiazine Other effects: anticholinergic (blurry vision), moderate sedation, antiserotonin, α-adrenoceptor block (orthostatic hypotension); Na+ channel block (more potent than procaine as local anesthetic) Uses: Allergic Rhinitis (Hay Fever), urticaria (very effective when given before exposure); largely ineffective in bronchial asthma and involves many mediators other than Histamine; motion sickness; antiemetic

Answer 71

Anti-serotonergic (& H1 Antagonist) 1st Generation: Readily enters the CNS Rapidly absorbed; peak blood at 1-2 hrs; DOA 4-6 hrs related to Phenothiazines effects: moderate sedation, anticholinergic, antiserotonin (5-HT2), Uses: cold-induced urticarial; SM manifestations of carcinoid tumor (ie; relieves bronchoconstriction), serotonin syndrome

Answer 72

H1 Antagonist 2nd Generation: Not likely to block H autonomic receptors; don’t distribute to the CNS; DOA 12-24 hrs **(Longest acting)** Rapidly absorbed; peak blood at 1-2 hrs Uses: Allergic Rhinitis (Hay Fever), urticaria (very effective when given before exposure); largely ineffective in bronchial asthma and involves many mediators other than Histamine. **Cetirizine (children's zyrtec)**:Other: Inhibit Mast cell release of Histamine.(Beneficial in the treatment of rhinitis for children) **Fexofenadine:** me too drug

Answer 73

**Cimetidine and Ranitidine** H2 receptor antagonists counteract the gastric secretions promoted by histamine. OTC agents used to help treat PUD

Answer 74

Corticosteroids and stimulation of lung maturation in fetus: treating mother with glucocorticoids reduces the incidence of respiratory distress syndrome in premature infants. when delivery is expected 34 weeks or before, **betamethasone** is used (good protein binding and placental metabolism allowing increased transfer across placenta into the fetus)

Answer 75

Rapid uptake of N₂O from alveolar gas serves to concentrate co-administered halogenated anesthetics, which speeds the induction of anesthesia (this is second gas effect) On discontinuation of N₂O, nitrous oxide gas can diffuse from blood to the alveoli, diluting O₂in the lung. This can produce diffusional hypoxia. To avoid, give 100% O₂ rather than air following discontinuation of nitrous oxide

Answer 76

A broad spectrum penicllin important for patients with gram-negative infections associated with bacteremias, pneumonias, infections following burns, and UTIs. Main one that can treat *P. aeuroinosa*. Often combined with tazobactam, a B-lactamase inhibitor

Answer 77

A penicillin similar to carbenicillin but is 2-3 times more active against *P. aeru**g**inosa*. Inferior to Piperacillin for infections caused by *P. aeruginosa* Marketed in combination with clavulanate

Answer 78

B-lactam antibiotic that is resistant to most B-lactamses Used against *S. pneumoniae* (penicillin resistant), enterococci, staphylococci, and *Listeria* species, especially hostpital acquired Not absorbed orally May cause nausea,vomitting, seizures, and hypersensitivity reactions Used for UTI and lower respiratory tract infections, skin, soft tissue, bone, and joint, GYN, and intra abdominal infections. Should not be used as monotherapy against *P. aeruginosa* because of risk of developing resistance. **Marketed in combination with cilastatin, which decreases imipenem degradation by the kidney**

Answer 79

B-lactam antibiotic with some activity against imipenem resistant *P. aeruginosa* but less activity against gram positive cocci derivative of thienamycin that does not require co-administration with cilastatin becaue it is not sensitive to renal dipeptidase Less liklihood of causing seizures compared to Imipenem

Answer 80

B-lactam antibiotic that induces the formation of long filamentous bacterial structures. Resistant to many B-lactamases of gram-negative bacteria (has *no* effect against gram-positive bacteria) Antimicrobial activity resembles that of an aminoglycoside Acitivity is excellent against *P. aeruginosa* Given IM or IV well-tolerated (**patients with hypersensitivity to penicillins often don't react to this one**)

Answer 81

inhibit bacterial cell wall synthesis similar to B-lactams Classified by arbitrary generations None are effective against enterococci, MRSA, or listeria Patients often show a positive Coombs test after large doses. 1st generation: good againts gram-positive and modest against gram-negative 2nd generation: increased activity against gram negative (oral administration for respiratory tract infections) 3rd: Substantial increase in activity against gram-negative bacteria, but much less so against gram-positives 4th: wide spectrum of positive and negative Resistance: changing PBPs, destruction of the B-lactam ring

Answer 82

Second-Generation Cephalosporin broader gram-negative activity against some *Citrobacter* and *Enterobacter*. Lacks activity against *B. fragilis.* Effective in treating meningitis due to *H. influenzae, N.meningitidis,* and ***S. pneumoniae***

Answer 83

Orally administered third generation cephalosporin that is similar to fourth generation cefepime except that it is not more active against *Enterobacter* or *Pseudomonas sp*.

Answer 84

Third-Generation Cephalosporin highly resistant to many B-lactamses and has good activity against many gram positive and gram negative bacteria. (but not *B. fragilis*) Has been used effectively for meningitis caused by *H. influenzae, * penicillin-sensitive ***S. pneumoniae***, and *N. meningitides*.

Answer 85

A Third Generation Cephalosporin with **good activity against *Pseudomonas*.** Not as active as cefotaxime against gram-positive organisms.

Answer 86

Similar activity as cefotazime and ceftizoxime. A T_1/2 of 8 hrs is the outstanding feature of this drug Has been used for patients with meningitis, gonorrhea, et c with less doses than others

Answer 87

Fourth Generation Cephalosporin Resistant to almost all B-lactamases, and is therefore effective against Enterobacteriaceae that are resistant to other cephalosporins Has comparable activity to Ceftazidime in treatint Pseudomonas.

Answer 88

Most effective against plasmid encoded B-lactamases (inactive against the type I chromosomal B-lactamases) Clavulanic Acid: suicide inhibitor that is well absorbed by mouth. Has been combined with amoxicillin and ticarcillin Sulbactam: similar to clavulinic acid, given orally or parenterally Tazobactam: penicillanic acid sulfone-B lactamase inhibitor that has poor activity against the Type I lactamases. Combined with piperacillin. May not be as effective as piperacillin alone when treating resistant *P. aeruginosa*

Answer 89

Macrolide Bacteriostatic (-cidal in large conc.) agent that binds to 50S subunit of bacterial ribosomes Most active against aerobic gram-positive cocci and bacillus, inactive against most aerobic enteric gram-negative bacteria Active against S pneumoniae, *M. pneumoniae and a ton other* Stomach acid breaks it down, given in protective tablet; food delays absorption. Does not enter CNS Oral administration of this can lead to epigastric distress (activates motility), Can also lead to cholestatic hepatitis

Answer 90

Ketolide similar to macrolides in MOA, but less susceptible to methylase mediated and efflux-mediated mechanisms of resistance than the Macrolides. Similar activity as clarithromycin and azithromycin, often used for macrolide resistant *S. aureus and S. pneumo* Same 50S ribosomal target as macrolides No parenteral form Contraindicated in Mysasthenia Gravis patients, also associated with loss of conscioiusness and visual disturbances

Answer 91

Slightly more active against **strep** and staph compared to Erythromycin Activity against *M. leprae, MAC complexes* Absorbed rapidly from GI tract, can be given with or without food Resistant to methylation of the 50S, as it does not induce methylation of the 50S subunit (also not a substrate for efflux pump)

Answer 92

Less active than erythromycin against gram-positive organisms, but more active against *H. influenzae* and *Camplyobacter*. It and clarithromycin have enhanced activity against *M. avium*. Rapidly absorbed and distributed (but not in CNS). Should *not* be administered with food Can treat MAC complexes

Answer 93

Bind to 50S ribosomal subunit and inhibit **translocation** Resistance: 1)drug efflux by an active pump mechanism (*mrsA, mefA, or mefE*) 2) ribosomal protection by inducible/constituitive methylase enzymes modifying ribosomal target (*erm* genes) 3) macrolide hydrolysis by esterases (Enterobacteriaceae) 4) chromosomal mutations that alter 50S subunit All but azythromycin inhibit CYP3A4 Side Effects: hepatotoxicty (more so in erythromycin than in Clarithromycin or Azithromycin). All but azithromycin have been shown to cause cardiac arrhythmias (QT prolongation, bradycardia)

Answer 94

Target bacterial DNA gyrase (more for gram-negatives) and topoisomerase IV (more for gram-positives) Potent against *E. coli, Salmonella, Shigella, Enterobacter, Campylobacter,* and *Neisseria*. Can be used against multidrug resistant TB, *M. avium*, and atypical mycobacterial infections Resistance: mutations in gyrase or Topo IV or by active transport out of the cell (no quinolone modifications) Well absorbed following oral administration; cleared by kidney (watch for kidney problems) Well tolerated; some GI discomfort; may cause joint problems in children Use with caution in pateints on class III and class IA antiarrhythmics

Answer 95

A quinolone that is useful against streptococci the antibiotic of choice for L. pneumophila

Answer 96

A quinolone that is useful against streptococci Cleared by the liver (watch for hepatic failure)

Answer 97

A quinolone that is useful against streptococci Associated with both hypo- and hyperglycemia in older adults No longer on the market because of these problems

Answer 98

Trimethoprim inihibits bacterial DHFR Sulfamethoxazole inhibits incorporation of PABA into folic acid Used to treat *S.pneumoniae* along with a ton more Resistance is through a plasmid encoded altered DHFR Effective for acute exacerbations of chronic bronchitis. It should *not* be used to treat strep pharyngitis. Also effective for acute otitis media in children and acute maxillary sinusitits in adults caused by *H. influenzae* and *S. pneumoniae*. Also useful to treat *Pneumocystis jiroveci* and used prophylatically for patients with neutropenia. Relatively well tolerated, but may induce folate deficiency in patient's already suffering from low folate

Answer 99

Polyene MOA: forms pores by binding to ergosterol in fungi cell membranes Four formulations: conventional (DOC or C-AMP), liposomal, lipid complex (most expensive), and colloidal dispersion GI absorption is negligible Works against *Candida, Crytococcus, Blastomyces, Histoplamsa, Sporothrix, Coccidiodes, Paracoccidioides, Aspergillus,* and the agents of mucormycosis *Aspergillus terreus* and *nidulans* may be more resistant than other Aspergillus species. Resistance is by replacing ergosterol with other precursor sterols Side Effects: fever and chills, nephrotoxicity (least with the lipid formulation). Tachypnea and respiratory stridor or modest hypotension may also occur, but these effects are short lived (30-45 minutes). Azotemia occurs in 80% of patients with C-AMB. Anemia may also occur due to decreased production of erythropoietin

Answer 100

Fluorinated pyrimidine that is deaminated to fluorouracil, formed into FUMP, and incorporated into RNA or formed into FdUMP which blocks thymidylate synthetase. MOA: DNA synthesis is impaired Used against *Cryptococcus, Candida,* and the agents of chromoblastomycosis Resistance: occurs often when used as monotherapy; either loses permease needed for cytosine transport or decreases activity of enzymes needed for metabolism. Absorbed well from GI tract (reduce doses in patients with renal problems) Used in combination with amphotericin B Side Effects: may depress bone marrow, rash, nausea, vomiting, diarrhea, enterocolitis (all more frequent in AIDS patients)

Answer 101

MOA: 14 alpha-lanosterol demethylase inhibitors that serve to inhibit ergosterol synthesis Resistance: mutations in gene for demethylase, increased azole efflux via an ABC, increased production of the demethylase Interact with hepatic CYPs

Answer 102

Imidazole Largely replaced by itraconazole except when cost is prohibitive Administered orally, also available for topical use Has some effect on corticosteroid suppression, can be used in Cushing's Lots of hepatotoxicity

Answer 103

Synthetic triazole Can be taken orally, is a substrate and inhibitor of CYP3A4 (watch for quinidine, halfantrine, levomethadyl) Use for indolent, nonmeningeal infections due to *B. dermatitidis, H. capsulatum, P. brasiliensis,* and *C. immitis* (as well as some indolent invasive aspergillosis) Not recommended for cryptococcal infections in AIDS patients due to high relapse ratios Side Effects: potential hepatotoxicity, congestive heart failure in patients with impaired ventricular function, GI complaints, rash

Answer 104

Triazole Completely absorbed in the GI tract, enters the CSF well; it is an inhibitor of CYP3A4 Used especially in candidiasis and crytococcosis (meningitis in AIDS patients), coccidiodal meningitis No activity against histo, blasto, aspergillus, mucomycosis or sporotrichosis Side Effects: nausea, headache, potentially teratogenic

Answer 105

Triazole Orally available, genetic polymorphisms in population can affect metabolism Better than amphotericin B for invasive aspergillosis, also used for candidiasis. Also for pneumocystis jiroveci Side Effects: contraindicated in pregnancy, causes occasional hepatotoxicity, prolongation of QT interval, visual side effects.

Answer 106

Triazole **Good against mucormycosis** Bioavailability enhanced by taking with food/increased gastric acid; metabolized by UDP glucuronidation As good as fluconazole for candidiasis Inhibits CYP3A4 Good safety profile with nausea, vomiting, diarrhea, abdominal pain, and headache most common side effects

Answer 107

Anti-Influenza Agents Rimantadine is a derivative of amantadine MOA: inhibit **viral uncoating** and alter hemagglutinin processing on the **influenza A (only)** virus M2 protein Well absorbed after oral administration (elderly need less of a dose). Side Effects: dose-related CNS (nervousness, light headedness, insomnia) and GI side (effectsloss of appetite or nausea) Can be used prophylactically Effective if used within 2 days of onset of symptoms Resistance is prevalent due to a mutation in the M2 protein

Answer 108

Anti-influenza Agent Transition-state analog of sialic acid that is a potent selective inhibitor of influenza A and B virus neuramidases Inhibits viral release from host cells Mutations in neuramidase lead to resistance (seasonal flu is 100% resistant, H1N1 is susceptible) Given orally Side Effects: nausea, abdominal discomfort, emesis (preventable with administration with food)

Answer 109

Combination therapy in practice is isoniazid, rifampin, and pyrazinamide for two months (initiation phase) followed by intermittent rifampin and isoniazid (continuation phase)

Answer 110

Nasally inhaled dry powder Binds to neuramidase like oseltamivir Used against A, B and H1N1 MOR: mutations in neuramidase or hemagglutinase Well tolerated, but don't use with patients with respiratory diseases like asthma

Answer 111

ET-1 antagonist (endothelin) Used to treat pulmonary arterial hypertension, decreasing pulmonary vascular resistance

Answer 112

Muscarinic receptor agonist Used in asthma challenge test

Answer 113

Mucolytic- can loosen mucous plugs in CF patients Antidote for acetaminophen overdose

Pulmonology Flashcards

(138 cards)