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Flashcards in Pharmacology Deck (203):
1

Effect of NSAID's on loop diuretics. Why?

- Loop diuretics▶️⬆️PG▶️dilatation of renal vasculature▶️⬆️renal blood flow▶️⬆️renal function (GFR)
- NSAIDs ▶️⬇️PG▶️block vasodilator effect▶️⬇️diuretic response

2

What is Nesiritide? Function.

BPN analog▶️diuretic and vasaodilator▶️used for acute and decompensated heart failure

3

Effect of inhaled anesthetics on brain

⬇️Vascular resistance▶️⬆️cerebral blood flow (undesirable) ▶️⬆️intracranial pressure

4

Mechanism of action of Danosumab. Uses.

Monoclonal antibody treatment postmenopausal osteoporosis
Like-Osteoprotegerin ▶️ bind RANK-L ▶️ block interacion with RANK ▶️ ⬇️ Osteoclast differentiation

5

Effect on the cAMP of atenolol in heart, kidney and blood vessel

Atenolol - selective beta blocker
- heart and kidney ▶️ ⬇️ cAMP ▶️ both have B1 receptor (Gs coupled)
- blood vessel ▶️ no change cAMP ▶️ not B1, have B2

6

Which drug used for rheumatoid arthritis can cause interstitial pneumonitis and fibrosis?

Methotrexate

7

Treatment for restless leg syndrome. Include pharmacologic and non-pharmacologic measures.

- Avoid alcohol and sleep deprivation
- Dopamine agonists (pramipexole, ropirinole)
- Excercise, leg massage, heating pads

8

When occur and how can you avoid the nitrate tolerance?

- Chronic nitrate treatment ▶️ attenuation of blood pressure response and antianginal effects
- Give sublingual nitroglycerin intermittent, as-needed basis, free interval

9

Differences in uses of nytroglicerin sublingual vs isosorbide dinitrate or mononitrate.

- Sublingual Nitroglycerin: acute episodes of ischemia, prevention angina before strenuous exercise
- Isosorbide: chronic stable angina - prevent recurrent anginal episodes

10

Treatment of Cataplexia. Why?

- Muscarinic antagonists
-

11

Why chronic use of glucocorticoids is a major risk factor (modificable) for osteoporosis?

- ⬇️ absorption of Calcium
- Inhibit collagen synthesis by osteoblasts
- ⬇️ GnRH ▶️ hypogonadism
- ⬆️ urinary calcium loss

12

Mechanism of action of varenicline. Uses.

- Partial agonist of nicotinic receptor (alfa4, beta2) of CNS ▶️ competes with nicotine (full agonist) ▶️ low ⬆️ dopamine ▶️ less stimulation of reward pathway that nicotine.
- ⬇️ withdrawal cravings in cessation of tobacco

13

Mechanism of action of a substance that is low molecular weight fraction, negatively charged and stored on mast cells granules.

Binding and ↑ action of antithrombin III (natural anticoagulant)

*Heparin

14

Difference in action of unfractionated heparin and Low molecular weight heparin (LMWH).

- LMWH ▶️ AT III(a) ▶️ bind factor Xa
- Unfractionated Heparin ▶️ (via pentasacharide in heparin chain) AT III(a) ▶️ bind factor Xa and thrombin

15

How do the PGF2alpha analogs (latanoprost, Bimatoprost) function to treat glaucoma?

⬇️ collagen content in the Uveosclerar outflow pathway ▶️ ⬆️ outflow of aqueous humor

16

Which glaucoma drug is contraindicated in closed-angle glaucoma? Why?

Alpha-1 agonist (Epiniphrine) ▶️ mydriatic effect
- mydriasis close more the iridocorneal angle ▶️ trabecular meshwork less accesible to outflow

17

Target structure of Timolol in glaucoma treatment. Mechanism of action.

Epithelial cells of ciliary body ▶️ ⬇️ production of aqueous humor

18

Mechanism of action of cholinomimetics in glaucoma treatment.

- ciliary muscle contraction ▶️ opening trabecular meshwork
- esphincter of iris contraction ▶️ miosis ▶️ wider anterior chamber (open angle) ▶️ trabecular meshwork more accesible to outflow

19

What could be the cause of a first-dose hypotension by ACEI?

*Which is the mechanism?

Volumen depletion state (diuretic use or heart failure) ▶️ ⬆️ plasma renin activity ▶️ ⬆️ Ag II effect (compensatory)

*Abrupt removal of vasoconstrictory effect of Ag II ▶️ ⬇️ peripheral vascular tone ▶️ ⬇️ BP in susceptible patients.
Prevent ▶️ start ⬇️ doses

20

How can you reverse the toxic effect in a MTX overdose?

Leucovorin (folinic acid) ▶️ NOT requires DHFR to become Tetrahydrofolate
Rescue bone marrow, GI tract (rapid dividing normal cells) ▶️ pancytopenia, aphtous ulcers

21

Mechanism of action of metimazole and propylthiouracil

- Thioamide drug (also propylthiouracil) ▶️ ❌ thyroid peroxidase ▶️ ❌ iodine organification (MIT, DIT formation) and coupling iodotyrosines (T3, T4 formation)
- Propylthiouracil ▶️ also ⬇️ peripheral conversion T4 ▶️ T3 (active)

22

Why you should avoid ACEI in patients with C1 esterase inhibitor deficiency? Which is this disease?

- Hereditary angioedema
- ACEI ⏩ ⬆️ Bradykinin ▶️ precipitate disease episodes

*ACE ▶️ Bradykinin ▶️ inactive products

23

When can you give Vitamin K alone?

Abnormal coagulation tests (PT or PTT) but NO bleeding

24

Which calcium channel blockers you must avoid in patients with conduction abnormalities (AV block) and bradycardia? Why?

- Nondihydropyridines ▶️ verapamil, diltiazem ▶️ ⬇️ heart rate (negative chronotropic effect), ⬇️ contractility (negative inotropic effect)
- worsen bradycardia and AV block.

25

Why do the proton pump inhibitors associate with higher risk of osteoporosis?

Long term acid supression→↓acidic environment→↓Calcium absorption (need acid environment to be absorbed)

26

Why are the class IV antiarrhythmics useful to prevent recurrent nodal arrhythmias (ex paroxysmal supraventricular tachycardia)?

Block Calcium channels in cardiac slow response fibers (SA and AV nodes) ▶️ ⬇️ phase 0 (conduction) and 4 (depolarization) ▶️ ⬇️ diastolic depolarization

27

Ocular side effects of first generation antihystamines (chlorpheniramine, diphenhydramine). Why do the occur?

- Blurred vision for close objects (noticeable when read, no when driving), mydriasis
- anticholinergic effect ▶️ impair accomodation (contraction of ciliary muscle ▶️ ⬆️ refractive power of lens) and contraction of pupillary sphincter (PANS control)

28

Which adverse effect is increased in a coadministration of Ganciclovir with TMP-SMX or zidovudine [AZT]? The previous is possibly treating which scenario?

- Bone marrow suppression ▶️ Neutropenia, leukopenia, thrombocytopenia.
- CMV hemorrhagic colitis in HIV patient. Add TMP-SMX is though as prophylaxis.

29

Lipoatrophy and central fat deposition (redistribution of fat from extremities to the trunk) is a common side effect of which drugs?

- Lipoatrophy ▶️ loss or wasting fat from extremities, face and buttocks ▶️ NRTI (stavudine, zidovudine), protease inhibitor
- Central fat deposition ▶️ ⬆️ abdominal girth, buffalo hump ▶️ any HAART

30

Mechanism of action of Tacrolimus and Cyclosporine. Uses. Side effects.

- Inhibition of Caclineurin

*Normally Calcineurin [serine, threonine phosphatase] ► dephosphorylate to NAFT (transcription factor) ▶️ nucleus ➕ IL-2 promoter ▶️ ⬆️ IL-2 ▶️ differentiation and proliferation of T-cells

- Transplant rejection and prophylaxis. Cyclo also psoriasis, RA.
- Cyclo ▶️ bind cyclophilin
- Tacro ▶️ bind FK506 binding protein (FKBP)

- Highly Nephrotoxic

31

Which drug can increase the QRS duration during exercise? How does it call? Which is the normal (without drug) reaction on QRS during exercise?

Flecainide, Strong use-dependence ▶️ slowest to dissociate from Na channel ▶️ ⬆️ Na blocking effects in ⬆️ HR ▶️ less time between action potential for the drug to dissociate from receptor.

- Normally Exercise ▶️ ⬆️ Heart rate ▶️ ⬆️ cardiac conduction velocity ▶️ ⬇️ QRS duration
- Drug Exercise (test) ▶️ ⬆️ Heart rate ▶️ 🚫 fast Na channels (phase 0 depolarization of cardiac myocytes) ▶️ ⬆️ QRS duration

32

Drug of choice in a myoclonic seizure. Which type of seizure is it?

- Broad spectrum anticonvulsivants ▶️ lamotrigine, levetiracetam, topiramate, valproic acid (Tx most seizures focal or generalized at onset) ⤵️ (drug of choice)
- Generalized seizure (involve both hemispheres at onset)

33

Why do you use Rifamixin and lactulose to treat hepatic encephalopathy?

- Lactulose ▶️ ⬇️ colonic pH ▶️ facilitates NH3 ⏩ NH4+
- Rifamixin ▶️ change GI bacterial flora ▶️ ⬇️ production of NH3

34

Which drug for the treatment of tuberculosis acts by disrupting the cell wall of the bacilli? What property can the mycobacterium lose?

- Isoniazid ▶️ 🚫 mycolic acid synthesis
- lose acid-fastness, unable to synthesize new cell wall or multiply

35

Which site of the brain drive the nausea and vomiting reaction when give systhemic chemotherapy for cancer?

Area postrema (dorsal medulla, caudal fourth ventricle end)→Chemoreceptor trigger zone (CTZ)

*Recieves blood from fenestrated blood vessels (absent BBB)→sample chemicals in blood

36

What side effect of levodopa will be present although adding carbidopa?, which side effect do you avoid?

- ↑Dopamine in brain→Agitation and anxiety (central side effect)
- ↓Dopamine in periphery→Nausea and vomiting (area postrema outside BBB)→(+)emetic center at brain stem [area postrema]; ↓tachyarrhythmia, postural hypotension and hot flashes

37

Why you should replace Rifampin by Rifabutin in treatment of TB in patient HIV (+) in HAART including Protease inhibitor?

Rifampin ▶️ ⬆️ activity cytochrome P450 ▶️ metabolizes Protease inhbitors (really PI 🚫 C P450) ⏩ ⬇️ levels of PI

38

Contraindication of primaquine, why?

Glucose 6-P dehydrogenase deficiency
Can cause hemolysis

39

What drug do you use to confirm diagnosis of asthma during lung test function, and when do you use it?

Lung test function normal, and history suggest asthma ▶️ methacoline ▶️ muscarinic cholinergic agonist ▶️ bronchoconstriction and ⬆️ mucus production ▶️ broncoprovocation ⏩ ⬇️ FEV1 after mechacoline challenge

40

Mechanism of Jimsom weed poisoning ("Gardener mydriasis"). Treatment.

- Jimsom weed ▶️ toxins (belladona alkaloids) ▶️ ❌ muscarinic cholinergic visceral receptors ▶️ atropine-like syndrome
- Physostigmine ▶️ cholinesterase inhibitor ▶️ ⬆️ Ach in synaptic cleft

41

First line of treatment for absence seizures. Mechanism of action.

Ethosuximide ▶️ blocks thalamic T-type calcium channels

42

Mechanism of action of vigabatrin and uses

- 🚫 GABA transminase irreversibly ▶️ ⬆️ GABA
- Treatment of resistant epilepsy

43

Risk of vertical transmision of HIV with and without HAART. Which pregannt women should take HAART?

- No HAART→35%, HAART→1-2%
- All mothers regardless CD4 count or viral load until breastfeeding period

44

What antiretroviral is teratogenic and which is used to profilaxis for HIV in the newborn?

- Teratogenic→Efavirenz
- Newborn prophylaxis→Zidovudine

45

What adverse effects characterized Foscarnet? why do they happen?

- Hypocalcemia, hypomagnesemia→seizures
- Chelate Ca, ↓PTH release, ↑renal wasting of Mg

46

Which drug do you use to treat nausea and vomiting in diarrhea/vomiting disease (traveler diarrhea), motion sicknes disease and migraine or central nausea?

- GI insults (infections, chemotherapy, distention)→↑5HT→(+)5HT3 receptors ► 5HT3 receptors antagonists (Ondansetron)
- Central nausea (migraine)→DA2 receptor antagonists (metochlopramide, prochlorperazine)
- Vestibular nausea→First generation H1 receptor antagonist, M1 receptor antagonists

47

How is call the pharmacologic principle when cortisol increases the response of norepinephrine?

Permissiveness→One hormone allows another compound exert its maximal effect

48

How does the cocaine exert its sympaticomimetic effect? Signs and symptoms that you expect to see in a intoxication.

- Indirectly→Inhibit presynaptic reputake of monoamines (catecholamines - NE, DA, 5HT)
- HTN, ↑HR, mydriasis (SANS +), CNS +→agitation, seizures, ↑arousal. Vasoconstriction→coronary vasospasm+↑platelet aggregation→myocardial ischemia; mucosal atrophy→nasal septal perforation

49

Most common situations in which ACEI can cause hyperkalemia

- Renal insufficiency
- Spare-K+ diuretics ▶️ amiloride, espironolactone, triamterene
- K+ supplements

50

What do you suspect in a hyperthyroidism patient with fever and sore throat, oral ulcerations in treatment with antithyroid drugs? What do you do if suspect it?

- Thionamide-induced agranulocyotsis (absolute neutrophil count<500/uL)
- Suspend drug, white blood cell count with differential to confirm Dx

*In 0,5% of patients within first few months of Tx.

51

Different useful situations of antithyroid drugs

- Metimazol ▶️ initially because potentially severe hepatotoxic propylthiouracil
- Propylthiouracil ▶️ 1st trimester of pregancy because teratogenic metimazol; life-threatening thyroid storm because additional effect to 🚫 conversion T4⏩T3 in peripheral tissues

52

Common side effects of sotalol and why?

- Bradycardia ▶️ beta-adrenergic blocking
- QT interval prolongation ▶️ Proarrhythmic ▶️torsades de pointes ▶️ class III (K+ channel blocking)

*Rhythm control of paroxysmal atrial fibrillation

53

Most important side effect of anthracyclines (doxorubicin, daunorubicin, epirubicin, idarubicin) and why does it occur? Treatment to it.

- Oxygen free radicals in myocardium ▶️ cumulative dose-related dilated cardiomyopathy ▶️ left and right ventricular CHF
- Desrazoxane ▶️ iron chelating agent ▶️ ⬇️ O2 free radicals

54

Treatment of inflammatory bowel disease. Mechanism of action.

Chron's disease, ulcerative colitis ▶️ 5-aminosalicylates (sulfasalazine [sulfapyridine + 5-aminosalicylic acid], mesalamine) ▶️ ⬇️ CK's, PG's, leukotrienes during inflammation

55

Side effects of erythropoeisis-stimulating agents (ESAs) and why do they occur? Example of those agents.

- Hypertension ▶️ activation of erythropoietin receptors on vascular endothelial and smooth muscle cells
- Thromboembolic events ▶️ ⬆️ RBC mass ▶️ ⬆️ blood viscosity
- Erythropoietin, darbepoetin

56

Mechanism of action of mifepristone. Uses.

- Progesterone antagonist ▶️ apoptosis and necrosis of decidua ▶️ ❌ further development of the first trimester of pregnancy
- With misoprostol (PGE-1 analog ▶️ softening of cervix, ⬆️ uterine contractions) to pregnancy termination

57

Why do the loop and thiazide diuretics cause hyperuricemia?

Hypovolemia→↑Uric acid absorption

*Potentially precipitate gout attack

58

Why do the thiazides and loop diuretics cause hypokalemia and metabolic alkalosis?

↓Intravascular volume→(+) aldosterone→↑secretion of H+ and K+ at collecting ducts

59

Mechanism of action of ionizing radiation in the treatment of cancer

- Break double stranded DNA (both strands)
- Free radical formation→ROS formed by ionization of H2O→cellular and DNA damage

60

Which antiarrhythmic drugs that blockade Na channels have the less and higher use dependence effect?

- Use dependence effect ▶️ higher rates of depolarization lead in more Na channel blockade
- Drugs with ⬆️ use dependence effect spend more time bound to Na channel (activated-inactivated)
- 1C>1A>1B

*Dissociation of 1B from Na channels is more rapidly and less cumulative effect over multiple cardiac cycles ▶️ little use dependence

61

Mechanism of action of thizolidinedione. Example of one of them.

- Pioglitazone
- Bind to PPAR-γ ▶️ heterodimer complex with retinoid X receptor ▶️ binds to transcriptional regulatory sequences of some genes. Ex: ⬆️ Adiponectin ▶️ ⬆️ insulin sensitivity and fatty acid oxidation

62

Mechanism of action of theophylline. Indications. Important features about it uses.

- Inhibit cAMP phosphodiesterase ▶️ ↑ action of cAMP→(+)PKA→(-)myosin light chain kinase at smooth muscle (activated allow cross myosin-actin→contraction)
- Blocks actions of adenosine (normally ↑bronchoconstriction)
- Tx bronchial asthma; narrow therapeutic index
(cardiotoxicity, neurotoxicity); metabolized by cytochrome P-450

63

What could occur if you give ACEI or ARB in a patient with BILATERAL renal artery stenosis? why?

- Bilateral renal artery stenosis→↓RBF→↓GFR►maintain GFR►Ag II→Efferent arteriole constriction→↑GFR
- ACEI or ARB→↓Ag II→efferent arteriolar vasodilation→↓GFR►acute renal failure

64

Treatment of choice for absence associated with tonic-clinic seizures.

Valproate

*Ethosuximide effective against absence seizures but not for tonic-clonic seizures

65

What drug you must avoid in a glaucoma patient?

Systemic or local anticholinergic (atropine, etc) ▶️ mydriasis ▶️ narrowing anterior chamber ▶️ ⬇️ outflow of aqueous humor ▶️ ⬆️ intraocular pressure ▶️ precipitate closed-angle glaucoma in patients with shallow anterior chamber or higher than normal intraocular pressure

66

Mechanism of action of meglitinide (repaglinide, nateglinide). Uses.

- Inhibit the ATP-dependent K+ channels in pancreatic B cell membrane→Depolarization→open L-type calcium channel→↑calcium influx→↑insulin releasing
- Postprandial hyperglycemias in DM

*Insulin secretagogue (sulfonylurea also)

67

What type of neuropathy can cause Isoniazid?, why?, more sensible patients.

- Peripheral neuropathy
- Vitamin B6 participate in synthesis of many neurotransmiters (DA, NE, Epi, 5TH, GABA)
- Isoniazid similar structural to B6→↑urinary excretion, compete binding sites→B6 deficiency
- Elderly, acoholics, liver or kidney dysfunction

68

What mechanism produce angioedema by ACEI?

↑↑Bradykinin (ACE→break bradykinin)→powerful vasodilator→↑vascular permeability

*Differentiate angioedema by hereditary esterase C1 inhibitor by age and history of taking ACEI

69

Long-term use of thiazolidinedione (pioglitazone) is associated with what condition?

Urinary bladder cancer

70

How much rectal drug administration bypass the first-pass metabolism? how does it happen?

Partially bypasses first-pass metabolism. Rectum drainage:
- Superior rectal vein→inferior mesenteric vein→portal circulation (first-pass metabolism) (1/3 of drug)
- Middle and inferior rectal vein→internal iliac and internal pudendal veins→systemic circulation (2/3 of drug)►↑bioavailability

71

Adverse effect of the mu opioids on common bile duct and gallbladder and mechanism of it.

Contraction of smooth muscle cells of sphincter of Oddi→spasm→↑pressure in common bile duct and gallbladder►biliary colic

72

When is useful to give pulsatile administration of GnRH?

Hypogonatropic hypogonadism→anovulation→infertility

*Normally from hypothalamus pulsatile→upregulation of its receptors in gonadotropin pituitary cells→↑LH and FSH►development of the dominant follicle→ovulation

73

When is useful an long-acting analog of GnRH? why?

Prostatic cancer, premenopausal breast cancer, endometriosis, precocious puberty

*When supression of gonadal function is desired►downregulation of GnRH receptors→↓LH and FSH

74

Major causes of death by tricyclics andtidepressants (TCA) overdose.

- Inhibit fast Na+ channel conduction→↓myocardial depolarization→cardiac arrhythmias (most common cause of death)
- Antagonist of peripheral alpha-1 adrenergic receptor→refractory hypotension

75

Side effects of selective arteriolar vasodilator (direct relaxation of smooth muscle of arterioles and no veins).

- Normal effect→↓systemic vascular resistance→↓blood pressure:
♦ Stimulation of baroreceptors→(+) sympathetic nervous system→↑HR, contractility►↑cardiac output
♦ SANS→renin-angiotensin-aldosterone system→↑Na and fluid retentetion (peripheral edema)

*hydralazine, minoxidil

76

Why a calcium channel blocker (ex verapamil) affects contraction of myocyte of smooth and cardiac muscle, and not of skeletal muscle?

- Smooth and cardiac muscle need influx of extracellular calcium through L-type Ca channel (blocked CCB) to activate RyR receptor at sarcoplasmic reticulum and release more Ca to contraction
- Skeletal muscle is not dependent of extracellular influx of Ca. Depolarized receptor activate RyR without Ca influx.

77

Mechanism of action and most important side effects of carbamazepine

- ⬇️ Na channel ability to recover from inactivation
- Bone marrow suppression ▶️ thromobocytopenia, anemia, agranulocytosis
- Syndrome of inappropiate ADH secretion ▶️ hyponatremia

78

Treatment and prevention of gynecomastia in patient receiving androgen depriving therapy (ADT). What ADT are possible and in what case in men?

- Tamoxifen ▶️ selective estrogen receptor modulator ▶️ inhibit effect of estrogen in breast
- ADT ▶️ orchiectomy, long-acting GnRH agonists therapy, androgen receptor inhibitors
- Prostate cancer

79

Treatment for enterobiasis (pinworm) in pregnant women. First line in non-pregnant individuals.

- Pregnant→pyrantel pamoate
- Non-pregnant and others→albendazol

80

Uses and mechanism of action of Naltrexone

- Block mu-opioid receptors
- Alcohol dependence→Block rewarding and reinforcing, ↓craving, can be initiated while still drinking

*Use long-acting depot form (monthly) for risk of non-adherence to dialy administration

81

Treatment options for clostridium difficile infection. Which of them inhibits the sigma subunit of RNA polymerase and what is its proper use?

- Metronidazol, Vancomycin
- Fidaxomicin→macrocyclic (related to macrolides), inhibit the sigma subunit of RNA polymerase→impairment protein synthesis→cell death (bacteriocidal)

*Useful in recurrent infection and ↑risk recurrence (recent antibiotic use, gastric acid supression)

82

Manifestations of acute dystonia as adverse effect of antipsychotics. Which type of antipsychotics can cause them and how?

- 4 hours to 4 days after initiate drug
- Muscle spasm (acute torticolis), stiffness, oculogyric crisis, opisthotonus, laryngospasm (rare)
- 1st generation High-potency antipsychotics→D2 antagonism in nigrostriatal pathway►predominates excess action of M1

83

How do you treat acute dystonia as a side effect of antipsychotic therapy?

Block excess action of M1 (cholinergic muscarinic neurons)►Benztropine, diphenhydramine→re-establish dopaminergic-cholinergic balance

84

Most common adverse effects of psychostimulants for treatment of ADHD.

Decreased appetite, weight loss and insomnia

*Less common→↑ HR and blood pressure►monthly follow up

85

Most important side effect of lamotrigine. Uses.

- Stevens-Johnson syndrome (life-threatening rash)
- Anticonvulsivant, bipolar disorders

86

Drugs that impair periphery conversion of T4 to T3

Amiodarone, non-selective ß-blockers, propylthiouracil, glucocorticoids, iopanoic acid

87

How do you measure the solubility of an gas anesthetics and determine a high or low solubility? What is the consequence in the onset of action?

Blood/gas partition coefficient
- ↓coefficient►low solubility→blood saturates quickly→fast↑ in partial pressure→fast brain saturation→↓onset of time→rapid onset of action
- ↑coefficient►high solubility→blood saturates slowly→delayed↑ in partial pressure→slow brain saturation→↑onset of time→slow onset of action

88

How do you measure potency in a gas anesthetics?

Minimal alveolar concentration→concentration of gas in the lungs that produces the desired effect in 50% patients

*Potent anesthetics→lower partial pressure to be effective

89

Treatment of Beta-blocker overdose. Mechanism of action.

Glucagon→↑intracellular cAMP→→↑Ca during muscle contraction→↑HR, cardiac contractility, blood pressure in minutes

90

Why if manitol is a diuretic can worsen pulmonary edema? What is its mechanism of action?

- Causes initial intravascular volume expansion
- Osmotic diuretic inhibit water and NaCl reabsorption in the PT and descending limb of loop of henle

91

Mechanism of action of Oseltamivir

- Sialic acid analogue▶️competitively inhibits influenza neuraminidase▶️❌release of viral progeny

*Neuraminidase cleaves terminal acid residues on glyconjugate receptors▶️release of attached influenza virions from infected cells

92

Mechanism of action of Oseltamivir

- Sialic acid analogue▶️competitively inhibits influenza neuraminidase▶️❌release of viral progeny

*Neuraminidase cleaves terminal acid residues on glyconjugate receptors▶️release of attached influenza virions from infected cells

93

What is cinacalnet and what is used for?

- Calcimimetic allosterically activates calcium-sensing receptor in parathyroid gland▶️⬇️PTH release
- Secondary hyperparathyroidism in dialysis

94

What is the sevelamer and what is used for?

- Non-absorbable phosphate-binding polymer▶️⬇️absorption of PO4 in GI tract
- Hyperphosphatemia in dialysis

95

How do you distinguish a neuroleptic malignant syndrome and serotonin syndrome?

Both▶️mental status change, autonomic instability, hyperthermia
- Serotonin▶️neuromuscular hyperactivity▶️shivering, clonus, hyperreflexia (vomiting and diarrhea most common than NMS)
- NMS▶️diffuse rigidity and hyporreflexia

96

Which compounds rise and decrease in blood the thiazide diuretics?

⬆️ glucose, lipids (cholesterol LDL), uric acid, calcium
⬇️ sodium, magnesium, potassium (metabolic alkalosis)

97

Mechanism of action of opiates

- High affinity for the mu receptor▶️coupled to inhibitory G proteins and higher analgesic effects
- Primary afferent neuron▶️activation of mu R▶️close voltage-gated calcium channel▶️⬇️ neurotransmitter release (Ach, NE, Epi, Substance P, etc) from presynaptic membrane
- Postsynaptic membrane ▶️bind to mu R▶️open potassium channels▶️K efflux▶️membrane hyperpolarization

*Opiated-induced inhibition of synapse activity in CNS▶️attenuated pain

98

Mechanism of action of flutamide. Common use in a prostate cancer.

- Competitive testosterone receptor inhibitor
- Sometimes prescribed concurrently with long-acting GnRH agonist▶️initial and transient ⬆️LH and testosterone (avoid the androgen effect▶️worst symptoms)

99

Indication and mechanism of action of Diphenoxylate. How do you avoid the abuse of it?

- Low-potency opioid agonist▶️bind mu receptor at GI tract▶️⬇️ motility
- Empiric symptomatic therapy for uncomplicated diarrhea▶️Ex; inflammatory bowel disease, functional diarrhea. (Must be avoided in diarrhea due toxin, invasive organism or clostridium difficile).
- Combined with atropine▶️if take higher doses▶️adverse effects of atropine (dry mouth, tachycardia, blurry vision) would decrease subsequent increase doses by abuse

100

What oral anti-diabetic agent can cause as side effect, exacerbation of heart failure (and why) and hepatotoxicity?

Thiazolidinediones (ex, pioglitazone, rosiglitazone)
- Fluid retention→exacerbate HF→assess risk and signs of HF
- Hepatotoxicity→periodic liver function tests (with troglitazone, no longer available)

101

Mechanism of action of biphosphonate. Effects bone metabolism.

- Similar structure to pyrophosphate→attach to hydroxyapatite binding sites→Osteoclast take up the biphosphonate→unable to continue resorption►↓osteoclast activity
- Induce osteoclast apoptosis, ↓development/recruitment of osteoclast precursors cells

102

Mechanism of action of Teriparatide

Similar 34 amino acid sequence at N-terminal of PTH
- Maturation of pre-osteoblasts into bone-forming osteoblasts
- ↑Ca intestinal absorption, renal reabsorption

103

What drug can elevate the concentration of statins and increase risk of myopathy and why? What is statin exception?

- CYP450 inhibitors→Cimetidine, erythromycin (also claritromycin, No azitromycin), ciprofloxacin, azole antifungals, Isoniazid, Ritonavir, grapefuit juice
*Statins are metabolized by the liver cytochrome P-450 3A4, except pravastatin. Atorvastatin can ↑40%.

104

Mechanism of action of Lumacaftor and Ivacaftor. Indications.

CFTR-modulating medications
- Lumacaftor→restoring CFTR proteins to the membrane
- Ivacaftor→enhancing protein function (ex, chloride transport) at the membrane
*Improve predicted forced expiratory volume (FEV) and ↓rates of pulmonary exacerbations in Cystic Fibrosis

105

Side effects of ACEIs

- ↓GFR→not concerned unless ↓>30% (long-term benefits well known)
- Hypokalemia
- Cough
- Angioedema

106

How much time must patient wait when switch from MAOI to SSRI and why?

- 2 weeks→regeneration of MAO
- Contraindicated coadministration of SSRI and MAOI→↑↑risk of serotinin syndrome

107

Why are long-acting nitrates provided with free-interval dosing?

Decrease tolerance development

*Night▶️sleep and cardiac work is least

108

Which opoids side effects persist with higher doses of them, when tolerance have developed for analgesic effects and most side effects?

Constipation and miosis

109

Non-systemic treatment for postherpetic neuralgia (PHN)

- Lidocaine patches→↓depolarization of neurons in peripheral nerves
- Topical Capsaicin→Loss of membrane potential in nociceptive fibers, ↓substance P

110

Which are the compartments of the multi-compartment model of distribution of a drug?

*To what drugs apply this model?

- Central compartment→plasma
- Well-vascularized peripheral compartment→brain, liver, kidney, lung►quickly distributed
- Poorly-vascularized peripheral compartment→skeletal muscle, fat, bone►redistribution

*Accounts for the short duration of action of many commonly anesthetics (propofol - highly lipophilic)

111

What type of heparin is most effective innactivating thrombin?

- Unfractionated heparin→pentasaccharide sequence long enough→binds to antithrombin►conformational change→inactivate factor Xa, and thrombin
- unlike LMWH→ inactivate factor Xa>thrombin

112

Mechanism of action argatroban, dabigatran, bivalirudin, hirudin, lepirudin. Drug of choice of which condition?

- Binding to thrombin active site▶️direct thrombin inhibitors (don't need antithrombin III)
- Heparin induced thrombocytopenia (HIT) [antibodies to heparin and platelet factor IV▶️unfractionated heparin>LMWH]▶️paradoxical thrombosis

*Suspect HIT▶️suspend all forms of heparin

113

Mechanism of action and adverse effect of daptomycin.

- Creates transmembrane channels▶️intracellular ion leakage▶️disrupt bacterial membrane (cellular membrane depolarization), inhibition of macromolecules synthesis (DNA, RNA, proteins)
- Myopathy, ⬆️Creatinphosphokinase (CPK)▶️disrupt muscle fiber membrane [most with other drugs myopathy associated - statin]

*Limited to gram (+) infections

114

In what cases is daptomycin ineffective?

- No penetrate outer membrane of gram (-)▶️innecfetive treating gram (-) infections
- Innactivated by pulmonary surfactant▶️innecfective to treat penumonia

115

Which antibiotic can increase the risk of serotonin syndrome? In what case?

- Linezolid
- Concomitant use with proserotoninergic drugs (ex,SSRI)

116

Treatment for intractable parkinson symptoms (bradykinesia, rigidity). Why target those structures?

High frequency deep brain stimulation of globus pallidus internus or subthalamic nucleus▶️🚫them▶️thalamo-cortical desinhibition▶️improve motility

*Nigrostriatal degeneration in parkinson▶️➕subthalamic nucleus▶️⬆️➕globus pallidus internus▶️🚫thalamus

117

What drug inhibit the action of a enzyme induced by IL-1 and TNF-alpha during inflammation by inflammatory cells and no by normal surrounding tissue? Advantage of those drugs.

- Selective COX-2 inhibitors
- Spares COX-1→maintain gastric mucosa
- Spares platelet function as TXA2 production is dependent on COX-1

118

Mechanism of action of antibiotics which side effect is ototoxicity (tinnitus, hearing loss) and nephrotoxicity. In which infections they are not effective?

- Aminoglycosides▶️bactericidal▶️irreversible inhibition of initiation complex▶️binds to 30S ribosomal subunit▶️misreading of mRNA▶️🚫Protein synthesis
- Requiere O2 for uptake▶️ineffective against anaerobes

*Useful for severe gram (-) infections. Synergistic with B-lactams (affect cell wall synthesis)

119

Mechanism of action of Entacapone, Tolcapone

⬇️ Peripheral degradation of levodopa
🚫Catechol-O-methyltransferase (COMT)⏩Levodopa▶️3-O-methyldopa

120

Indication of treatment of hepatitis C infection.

Rivabirin and interpheron alpha▶️virologic and histologic evidence of chronic infection▶️HCV RNA in serum, chronic inflammation with fibrosis in liver Bx

121

Mechanism of action, uses and characteristic feature of Buspirone.

- Partial agonists of 5TH1A receptors
- Generalized anxiety disorders
- Slow onset of action (1-2 weeks). No cause sedation, addiction, tolerance or withdrawal

122

Mechanism of action and uses of Bosentan.

- Endothelin-receptor antagonist→block endothelin►potent vasoconstrictor, endothelial proliferation activator
- ↓Pulmonary arterial pressure, ↓progression of vascular and right ventricular hypertrophy

123

Mechanism of action of selective estrogen receptor modulators. Examples and differences between them.

- Mixed agonist/antagonists depending on tissue
- Tamoxifen:
*Breast►antiestrogenic effect (adjuvant tx of positive estrogen receptor breast cancer)→↓recurrence Ca, ↓estrogen-dependent benign breast lesions (fibroadenoma, cystic changes)
*Endrometrial tissue►endometrial hyperplasia and cancer (No risk with Raloxifen)
*Bone►agonist estrogen receptor→↑bone mineral density after menopause

124

Target of monoclonal antibody used for HER2 positive invasive ductal breast carcinoma

Trastuzumab→binds extracellular portion of HER2→prevents activation of transmembrane tyrosin kinase receptor►↓proliferation and ↑apoptosis

*HER2(+)→20% of invasive breast cancers

125

Treatment of hormone receptor positive breast cancer (ER and/or PR) in premenopausal and postmenopausal women

- Premenopausal→selective estrogen receptor modulator (Tamoxifen)
- Postmenopausal→aromatase inhibitors (anastrozole, letrozole)

126

Treatment of wilson disease

D-penicillamine→free sulfhydryl group→copper chelator

127

Which diuretic is recommended by some experts when associated high risk of osteoporotic fracture? why? what other benefit respect this effect is seen?

- Hydroclorothiazide→↑Calcium reabsorption in distal tubule→↑bone mineral density→↓risk of fracture for osteoporosis
- Hypocalciuria→↓recurrent renal stones

128

What mutation make anti-EGFR (epidermal growth factor receptor) therapy resistant? which are those drugs?

- Mutation of KRAS (proto-oncogen)→GTP binding protein→transduce signals from some receptors (EGFR)→cell proliferation and growth
- Activating Mutation→resistant to Tx→cetuximab, panitumumab→metastatic colon cancers (Stage IV wild-type KRAS)

*Genetic testing to identify wild-type and mutated KRAS prior Tx

129

What antibiotic can precipitate serotonin syndrome if combined with SSRI? Why?

Linezolid▶️has MAOI activty

*Gram (+), vancomycin resistant enterococcus, MRSA

130

Potential ocular adverse effect of oxygen therapy

Retinopathy of prematurity or retrolental fibroplasia: ⬆️⬆️O2▶️⬆️VEGF⬆️neovascularization and retinal detachment with blindness

131

Mechanism of action of arterial vasodilator used for hypertensive emergency crisis with effect on renal arterial vascular bed. What is its renal effect?

- Fenoldopan▶️short acting, selective, peripheral Dopamine-1 receptor agonist (no effect on alpha or beta)▶️➕adenyl cyclase▶️⬆️cAMP▶️vasodilation in most arterial beds
- Renal vasodilation▶️⬆️renal perfusion, diuresis, natriuresis (beneficial specially for acute renal failure)

*Remember hydralazine also arterial vasodilator but NO renal effect▶️no used in HTN crisis▶️reflex sympathetic➕▶️⬆️HR, contractility; fluid, Na retention

132

Treatment of nephrogenic diabetes insipidus

- Thiazide diuretics▶️induce mild hypovolemia▶️⬆️Na and water reabsorption at proximal tubules
- Indomethacin▶️⬇️PG synthesis▶️normally 🚫ADH

133

Treatment of central diabetes insipidus

Desmopressin (synthetic ADH)

134

Effect of benzodiazepines and barbiturates on GABA receptor

Positive allosteric modulation. In respondo to GABA stimulation:
- BZD▶️⬆️frequency of open the chloride channel of the GABA A receptor
- Barbiturates▶️⬆️time of open the chloride channel of GABA A receptor

135

Mechanism of action of baclofen, uses.

- GABA B receptor agonist▶️G-protein pathway
- Muscle relaxant

136

Why dextrose infusion and heme can improve acute intermittent porphyria symptoms?

Downregulates expression of ALA synthase▶️⬇️ALA▶️⬇️PBG which is ⬆️⬆️ by PBG deaminase deficiency

137

Uses and mechanism of action of vitamin D analogs.

- Psoriaris▶️topical⏩calciprotiene (calcipotriol), calcitriol, tacalcitol
- 🚫(Vitamin D receptor) nuclear transcription factor▶️❌keratinocyte proliferation; ➕keratinocyte differentiation
- 🚫 T cell proliferation and other inflammatory mediators

138

Mechanism of action of Oseltamivir

🚫Neuraminidase▶️❌release of new virus attached to cellular surface▶️new formed virions remain adherent to infected cells▶️❌viral spread

*Neuraminidase cleave at sialyc acid residues of host cell glycoconjugate receptors that bind Hemaglutunin of virus▶️release attached virions from infected cells

139

Uses and mechanism of action of Bevacizumab and Trastuzumab

- Bevacizumab→anti-VEGF►Tx Ovarian cancer
- Trastuzumab→anti-HER2►Tx Breast cancer

140

Immediate reverse of anticoagulation in patient in treatment with Dabigatran

Idarucizumab→atracts dabigatran 350x more than thrombin (binds free and thrombin bound)

141

Uses and mechanism of action of Natalizumab and Vedolizumab

- Natalizumab→alpha-4-beta-1 integrin cell adhesion molecule inhibitor (CNS)►Tx Multiple sclerosis; alpha-4-beta-7 integrin cell adhesion molecule inhibitor (Gut)►Tx Crohn's disease
*Associated with progressive leukoencephalopathy, reactivation of JC virus
- Vedolizumab→alpha-4-beta-7 integrin cell adhesion molecule inhibitor only (Not associated with PML)

142

Uses and mechanism of action of Secukinumab

IL-17 inhibitor→Tx Psoriasis

143

What is Romiplostin and its uses?

- Fusion antibody peptide
- Thrompoetin agonist→megakaryocytic proliferation and stimulation►Tx Idiopathic thrombocytopenic purpura in patients with no response to splenectomy

144

Uses and mechanism of action of Sacubitril

- Neprilysin Inhibitor [member of Angiotensin Receptor Neprilysin Inhibitor (ARNI)]→↑Bradikynin→cardiac muscle relax; ↑Natriuretic peptides
- Tx Congestive heart failure, NYHA II-IV with ↓ejection fraction

*Neprilysin→zinc-dependent metalloprotease→ breakdown bradikynin and natriuretic peptides
*Is a prodrug activated by plasma esterase

145

Uses and mechanism of action of Patiromer. Possible side effects and contraindication.

- Non-absorbed cation exchange polymer with calcium as a counter ion
- Chronic hyperkalemia in CKD on RAAS inhibition (ACEI or ARB) and ↑risk of hyperkalemia and arrhythmia. NOT for acute hyperkalemia.
- Contraindication: Avoid in mechanical bowel obstruction
- Side effects: Hypomagnesemia, hypercalcemia

*Allow use ARB and ACEI and delay progression of renal injury

146

Treatment of primary myelofibrosis, why?

- Ruxolitinib▶️JAK2 inihibitor
- Associated with V617F JAK2 mutation →oncogene (Gain of function)►myeloproliferative disorders: polycythemia vera, essential thrombocythemia, myelofibrosis, except CML (philadelphia chromosome)

147

Principal target of nitroglycerin

Large veins▶️venodilator

*larger dosis▶️arteriolar dilation▶️headache, flushing

148

A positive test of HLA-B*57:01 is relevant in a HIV patient considering treatment with which drug?

- Abacavir (NRTI)
- 2-8% patients▶️abacavir hypersensitivity reaction (AHR): strongly associated with the allele▶️bind abacavir to HLA-B*57:01▶️alter self-peptide presentation▶️delayed hypersensitivity reaction (type IV)

149

Which type of insulin would be more appropriate to control postprandial high blood glucose levels?

- Lispro, Aspartat, Glulisine (monomeric insulins)▶️mean peak 45 to 75 minutes. Before each meal.

*Regular▶️dimeric and hexameric▶️⬆️time to dissociate and absorb▶️peak 2-4 hours▶️after postprandial glucose peak▶️inadequate control of Glc following meals

150

What antiarrhythmic can increase the QRS (phases 0) and have minimal effect on QTc?

Class IC▶️Na channel blocker at myocyte▶️⬇️initial depolarization, ⬆️QRS; little effect on QTc▶️lack K channel blocking activity [Flecainide, propafenone]

151

Treatment of VIPoma

Somatostatin (octreotide)▶️⬇️production of many GI hormones (VIP, gastrin, glucagon, CCK)

152

How do the Beta-blockers affect the RAAS system? what is the effect on each component?

- Block B1 receptor in juxtaglomerular cells→↓renin
- ↓Renin, ↓Angiotensin I, ↓Angiotensin II, ↓Aldosterone, no affect Bradykinin

153

How much time would a drug metabolized by first order kinetcs require to achieve a 95% plasma steady state concentration during continous infusion?

4 to 5 half-lifes

154

Treatment for congenital adrenal hyperplasia

Low doses of exogenous corticosteroids→supress ACTH secretion→↓androgen by adrenal cortex

155

Mechanism of action of Bupropion, potential side effect and which patients are at higher risk of it?

- Norepinephrine/dopamine reuptake inhibitor (amphetamine-like effect)
- Seizures→eating disorders (anorexia and bulimia nervosa), previous seizure disorders►contraindicated

*No sexual dysfunction or weight gain

156

Potential consequence of use ACEI and ARBs during pregnancy, why?

- Fetal low angiotensin II→fetal renal maldevelopment (required for normal renal development)►↓diuresis→oligohydramnios→pulmonary hypoplasia, skeletal defects (limb deformities)
- ↓AgII→impaired cranial vascularization→hypocalvaria (hypoplasia of skull bones)

*Potter sequence

157

Mechanism of action of adenosine on myocardial cells and uses.

A1 receptor▶️⬆️K+ out of cells▶️hyperpolarization and ⬇️ICa▶️transient conduction delay at AV node⏩Dx/terminating certain forms of SVT

158

Anticonvulsivants associated with Steven-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)

Lamotrigine
Carbamazepine
Phenobarbital
Phenytoin

159

Mechanism of action of cromolyn and negocio mil (cromoglycate) and indication

- 🚫Mast cell degranulation▶️❌release of preformed inflammatory mediators
- Do not influence bronchial constriction directly, used to prevent acute attacks of asthma

*Good prophylaxis for exercise induced attack, aspirin hypersensitivity, seasonal symptoms

160

Mechanism of action of Triptans. For what are they used?

- Serotonin 5HT1B/5HT1D agonist→↓release of vasoactive peptides (substance P, calcitonin gene-related peptide [CGRP] - vasodilation, plasma protein extravasation►neurogenic inflammation)→vasoconstriction, block pain pathways in brainstem
- Abortive therapy for the outpatient acute migraines

161

Why are the selective COX-2 inhibitors associated with increased risk of cardiovascular events?

COX-2 in vascular endothelial cells and vascular smooth cells→prostacyclin synthesis→anticoagulant and vasodilatory
- Selective COX-2 inhibitors→↓Prostacyclin

162

Treatment of serotonin syndrome

- Supportive→airway maintenance, hydration, temperature maintenance
- Cyproheptadine→1st generation histamine antagonist with nonspecific 5HT1, 5HT2 receptor antagonist

163

Why amphotericin B can cause premature ventricular beats, presented as palpitations and weakness?

Renal tubular dysfunction▶⬆membrane permeability of distal tubule▶hypokalemia, hypomagnesemia▶arrhythmia and weakness

*if profound hypokalemia▶ventricular tachycardia or fibrillation

164

Cause of acyclovir nephrotoxicity and how can be prevented?

- Acyclovir concentration in collecting duct exceeds its solubility→crystallization, crystalluria, renal tubular damage
- Transient, prevented and treated→adequate hydration, dosage adjustment, slow rate of infusion

165

Which is the only antiarrhythmic that slows the heart rate (negative chronotropic) with no effect on cardiac contractility (inotropy) and/or relaxation (lusitropy)? Mechanism of action.

- Ivabradine→inhibition of funny sodium channels (If)→slows the rate of sinoatrial node firing►prolong the slow depolarization phase (phase 4)

166

Why do thiazolidinediones cause water weight gain, peripheral edema and adipose weight gain?

- ↑Na reabsorption in renal collecting ducts→may decompensate congestive heart failure
- ↑Storgae in adipocytes and ↑number of adipocytes

167

Major side effect of nondihydropyridine CCB

Constipation

Verapamil, Diltiazem, also bradycardia, AV block (negative chronotropy), worse HF (negative inotropic)

168

Major side effect and mechanism of action of Vincristine.

- Neurotoxicity→peripheral neuropathy►disruption of neuronal microtubules
- Inhibit microtubule formation on M phase of cell cycle→replicated chromosomes are unable to align and segregate into the daughter cells

169

What is the difference between glyburide and glimeperide vs glipizide?

All are second generation sulfonylurea
- Glyburide and glimepiride→long acting►higher incidence of hypoglycemia
- Glipizide→short acting►lower incidence of hypoglycemia

170

What is the rinitis medicamentosa and why may it occur?

Rebound rinorrhea (no cough, sneezing or postnasal drip)→tachyphylaxis by topical alpha-adrenergic agonists descongestants (>3 days of use)→negative feedback in norepinephrine synthesis and release→remove normal vasoconstrictive tone

*Similar effect with Nitroglycerine

171

Special indications of use class IB antiarrhythmics. Which are they?

- Acute ventricular arrhythmias (specially post-MI), digitalis-induced arrhythmias
- Lidocaine, Mexiletine
*Phenytoin also fall in this category

172

What properties of penicillins allow them to inhibit the transpeptidase?

Structurally similar to D-alanine-D-alanine→bind convalently to the active site of transpeptidase

*Transpeptidase→final cross-linking step in peptidoglycan cell wall formation→joining of amino acid in third position of a peptidoglycan molecule to the terminal D-alanine D-alanine of another peptidoglycan molecule

173

Which is the main difference between dihydripyridine and non-dihydropyridine calcium channel blockers?

- Dihydropyridine (amlodipine, clevidipine, nicardipine, etc)→act on vascular smooth muscle►vasodilator
- Non-dihydropyridine (verapamil, diltiazem)→act on heart►↓muscle contractility, ↓conduction velocity. Rate control in atrial fibrilation

174

What would be the effect to take cimetidine and warfarine simultaneously? Why?

Cimetidine potent (-) cytochrome P450→↓warfarin metabolism►↑↑warfarin blood levels→↑effects or toxic→risk of bleeding

175

Major adverse effect of clozapine

Neutropenia and potential life-threatening agranulocytosis

176

Why aromatase inhibitors may work for treatment of breast cancer? in which case?

- Breast cancer Estrogen receptor (+)
- Anastrazole, letrozole, exemestane→↓synthesis of estrogen from androgens→↓estrogen in postmenopausal►slow progression of ER (+) tumors

*Less effective as monotherapy in premenopausal→ovarian aromatase is upregulated by gonadotropins

177

How can be accomplished the resistance to isoniazid by mycobacterium tuberculosis?

- Non-expression of catalase peroxidase (needed to activate INH)
-Mutation of INH binding site on mycolic acid synthesis enzyme (target of INH)

178

Uses of Vemurafenib. Mechanism of action.

- BRAF V600E (+) Melanoma
- Inibitor of mutated BRAF→↑activation on the signaling pathways for melanocyte growth, survival and metastasis

179

Why do phenytoin cause gingival hyperplasia?

↑Platelet-derived growth factor (PDGF)→Gingival macrophages (+) proliferation of gingival cells and alveolar bone

*Regress after discontinuation

180

For what you can give aspirin previously to Niacin?

Avoid flushing, warmth, itching→mediated by release of prostaglandins (PGD2, PGE2)

181

Mechanism of action of niacin.

- Inhibit lipolysis (hormone sensitive lipase) in adipose tissue
- ↓Hepatic TG syntesis→↓VLDL (subsequently metabolized to LDL in circulation)→↓LDL
- Most effective ↑HDL (Reduce the clearance)

182

Which are the PCSK9 inhibitors and mechanism of action?

- Proprotein convertase subtilisin kexin 9 (PCSK9)→↑degradation of LDL receptors
- PCSK9 inhibitor→monoclonal antibody (alirocumab, evolocumab)→↑availability of LDL receptor on hepatocyte→↑clearance of LDL from blood

183

What could happen if patient take together cyclosporine and grapefruit juice?

Grapefruit juice (furocoumarins)→inhibit liver and GI tract cytochrome P450 (CYP3A isoenzymes)►metabolizes cyclosporine→↑levels►dose dependent renal vasoconstriction and tubular cell damage→acute renal failure→Nephrotoxicity (↑creatinine), hypertension

184

Which laboratory finding may suggest digitalis toxicity? Clinical presentation.

- Block Na-K-ATPase→↑extracellular K→Hyperkalemia
- Cardiac arrhytmias→bradycardia, junctional scape beats (↑AV nodal block)
- GI→Nausea, abdominal pain, vomiting
- Neurologic→fatigue, confusion, weakness, color vision alteration

185

Mechanism of rate lowering effect of digoxin.

↑Parasympathetic tone→(-) AV nodal conduction
*Block Na/K ATPase pump:
- In vagal afferent fibers→sensitizes arterial baroreceptors, cardiac receptors→↑afferent input from CV system to brain
- ↑Efferent parasympathetic ganglionic transmission
- Potentiate end organ responde to Ach→↑vagal output

186

Mechanism of action and uses of Sirolimus

mTOR inhibitor
Binds FKBP (FK506 binding protein)
- Block T cell activation and B cell differentiation by preventing reponse to IL-2

187

What means an increased or decreased arteriovenous concentration gradient of a gas anesthetic?

Reflects the overall solubility of an anesthetic→rate of of induction
- High solubility→large amount of anesthetic is taken from arterial blood, low venous concentration►large AV gradient→slow onset of action
- Low solubility→less peripheral uptake►small AV gradient (blood saturation is rapid)→fast onset of action

188

Why do Fibrates can predispose the formation of cholesterol gallstones?

Inhibition of cholesterol 7 alpha hydroxylase→rate limiting step in synthesis of bile acids→↓cholesterol solubility

189

Side effects of Niacin

- Flushing, hyperglycemia, hepatotoxicity
- ↓Renal excretion of uric acid→↑risk for acute gouty arthritis

190

How do you distinguish side effects by amiodarone and digoxin if both cause vague symptoms, arrhythmias and color visions alterations?

Hyperkalemia is sign of digoxin toxicity (Na/K ATPase pump inhibition)

*Amiodarone doesn't cause hyperkalemia

191

What is the anti-PD1 therapy and its uses?

- Monoclonal antibody against PD1→block inhibition of T-lymphocyte by tumor cells►restore cytotoxic T cell response→promote apoptosis of tumor cells
- Melanoma, some types of lung cancer
+Nivolumab

*PD1 (programmed death receptor 1) of cytotoxic T-lymphocyte binds to PD1L (PD1 ligand) of tumor cells (↑ in tumor cells)►Inhibition of T-lymphocytes (similar to CTLA4)→evasion of immune system

192

Mechanism of tricyclic antidepressant overdose that can cause death

- Cardiac fast sodium channel inhibition (myocytes and His-Purkinje system)→arrhythmias
- Refractory hypotension→↓cardiac contractility and direct peripheral vasodilation (alpha-1 antagonist)

193

Mechanism of action of hydroxyurea to treat sickle cell disease

↑ Fetal Hemoglobin (HbF) (incompletely understood mechanism)→protection against polymerization of sickle cells

*Originally to treat neoplasia

194

Mechanism of Gardos channel blocker to treat sickle cell disease

Calcium-dependent (Gardos) potassium channel→efflux of K and H2O from RBC→block it to ↓efflux and avoid dehydration→↓polymerization of HbS

195

Treatment of tricyclic antidepressant overdose and when do you use it?

- Sodium bicarbonate:
*↑serum pH→non-ionized (neutral) form of drug→less accesible to bind Na channel
*↑Na→overcome the competitive, rapid Na channel blockade
- Widened QRS interval or ventricular arrhythmias

196

Which organisms based in their structure can be resistant to antibiotics that inhibit peptidoglycan cell wall synthesis? What antibiotics can be used to kill them?

- Mycoplasma, Ureaplasma urealyticum→lack peptidoglycan cell wall
- Anti-ribosomal agents (tetracycline, macrolides)

197

Mechanism of action of Ramelteon and its uses?

- Melatonin agonist→high affinity binding to melatonin receptors in suprachiasmatic nucleus
- Insomnia treatment in elderly patients (few side effects)

*Avoid benzo, antihistamines, sedating antidepressants in Tx insomnia in elderly

198

How can be induced apoptosis in malignant plasma cells of multiple myeloma?

Bortezomib (boronic acid containing dipeptide)→proteasome inhibitor►accumulation of toxic intracellular proteins, excess of proapoptotic proteins►Apoptosis

199

In which situation does Buprenorphine precipitate opioid withdrawal?

- Partial opioid agonist with low intrinsic activity (efficacy) for opioid mu receptors
- Binds with high affinity (potency)→prevent binding or displaces other opioids►opioid receptor antagonist in the presence of full opioid agonists

200

What is the coronary steal phenomenon and which drugs can cause it? Uses of it.

- Blood flow in ischemic areas is reduced due arteriolar dilation in nonischemic areas→hypoperfusion, worsening of existing ischemia
- Adenosin, Dipyridamole→selective vasodilators of coronary vessels►used in myocardial perfusion studies→detection of ischemic areas

201

What drug is used to avoid reccurent calcium oxalate urinary stones formation and which is its mechanism for it?

- Tiazide diuretics (ex, Hydrochlorotiazide)→↓urinary calcium excretion, ↑calcium absorption:
*Block Na/Cl cotransporter at DCT→↓Na absorption→(+) basolateral Na/Ca antiporter→out Ca, in Na►↑Ca luminal reabsorption
*Hypovolemia induced→↑Na and H2O absoprtion at PT!→passive ↑paracellular Ca reabsorption

**Indication→Hypercalciuria, Contraindicated→hypercalcemia

202

Use and mechanism of action of Fomepizole.

- Methanol or ethylene glycol poisoning
- Inhibits alcohol dehydrogenase→Ex, methanol poisoning►block methanol→Formaldehyde (toxic)

203

Which property must have a substance or drug to cross the placenta?

- Hydrophilic→Don't cross the placenta (Ex, conjugated bilirrubin, fractionated and no fractionated heparin)
- Lipophilic→Cross the placenta (Ex, unconjugated bilirrubin, warfarin)