Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

Pharm > Test 3 > Flashcards

Test 3 Flashcards

1
Q

Proximal Convoluted Tubule

A

Highly permeable to H2O and reabsorbs 65% of NaCl

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Thin Descending Limb of Loop of Henle

A

Highly permeable to H2O but impermeable to NaCl and Urea (Concentrating Segment)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Thin Ascending Limb of the Loop of Henle

A

Passively reabsorbs NaCl but impermeable to H2O

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Thick Ascending Limb of the Loop of Henle

A

Actively reabsorbs most of the NaCl absorbed in loop, impermeable to H2O (diluting segment), and contains macula densa located between afferent and efferent arterioles.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Tubuloglomerular feedback

A

Signal sent from macula densa to afferent arteriole of same nephron causing vasoconstriction when amount of NaCL leaving the Loop is too high. Vasoconstriction –> decrease GFR

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Distal Convoluted Tubule

A

Actively transports NaCl but is impermeable to H2O (diluting segment)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Collecting Duct

A

Fine control of ultra filtrate composition, controlled by aldosterone (increased NaCl and H2O reabsorption) and ADH (increased H2O reabsorption)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Chloride Reabsorption

A

Generally follows Na, Symport with K+ in proximal tubule and thick ascending limb, Antiport with Na+/HCO3- in proximal tubule, and Cl- channels in thick ascending limb, DCT, and Collecting Duct

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Renal handling of Potassium

A

80-90% absorbed in proximal tubule via diffusion, paracellular pathways are used in thick ascending limb, DCT and Collecting duct K+ secretion by a conductive pathway.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Renal Handling of Calcium

A

70% reabsorbed by proximal tubule but passive diffusion through a paracellular route, 25% is absorbed by thick ascending limb, remaining 5% is reabsorbed in DCT by transcellular pathway.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Renal Handling of Inorganic Phosphate

A

Largely reabsorbed by proximal tubule (80%)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Renal Handling of Magnesium

A

Bulk reabsorbed in Thick ascending limb via paracellular pathway, 20-25% reabsorbed in proximal tubule, 5% is by DCT and collecting duct

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Relationship between sodium reabsorption and potassium secretion in the Collecting Duct

A

More Na+ reabsorbed = More potassium excreted, More sodium in collecting duct –> more compensation –> more K+ excretion (hypokalemia).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Targets of Diuretics

A

Diuretics target Na+ transporters and channels on the luminal side of tubules –> more Na+ excretion in urine (natriuresis) –> More H2O excretion in urine (Diuresis)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Prototype Carbonic Anhydrase Inhibitor

A

Acetazolamide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Site of action of Carbonic Anhydrase Inhibitors

A

Proximal Tubule

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Mechanism of Action of Carbonic Anhydrase Inhibitors

A

Competitive inhibitors of luminal and cytosolic carbonic anhydrase, Causes decreased reabsorption of HCO3-, decreased secretion of H+ –> decreased Na+ reabsorption.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Efficacy of Carbonic Anhydrase inhibitors

A

Modest because distal segments of nephron can compensate for increased Na+ concentration.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Renal hemodynamic effects of Carbonic Anhydrase inhibitors

A

-Because of increased Na+ concentration at macula densa, afferent vasoconstriction –> decreased GFR

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Adverse effects of Carbonic Anhydrase Inhibitors

A

-Hypokalemia (potassium wasting) due to compensation by Na+/K+ exchange in distal nephron -Urinary alkalization due to increased HCO3- excretion –> metabolic acidosis. -Renal stone formation b/c Ca2+ is insoluble at alkaline pH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Therapeutic Uses of Carbonic Anhydrase Inhibitors

A

-Rarely used as diuretic -Open-angle glaucoma -Altitude sickness -Epilepsy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Urinary Electrolyte changes due to Carbonic Anhydrase inhibitor (Acetazolamide)

A

-Increase pH due to increased HCO3- excretion -Increased Na+ excretion due to decreased H+/Na+ antiport action -Increased K+ excretion due to increased K+/Na+ antiport action caused by increased [Na+] in distal nephron

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Prototype Loop Diuretic

A

Furosemide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Loop Diuretic Site of Action

A

Thick ascending limb of Loop of Henle

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Loop Diuretic Mechanism of Action
Inhibits Na+ K+ 2 Cl- transporter, abolishes transepithelial potential gradient that drives paracellular Mg 2+ and Ca 2+ reabsorption leading to increased Mg and Ca excretion in urine
26
Loop Diuretic Effects on Tubuloglomerular Feeback
-Inhibit TGF because they inhibit salt transport in macula densa, so kidneys don't "see" excess Na+.
27
Renal Hemodynamic effects of Loop Diuretics
-Increase in RBF (prostaglandin mediated effect -Stimulates Renin release via SNS activation due to volume depletion -Increases venous capacitance and decreases left ventricular filling pressure
28
Pharmacokinetics of Loop Diuretics
-Highly protein bound (must use transporter) -Uses OAT 1 for apical deliverance (OAT 1 also used by NSAIDs) -Short elimination T1/2
29
Therapeutic Uses of Loop Diuretics
-Pulmonary edema -Congestive heart failure -Hypercalcemia
30
Adverse Effects of Loop Diuretics
-Hypo: Natremia, Kalemia, Calcemia -Ototoxicity -NSAIDs reduce diuretic efficacy -Hyperglycemia (use caution with sulfonylureas
31
Prototype Na+ Cl- Symport Inhibitor
Chlorothiazide and Chlorthalidone
32
Site of action of Na+ - Cl- symport inhibitors
Distal convoluted tubule
33
Mechanism of action of Na+ - Cl- Symport inhibitors
Inhibits Na+ - Cl- symporter, also weak carbonic anhydrase inhibitor, Efficacy is substantially reduced with low GFR.
34
Effects of Na+ - Cl- Symport inhibitors on Urinary electrolyte concentrations
-Decreases Ca 2+ due to development of transepithelial potential gradient -Increases Na+, K+, and Cl- excretion in urine. -Reduces ability of kidney to dilute urine during diuresis
35
Pharmacokinetics of Chlorothiazide (Na-Cl symport inhibitor)
-Longer half life than loop diuretics -Delivered to lumen by organic anion transporter
36
Therapeutic uses of Chlorothiazide
-1st line for mild to moderate hypertension -Mild Edema -Nephrogenic Diabetes insipidus (paradoxical effect decrease Plasma volume leads to decreased GFR which leads to increased proximal tubule absorption.
37
Adverse effects of Na+ - Cl- Symport inhibitors
Hypo: Kalemia, natremia Hyper: Glycemia, uricemia, and lipidemia ED NSAIDs reduce efficacy
38
Prototype Potassium Sparing Diuretics
-Triamterene and Amiloride (ENaC inhibitors) -Spironolactone and Eplerenone (Aldosterone Antagonists)
39
Mechanism of Action of Potassium Sparing Diuretics
-ENaC inhibitors: Block epithelial Na+ channels on the apical membranes of principal cells -Aldosterone Antagonists: Block cytosolic mineralocorticoid receptors to reduce expression of aldosterone induced proteins -Both types abolish transepithelial gradient that causes K+ and H+ secretion in to kidney lumen.
40
Therapeutic Uses
-Not for Diuretic Effect -Used with other K+ wasting diuretics to prevent hypokalemia -ENaC inhibitors used to treat Liddle Syndrome and Cystic fibrosis -Aldosterone Antagonists used for primary hyperaldosteronism, hepatic cirrhosis, and CHF
41
Adverse Effects
-Hyperkalemia (use with caution with ACE inhibitors and NSAIDs -Spironolactone: Affinity for steroid receptors (gynecomastia, impotence, hirsutism, decreased libido) -Eplerenone: Lower incidence of progesterone related effects due to high specificity
42
Maximum time after onset of flu symptoms to start chemotherapy
48 hrs
43
Prototype Adamantane
Amantadine
44
Amantadine Mechanism of Action
Blocks M2 ion channel in influenza A. Stops influx of proteins and interferes with viral uncoating.
45
Amantadine Resistance
Nearly 100% but may need to be used in future with evolution of influenza A
46
PK Amantadine
Orally available and well absorbed from GI tract. Eliminated by renal excretion.
47
Therapeutic uses of Amantadine
-Influenza A treatment when used with Neuraminidase inhibitors. -Parkinson's Disease
48
Adverse Reactions of Amantadine
-Contraindicated in Pregnancy -Drug interactions with Anti-cholinergics -CNS effects
49
Prototype Neuraminidase Inhibitor
Oseltamivir
50
Oseltamivir Structure & MOA
-Analog of Neuramic Acid -Competitive inhibitor of neuraminidase, interferes with replication and spread of Influenza A & B by preventing release from infected cells.
51
Oseltamivir PK & Resistance
-Orally available prodrug that is metabolized --\> active carboxylate in Liver and excreted as carboxylate from kidneys -Resistance is variable in seasonal flu, some resistance seen in H5N1.
52
Zanamivir
-Low oral bioavailability oral inhalation neuraminidase inhibitor. -SHOULDN'T be used in people with ASTHMA or COPD
53
Drugs used to treat CMV (Herpes Virus)
-Ganciclovir (Nucleoside analog) -Cidofovir (Nucleotide analog)
54
Drugs used to Treat HSV and VZV
Acyclovir and Valacyclovir
55
Prototype Nucleoside analog for HSV and VZV
Acyclovir
56
Acyclovir Structure and Spectrum
-Acyclic guanine nucleoside prodrug w/o 3'-OH -HSV \>\> VZV \>\>\>\> CMV
57
Acyclovir MOA
-Selectively --\> acyclo-GMP (Viral thymidine Kinases in cytoplasm of infected cells) -Host Cell Kinases acyclo-GMP --\> acyclo GTP -Acyclo-GTP --\> Nucleus where it is inserted in to Viral DNA by viral DNA polymerase and causes chain termination -Competitive inhibition of Viral DNA polymerase (100-fold greater affinity for viral DNA poly than Mammalian)
58
Acyclovir Resistance & Therapeutic Uses
-Resistance is by Viral TK deficiency, major concern in immunocompromised receiving prolonged therapy. -HSV (genitial, Herpetic gingivostomatitis, prophylaxis of mucocutaneous HSV in immunosuppressed patients, HSV encephalitis) -VZV (Varicella infections in children and adults, Elderly and immunocompromised with HZV)
59
Valacylovir
-L-Valyl ester prodrug that has 5-fold greater oral bioavailability -converted to acyclovir by liver in first pass hepatic metabolism
60
Adverse effects of Acyclovir
-neurotoxicity: tremor, myoclonus, seizures, and extrapyramidal signs -Reversible Renal Dysfunction: Crystalline nephropathy due to precipitation of drug
61
Prototype NucleoSIDE analog for CMV
Ganciclovir
62
Ganciclovir: Structure and MOA
-Acyclovir Analog but WITH 3'-OH -Converted to mono PO4 by VIRAL kinase (CMV UL97) -HOST cell Kinases --\> tri-PO4 -Inhibits Viral DNA polymerase but no chain termination because of 3'-OH -Selectivity of CMV is much less than acyclovir for HSV.
63
Ganciclovir PK
-Orally effective but low bioavailability. Valganciclovir has a much higher oral bioavailability.
64
Ganciclovir Therapeutic Uses & Adverse effects
-CMV Retinitis in immunocompromised patients -Prevention of CMV in transplant patients. -Myelosupression treated with G-CSF -CNS effects (Headache, fever, convulsions and behavior changes)
65
Prototype NucleoTIDE analogs for CMV
Cidofovir
66
Cidofovir Structure and MOA
-Cytidine nucleoTIDE analog -DOESN'T use Viral TK, converted to active di-PO4 by host cell kinases -Inhibits viral DNA polymerase
67
Cidofovir: PK
-Given IV -Prolonged T 1/2 -Renal glomerular filtration given with probenecid to block OAT-1
68
Cidofovir Therapeutic Use
-CMV retinitis in AIDS patients, alternative to ganciclovir and foscarnet
69
Cidofovir Adverse effects
-Nephrotoxicity (PCT dysfunction, major dose limiting toxicity, probenecid and saline reduce risk) -Neutropenia
70
Prototype Non-Nucleoside analogs for drug resistant HSV and CMV
Foscarnet
71
Foscarnet: Structure and Function
-Phosphorylated Analog of Formic Acid -BROAD SPECTRUM: ALL HERPES VIRUSES and HIV -Inhibits HSV DNA polymerase -Inhibits HIV RT -NOT phosphorylated by VIRAL or HOST kinases.
72
Foscarnet PK
-Given IV -Taken up slowly and not metabolized -80% unchanged excretion in Urine
73
Foscarnet: Therapeutic Uses
-CMV retinitis (including Ganiciclovir resistant) In AIDS patients -Acyclovir Resistant HSV and VZV infections
74
Foscarnet Adverse effects
-Nephrotoxicity -Pronounced Electrolyte disturbances (symptomatic hypocalcemia)
75
How is the efficacy of Antiviral treatment measured?
Sustained Viral Response (SVR): Absence of HCV RNA by PCR 24 weeks after stopping treatment.
76
Ribavirin: Structure and antiviral activity
-Purine Nucleoside analog prodrug -Broad spectrum activity against DNA and RNA viruses
77
Ribavirin: MOA and PK
-MOA: Converted to mono, di, and tri phosphates by HOST CELL KINASES, Inhibits IMP dehydrogenase --\> decreased GTP, Causes lethal mutation in RNA viruses -PK: Given Orally (HCV) or via Inhalation (RSV), LONG half life and High Vd, Hepatic metabolism and renal excretion
78
Ribavirin: Therapeutic Uses and Adverse RXNS
-Given orally in fixed does with IFN for chronic HCV, Given via inhaler for RSV -Hemolytic anemia and contraindicated in pregnancy.
79
Interferons: Antiviral spectrum and MOA
-Broad Spectrum -Bind receptors on host cells that activate JAK-STAT pathway that leads inhibits viral protein synthesis, maturation, and release, Stimulates host immune system by up regulating MHC I and II
80
Pegylated INF-alpha 2 A
-INF- alpha 2 a with a polyethylene glycol residue added to improve SVR and half life.
81
IFN therapeutic uses
-Chronic HCV and HBV, genital warts (administered directly on to lesions), Some cancers.
82
IFN Adverse effects
-Flu like symptoms that decrease with time. -Depression (black box) -Myelosuppression
83
Direct acting Antivirals for HCV
-Simeprevir: (Protease inhibitor) -Sofosbuvir: Nucleotide prodrug
84
Simeprevir: MOA and Resistance
-MOA inhibits HCV viral protease needed for viral maturation -Resistance is high if used alone
85
Simeprevir: PK and adverse reactions
-Orally once per day with Ribavirin/IFN -Contraindicated during pregnancy and CYP3A4 related drug interactions.
86
Sofosbuvir: MOA and efficacy
-Nucleotide prodrug that is converted to active triphosphate, inhibits viral RNA polymerase and chain terminator -Efficacy across all HCV genomes
87
Prototype Nucleoside reverse transcriptase inhibitor
Zidovudine (AZT)
88
Zidovudine: Structure and MOA
-Structure: Thymidine Analog (Prodrug) -MOA: Converted by host cell kinases to active triphosphate competes with endogenous TTP for RT binding site and causes chain termination
89
Zidovudine: Resistance and Combination drug
-Patients develop resistance if drug is used alone. Prolonged mono therapy also promotes cross resistance to other NRTIs -Combined with Lamivudine to decrease viral load and prevent development of resistance
90
Zidovudine: PK and Therapeutic Uses
-Orally available and widely distributed, Eliminated by hepatic glucuronidation -Used with Lamivudine for HIV infection, Prevention of HIV transmission Mother --\> Child, Prophylaxis in healthcare workers
91
Zidovudine: Adverse effects
-Lactic acidosis and hepatic steatosis
92
Lamuvidine
-Lower toxicity than Zidovudine and also used to treat HBV
93
Emtricitabine
Lamivudine analog with once a day dosing
94
Tenofovir
NucleoTIDE analog also treats HBV
95
Non-Nucleoside Reverse transcriptase Inhibitors
-Efavirenz
96
Efavirenz: Structure and MOA
Structure: Not related to endogenous nucleosides MOA: Allosteric inhibitor of HIV-1 RT, NO phosphorylation required, DOESN'T inhibit host cell polymerases
97
Efavirenz: Resistance and PK
-Resistance: Highly susceptible due to single AA mutations in RT, HIV-2 is intrinsically resistant -PK: Orally, Cleared by CYPs, Can be given in once daily dosage
98
Efavirenz: Therapeutic Uses and Adverse Effects
-Therapeutic Uses: HIV-1 infection used once daily in fixed dose with Tenofovir and Emtricitabine, EFFECTIVE FOR THOSE WHO HAVE FAILED PREVIOUS ANTIRETROVIRAL THERAPIES NOT CONTAINING NNRTI -CNS symptoms, Rash (can be life threatening), Teratogen
99
Nevirapine
-Same uses as efavirenz but boxed warning for liver toxicity
100
Prototype Protease Inhibitor
-Lopinavir and Ritonavir fixed dose combo
101
Lopinavir and Ritonavir: MOA and PK
-Competitive inhibition of HIV protease, prevents cleavage of gag and pol precursor poly proteins, Human proteases not inhibited -PK: Orally available and well absorbed, Ritonavir only boosts lopinavir activity by inhibiting CYP mediated clearance (CYP 3A4)
102
Lopinavir and Ritonavir: Adverse effects
-GI intolerance and lipodystrophy syndrome with long term use
103
Atazanavir
Protease inhibitor with same function and Lopinavir and Ritonavir, don't use with PPI
104
Prototype Fusion inhibitors
-Enfuvirtide
105
Enfuvirtide: Structure and MOA
-36 AA synthetic peptide mimic of GP-41 -MOA: Bind HIV GP-41 and prevents HIV envelope fusion with CD4
106
Enfuvirtide: PK and Therapeutic uses
PK: SC 2x/day Therapeutic Uses: Added to existing regimens when there is evidence of replication despite continued therapy
107
Enfuvirtide: Adverse effects
-Injection site reactions, elevated risk of bacterial pneumonia
108
Maraviroc:
-Block chemokine CCR-5 Co-receptor and prevents binding of Viral GP-120 (only RV to target host protein) -Used only in CCR-5 Tropic infections
109
Prototype Intergrase Inhibitor:
Raltegravir
110
Raltegravir: MOA and Therapeutic uses
-Inhibits HIV Integrase, human DNA doesn't undergo this process -HIV infections in HAART

Pharm (8 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions