class V- MISC

MOA:

   1) inhibition of Na/K ATPase--> Less Na/Ca exchange----> ^ Ca sER--> contractility,

   2)Indirect: inhibits Na/K-ATPase of neurons, depolarization of ANS  -->

    - PANS: lower HR, ^ diastolic filling--> ^SV

    - SANS: ventricles ^ contractility

PK: long t1/2, renal clearance, binds tissue protein*

* Amiodarone, Propafenone, Quinidine, Verapamil

Side effect: Early: N/V/D late: visual (orange halos), disoriented

Toxic: arrhythmias, ECG: inverted T, ST depression, premature ventricular beats give antibodies, electrolytes and Class IB)

 Electrolytes induce arrhythmias: low K, ^Ca(thiazide), low Mg (loops)

a-methyl-norepinephrine agoinst at presynaptic a2 in brainstem-->lowers SANS and lowers Bp by B1, a1 tone

1# for mild - moderate in PREGO

Adverse: positive Coombs test in 20% but not full blown hemolytic anemia 

agoinst at presynaptic a2 in brainstem-->lowers SANS and lowers Bp by B1, a1 tone

useful in bp and opiate w/d

AntiHTN

irreversibly blocks VMAT, which transports NE,DA,   5-HT from being transported to vesicles--> depletion of NTs--> low SANS, LONG ACTING

Side Effects: Major depression-like syndrome 

Anti-HTN

NE-transporter takes it up in vesicles so NE doesnt go in vesicles and its a fake

TCA block reuptake of guanethidine

doxazosin

terazosin

Prazosin

antagonist of peripheral a1 ( relax ss )

not used for HTN due to first dose syncope, used for BPH, modestly lowers LDL and ^ HDL

tamusolin is very specific for prostate, no affect on vessels

prodrug of NO

safe in prego for mod-severe HTN

Side Effects: SLE-like syndrome (in slow acetylators), tachycardia, fluid retention

mild HTN in prego= methyldopa

NO--> ^^ guanylate cyclase--> cGMP--> PKC--> posphatase takes of P of MLC--> inactive

All direct vasodilators, when given alone will cause tachycardia (B1 blocker) and edema (give diuretic)

NO prodrug also acts on veins

NO--> ^^ guanylate cyclase--> cGMP--> PKC--> posphatase takes of P of MLC--> inactive

IV for HTN emergency, slow infusion bc converted to cyanide (binds cytochrome C)

Antidote to cyanide poisoning: Sodium nitrite ( makes Heme's iron Fe2--> Fe3--> methemoglobin which CN loves)  then Sodium thiosulfate (cosubstrate that chealates CN)

Minoxidil

Diazoxide

Direct vasodilator, Diazoxide sole use in insulinomas

opens ATP/K channel--> ^ hyperpolarized-->->-> ^ phosphatase

Potent, used for refractory HTN  (HTN not responding to treatment like renal artery stenosis)

Side effect: Hypertrichosis, hyperglycemia (beta cells of pancreas also have ATP/K channels) 

Amiodipine, Isradipine etc

L type Ca channels in vascular smooth muscle, doesnt act on heart

Adverse:  Gingival Hyperplasia* except Isradipine, reflex tachy, lower edema

* Phenytoin, Ethosuximide, topiramate, valproate, cyclosporine

Verapamil, Diltiazem

Blocks cardiac Ca channels--> lower HR, contractility

HTN in patients with angina that cant tolerate B-blockers

Adverse: AV block, Heart failure, Constipation (verapamil)

--pril, Enalapril, captopril, etc

No angiotensin II --> lower afterload, efferent arteriolar dilation of kidney, lower aldosterone, ^ bradykinin (vasodilation, dry cough)

C/I : in bilateral renal artery stenosis, or if patient has 1 kidney. Prego

Side effects: Angioedema, hypotension, Hyperkalemia (lower filtration rate), NSAIDS potentiate renal dysfunction

--sartan, Losartan etc

No effect on bradykinin, also causes efferent arteriolar dilation

C/I : in bilateral renal artery stenosis, or if patient has 1 kidney. Prego

Side effects: hypotension, Hyperkalemia (lower filtration rate), NSAIDS  potentiate renal dysfunction

Inhibits enzyme renin

Adverse: hyperkalemia

Brain natriuretic peptide analog--> guanylate cyclase--> ^ cGMP--> vasodilation, natriuresis--> low preload

Use: Acute Decompensated CHF

Endothelin receptor antagonist

ETa and ETb receptors

Use: Pul HTN, Cor Pulmonale ---Prevents vasospams

Side effect due to vasodilation: hypotension, ^ HR, flushing, headache

Endothelin receptor antagonist

ETa receptor

Use: Pul HTN, Cor Pulmonale-- Prevents vasospams

Side effect due to vasodilation: hypotension, ^ HR, flushingm headache

Sildenafil

&

Tadalafil

Phosphodiesterases inhibitor type V --> ^ cGMP--> dilation

Pul HTN, Cor Pulmonale, erectile dysfunction

Not w/ nitrates (too much relax)

3 Prostacyclin analogs

(prostaglandins--> vasodilation)

Epoprostenol --- IV infusion

Iloprost, Treprostinil = inhalation

Gs--> cAMP--> PKA-- phosphatase--> MLC un-P

Pul HTN, Cor Pulmonale

Oral guanylate cyclase Activator

C/I: nitrates, PDE type V inhibitors

vasodilation

Pul HTN, Cor Pulmonale

ACE inhibitors

ARBs

a, B blocker

Diuretics

Isosorbide mono/di- nitrate  (long)

Nitroglycerin  (short except patch)

Nitrate--> NO--> guanylate cyclase--> cGMP--> MLCP--> large vein dilation, arteriolar dilation, dilation of coronary arteries (minor)

Tachyphylaxis so drug free when sleeping

PDE5 inhibitors

Reduce MI, mortality and stroke risks

MOA: competative HMG-CoA reductase inhibitor   causing ^ LDL hepatic receptors, lowers VLDL synthesis (cholesterol + triglyceride)

Adverse: Hepatotoxicity  (If AST 3X normal), rhabdomyolysis (no farnesyl pyrophosphate= no coenzyme Q)

D-D: Inhibitors of P450,grapefruit  red yeast rice (acts like statins)

Gemfibrozil

&

Fenofibrate

PPAR-a agonists

Induce lipoprotein lipase--> lowers VLDL

lowers TGL (since VLDL is high in TGL) , ^ HDL

hypertriglyceremia  

Adverse: Cholethiasis (more FA in bile), Hepatitis, Myositis (lower clearance of statins )

Colesevelam

(name 2 more in class?)

Bile acid sequestrants (cholesterol)

Cholestyramine, Colestipol

hepatic LDL receptor ^, clears LDL from plasma

some ^ HDL ....

^ VLDL synthesis so dont give to peeps with ^ TGL

Adverse due to fat malabsorption: G.I distress, Vit DAKE,

MOA: lowers production of VLDL, hence LDL

(probably inhibits hormone sensitive lipase)--> less release of fat b/t meals so liver maintains more fat and doest make VLDL --> ^ HDL ( no longer has to transfer cholesterol to IDL remnents

Adverse: flushing, pruritus from mast cells give aspirin before

MOA: blocks cholesterol at brush border

lowers LDL good w/ statin

doesnt impair absorption of TGL,fat vitamins

Antisense oligonucleotide against ApoB-100 mRNA

homozygous familial hypercholesterotemia

irreversible acetylation of COX-1--> less TXA2--> no platelet activation

Adverse: GI distress, bleeding

Cloidogrel

(can you name others)

Ticlopidine, Prasugrel, Ticagretor

Inhibits P2Y-12 receptor so ADP can not bind (normally: ADP--> lowers cAMP--> platelet activation)

Abciximab

(2 others)

Eptifibatide, Tirofiban

Inhibits IIb/IIIa (binds fibrinogen)

Adverse: bleeding

Dipyridamole

(one more?)

Selective vasodilators of cardiac vessels also

Cilostazol, adenosine (steal from hypoxic areas)

Inhibits cAMP/cGMP phosphodiesterase inhibitors--> ^ cAMP (no aggregation) and ^cAMP or cGMP = vasodilation

Diapyridamole: alternative to treadmill for cardiac stress test.

large, water soluble

IV, SubQ, multi-organ elimination, T1/2: 2 hrs

ok for prego

MOA: catalyzes antithrombin III binding to IIa, IXa, Xa, XIa, XIIa----moniter PTT

Antagonist: Protamine sulfate

Use: in hospital

adverse: HIT (antibody to heparin + platelet factor 4)* , bleeding, osteoporosis, hypersensitivity

* give: argatroban, lepirudin = direct thrombin inhibitor

small, lipid soluble-- Heparin first

Oral, 98% bound to protein (sulfonamides displace) , liver metabolism, T1/2: 30 hrs, not in prego.. PT monitoring

MOA: inhibits vit K epoxide reductase--> no y-COOH--> no II,VII,IX,X, protein C (V,VIII)/S

Outpatient

antidote: Vit K (slow), fresh frozen plasma (fast)

Adverse: Skin necrosis ( if low C, since its supressed 1st), teratogenic

Lower efficary (low PT): lipid malabsorption ( cholestyramine, colestipol, colesevelam), Antacids, green leafy vegs ( ^ K, competes),inducers

^ efficacy: inhibitors, synergistic (aspirin, heparin, 3rd gen cephalosporins)

Dalteparin

(one more?)

Low molecular weight heparins

Enoxaparin

Increased activity against Xa (not PTT but moniter Xa)

low molecular weight heparin

selective antithrombin III mediated Xa inhibition

Alteplase

(one more?)

Streptokinase

activates plasminogen to plasmin

E- aminocaproic acid

 (1?)

Antifibrinolytics

tranexamic acid

inhibits competatively plasminogen activation

Dronabinol

(Neuronal) CB1> CB2 (PNS)

Antiemetic (low 5-HT3 stimulation), anorexia or cachexia ( low leptin)  

Penicillins

Additives?

MOA: Binds PBP aka transpeptidase--> prevents transpeptidation, inhibits cross linking  (all B-lactams)

PK: unmetabolized through kidney

(ex: Nafcillin, Oxacillin, dicloxacillin = bile)

Resistance: B-lactamases, methicillin resistance = weak PBP binding.

Adverse: hypersensitivity, pseudomembranous colitis (ampicillin)

Additives: clavulanic acid, sulbactam, tazobactam & probenecid

Methicillin

(3 others, NOD)

B-lactamase resistant penicillins, only anti-staph not used bc interstitial nephritis,(Typer III) used to see if it works, because if its resistant than its due to PBP shape change

Nafcillin

Oxacillin

Dicloxacillin

MRSA: vancomycin--> linezolid or quinupristin/ dalfopristin

Aminopenicillins: B-lactamase Sensitive, Broad

IV

G+, G-

Used for suspected  L. meningitis

Nonallergic rash (mono)

Combo w:

    - Aminoglycosides: (synergy, lower resistance especially endocarditis)

    - sulbactam

Aminopenicillins: B-lactamase Sensitive, Broad

G+, G-

oral

ottis media, CAP, sinusitis, GI,GU

Combo w:

    - Aminoglycosides: synergy, lower resistance especially gentamicin for (enterococcal) endocarditis

    - Clavulanic acid- suicide inhibitors, not antibiotics combo  for prophylaxis in dog, cat, human bites

Carbenicillin

Ticarcillin

Piperacillin

Azlocillin

B-lactamase sensitive, Extended spectrum

Anti-pseudomonal

IV 

Cefazolin

Cephalexin

(if it has ph its a 1st generation)

First gen cephalosporins

MOA & resistance : same as penicillin

excreted unchanged in kidney (bile excretion: nafcillin, oxacillin)

G+ cocci, E. coli, K. pneumoniae, Proteus mirabilis

Cefazolin used for surgical prophylaxis

Adverse: Hypersensitivity (give macrolides or aztreonam for G- rods only)

Cefuroxime

Cefotetan, Cefoxitin

Not that important, not used often

2nd gen cephalosporins

MOA & resistance : same as penicillin

excreted unchanged in kidney

more G- than G+

Active against Beta lactamse producing  H. influenza, K. pneumoniae, penicillin resistant streptococci

  Cefamandole, cefotetan only = Disulfiram-like & less Factor II

Disulfiram: any drug that has the word azole (here is exception)

Cefixime, Cepodoxime, Cefotaxime

Ceftazidime, Ceftriaxone, Ceftizoxime

( it T after F, its 3rd gen)

3rd gen cephalosporins

MOA & resistance : same as penicillin

excreted unchanged in kidney, ceftriaxone= bile

not for LAME: Listeria, Atypical, MRSA, Enterococci

( give: ampicillin, macrolide, Vancomycin, Ampicillin + aminoglycogin or vancomycin respectively)

empirical mgmt of  meningitis and sepsis

4th gen cephalosporins, resistant to most B-lactamses

MOA & resistance : same as penicillin

excreted unchanged in kidney

Adverse: FOR ALL cephalosporins,  Hypersensitivity give  macrolides(G-/G+) or aztreonam for G- rods only

Imipenem/Cilastatin

Meropenem, Doripenem, Ertapenem

Carbapenems: most potent lactam antibiotic, resistant to beta lactamases

Cilastatin: inhibits renal enzyme dehydropeptidase  that converts Imipenem to toxic: seizures.... others dont need it

Severe nosocomial infections

Monobactam

( no cross allergy w/ cepha, penicillin)

MOA: same as penicillin

G- rods only, including pseudomonas

Telavancin

Vancomycin

Glycopeptide

MOA: binds D-ala-D-ala, no transglycosylation--> no elongation of peptide (NOT transpeptidation, cross linking)

IV or drink for difficile , renal clearance

 Telavancin also disrupts bac cell membrane

MRSA, Enterococci (D-ala-D-lactate = VRE)

(similar resistance VRSA)

Adverse: Ototoxicity, Nephrotoxicity, Red man--> histamine release w/ fast infusion--> rash on face, upper torso w/ drop in BP (type I, also give diphenhydramine)

Antibiotic, Lipopeptide

alternative to vancomycin= G+ cocci

MOA: inserts in plasma membrane--> disruption

IV, renal clearance

Adverse: allergic, rhabdomyolysis moniter CK

MOA: prevents de-P of  a lipid carrier* used to transport peptidoglycan building blocks

*isoprenyl pyrophosphate/bactoprenol

topical

G+ bac

Adverse: severe nephrotoxicity in IV

Gentamicin

Gent K.A.N.T.S

Aminoglycoside: Bactericidal

Streptomycin, Amikacin, Neomycin(topical) , Tobramycin, Kanamycin

Needs 02-dependent uptake,

Used:

 Ampicillin + gentamicin = E. faecalis, listeria

 Vancomycin* + Gentamicin = E. Faecium

 Antipseudo penicillin or 3rd cephalosporin or carbapenem + aminoglycoside

 TB & bubonic plague

MOA: binds 30S at P site, inhibits initiation complex and causes misreading

1 daily dosing to lower toxicity since bactericidal, conc dependent killing and time dep toxicity

Resistance: Transferases (conjugation), change porin channels(entry), change in rRNA (30S)

Adverse: ototoxicity, (ethycrinic acid)  Nephrototoxicity*, NMJ blockade at ^ doses, dermatitis for neomycin

Doxycycline

vs

Minocycline

Tetracycline, Demeclocycline

Passive diffusion so broad

ALL bac + protoza

Absorption is prevented by *(Ca, Mg, Fe2+, Al3+)- dairy, antiacids, supplements

Renal and bile clearance

MOA: 30S A site ( inhibits elongation)

Doxycycline more lipid soluble so DOC: Vibrio, Spirochete(rickettsia, borrelia) , Mycoplasma, Chlamydiae, Brucella (w/ rifampin)

Mino is very water soluble in tears, saliva= asymptomatic meningococcal carriers, Doxy is lipid and not cleared by renal

TCA resistance: pumps increasing efflux, change in ribosome binding site, inactivates enzyme

Adverse: ^^ clostridium, *bone and teeth(enamel hypolasia or permanent tooth discoloration,photosensitivity**, Demeclocycline (ADH receptor blocker used in SIADH, so never used as ATX)

** Quinolones, Sulfonamides  (rash due to sun)

 similar to Tetracycline

IV hospital setting ( ^ mortality)

 MOA: Binds 30S A site

renal, bile clearance

 MRSA, VRE,VISA not effective against pseudomonas, proteus

MOA: binds 50S, P site (initiation)

VRE, nosocomial pneumonia, skin infections

Adverse: Anemia, thrombocytopenia, neutropenia, weak MAO inhibitor so Serotonin syndrome with SSRI

bactericidal

Dalfopristin changes shape in A site-->^ quinupristin binding (elongation) 50S

VRE. faecium not E. faecalis

skin infection of s.aureus, S. pyogenes

inhibit 3A4

Adverse: infusion related (pain at IV, flu-like)

Azithromycin

(this one has long T1/2)

Macrolides

Clarithromycin, Erythromycin, Tellthromycin,     Ketolide: Telithromycin: CAP, effective in macrolide resistant strains, inhibits 3A4

hepatic,bile clearance,  inhibits 3A4 except Azithromycin and has long half life reason given for chylamydia over doxycycline

MOA:  binds 50S, translocation

Broad

DOC: C. diphtheriae, Legionella, Campylobacter

Macrolides resistance: CH3-- of 50s rRNA by methylases, efflux pumps  

Adverse: Stimulates motilin receptors ( less w/ Clarithro), QT prolongation, cholestasis w/ erythro

 MOA: Binds 50S, translocation

G+ cocci & anaerobes*

DOC: aspiration pneumonia*

good distribution: bone, skin, tendon good for osteomyelitis S.aureus (osteomyelitis with G- quinolones)

C. diffucile colitis

Chloramphenicol

Phen= lipid soluble (oral, brain, metabolize in liver probably blocks with P450s.

Broad spectrum antibiotic

Inhibitor of P450

MOA: binds 50S (Transpeptidase enzyme)

wide spectrum--- backup drug

hepatic clearance

Adverse: fatal blood dyscrasias, gray baby syndrome (cant conjugate, this drug nees glucuronidation)

Sulfonamides (usually given with DHF reductase inhibitors to--] dihydrofolate reductase, ONLY IN BAC)

DHFR: T,A,G

Broad spectrum(G+, G-,chlamydia),DOC: toxoplasmosis

Bacteriostatic

PK: High albumin binding, displaces bilirubin, liver metabolism

MOA: inhibits dihydropteroate synthase (PABA analogs)

Resistance is common: affinty for synthase, ^efflux, less influx, ^ PABA (Staph)

Adverse: Acute hemolysis in G6PD patients, Hypersensitivity: stevens johnson, photosensitivity

Trimethoprim

vs

Pyrimethamine

Dihydrofolate Reductase Inhibitors

given with sulfonamides for synergy

Trimethoprim is for prokaryotes other is for protozoa

May cause BM suppresion with folate deficient patients

Sulfonamides (usually given with DHF reductase inhibitors to--] dihydrofolate reductase)

Broad spectrum(G+, G-,chlamydia), Enterobac, community acquire MRSA

DOC: Haemophilus, Nocardia, P. jiroveci (prophylaxis)

Bacteriostatic

PK: High albumin binding, displaces bilirubin*, liver metabolism

MOA: inhibits dihydropteroate synthase (PABA analogs)

Resistance is common: affinty for synthase, ^efflux, less influx, ^ PABA (Staph)

Adverse: Acute hemolysis in G6PD patients, fetal kernicterus in neonates*,Hypersensitivity: stevens johnson, photosensitivity

Sulfonamides

Ulcerative colitis

Gut bac-->  Sulfapyridine (absorbed) + 5-aminosalicyclic acid (NSAIDs for gut)

Bacteriostatic

PK: High albumin binding, displaces bilirubin*, liver metabolism

MOA: inhibits dihydropteroate synthase (PABA analogs)

Resistance is common: affinty for synthase, ^efflux, less influx, ^ PABA (Staph)

Adverse: Acute hemolysis in G6PD patients, fetal kernicterus in neonates*,Hypersensitivity: stevens johnson, photosensitivity

Ciprofloxacin- seizures

Ofloxacin

Levofloxacin

Norfloxacin

Moxifloxicin

Gemifloxacin

Moxi, gemi more G+ then those underlined even cipro resistant S. pneumonia , G->G+

Quinolones

MOA: block topoisomerase II (G-), Topoisomerase IV G+,

Bactericidal

Resistance: change in topoisomerase, ^ efflux pump

Use: UTI and gastroenteritis alternative to TMP-SMX, DOC in shigella, Cipro= anthrax, Osteomyelitis, septic arthritis, skin infections of G- DM, ss

PK: renal clearance, multivalent cations lower absorption

Inhibits P450 1A2: ^ TCA, clozapine, theophylline

Adverse: tendonitis & rupture (C/I children, prego), photosensitivity ^QT: levo, gemi, moxi

Antiseptic

UTI's for E.coli, Enterococci

Prodrug, bac activate--> DNA damage

brown urine

Adverse: G6PD hemolysis

Rifamycin

Rifampin

(one question gives ask, which one for tb, answer is the one with most combination of drugs possible

Antiprotozoal DOC: Giardia, Trichomonas, Entamoeba

Antibacteria DOC: Bacteroides, C. difficile

Prodrug--> nitro radical kills anaerobes

Adverse: Metallic taste*( dysgeusia) , Disulfiram-like

SJS w/ menbendazole

 Basic Peptides (detergent) for G-

topical

topic

G+ cocci including MRSA

MOA: blocks isoleucyl-tRNA synthetase

MOA: Guanosine analog, first P by viral thymidine kinase--> chain termination, no 3'OH

Use: HSV1, HSV2, VZV, 

Resistance: Absence or less viral TK

Pk: goes to CSF,  Valacyclovir is prodrug

Adverse w/ IV: Nephro, neuro, thrombocytopenia w/ valacyclovir

Oral prodrug needs v-Tk activation,

 Guanosine analog

not a chain terminator, has 3'OH so competative

HSV1,2 VZV

guanosine analog prodrug needs viral phosphotransferase UL97* for 1st P, chain terminator (also can use v-TK)

Disseminated CMV, CMV retinitis Tx and prophylaxis (transplants)

* resistance

Pk: introcular implant, valganciclovir is prodrug (oral)

Adverse: BM suppression (dose limiting)-- give filgrastim

pyrophosphate analog

MOA: blocks v-DNA pol*, v-RNA pol

* resistance

IV

used for ganciclovir CMV or acyclovir resistant HSV, VZV

Adverse: Nephrotoxicity &  hypoCa2+, IV pentamidine ^ risk of hypo Ca ( arrhythmia, tetany, seizures)

fusion  Inhibitor

HIV-1

MOA: binds gp41

MOA: CCR5 antagonist so that gp41 can bind

 tropism testing wont work w/ CXCR4 or mixed

HIV-1

substrate 3A4 

Adverse: Upper Resp infection, hepatotoxicity

Elvitegravir

Raltegravir

MOA: inhibits integrase pol

HIV

metabolized by glucoranation* not P450

Adverse: myopathy, rhabdomyolysis** (check CK)

*blocked by atazanavir, indinavir

** statins (coQ), Daptomycin

Zidovudine

( + lamivudine given to healthcare pros)

Competitive Nucleoside reverse transcriptase inhibitor  (NRTIs), chain termination

Thymidine analog, activated by cellular kinases

Resistance is based on the analogs

HIV 1,2

Adverse mitochondria toxic (DNA pol-y):  lactic acidosis, hepatitis,pancreatitis, P. neuropathy,  BM suppression, myopathy

Competitive Nucleoside reverse transcriptase inhibitor  (NRTIs), chain termination

Thymidine analog, activated by cellular kinases

HIV 1,2

Adverse mitochondria toxic: P. neuropathy, Fat wasting, avoid didanosine ( additive neuropathy, fatal pancreatitis), avoid zidovudine (competes)

Competitive Nucleoside reverse transcriptase inhibitor  (NRTIs), chain termination

Cytosine analog, activated by cellular kinases

HIV 1,2, HBV

Adverse mitochondria toxic: not so toxic  hyperpigmentation of skin

Competitive Nucleoside reverse transcriptase inhibitor  (NRTIs), chain termination

Cytosine analog, activated by cellular kinases

HIV 1,2, HBV

Adverse mitochondria toxic: least toxic, avoid with emtricitabine (competes)

Competitive Nucleoside reverse transcriptase inhibitor  (NRTIs), chain termination

Adeanine analog, activated by cellular kinases

HIV 1,2

Adverse mitochondria toxic: P. neuropathy, pancreatitis (avoid stavudine)

Competitive Nucleoside reverse transcriptase inhibitor  (NRTIs), chain termination

Adeanine Nucleotide analog, but still prodrug activated by cellular kinases

HIV 1,2, HBV

blocks metabolism of didanosine ( ^ AUC)* , do not give together

Adverse mitochondria toxic: * pancreatitis, neuropathy

Competitive Nucleoside reverse transcriptase inhibitor  (NRTIs), chain termination

Guanosine analog, activated by cellular kinases

HIV 1,2

Adverse: Hypersensitivity: fever, ab pain, rash w/in 1st 6 wks (restarting on abacavir --> shock, death) screened with linked to HLA B5701

NNRTI

noncompetitive inhibitor of RT,not a prodrug

HIV-1

Metabolized by CYP450-3A4

Inducer of 3A4

Adverse: skin rash-stevens johnson, liver toxicty

NNRTI

noncompetitive inhibitor of RT

 Rilpivirine: less CNS symptoms

HIV-1

not a prodrug, Metabolized by CYP450-3A4

Inducer of 3A4

Adverse: skin rash, stevens johnson,

CNS: nightmares, psychosis, teratogen,

NNRTI

noncompetitive inhibitor of RT, not a prodrug

HIV-1

 Metabolized by CYP450- 3A4

Inhibitor of CYP450-3A4

Adverse: skin rash, stevens johnson

Atazanavir

Delavirdine^

competative HIV aspartyl protease inhibitor

PD: least insulin resistnace ( ^lipids, ^ glucose,cushing-like) (proinsulin)

PK: All are cleared by 3A4*, All induce 3A4*, inhibits glucuronidation--> hepatotoxicity--> ^ indirect bili (also indinavir, tipranavir)

 ^ inhibitor but not inducer

competative HIV aspartyl protease inhibitor

PD: insulin resistnace ( ^lipids, ^ glucose,cushing-like) (proinsulin)

PK: All are cleared by 3A4*, All induce3A4*, inhibits glucuronidation--> hepatotoxicity--> ^ indirect bili (also indinavir, tipranavir)

nephrotoxicity, nephrolithiasis

competative HIV aspartyl protease inhibitor

PD: insulin resistnace ( ^lipids, ^ glucose,cushing-like) (proinsulin)

PK: All induce 3A4*,

PK: hepatic clearance P450-2C19,

competative HIV aspartyl protease inhibitor

PD: insulin resistnace ( ^lipids, ^ glucose,cushing-like)-

PK: hepatic clearance P450-3A4, Strong inhibition 3A4 and 2D6

Rivastigmine, Donepezil- Alzheimer, Parkinson's dementia Edrophonium- Dx: MG, DDx: MG or crisis

Neostigmine: Tx: MG

Pyridostigmine: reverse competitive NMJ block: post GI, GU retention

Physostigmine: antiACh toxicity, cross BBB

Nerve gas: Tabun, sarin, soman

Organophosphates=(Malathion, parathion, diazinon,chlorpyrifos) give atropine, pralidoxime to save AChE

Atropine

( I,S,B,Toi,C,Tri,O,Tro)

Nn antagonist

(H,M,V)

Nm agonist

(S,S)

Isoniazid

(5 side effects) 

1st tb: Isoniazid, rifampin, pyrazinamide, ethambutol

2nd: streptomycin, cycloserine, quinolone

Bactericidal

Prodrug: activated by cat peroxidase (KatG) a heat sensitive catalase, inhibits mycolic acid synthesis

block enoyl- carrier protein reductase, B-ketoacyl-ACP synthase

Resistance: mutation in KatG gene

Adverse: hepatitis, P. neuropathy, seizures (give B6--> low GABA), SLE in slow acetylators, hemolysis in G6PD

MCC of iatrogenic sideroblastic anemia: B6 for 0-aminolevulinic acid synthase, chronic alcohol is MCC that is not aitrogenic

Bactericidal

Rifabutin: M. avium intracellular (w/ Macrolides, ethambutol)

TB, erradication of asymptomatic meningococcal carrier,H influenza meningitis, with vancomycin or B-lactams for staph endocarditis, osteomyelitits

blocks DNA dep RNA pol ( b-subunit of prokaryotic RNA polymerase), blocks transcription 

orange red color: all fluids

inducer of P450, hepatotoxicity

Anti-TB

prodrug, kills bac in lysosomes

Adverse: gout, hepatotoxicty

anti-TB

bacteriostatic

inhibits arbinosyltransferase (prevents arabinogalactan synthesis, cell wall)

Adverse: Optic neurits ( red, green blindness, blurry)

Capreomycin

Cycloserine

(rare on exam)

inhibits RNA synthesis -- nephro, ototoxicity

inhibits mycobac cell wall sinthesis by blocking peptide formation---seizures

TB treatment for:

prophylaxis

active tuberculosis

Prego

Isoniazid for 6 months

vs

4 drug regimen until sensitivity is known:

isoniazid*, rifampin*, pyrazinamide, ethambutol

then: * for nine months or ___ for 6 months

Prego: isoniazid, rifampin, ethambutol

sulfonamide

Leprosy, bites from brown recluse spider bite

dihydropteroate synthetase inhibitor, competes with para aminobenzoate (PABA)

fungus treatment

Histopaslmosis, Blastomycosis, coccidiodiosis- Itraconazole

 Aspergillosis: voriconazole

Candidiasis: Fluconazole

Zygomycosis ( mucor): control DM, posaconazole   

Pneumocystosis:  TMP-SMX

 Cryptococcosis: Amphotericin B + Fluconazole

Wide spectrum, very toxic

Binds ergosterol --> pores

resistance low ergosterol in membrane

IV no CNS, need intrathecal

Infusion related: fever, chills, hypotension--> due to histamine release ( NSAIDs, anti-H, corticoids)

 MOST Nephrotoxicity: chronic renal failure ( low EPO, renal tubular acidosis, normochromic normocytic anemia, glomerulus damage)

Ketoconazole (Imidazole)

Miconazole, clotrimazole

vs

Fluconazole (triazoles- less effec on human steroid synthesis)

itraconazole, voriconazole, posaconazole

Inhibit fungal CYP450 enzyme 14a-sterol demethylase* last step in ergosterol synthesis

* resistance: mutation in candida

oral, IV, fluconazole CSF

inhibitors of CYP450

Adverse: drug interactions, can lower androgen, cortisol

Activated by funcal cytosine deaminase to 5-fluorouracil --> blocks thymidylate synthase, disrupts DNA synthesis

BM suppression

block B-glucan synthase

IV

Oral, topical

superficial mycosis

inhibits fungal squalene epoxidase (first step in ergosterol synthesis

Superficial mycosis

oral

binds microtubules (mitosis) only goes to keratin ( hair, nails, skin)

Combination Therapy for HIV

Health care professional?

Prego?

Most common intial:  Tenofovir and emtricitabine +

raltegravir or

Efavirenz or

atazanavir w/ ritonavir boost

elvitegravir w/ cobicistat ( - 3A4 only) boost

Health care Pros: zidovudine + lamivudine for 1 month

Prego: Zidovudine throughout and to infant ( same effective if started at labor, no breast feeding)

Amantadine

Rimantadine

Inhibit uncoating of influenza A block M2 proton channel of virus  (pandemics)

Adverse: atropine like, livedo reticulars (DA, edema)

used in parkinsons (^ M, ^ DA)

Zanamivir- inhaled

Oseltamivir - oral

Inhibits Neuraminidases of influenza A and B

(analog of sialic acid compete with hemagglutinin binding)

Prophylaxis

HBV

therapy

^^^ALT/^AST ( alchol is opp)

Nucleoside/neculeotide analogs, interferon a

1st line:

pegylated interferon a

     activate JAK-STAT pathway, ^ MHCI, ^phosphodiesterase that cleave v-RNA

 BM suppression, neurotoxic, alopecia, thyrois dysfunction

Entecavir  :

     guanosine analog, HBV DNA pol

Tenofovir

Emtricitabine

IFN-a

ribavirin:

1)guanosine analog ( prodrug)

2) ribavirin mono-P blocks IMP dehydrogenase ( inosine mono-P--> xanthine mono-P (halts purines)

BM suppression

Boceprevir : protease inhibitor

Phenylephrine

(M,M,M)

A1 agonist others: mephentermine, metaraminol, midorine

decongestant, dialte pupil, ^blood pressure

Clonidine

(G,G,B,T)

Isoproterenol

D,A,F,S,T,M

B agonist

Isoproterenol: B1= B2

Dobutamine : B1

albuterol, formoterol, salmeterol: B2 others: terbutaline, metaproterenol(B2)

D1 agonists

vasodilation and ^ renal perfusion

nonselective alpha  blockers

Phentolamine is reversible

3rd generation B blockers

L,C

Mannitol

Chronic use of diuretic in general?

Osmotic diuretic

No ^ in Na excretion, most of its action at PCT

 Acute glaucoma, lower ICP, preserve urine vol, clear out toxins or rhabdomyolysis

Chronic: 2nd hyperaldosterone --> hypokalemia, metabolic alkalosis

Carbonic anhhydrase inhibitors

No: HCO3 + H --> CO2 + H2O

Excretion of HCO3, Na

renal tubular acidosis II

Use:

glaucoma (lowers aqueous humor production

Alkalinize urine to clear acidic drugs, uric acid, cysteine

Acute altitude sickness: Hyperventilation causes resp alkalosis, In brain and lungs hypoxic vasoconstriction causes edema... Drug causes acidosis, diuresis

Adverse: segments of kidney after PCT are hyper: Hyperchloremic metabolic acidosis, hypokalemia, P+ C + ^ pH urine = kidney stones, Sulfa allergy

Bumetanide, Torsemide, Furosemide

Ethcrynic= no sulfa allergy

All electrolytes are lost but distingished by: Ca, Mg excretion, Induces expression of cox-2--> ^ PGE2--> vasodilation

Uses: HTN, ^ Ca, ^ K, edema,  Anion overdose since they will follow Na, K, Ca, Mg

Adverse: ^ uric acid (all dieuritics are weak acids and compete for excretion), Ototoxicity ( Aminoglycosides, vancomycine, cisplatin)

Drug-Drug: NSAIDs, Digoxin

Hydrochlorothiazides,

Chloerthalidone, Metolazone

in DCT inhibits NaCl cotransport--> Intracellular Na goes down, In the back end the Na/Ca antiporter (Na in cell, Ca towards blood) is inhanced, Ca ^ in blood, less in urine

also opens K/ATP channesl in vessels, B cells --> less insulin

Use: 1st line HTN, renal stones, Nephrogenic diabetes insipidus ( causes the more distal segments to ^ Na absorption, ^ aldosterone, ^ H20 reabsorption) before the urine hits the vasopressin section)

Spironolactone, Eplerenone

vs

Amiloride, Triamterene

K sparing Diuretics

Amiloride, Triamterene

( late DCT)  Principal cells: block Na channels, less Na in = less K out

(collecting duct) Intercalated cells:  Higher + potential in lumen, H (acid) cant get out

Spironolactone, Eplerenone : only difference is  blocks aldosterone receptor in principal cell:  which ^ Na channels on lumen, Na-K/ATPase on back end... This prevent cardiac remodeling

UseL Adjunct to k wasting diuretic, Hyperaldosterone, Hypercortisolism, Li nephrogenic Diabetes insipidus use amiloride

Adverse: acidosis, ^ K, Spironolactone antagonist of androgen receptor