Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
743 Cards in this Set
- Front
- Back
What's Epi/NE's location/effect on: vascular smooth mm.
|
alpha1/beta2
|
|
What's Epi/NE's location/effect on: Renal vasculature
|
D1 (vasodilation)
|
|
What's Epi/NE's location/effect on: heart
|
beta-1
|
|
What's Epi/NE's location/effect on: pulmonary bronchioles
|
beta2
|
|
What's Epi/NE's location/effect on: pre-synaptic neurons
|
alpha2
|
|
What's Epi/NE's location/effect on: pupillary sphincter
|
alpha1 - mydriasis
|
|
What's Epi/NE's location/effect on: kidney JGA
|
Beta1 - renin release and decreased BP
|
|
What's Epi/NE's location/effect on: Beta cells of pancreas
|
alpha2 - inhibits insulin release
|
|
What's Epi/NE's location/effect on: alpha cells of pancreas
|
increased glucagon release
|
|
What's Epi/NE's location/effect on: liver
|
beta2 - glycogenolysis + gluconeogenesis
|
|
Treatment for: alcohol withdrawal
|
benzos
|
|
Treatment for: anorexia/bulimia
|
SSRIs
|
|
Treatment for: anxiety
|
Benzos, buspirone, SSRIs
|
|
Treatment for:ADHD
|
methylphenidate (ritalin)Amphetamines (dexedrine)dextroamphetamine (adderall)
|
|
Methylphenidate uses
|
ADHD, major depressive disorder, especially in elderly (as it has quick effect), narcolepsy, daytime sleepiness
|
|
Treatment for: Atypical depression (mood reactivity, leaden fatigue, rejection sensitivity, reversed vegetative states of increased sleep+appetite)
|
MAOI SSRIs Both better than TCAs
|
|
Treatment for: Bipolar disorder
|
Mood stabilizers: Lithium Valproic acid, Carbamazepine, Lamotrigine (these three anticonvulsants) Atypical antipsychotics: olanzapine, aripiprazole
|
|
Treatment for: Depression
|
SSRIs, NSRIs, TCAs
|
|
Treatment for: Depression with insomnia
|
Mirtazapine (tetracycline), Trazodone, Nefazodone (SNRI)
|
|
Treatment for: OCD
|
SSRIs, Clomipramine
|
|
Treatment for: Panic Disorder
|
SSRIs, TCAs, Benzos, beta-blockers, desensitization, CBT
|
|
Treatment for: PTSD
|
SSRIs, psychotherapy
|
|
Treatment for: Schizophrenia
|
Antipsychotics
|
|
Treatment for: Tourette's Syndrome
|
Antipsychotics (haloperidol)
|
|
Withdrawal symptoms: Post-use crash, including depression, lethargy, headache, stomach cramps, hunger, hypersomnolence [suicidality, fatigue, malaise, severe psychological craving]
|
Amphetamines, [cocaine]
|
|
Intoxication symptoms: Psychomotor agitation, impaired judgment, pupillary dilation, tachycardia, hypertension, hallucinations
|
amphetamines - inc. prolonged wakefulness and attention, cardiac arrhythmias, delusions, fever Cocaine - hallucinations includng tactile, paranoid ideations, angina, sudden cardiac death
|
|
Intoxication symptoms: restlessnes, insomnia, arrhythmias
|
caffeine - also: diuresis, muscle twitching Nicotine - anxiety
|
|
Withdrawal symptoms: Headache, weight gain
|
Caffeine - also lethargy, depression Nicotine - Irritability, anxiety, craving
|
|
Intoxication Symptoms: respiratory depression, low safety margin
|
Barbs - greater respiratory depression, lower safety margin Benzos - lesser respiratory depression, greater safety margin. Also: amnesia, ataxia, somnolence, additive effects with alcohol
|
|
Intoxification Treatment: Barbs and Benzos
|
Barbs - symptom management (assist respiration, increase BP) Benzos - Flumazenil (too much can induce withdrawal symptoms)
|
|
Withdrawal symptoms: Anxiety, seizures, life-threatening
|
Barbs - also delirium, cardiovascular collapse Benzos - rebound anxiety, tremor, insomnia
|
|
Intoxication Symptoms: Pinpoint pupils, constipation, seizures, CNS depression, nausea, vomiting
|
Opioids - OD is life-threatening b/c of seizures, no tolerance to constipation/pupillary constriction Tx: naloxone, naltrexone
|
|
Withdrawal Sx: piloerection, rhinorrhea, yawning. Also: insomnia, anorexia, sweating, dilated pupils, fever, nausea, stomach cramps, diarrhea (flu-like symptoms)
|
Opioids
Tx: symptomatic, not life-threatening |
|
Intoxication Sx: serum gamma-glutamyltransferase is sensitive indicator of use
|
Alcohol - also emotional lability, slurred speech, disinhibition, ataxia, coma, blackouts. AST>ALT elevation
|
|
Withdrawal Sx: Life-threatening, tachycardia, hypertension, malaise, nausea, seizures, delirium tremens (DTs), tremulousness, agitation, hallucination (inc. tactile, like crawling bugs)
|
Alcohol
Tx: Benzos |
|
Intoxication Sx: belligerence, impulsiveness, homicidality, psychomotor agitation, vertical and horizontal nystagmus, tachycardia, ataxia, psychosis, delirium
|
PCP
|
|
Withdrawal Sx: depression, anxiety, irritability, restlessness, anergia, disturbances of thought and sleep, homicidality, vertical/horizontal nystagmus, tachycardia, ataxia
|
PCP
actually reintoxication from GI reabsorption |
|
Intoxication Sx: flashbacks, visual hallucinations, marked anxiety or depression, delusions, pupillary dilation
|
LSD - no other withdrawal Sx
|
|
Intoxication Sx - increased appetite, hallucinations, conjunctivitis, euphoria, anxiety, paranoid delusions
|
Marijuana - withdrawal - depression, irritability, insomnia, nausea, anorexia, most symptoms peak in 48 hours, last for 5-7 days, can be detected up to 1 month in urine.
|
|
Tx: Systemic Mycoses (histo, blasto, coccidio, paracoccidiodo, etc.), local and systemic
|
Local: fluconazole or ketoconazole
Systemic: Amphotericin B |
|
Tx: Tinea versicolor
|
topical miconazole, selenium sulfide
|
|
Tx: Tinea pedis, cruris, corporis, capitis, unguium
|
Topical azoles, except:
ungium/capitis: terbenafine or griseosulvin |
|
Tx: Candidiasis
|
nystatin (superficial), amphotericin B (serious systemic)
|
|
Tx: PCP
Start prophylaxis when? |
TMP-SMX, pentamidine, dapsone (if sulfa allergy).
Prophylaxis with TMP-SMX when CD4 <200 |
|
Tx: Sporothrix Schenckii
|
itraconazole or potassium iodide
|
|
Mechanism of terbinafine
|
antifungal
blocks ergosterol synthesis by blocking squalene epoxidase-catalyzed squalene --> Lanosterol step (Squalene --> Lanosterol --> Ergosterol) |
|
Mechanism of azoles
|
Antifungal
Block ergosterol synthesis from lanosterol (Squalene --> Lanosterol --> Ergosterol) |
|
Mechanism of Griseofulvin
|
Antifungal
Disrupts microtubules |
|
Mechanism of Flucytosine
|
Antifungal
Blocks precursors --> Pyrimidines (which are then converted to nucleic acids) |
|
Mechanism of Amphotericin B and Nystatin
|
Antifungals
Form pores in cell wall, disrupting membrane |
|
Amphotericin B clinical use
|
wide spectrum of systemic mycoses - crypto, histo, coccidio, aspergillus, blasto, candida, mucor
Given intrathecally (into CSF) for fungal meningitis (does not cross BBB) |
|
Clinical use: Nystatin
|
oral candidiasis (swish/swallow)
diaper rash/vaginal (topical) |
|
Clinical Use: -azoles
|
Crypto meningitis - fluconazole (also amphotericin B) because it can cross BBB
Candidiasis - Fluconazole Blasto, Coccidio, Histo, Candida - Ketoconazole Topical fungal infections - Clotrimazole, miconazole Hypercortisolism - especially ketoconazole |
|
Mechanism: Flucytosine
|
Antifungal
FLUcytosine --> 5-FLUorouracil Inhibits DNA synthesis |
|
Clinical use: Flucytosine (what is it used in combo with?)
|
systemic fungal infections (e.g. candida, crypto) IN COMBINATION with ampho B
|
|
Mechanism: Caspofungin
|
Antifungal
inhibits cell wall synthesis by inhibiting synthesis of beta-glycan |
|
Clinical Use: Caspofungin
|
Antifungal
cASPofungin = invasive ASPergillosis |
|
Clinical Use: Terbinafine
|
Antifungal
Used to treat dermatophytoses - oral (because nail [onychomycosis] or follicle [capitis]) |
|
Griseofulvin
|
Antifungal
Like terbinafine, taken orally to treat superficial infections of nail/follicle |
|
Clinical use: Nifurtimox
|
Trypanosoma cruzi (Chagas' disease)
|
|
Clinical use: Suramine, Pentamidine, Melarsoprol
|
Sleeping sickness
Blood-borne - SURamin + pentamidine CNS penetration - MELArsoprol 'It SURe is nice to get sleep. MELAtonin helps with sleep) |
|
Clinical use: sodium stibogluconate
|
Leishmaniasis
|
|
Name four malaria Rx combinations
|
1: Chloroquine + primaquine - prevents relapse of vivax/ovale. Also used as prophylaxis
2: sulfadoxine + pyrimethamine 3: mefloquine (alone) 4: quinine (not approved for restless leg syndrome) + doxycycline |
|
Monotherapy for Malaria
|
mefloquine
|
|
Primaquine
|
Malaria drugs
1: Chloroquine + primaquine - prevents relapse of vivax/ovale. Also used as prophylaxis 2: sulfadoxine + pyrimethamine 3: mefloquine (alone) 4: quinine (not approved for restless leg syndrome) + doxycycline |
|
Chloroquine
|
Malaria drugs
1: Chloroquine + primaquine - prevents relapse of vivax/ovale. Also used as prophylaxis 2: sulfadoxine + pyrimethamine 3: mefloquine (alone) 4: quinine (not approved for restless leg syndrome) + doxycycline |
|
Sulfadoxine
|
Malaria drugs
1: Chloroquine + primaquine - prevents relapse of vivax/ovale. Also used as prophylaxis 2: sulfadoxine + pyrimethamine 3: mefloquine (alone) 4: quinine (not approved for restless leg syndrome) + doxycycline |
|
Pyrimethamine
|
Toxoplasmosis
(and...) Malaria drugs 1: Chloroquine + primaquine - prevents relapse of vivax/ovale. Also used as prophylaxis 2: sulfadoxine + pyrimethamine 3: mefloquine (alone) 4: quinine (not approved for restless leg syndrome) + doxycycline |
|
Mefloquine
|
Malaria drugs
1: Chloroquine + primaquine - prevents relapse of vivax/ovale. Also used as prophylaxis 2: sulfadoxine + pyrimethamine 3: mefloquine (alone) 4: quinine (not approved for restless leg syndrome) + doxycycline |
|
Quinine
|
Malaria drugs
1: Chloroquine + primaquine - prevents relapse of vivax/ovale. Also used as prophylaxis 2: sulfadoxine + pyrimethamine 3: mefloquine (alone) 4: quinine (not approved for restless leg syndrome) + doxycycline |
|
Doxycycline
|
(also antimicrobial)
Malaria drugs 1: Chloroquine + primaquine - prevents relapse of vivax/ovale. Also used as prophylaxis 2: sulfadoxine + pyrimethamine 3: mefloquine (alone) 4: quinine (not approved for restless leg syndrome) + doxycycline |
|
Tx for Entamoeba histolytica
|
Metronidazole (GET GAP on the Metro) and iodoquinol
|
|
Iodoquinol
|
used with Metronidazole for amoebiasis
|
|
Tx: Enterobius vermicularis
|
Mebendazole (worms BEND)
Pyrantel pamoate |
|
Pyrantel pamoate
|
Helminths:
Enterobius vermicularis (pinworm), Ascaris lumbricoides (giant roundworm), Ancylostoma duodenale, Necator americanus (hookworms) |
|
Tx: Ascaris lumbricoides
|
Mebendazole (worms BEND)
Pyrantel pamoate |
|
Thiabendazole
|
Trichinella spiralis
Strongyloides stercoralis |
|
Tx: Ancylostoma duodenale
|
Mebendazole (worms BEND)
Pyrantel pamoate |
|
Tx: Necator americanus (hookworms)
|
Mebendazole (worms BEND)
Pyrantel pamoate |
|
Tx: Diphyllobothrium latum
|
Praziquantel
|
|
Tx: Echinococcus granulosus
|
Albendazole
|
|
Tx: Schistosomes
|
Praziquantel (as with all trematodes - flukes)
|
|
Tx: Clonorchis sinensis
|
Praziquantel (as with all trematodes - flukes)
|
|
Praziquantel
|
Helminths:
All Trematodes (Schistosomes, Clonorchis sinensis, Paragonimus westermani) And two Cestodes (Diphylllobothrium latum and intestinal worms/cysticercosis of Taenia solium) |
|
Tx: Pediculosis capitis/pediculosis pubis
|
lice - malathion, pyrethrin, permethrine
crabs - pyrimethamine, pyrethrin, malathion Lindane not first line because of neurotoxicity |
|
Tx: Roundworm
|
BEND drug
|
|
MAI prophylaxis
|
CD4 < 100 : azithromycin
CD4 < 75 : clarithromycin |
|
Tx (alternative): Leprosy
|
Rifampin
Clofazimine/Dapsone combination |
|
Tx (primary): Leprosy
|
Long-term dapsone
6 mos - 2 years Toxicity - hemolysis, methemoglobinemia |
|
Tx: Haemophilus influenzae meningitis
|
ceftriaxone
(same for GC meningitis) |
|
Tx: atypical pneumonias
|
Macrolides - azithro/erythromycin
|
|
Tx: Legionella pneumophila
|
erythromycin
|
|
Block cell wall synthesis by inhibition of peptidoglycan cross-linking
|
penicillin, ampicillin, ticarcillin, piperacillin, imipenem, aztreonam, cephalosporins
|
|
Block peptidoglycan synthesis
|
Bacitracin, vancomycin
|
|
Disrupt bacterial cell membranes
|
Polymyxins
|
|
Block nucleotide synthesis
|
Sulfonamides, TMP
|
|
Block DNA topoisomerases
|
Quinolones
|
|
Block mRNA synthesis
|
Rifampin
|
|
Block protein synthesis at 50S subunit
|
Chloramphenicol, macrolides, clindamycin, streptogramins (quinupristin, dalfopristin), linezolid
|
|
Blocks protein synthesis at 30S subunit
|
Aminoglycosides, tetracyclines
|
|
Bacteriostatic: ECSTaTiC
|
We're ECSTaTiC about bacteriostatics:
Erythromycin Clindamycin Sulfamethoxazole Trimethoprim Tetracyclines Chloramphenicol All involve nucleotide formation or protein synthesis |
|
Bacteriocidal:
Very Finely Proficient At Cell Murder |
Vancomycin, Fluoroquinolones, Penicillin, Aminoglycosides, Cephalosporins, Metronidazole
Aminoglycosides exceptional for being involved in protein synthesis |
|
Penicillin mechanism
|
Bind penicillin-binding proteins
Block transpeptidase cross-linking Activate autolytic enzymes |
|
Clinical use: Penicillin
|
Bactericidal for gram+ve cocci, rods, gram-ve rods (Neisseria), spirochetes. Not penicillinase resistant
|
|
Mechanism: Methicillin, nafcillin, dicloxacillin
|
penicillinase-resistant penicillins
Same mechanism as PCN Narrow spectrum Penicilinase resistant because of bulkier R group |
|
Clinical use: Penicillinase-resistant PCNs
|
Nafcillin, methicillin, dicloxacillin
S. aureus (except MRSA - resistant because of altered PCN-binding protein) Use naf for staph |
|
Mechanism - aminopenicillins
|
same as penicillin, wider spectrum, PCNase sensitive. Can combine with clavulinic acid to enhance spectrum
amOxicillin has greater Oral bioavailability than ampicillin (which is given IV) |
|
Clavulinic acid, sulbactam
|
block beta-lactamase in gram-ve periplasm (inside the outer cell membrane)
|
|
Clinical use: aminopenicillins
|
extended-spectrum PCN - certain gram+ve bacteria and gram-ve rods (Haemophilus, E. coli, Listeria, Proteus, Salmonella, enterococci)
'Amp/amox - HELPS kill enterococci and gram+ves' |
|
Mechanism: antipseudomonals
|
Same as PCN, extended spectrum
|
|
Clinical use: antipseudomonals
|
Pseudomonas spp. and gram-ve rods. Susceptible to penicillinase, use with clavulanic acid
|
|
Beta-lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases - bactericidal
|
Cephalosporins
|
|
Clinical use:
1st Generation Cephalosporins |
cefazolin, cephalexin
PEcK + gram+ve Proteus E. coli Klebsiella +gram+ves |
|
Clinical use:
2nd Generation Cephalosporins |
Cefoxitin, cefaclor, cefuroxime
HEN PEcKS + gram+ve Haemophilus Enterobacter aerogenes Neisseria spp. Proteus E. coli Klebsiella Serratia +gram+ves |
|
Clinical use:
3rd Generation Cephalosporins |
ceftriaxone, cefotaxime, ceftazidime
serious gram-ve infections resistant to other beta-lactams Meningitis (most penetrate BBB) e.g.s ceftazidime for Psuedomonas, ceftriaxone for gonorrhea |
|
Clinical use:
4th Generation Cephalosporins |
Cefepime
Increased activity against Pseudomonas and gram+ve organisms |
|
Cephalosporins through the generations
|
Increasing Gram-ve/decreasing gram+ve spectrum from 1-->3
4 reverses somewhat - increased activity against pseudomonas and gram+ve organisms |
|
Mechanism: Aztreonam
|
monobactam resistant to beta-lactamases, inhibits cell wall synthesis, binds PBP
Synergistic with aminoglycosides (starts with A like them, treats gram-ve rods like them) |
|
Clinical use: Aztreonam
|
Synergistic with Aminoglycosides. Like them, acts on severe gram-ve rods, not anaerobes or gram+ves. Ksp: Klebsiella, Serratia, Pseudomonas
For PCN-allergic pts and those with renal insufficiency who cannot tolerate aminoglycosides |
|
Mechanism: Imipenem/cilastatin, meropenem
|
imipenem - broad-spectrum, beta-lactamase-resistent carbapenem
Cilastatin - inhibitor of renal dihydropeptidase 1 to decrease inactivation in renal tubules. Meropenem similar but dihydropeptidase 1 resistant |
|
Clinical use: Imipenem/cilastatin, meropenem
|
gram+ve cocci, gram-ve rods, anaerobes. Drug of choice for enterobacter. General surgeon's best friend. Only used with life-threatening, refractive infections (b/c of side effects)
|
|
Mechanism: Vancomycin
|
Bactericidal by binding D-Ala D-Ala portion of cell wall precursors
|
|
Clinical use: Vancomycin
|
serious, gram+ve multi-drug resistant organisms, including S. aureus, C. dif, coag-ve endocarditis
|
|
Protein synthesis inhibitors
|
buy AT 30, CCELL at 50
30S Aminoglycosides (strepto, genta, tobramycin, amikacin [bactericidal]) 50S Chloramphenicol, Clindamycin (bacteriostatic) Erythromycin (bacteriostatic) Lincomycin (bacteriostatic) Linezolid (variable) |
|
Mechanism: Aminoglycosides
|
Gentamycin, Neomycin, Amikacin, Tobramycin, Streptomycin
Bactericidal (only protein synthesis inhibitor MEAN enough to kill) Inhibit formation of initiation complex (bind 30S) and cause misreading of mRNA. Require O2 for uptake |
|
Clinical use: Aminoglycosides
|
severe gram-ve rod (e.g. pseudomonas) infections, synergistic with beta-lactams, neomycin for bowel surgery.
Inactive against anaerobes - aminO2glycoside |
|
Mechanism: Tetracyclines
|
Bacteriostatic, bind 30S, prevent attachment of aminoacyl tRNA. Limited CNS penetration. GI absorption inhibited by divalent cations
|
|
Doxycycline
|
Tetracycline that is fecally eliminated (good for pts with renal failure).
|
|
Clinical use: Tetracyclines
|
VACUUM THe BedRoom
Vibrio, Acne, Chlamydia, Ureaplasma, Urealyticum, Mycoplasma pneumoniae, Tularemia, H. pylory, Borrelia burgdorferi, Rickettsia |
|
Mechanism: Macrolides
|
Protein synthesis inhibitors - bind 23S rRNA of 50S subunit, blocking translocation
Bacteriostatic |
|
Clinical Use: Macrolides
|
PUS
Pneumonia (atypical) URIs STDs (GC/Chlam) Gram+ve cocci (strep infections for pts with PCN allergies) Mycoplasma, Legionella, Chlamydia, Neisseria |
|
Clinical use: Erythromycin (alternate)
|
Increases GI motility - used in ileus
|
|
Mechanism: Chloramphenicol
|
Inhibits 50S peptidyltransferase activity.
Bacteriostatic. |
|
Mechanism: Linezolid
|
Binds 23S rRNA, interacts with bacterial protein synthesis initiation complex
Oral |
|
Mechanism: Binds 23S rRNA, blocks initiation complex
|
Linezolid
|
|
Mechanism: Inhibits 50S peptidyltransferase activity.
|
Chloramphenicol
|
|
Mechanism: bind 30S, prevent attachment of aminoacyl tRNA
|
Tetracyclines
|
|
Binds 23S rRNA on 50S subunit, blocks translocation
|
Macrolides, Clindamycin, Lincomycin
|
|
Binds 30S, blocking initiation, preventing mRNA reading
|
Aminoglycosides
|
|
Clinical use: Chloramphenicol
|
Meningitis - H. influenzae, N. meningitidis, S. pneumoniae. Conservative use b/c of toxicities
|
|
Clinical use: meningitis
|
Chloramphenicol
|
|
Mechanism: Clindamycin
|
Blocks peptide bond formation at 50S ribosomal subunit. Bacteriostatic
|
|
Clinical use: Clindamycin
|
anaerobes ABOVE diaphragm (vs. Metronidazole)
Narrow spectrum (imipenem would be broad-spectrum against anaerobes) Aspiration pneumonia is usually anaerobes, so clinda- good there too, and MRSA is very sensitive to it as well |
|
Clinical use: Anaerobes ABOVE diaphragm
|
Clindamycin
|
|
Clinical use: Anaerobes BELOW diaphragm
|
Metronidazole
|
|
Mechanism: Sulfonamides
|
PABA antimetabolites inhibit dihydropteroate synthetase (PABA + pteridine make dihydropteroate --> dihydrofolic acid --> THF --> --> DNA, RNA and Proteins)
|
|
Clinical use: Sulfonamides
|
gram+/-ves - nocardia, chlamydia
Triple sulfas or SMX for simple UTI |
|
Clinical use: TMP-SMX
|
Recurrent UTIs, Shigella, Salmonella, PCP, MRSA
|
|
Mechanism: Nitrofurantoin
|
bacteriocidal, reduced in urine by bacterial proteins, making it active
|
|
Clinical use: Nitrofurantoin
|
Cystitis, NOT pyelonephritis. Works on E. coli, Staph saprophyticus, NOT proteus
|
|
Mechanism: [Fluoro]quinolones
|
Inhibit DNA gyrase (topoisomerase II). Bactericidal. Must not be taken with antacids
|
|
Clinical use: [Fluoro]quinolones
|
Pneumonias, URIs
Gram-ve rods of UTI and GI infections (including Pseudomonas), Neisseria, some gram+ves |
|
Mechanism: Metronidazole
|
forms toxic metabolites in bacterial cell that damage DNA. Bactericidal, antiprotozoal
|
|
Clinical use: Metronidazole
|
GET GAP on the Metro!
Giardia Entamoeba Trichomonas Gardnerella Anaerobes (bacteroides, clostridium) below diaphragm h. Pylori (used in triple therapy) |
|
Triple therapy
|
1. bismuth, metronidazole and either tetracyclin or amoxicillin
2. (more costly) metronidazole, omeprazole, clarithromycin |
|
Mechanism: Polymyxin B and E
|
Myxins MIX up membranes
Bind to cell membranes of bacteria and disrupt osmotic properties. Cationic, basic proteins that act like detergents. |
|
Clinical use: Polymyxins
|
Resistant gram-ve infections, Pseudomonas on the skin
|
|
Antimycobacterial drugs
|
Rifampin, INH, Pyrazinamide, Ethambutol, Azithromycin, Streptomycin, Dapsone, Clofazimine
|
|
M. tuberculosis prophylaxis/Tx
|
Proph: INH
Tx: Rifampin, Isoniazid, Pyrazinamide, Ethambutol RIPE for Tx |
|
M. avium intracellulare prophylaxis/Tx
|
Proph:
CD4 under 100: Azithromycin Under 75 - Clarithromycin Tx: Azithromycin, Rifampin, Ethambutol, Streptomycin Go to war on MAI with ARES |
|
Tx: M. leprae
|
Dapsone, Rifampin, Clofazimine
|
|
Tx: Tb
|
1st: Streptomycin, Pyrazinamide, Isoniazid, Rifampin, Ethambutol (INH-SPIRE)
2nd - Cycloserine |
|
Tx: Pseudomonas
|
3rd Gen Ceph, Extended Spectrum PCNs (TCP), Aztreonam, Cefepime (4th gen Ceph), Aminoglycosides, quinolones, polymyxins
|
|
Mechanism: Isoniazid
|
decreased synthesis of mycolic acids
|
|
Clinical use: Isoniazid
|
M. tuberculosis - only agent used solo in prophylaxis against Tb and dormant Tb
|
|
Mechanism: Rifampin
|
Inhibits DNA-dependent RNA Polymerase, blocking formation of all three types of RNA
|
|
Rifampin characteristics - 4 Rs
|
RNA Polymerase inhibitor
Revs up microsomal P-450 Red/orange body fluids Rapid resistance if used alone |
|
Clinical use: Rifampin
|
Tb, delays dapsone resistance in leprosy Tx
Proph: meningococcal/H. influenzae type B Used with TMP-SMX or Clarithromycin for MRSA (never use alone) |
|
Resistance mechanism against:
PCN |
beta-lactamase cleavage of beta-lactam ring
Altered PBP in case of MRSA or PCN-resistant S. pneumoniae |
|
Resistance mechanism against:
Aminoglycosides |
Modification via acetylation, adenylation, phosphorylation
|
|
Resistance mechanism against:
Vancomycin |
Terminal D-ala of cell wall component replaced with D-lac, reducing affinity
|
|
Resistance mechanism against:
Chloramphenicol |
Modification via acetylation
|
|
Resistance mechanism against:
Macrolides |
Methylation of rRNA near erythromycin's ribosome-binding site
|
|
Resistance mechanism against:
Tetracycline |
decreased uptake, increased transport out of cell
|
|
Resistance mechanism against:
Sulfonamides |
Altered enzyme (bacterial dihydropteroate synthetase), decreased uptake or increased PABA synthesis
|
|
Resistance mechanism against:
Quinolones |
Altered gyrase, reduced uptake
|
|
Nonsurgical Antimicrobial prophylaxis:
Meningococcal Gonorrhea Syphilis Recurrent UTIs PCP Endocarditis with surgical/dental procedures |
Nonsurgical Antimicrobial prophylaxis:
Meningococcal - Rifampin (drug of choice), minocycline Gonorrhea - Ceftriaxone Syphilis - Benzathine PCN G Recurrent UTIs - TMP-SMX PCP - CD4 < 200 - TMP-SMX (Drug of choice - Dapsone if sulfa allergy), aerosolized pentamidine Endocarditis with surgical/dental procedures - PCNs. Ampicillin. 1st generation Cephs |
|
Tx: VRE
|
linezolid and streptogramins (quinupristin/dalfopristin)
|
|
Tx: HSV-1/2, EBV, VZV
|
acyclovir, valacyclovir, famcyclovir
|
|
Clinical use: Acyclovir
|
HSV-1/2, VZV, EBV
Old, cheap, 5x/day dosing |
|
Clinical use: Famcyclovir
|
HSV-1/2, VZV, EBV
Newer than Acyclovir, expensive, less frequent dosing, better compliance. |
|
Clinical use: Valacyclovir
|
HSV-1/2, VZV, EBV
Newer than Acyclovir, expensive, less frequent dosing, better compliance. |
|
Clinical use: Ganciclovir
|
CMV, especially in IC patients. Greater activity than acyclovir for CMV DNA polymerase
|
|
Mechanism: Acyclovir, Valacyclovir, Famcyclovir
|
DNA nucleotide analog
monophosphorylated (activated) by HSV/VZV thymidine kinase. Guanosine analog. Triphosphate formed by cellular enzymes. Preferentially inhibits viral DNA polymerase by chain termination |
|
Mechanism of resistance: Acyclovir, Valacyclovir, Famcyclovir
|
Lack of thymidine kinase
|
|
Mechanism: Ganciclovir
|
Nucleotide analog
5'-monophosphate formed by CMV viral kinase or HSV/VZV thymidine kinase. Guanosine analog. Triphosphate formed by cellular kinases. Preferentially inhibits viral DNA polymerase |
|
Mechanism of resistance: Ganciclovir
|
Mutated CMV DNA polymerase or lack of viral kinase
|
|
Clinical use: Foscarnet
|
CMV retinitis in IC patients WHEN ganciclovir fails. Acyclovir-resistant HSV. reverse transcriptase inhibitor in HIV
|
|
Mechanism: Foscarnet
|
Viral DNA-polymerase inhibitor that binds to the pyrophosphate-binding site of the enzyme. Does not require activation by viral kinase
FOScarnet = pyroFOSphate analog |
|
Mechanism of resistance: Foscarnet
|
Mutated DNA polymerase
|
|
Tx: HCV
|
Interferon-alpha + ribavirin
|
|
Clinical uses: Amantadine, Rimantidine
|
Flu (no longer used because 90% of influenza A strains resistant)
Parkinson's |
|
Mechanism: Amantadine, Rimantidine
|
blocks viral penetration/uncoating (M2 protein), buffers pH of endosome
Causes release of Dopamine from intact nerve terminals. Rimantidine is a derivative with fewer CNS side effects, does not cross BBB |
|
Mechanism of resistance: Amantadine, Rimantidine
|
Mutated M2 protein
|
|
Mechanism: Zanamivir, oseltamivir
|
Inhibit influenza neuraminidase, deceasing release of progeny virus
|
|
Clinical use: Zanamivir, oseltamivir
|
Influenza A/B, Avian flu
|
|
Mechanism: Ribavirin
|
Inhibits synthesis of guanine nucleotides by competitively inhibiting IMP dehydrogenase
|
|
Clinical Use: Ribavirin
|
HepC when used with IFN-alpha
|
|
HIV Prophylaxis
|
ZDV + 3TC
|
|
HAART
|
highly active antiretroviral therapy - protease inhibitor and RTIs. Initiated when CD4 < 500 or high viral load.
|
|
Mechanism: Protease inhibitors
|
inhibit maturation of new virus by blocking protease in progeny virions - inhibit assembly
|
|
Mechanism: RTIs
|
preferentially inhibit RT of HIV, prevent incorporation of DNA copy of viral genome into host DNA
|
|
Mechanism: Fusion inhibitor
|
bind viral gp41 subunit, inhibit conformational change required for fusion with CD4 cells, blocking entry and subsequent replications
|
|
Clinical use: Fusion inhibitor
|
in pts. with persistent viral replication in spite of RTI Tx, used in combination
|
|
Mechanism: Interferons
|
glycoproteins from human leukocytes that block various stages of viral RNA and DNA synthesis. Induce ribonuclease that degrades viral mRNA
|
|
Clinical use: Interferons
|
IFN-alpha - chronic HBV/HCV, Kaposi's
IFN-Beta - MS IFN-gamma - NADPH oxidase deficiency |
|
ABs safe in pregnancy for UTIs
|
nitrofurantoin, aminopenicillins, 1st generation Cephs
vs. Children - TMP-SMX Adults - fluoroquinolones |
|
Mechanism: Hydroxyurea
|
Inhibits Ribonucleotide Reductase (UDP → dUDP, which then goes on to form dUMP and then dTMP)
Works in S-phase |
|
Mechanism: 6-MP
|
Blocks de novo purine synthesis
|
|
Mechanism: Methotrexate (MTX)
|
Inhibits dihydrofolate reductase (DHFR)
Decreases dTMP levels. |
|
Drugs that act on MTs
|
Mebendazole/thiabendazole
Griseofulvin Vincristine/vinblastine (block polymerization) Paclitaxel (hyperstabilizes MTs, preventing disassembly Colchicine (anti-gout. Inhibits Macrophage movements/chemotaxis) |
|
Effect of glucocorticoids on collagen synthesis
|
Inhibitory. E.g. inject steroids into keloids to decrease abnormally increased production there
|
|
Clinical use: N-acetylcysteine
|
Inhaled in CF and ventilator pts to loosen mucous plugs (mucolytic - cleaves disulfide bonds within mucous glycoproteins). Prophylaxis to prevent contrast induced nephropathy (give 24 hrs prior and after dye). Antidote to acetaminophen hepatotoxicity induced by intermediate metabolite NAPQI
|
|
Mechanism: Fomepizole
|
inhibits alcohol dehydrogenase (converts ethanol to acetaldehyde and produces NADH)
vs. Disulfiram, which blocks next step, conversion of acetaldehyde → acetate (also producing NADH) |
|
Clinical Use: Benzoate
|
Tx of Ornithine transcarbamoylase (OTC) deficiency
|
|
Tx: OTC deficiency
|
Benzoate
|
|
Tx: PKU
|
Replace THB (since PKU pts lack THB cofactor for phenylalanine hydroxylase)
|
|
Tx: Cystinuria
|
Acetazolamide to alkalinize urine, increasing cystine solubility
|
|
Tx: Orotic aciduria
|
Oral uridine administration
|
|
Tx: Abetalipoproteinemia
|
Vitamin E – helps restore lipoproteins
|
|
Tx: Paroxysmal Nocturnal Hemoglobinuria (PNH)
|
Fe supplementation, warfarin, BM transplant
|
|
Tx: Chronic granulomatous disease
|
Susceptibility to S. aureus, E. coli, Aspergillus, Candida, Klebsiella. Treat with propylactic TMP-SMX, IFN-gamma
|
|
Mechanism: Cyclosporine
|
Immunosuppressant
Binds cyclophilins, complex blocking differentiation/activation of T cells by inhibiting calcineurin, preventing production of IL-2 and its receptor. |
|
Mechanism: Tacrolimus (FK506)
|
Immunosuppressant
Similar mechanism to cyclosporine. Binds FK-binding protein, then binding calcineurin, inhibiting secretion of IL-2 and other cytokines |
|
Clinical use: Cyclosporine
|
Transplantation, some autoimmune disorders
|
|
Clinical use: Tacrolimus (FK506)
|
Immunosuppressant
Organ transplants. Topical (called protopic) for eczema |
|
Clinical use: Pimecrolimus
|
Immunosuppressant
Used topically for eczema, as with Tacrolimus |
|
Clinical use: Muromonab-CD3 (OKT3)
|
Immunosuppressant after kidney transplantation
|
|
Mechanism: Muromonab-CD3 (OKT3)
|
Immunosuppressant
mAb that binds CD3 on T cell surface, blocking IL-2 production and T-cell signaling. |
|
Mechanism: Sirolimus (rapamycin)
|
Immunosuppressant
Binds FK binding protein which inhibits mTOR, inhibiting T cell proliferation in response to IL-2 |
|
Mechanism: Mycophenolate mofetil
|
Inhibits de novo guanine synthesis and blocks lymphocyte production. Blocks IMP dehydrogenase
|
|
Clinical use: Mycophenolate mofetil
|
Used for lupus nephritis, kidney/heart/liver transplants
|
|
Mechanism: Daclizumab
|
mAb with high affinity for IL-2 receptor on activated T cells
|
|
Mechanism: Thalidomide
|
Anti-angiogenic, affects TNF-alpha primarily
Contraindicated in pregnancy |
|
Clinical use: Aldesleukin
|
IL-2
Renal cell carcinoma, metastatic melanoma |
|
Clinical use: EPO
|
Anemias, especially in renal failure and chemo
|
|
Clinical use: Filgrastim
|
filGRAstim – GRAnulocyte colony stimulating factor. Used to recover BM
|
|
Clinical use: Sargramostim
|
sarGRAmostim – GRAnulocyte-macrophage colony stimulating factor, like IL-3
Used to recover BM |
|
Clinical use: alpha-IFN
|
HBV, HCV, Kaposi’s sarcoma, leukemias, malignant melanoma
|
|
Clinical use: beta-IFN
|
Multiple sclerosis
|
|
Clinical use: gamma-IFN
|
Chronic granulomatous disease
|
|
Clinical use: Oprelvekin
|
IL-11
Thrombocytopenia |
|
Clinical use: thrombopoietin
|
Thrombocytopenia
|
|
Tx: Actinic keratosis
|
Can freeze off with 5-FU
|
|
Volume of distribution Vd
|
Amount given IV / plasma [drug]
|
|
Clearance of drug
|
C = 0.7 x Vd / t1/2
|
|
Loading dose
|
LD = CSS x Vd
|
|
Maintenance dose
|
MD = CSS x Cl
|
|
Half time
|
t1/2 0.7 x Vd / Cl
|
|
Elimination of weak acid drugs
|
e.g. Phenobarbital, MTX, TCAs, aspirin. Trapped in basic environments. Treat OD with bicarbonate
|
|
Elimination of weak base drugs
|
e.g. amphetamines
Trapped in acidic environments. Treat OD with ammonium chloride |
|
Phase I metabolism of drugs
|
Reduction, oxidation, hydrolysis, yielding slightly polar, water-soluble metabolites, often still active. CYP450 catalyzed. Lost first in geriatric pts
|
|
Phase II metabolism of drugs
|
Acetylation, glucuronidation, sulfation, yielding very polar, inactive metabolites, renally excreted
|
|
Therapeutic index
|
= LD50/ED50
|
|
G-Protein linked 2nd messengers – G protein classes
|
Qiss qiq siq sqs
|
|
G-Protein linked 2nd messengers – Sympathetic - qiss
|
Alpha1 – Gq – increased vascular sm mm. contraction, increased pupillary dilator muscle contraction (mydriasis)
Alpha2 – Gi – decreased sympathetic outflow, decreased insulin release, decreased BP Beta1 – Gs – increased heart rate, increased contractility, increased renin release, increased lipolysis Beta2 – Gs – vasodilation, bronchodilation, increased heart rate, contractility, lipolysis, glucagon release. Decreased uterine tone. |
|
G-protein linked 2nd messengers – Parasympathetic – qiq
|
M1 – Gq – CNS, enteric nervous system
M2 – Gi – decreased heart rate and contractility of atria M3 – Gq – increased exocrine gland secretions, gut peristalsis, bladder contraction, bronchoconstriction, pupillary sphincter muscle contraction (miosis), ciliary muscle contraction (accommodation) |
|
G-protein linked 2nd messengers – Dopamine, Histamine, Vasopressin – si-q, s-qs
|
D1 – Gs – relaxes renal vascular sm mm.
D2 – Gi – modulates transmitter release, especially in brain H1 – Gq – increased nasal/bronchial mucus production, contraction of bronchioles, pruritis, pain H2 – Gs – increased gastric acid secretion V1 – Gq – increased vascular sm mm. contraction V2 – Gs – increased H2O permeability and reabsorption in collecting tubules |
|
Gq-coupled G-protein receptors – examples and mechanism
|
QtC (“cutesy”) for gQ and phospholipase/protein kinase C
HAVe 1 M&M H1, alpha1, V1, M1, M3 Gq → Phospholipase C → Lipids catalyzed to PIP2, which becomes IP3 (increasing [Ca]i) and DAG (increasing protein kinase C) |
|
Gi-coupled G-protein receptors – examples and mechanism
|
MAD 2s
M2, alpha2, D2 Gi → adenylyl cyclase → cAMP decreased → decreased PKA |
|
Gs-coupled G-protein receptors – examples and mechanism
|
Beta1/2, D1, H2, V2
Gs → adenylyl cyclase → increased cAMP → increased PKA Rate-limiting step of cholinergic transmission and drug that inhibits RLS – getting choline into neuron Hemicholinium inhibits this |
|
Mechanism: Vesamicol
|
Experimental anticholinergic drug that blocks Ach transport into secretory vesicles
Col = Chol |
|
What toxin blocks Ach release into synapse? What stimulates it?
|
Botulinum inhibits, black widow toxin stimulates
|
|
What blocks Tyrosine → DOPA conversion?
|
Metyrosine blocks this reaction, catalyzed by Tyr hydroxylase
|
|
What blocks Dopamine packaging in secretory vesicles?
|
Reserpine (depletory action)
|
|
What blocks NE release into synapse?
|
Guanethidine, Bretylium
|
|
What stimulates NE release into synapses?
|
Amphetamine, ephedrine, tyramine
|
|
What blocks reuptake of NE?
|
Cocaine, TCAs
|
|
Clinical use: Bethanechol
|
Direct cholinomimetic agonist
Post-op and neurogenic ileus and urinary retention Activates bowel and bladder |
|
Clinical use: Carbachol
|
Direct cholinomimetic agonist
Glaucoma, pupillary contraction, release of intraocular pressure Contracts ciliary muscle of eye (open angle), pupillary sphincter (narrow angle). Resistant to AChE |
|
Clinical use: pilocarpine
|
Direct cholinomimetic agonist
Potent stimulator of sweat, tears, saliva Used in acute glaucoma emergency Contracts ciliary muscle of eye (open angle), pupillary sphincter (narrow angle). Resistant to AChE |
|
Clinical use: Methacholine
|
Direct cholinomimetic agonist
Challenge test for Dx of asthma Stimulates muscarinic receptors in airway when inhaled |
|
Anti-AchE drugs – net effect
|
Increase of endogenous Ach
|
|
Clinical use: Neostigmine
|
Post-op and neurogenic ileus and urinary retention, MG, reversal of neuromuscular junction blockade (post-op). “NEO CNS” = No CNS penetration
|
|
Clinical use: Pyridostigmine
|
Cholinomimetic agent: Indirect agonist (anti-AchE). pyRIDostiGMine gets RID of MG (vs. Edrophonium, used for Dx)
Long acting MG Tx. Does not penetrate CNS, increases strength |
|
Clinical use: Edrophonium
|
Cholinomimetic agent: Indirect agonist (anti-AchE)
Dx of MG (vs. Tx as in pyridostigmine) – extremely short acting |
|
Clinical use: Physostigmine
|
Cholinomimetic agent: Indirect agonist (anti-AchE)
PHYS is for EYES Tx for glaucoma (crosses BBB) and atropine OD (“Fix”ostigmine – fixes atropine OD) |
|
Clinical use: Echothiphate
|
Cholinomimetic agent: Indirect agonist (anti-AchE)
Glaucoma |
|
Tx: Myasthenia Gravis
|
Direct/indirect cholinomimetic agonists, corticosteroids, thymectomy, plasmaphoresis (last ditch).
|
|
Clinical use: Tropicamide
|
Muscarinic antagonist
Atropine, Homatropine, Tropicamide Works on eye, producing mydriasis and cycloplegia (paralysis of the ciliary muscle of the eye, resulting in a loss of accommodation) |
|
Clinical use: Homatropine
|
Muscarinic antagonist
Atropine, Homatropine, Tropicamide Works on eye, producing mydriasis and cycloplegia (paralysis of the ciliary muscle of the eye, resulting in a loss of accommodation) |
|
Clinical use: Atropine
|
Muscarinic antagonist
Atropine, Homatropine, Tropicamide all work on eye, producing mydriasis and cycloplegia (paralysis of the ciliary muscle of the eye, resulting in a loss of accommodation) |
|
Clinical use: Benztropine
|
Muscarinic antagonist
Works on CNS – Parkinson’s disease – PARK my BENZ |
|
Clinical use: Scopolamine
|
Muscarinic antagonist
Motion sickness, end of life (decreases nausea, vomiting), sedation. Topical behind ear |
|
Mechanism/Clinical use: Ipratropium
|
Competitive Muscarinic antagonist, preventing bronchoconstriction. Also used for COPD. Add albuterol if used for acute asthma exacerbation. Given intranasally to pregnant women
Respiratory – Asthma, COPD – I PRAy I can breathe soon! |
|
Clinical use: Oxybutynin
|
Muscarinic antagonist
Genitourinary – reduces urgency in mild cystitis and reduces bladder spasms |
|
Clinical use: Glycopyrrolate
|
Muscarinic antagonist
Respiratory – used by anesthesiologists to decrease airway secretions |
|
Clinical use: Methscopolamine
|
Muscarinic antagonist
GI – Methscopolamine and Propantheline decrease salivation, GI motility and stomach acid |
|
Clinical use: Propantheline
|
Muscarinic antagonist
GI – Methscopolamine and Propantheline decrease salivation, GI motility and stomach acid. Propantheline – blocks M1 receptors on ECL (enterochromaffin-like cells), decreasing histamine secretion, and M3 receptors on parietal cells (decreasing H+ secretion) |
|
Clinical use: Hexamethonium
|
Ganglionic blocker – knocks out entire ANS. Used in experimental models to prevent vagal reflex responses to changes in BP, e.g. prevents reflex bradycardia caused by NE. Effect depends on dominant tone in each organ.
Arteries and veings – SNS – blocking effect → decreased BP, pooling of blood in veins → decreased return → decreased CO. Most everywhere else – PNS dominant, so hexamethonium causes SNS responses |
|
Tx: Alzheimer’s anticholinesterases
|
Donepezil (Aricept)
Galantamine Rivastigmine |
|
Mechanism/selectivity/Application: Epinephrine
|
Sympathomimetic – Direct
Alpha1/2, Beta 1/2, low doses selective for Beta1 (“B-low”) Anaphylaxis, open angle glaucoma, asthma, hypotension |
|
Mechanism/selectivity/Application: Norepinephrine
|
Sympathomimetic – Direct
Alpha1/2 > Beta Hypotension |
|
Mechanism/selectivity/Application: Isoproteronol
|
Sympathomimetic – Direct
Equal activity in beta1/2 Relaxes bronchial smooth muscle (beta2), causes tachycardia (beta1) – same with epinephrine. Used for asthma. Toxicity: AV block (rare) |
|
Mechanism/selectivity/Application: Dopamine
|
Sympathomimetic – Direct
D1=D2 > Beta > alpha, inotropic and chronotropic Shock, heart failure |
|
Mechanism/selectivity/Application: Phenylephrine
|
Sympathomimetic – Direct
Alpha1>alpha2 Pupillary dilation, vasoconstriction, nasal decongestion |
|
Mechanism/selectivity/Application: Albuterol
|
Sympathomimetic – Direct
Beta2 (relaxes bronchial smooth muscle) > Beta1 (heart) Acute asthma |
|
Mechanism/selectivity/Application: Terbutaline
|
Sympathomimetic – Direct
Beta2 > Beta1 Reduces premature uterine contractions |
|
Mechanism/selectivity/Application: Ritodrine
|
Sympathomimetic – Direct
Beta2 Reducsed premature uterine contractions |
|
Mechanism: Amphetamine
|
Sympathomimetic – Indirect
Indirect general agonist Releases stored catecholamines |
|
Mechanism: Ephedrine
|
Sympathomimetic – Indirect
Indirect general agonist Releases stored catecholamines |
|
Mechanism: Cocaine
|
Sympathomimetic – Indirect
Indirect general agonist Uptake inhibitor |
|
Clinical use: Amphetamine
|
Narcolepsy, obesity, ADD
|
|
Clinical use: Ephedrine
|
Nasal decongestion, urinary incontinence, hypotension
|
|
Clinical use: Cocaine
|
Vasoconstriction and local anesthesia
|
|
Clinical use: Clonidine
|
Sympathoplegic (decreases sympathetic discharge or its effect on the CNS)
HTN, especially with renal disease (no decrease in renal blood flow). 1/2 life = 8 hours, so dose qx3 to avoid rebound HTN |
|
Clinical use: alpha-methyldopa
|
Sympathoplegic (decreases sympathetic discharge or its effect on the CNS)
HTN, especially with renal disease (no decrease in renal blood flow). Safe in pregnancy |
|
Effect on BP, HR: Norepinephrine
|
Alpha > Beta
Widening of pulse pressure. Beta1 increase of systolic pressure > alpha1 increase of diastolic Reflex bradycardia decreases HR |
|
Effect on BP, HR: Epinephrine
|
Nonselective
Widening of pulse pressure. Beta1 increase of systolic pressure, Beta2 decrease of diastolic Beta1 increase of HR |
|
Effect on BP, HR: Isoproteronol
|
Beta > alpha
Slight decrease of systolic – Beta1. Greater increase of diastolic – Beta2 Beta1 increases HR, but so does reflex tachycardia due to drop in BP, so greater increase in HR than with Epi |
|
Epi/NE effect – which receptors dominate: vascular smooth mm.
|
Alpha1, Beta2
|
|
Epi/NE effect – which receptors dominate: Renal vasculature
|
D1 – vasodilation
|
|
Epi/NE effect – which receptors dominate: heart
|
Beta1
|
|
Epi/NE effect – which receptors dominate: Pulmonary bronchioles
|
Beta2
|
|
Epi/NE effect – which receptors dominate: Presynaptic neurons
|
Alpha2
|
|
Epi/NE effect – which receptors dominate: Pupillary Sphincter
|
Alpha1 – mydriasis
|
|
Epi/NE effect – which receptors dominate: Kidney JGA
|
Beta1 – renin release → increased BP
|
|
Epi/NE effect – which receptors dominate: beta cells of pancreas
|
Alpha2 – inhibits insulin release
|
|
Epi/NE effect – which receptors dominate: alpha cells pancreas
|
Beta2 – increased glucagons release
|
|
Epi/NE effect – which receptors dominate: Liver
|
Beta2 – glycogenolysis and gluconeogenesis
|
|
Clinical use: selective beta2 agonists
|
Asthma
Terbutaline given sub-Q. Also used to decrease premature uterine contraction or decrease uterine hyperstimulation. Salmeterol – long acting, not a rescue agent. |
|
Clinical use: Phenoxybenzamine
|
Pheochromocytome (use phenoxybenzamine before removing tumor, since high levels of released catecholamines will not be able to overcome blockage)
|
|
Clinical use: Prazosin
|
Hypertension (smooth muscle relaxer)
urinary retension in BPH (relaxes urethral sphincter) |
|
Clinical use: Terazosin
|
Hypertension (smooth muscle relaxer)
urinary retension in BPH (relaxes urethral sphincter) |
|
Clinical use: Doxazosin
|
Hypertension (smooth muscle relaxer)
urinary retension in BPH (relaxes urethral sphincter) |
|
Clinical use: Mirtazapine
|
Depression
|
|
What’s a good antidepressant for patients with insomnia or anorexia?
|
Mirtazapine – increases appetite (as well as serum cholesterol). Causes sedation
|
|
Effect of Epi on BP before/after alpha blockage
|
Epi – alpha1/2, Beta 1/2 agonist - nonselective
Before – Net pressor effect, with widening of pulse pressure After – Net depressor effect because no alpha-1 effect, beta2 mediated. Alpha1 and Beta2 are dominant receptors in vascular smooth muscle, so blocking alpha leaves unopposed beta2 vasodilation |
|
Effect of Phenylephrine on BP before/after alpha blockage
|
Phenylephrine pure alpha agonist – alpha1>2
Before – net pressor effect because primarily alpha1 agonist After – Suppression of pressor effect (no change) because alpha stimulation blocked and no beta stimulation. |
|
Beta blocker applications
|
HTN – decreased CO and renin secretion
Angina pectoris – decreased HR and contractility, resulting in decreased O2 consumption MI – beta blockers cardioprotective, decrease mortality SVT (propranolol, esmolol) – decrease AV conduction velocity (class II antiarrhythmic) CHF – slows pregression of chronic failure but can exacerbate very bad HF Glaucoma (timolol) – decreases secretion of aqueous humor |
|
Clinical use: Propranolol
|
SVT, Thyroid storm
|
|
Tx: SVT, thyroid storm, HTN, CHF
|
Propranolol
|
|
Tx: Glaucoma, HTN
|
Timolol
|
|
Beta blocker that’s not cardioprotective?
|
Atenolol
|
|
Short acting beta blocker given by IV?
|
Esmolol
|
|
Clinical use: Esmolol
|
See effect of beta blocker on patient with arrhythmia, since it’s short-acting
|
|
Why is a beta blocker not a good Tx for Cocaine OD?
|
Cocaine blocks uptake of catecholamines, which stimulate Beta1 (increased HR) and Beta2 (vasodilation), both of which would be blocked, but this would leave unopposed alpha1 vasoconstriction → increase in arterial BP
|
|
Tx: Aortic dissection
|
Beta blockers decrease BP and the slope of the rise in BP during contraction
|
|
Workup: Pt with tachycardia and 1st degree heart block
|
Test first with Esmolol to see if a Beta-blocker makes heart block worse
|
|
Things to give pt having (or had) MI – MONA
|
Morphine
O2 Nitrates Aspirin Beta blockers important too unless CHF. Also give ACE-I or ARBs. Statin, anti-coagulant |
|
Vaso/Venodilators and ACE-I/ARB effects on pre/afterload
|
Preload = ventricular EDV. Afterload = mean arterial pressure
Vasodilators (e.g. hydralazine) decrease afterload Venodilators (e.g. nitroglycerine) decrease preload ACE-I and ARB decrease Afterload AND Preload |
|
Tx: Wolff-Parkinson-White syndrome
|
Unlike most SVT, adenosine is contraindicated. Can use procainamide and amiodarone
|
|
Tx: A-fib
|
Warfarin
Rhythm control – get A + V back into normal rhythm – Amiodarone, sotalol Rate control – beta blockers, non-dihydropyridine Ca channel blockers, digoxin (it only affects resting rate and not if they increase their rate) |
|
How do you close a PDA? Keep it open?
|
Indomethacin. PGE2
|
|
Tx: Epstein’s anomaly
|
Findings: tricuspid leaflets displaced ito RV, hypoplastic RV, Tricuspid regurge and stenosis. 80% of pts with ASD with R→ shunt. Dilated RA, risk of ventricular tachycardia and WPW. Widely split S2, Tricuspid regurge on PE.
Tx: PGE2, digoxin, diuresis, propranolol (for SVT) |
|
Tx: Hypertrophic cardiomyopathy
|
Beta blocker or heart-specific calcium channel blocker (e.g. verapamil – not dihydropyridines)
|
|
Tx: Acute CHF
|
LMNOP
Lasix (furosemide) Morphine (decreases respiratory distress, vasodilation takes fluid elsewhere) Nitrates (same vasodilatory effect) Oxygen Pressors (e.g. dobutamine) |
|
Tx: Thrombosis
|
Can give tPA if massive. Have larger window if applied directly to site of clot
Otherwise, give heparin + warfarin. Warfarin inhibits proteins C+S so makes pt. hypercoagulable for first few days |
|
Tx: Pericarditis
|
High dose NSAIDs or Aspirin (if Hx of heart dz) and treatment of underlying dz
|
|
Tx: Raynaud’s disease
|
Dihydropyridine Ca channel blockers, aspirin, sildenafil
|
|
Tx: Wegener’s granulomatosis
|
Cyclophosphamide and corticosteroids (steroids the more important treatment in PAN)
|
|
Tx: Kawasaki dz
|
High dose aspirin, even to kids, to avoid infarctions
|
|
Tx: Polyarteritis Nodosa
|
Corticosteroids w/ or w/o cyclophosphamide (both in Wegener’s)
|
|
Tx: Temporal (Giant cell) arteritis
|
High dose steroids for one year
|
|
Mechanism: Hydralazine
|
Increases cGMP → smooth muscle relaxation. Vasodilates arterioles > veins → afterload reduction
|
|
Clinical use: Hydralazine
|
Severe HTN, CHF. First line for HTN in pregnancy, with methyldopa
|
|
Clinical use: Minoxidil
|
Severe HTN
|
|
Mechanism: Minoxidil
|
Anti-HTN
K+ channel opener – hyperpolarizes and relaxes vascular smooth muscle (arteriolar) |
|
Mechanism: Ca Channel blockers
|
Block voltage-dependent L-type Calcium channels of cardiac (non-dihydropyridine, e.g. Verapamil) and smooth muscle (Nifedipine, amlodipine), reducing muscle contractility
Vascular smooth muscle – nifedipine > diltiazem > verapamil (Verapamil = Ventricle) Heart – Verapamil > diltiazem > nifedipine |
|
Clinical use: Ca Channel blockers
|
HTN, angina, arrhythmias (not nifedipine), Prinzmetal’s angina (dihydropyridines), Raynaud’s (Dihydropyridines)
|
|
Mechanism: Nitroglycerin, Isosorbide dinitrate
|
Vasodilation by releasing NO in smooth mm., causing increase in cGMP and smooth mm relaxation. Dilate veins >> arteries, decreasing PREload
|
|
Clinical use: Nitroglycerin, Isosorbide dinitrate
|
Angina, pulmonary edema, aphrodisiac and erection enhancer
|
|
Tx: Malignant HTN
|
Nitroprusside – short acting, increases cGMP via direct release of NO
Fenoldopam – Dopamine D1 receptor agonist, relaxes renal vascular smooth muscle Diazoxide – K+ channel opener – hyperpolarizes and relaxes vascular smooth muscle |
|
Antianginal therapy
|
Goal – reduction of myocardial O2 consumption by decreasing one or more of: EDV, BP, HR, contractility, ejection time. Use Nitrates (affect preload), Beta blockers (affect afterload)
|
|
Antianginal therapy: Nitrates effect on EDV, BP, Contractility, HR, Ejection time, MVO2
|
Decrease preload
Decreased: EDV, BP, Ejection time, MVO2 Increased: Contractility + HR (both reflex response). Reflex contractility blocked by beta-blockers. MVO2 decreased more in combination with Beta blockers and more still with ACE-I as well. |
|
Antianginal therapy: Beta Blockers effect on EDV, BP, Contractility, HR, Ejection time, MVO2
|
Decrease afterload
Decreased: BP, Contractility, HR, MVO2 (decreased more in combination with Nitrates, and more so with ACE-I as well) Increased: EDV, Ejection time |
|
Antianginal therapy: Nitrates + Beta Blockers
|
Little/no effect: EDV, Contractility, Ejection time
Decreased: BP, HR Significantly decreased: MVO2 |
|
Antianginal therapy: Ca Channel Blockers
|
Nifedipine similar to Nitrates in effect. Verapamil similar to Beta blockers in effect
|
|
Antianginal therapy: Pindolol, Acebutolol
|
Partial Beta agonists – contraindicated in angina
|
|
Mechanism/Effects: Statins
|
Greatly decrease LDL, increase HDL, Decrease TGs
Blocks second step in: Acetyl-CoA → HMG-CoA → Mevalonate → → → cholesterol |
|
Mechanism/Effects: Niacin
|
Lipid lowering agent with significant decrease in LDL and significant increase in HDL. Decreases LDL
Inhibits lipolysis in adipose tissue, reduces hepatic VLDL secretion into circulation |
|
Mechanism/Effects: Cholestyramine, Colestipol, Colesevelam
|
Bile Acid Resin Lipid Lowering Agents
Significant decrease of LDL, slight increases in HDL, TGs Prevent intestinal reabsorption of bile acids. liver must use cholesterol to make more. Binds C-dif toxin |
|
Mechanism/Effects: Cholesterol absorption blocker
|
Ezetimibe
Significant decrease in LDL, no effect on HDL/TGs Prevents cholesterol reabsorption at SI brush border |
|
Mechanism/Effects: Fibrates
|
Lipid-lowering agents
Greatly decreased TGs, decreased LDL, increased HDL Upregulate LPL, leading to increased TG clearance Useful because high TGs lead to pancreatitis → ARDS |
|
Mechanism/Effects: Omega-3 Fatty Acids
|
Significantly decrease TGs
|
|
Cardiac drugs – site of action
|
Na/K pump increases extracellular Na, so that Na/Ca antiport can push Ca out. Ca comes in through Ca channels, triggering Ca release through SR Ca channel. Digoxin blocks Na/K pump. Ca channel/Beta blockers block the PM Ca Channel. Ryanodine, a poison, blocks Ca release from SR. Ca sensitizers increase Ca action on troponin/tropomyosin system. Beta1 receptors are Gs, activate PKA, which phosphorylates L-type Ca Channels and phospholamban, both of which increase intracellular Ca during contraction
|
|
Common Effect/Toxicity: Class I Antiarrhythmics
|
Decrease slope of Phase 0 and Phase 4 depolarization
Toxicity increased by hyperkalemia Slow or block conduction (especially in depolarized cells). Increased threshold for firing in abnormal pacemaker cells. State dependent (selectively depolarize tissue that is frequently depolarized) |
|
Effect: Class IA Antiarrhythmics
|
Procainamide, Disopyramide, Quinidine
Increased AP duration/ERP/QT Affect both A and V arrhythmias, especially reentrant and ectopic SVT and Vtach, e.g. WPW (use procainamide almost exclusively for this) Also block K channels, so have Class III effect – pushing out repolarization and increasing ERP |
|
Effects: Class IB Antiarrhyhmics
|
Tocainide, Lidocaine, Mexiletine
Affect ischemic or depolarized purkinje and ventricular tissue. Useful in acute Vtach arrhythmias (esp. post MI) and in digitalis-induced arrhythmias (can also use Phenytoin). Lidocaine is MC used Class I. Shorten phase 3 repolarization, decreasing ERP |
|
Effects: Class IC Antiarrhytmics
|
Flecainide Propafenone, Encainide
No effect on AP duration. Useful in Vtachs that progress to Vfib and in intractable SVT. Usually used only as last resort in refractory tach. For patients without structural abnormalities. Drastic slowing of phase 0 |
|
Mechanism: Class II Antiarrhythmics
|
Propranolol, esmolol, metoprolol, atenolol, timolol
Decrease cAMP and Ca currents. Suppress abnormal pacemakers by prolonging phase 4 depolarization. AV node particularly sensitive – increased PR interval. Esmolol very short acting (used to test potential adverse reaction to anti-arrhythmics) |
|
Clinical use: Class II Antiarrhythmics
|
Propranolol, esmolol, metoprolol, atenolol, timolol
Vtach, SVT, slowing ventricular rate during afib and atrial flutter |
|
Mechanism/Clinical use: Class III Antiarrhythmics
|
Sotalol, ibutilide, amiodarone
Increase AP duration and ERP, inhibit (pulling to right) Phase III. Increases QT, used when other antiarrhythmics fail. Used in A-fib |
|
Mechanism: Class IV Antiarrhythmics
|
Verapamil, Diltiazem
Primarily affect AV nodal cells, decreasing conduction velocity, increasing ERP and PR. Used in prevention of nodal arrhythmias (e.g. SVT). Decrease slope of Phases 1 and 2 and increase slope of Phase 3 |
|
Effects: Adenosine as a drug
|
Antiarrhythmic
Pushes potassium out of cells → hyperpolarizing cells and decreasing intracellular Ca. Drug of choice in diagnosing/abolishing AV nodal arrhythmias (like SVT. Don’t use in reentrant rhythms like WPW – can convert to a-fib). Very short acting (~15s). Stops heart for few seconds, can see what’s under the large QRS |
|
Mechanism: K+ as drug
|
Antiarrhythmic
Depresses ectopic pacemakers in hypokalemia (e.g. digoxin toxicity) |
|
Mechanism: Mg+2 as drug
|
Effective in torsades de pointes and digoxin toxicity
|
|
Effect of low Ca, low Mg on PTH. What causes low Mg? What does low Mg cause?
|
Decreased free serum Ca increases PTH secretion. Opposite for Mg
Decreased Mg causes arrhythmias and is caused by diarrhea, aminoglycosides, diuretics, alcohol abuse (last two MCC). Diuretic-induced hypomagnesemia problem in CHF patients, who’ll then get antiarrhythmics. They should be on supplemental Mg |
|
Mechanism: Nesiritide
|
ANP analog
Acts on cGMP pathway on ANP receptor → increased cGMP → activation of Protein Kinase G → relaxation of smooth muscle (vasodilation) → relaxes afferent glomerular arterioles → increased GFR → diuresis. |
|
Clinical use: Nesiritide
|
ANP analog. Used to treat HF
|
|
Tx: Heart failure/Hyperaldosteronism
|
Spironolactone, Epleranone
K+ sparing diuretics that act as aldosterone antagonists |
|
Clinical use: Epleranone
|
K+ sparing diuretic that acts as aldosterone antagonist, used in Tx of HF and hyperaldosteronism
|
|
Tx: Acromegaly
|
Pituitary adenoma resection, followed by octreotide administration
|
|
Mechanism/Clinical Use: Octreotide
|
Somatostatin analog. Inhibits most GI hormones/activity (and hormones in general), can use for pituitary excess (GH, TSH, ACTH), GI endocrine excess (e.g. Z-E syndrome), VIPoma, Carcinoid, Glucagonoma, Insulinoma, bleeding varices (decreases blood flow to splanchnic vessels).
|
|
Tx: Neuropathic pain in DM
|
Gabapentin or Pregabalin
|
|
Tx: Diabetic Ketoacidosis
|
Fluids, insulin, K+ (to replete intracellular stores, since H+ pumped into cells and K+ out to decrease acidosis). Glucose if necessary to prevent hypoclycemia. Mg+ also decreased with diuresis. Treat following anion gap, since glucose will normalize before it.
|
|
Tx: Diabetes Insipidus
|
Adequate fluid intake. For Central DI – intranasal desmopressin (ADH analog). For nephrogenic DI – hydrochlorothiazide (loss of electrolytes, not free water, as in loops. Combats hypovolemia due to increased Na/H2O absorption proximally, leading to less H2O in tubules distally, where ADH acts), indomethacin (decreases PG synthesis. PGs inhibit ADH) or amiloride (used in lithium toxicity in addition to HZT. Closes the Na channels opened by Li. 2nd line)
|
|
Clinical use: Desmopressin
|
ADH analog
Used in Central DI, von Willebrand’s Disease – promotes release of vWF from endothelial storage sites |
|
Insulin for DM – Long/short acting
|
Short acting: Lispro, Aspart, Regular
Intermediate: NPH Long-acting: Glargine, Detemir |
|
Clinical use: Insulin
|
Type I DM, Type 2 DM
Life threatening hyperkalemia (increases muscle uptake of K+) and stress-induced hyperglycemia |
|
Mechanism: Sulfonylureas
|
1st gen: tolbutamide, chlorpropamide. 2nd gen: glyburide, glimepiride, glipizide
Close K+ channel in beta cell membrane, so cell depolarizes, triggering increased insulin release via increased Ca influx |
|
Clinical use: Sulfonylureas
|
1st gen: tolbutamide, chlorpropamide. 2nd gen: Glyburide, glimepiride, glipizide
Stimulates release of endogenous insulin in Type 2 DM. Requires some islet cell functioning, so useless in Type I DM |
|
Tx: DM
|
Type 1 – low sugar diet, insulin
Type 2 – dietary modification, exercise for weight loss, oral hypoglycemics, insulin replacement Sulfonylureas, Biguanides, Glitazones and alpha-glucosidase inhibitors can be used together or alone |
|
Mechanism: Metformin/Biguanides
|
Unknown. Possibly decreases gluconeogenesis, increases glycolysis, decreases serum glucose levels. Overall acts as insulin sensitizer
|
|
Clinical use: Meformin/Biguanides
|
Oral hypoglycemic. Can be used in patients without islet cell function (vs. sulfonylureas). Used in PCOS, can be used in pregnancy, can be used to decrease weight.
|
|
Mechanism: Pioglitazone, Rosiglitazone
|
Glitazones (aka thiazolidinediones, aka TZDs)
DM Drugs Increase target cell response to insulin by acting as PPAR-gamma agonists |
|
Clinical use: Glitazone (aka thiazolidinedione, aka TZD)
|
DM Drug
Monotherapy for Type 2 DM or combined with other agents (e.g. Sulfonylureas, Biguanides, Alpha-glucosidase inhibitors) |
|
Mechanism: Pramlintide
|
Mimetic – DM drug
Amylin analog. Amylin is secreted by Beta cells, works like insulin, decreased in DM. Decreases glucagons, delays gastric emptying |
|
Clinical use: Pramlintide
|
Mimetic – DM 2 drug
|
|
Mechanism: Exenatide
|
GLP-1 (an incretin) mimetic – DM Drug
Increases insulin, decreases glucagon release |
|
Clinical use: Exenatide
|
GLP-1 (an incretin) mimetic – DM 2 Drug
|
|
Mechanism: Sitagliptin
|
Dipeptidyl-Peptidase-4 (DPP-4) inhibitor, Prolongs incretin secretion, increasing insulin and decreasing glucagon secretions. Delays gastric emptying
|
|
Clinical use: Sitagliptin
|
Dipeptidyl-Peptidase-4 (DPP-4) inhibitor
DM 2 |
|
Mechanism: Orlistat
|
Obesity drug – pancreatic lipase inhibitor – so can’t absorb fat and end up excreting
|
|
Clinical use: Orlistat
|
Obesity drug – pancreatic lipase inhibitor
Long-term obesity management (in conjunction with modified diet) |
|
Mechanism: Sibutramine
|
SNRI used for obesity. Peripherally acting, not in CNS.
|
|
Clinical use: Sibutramine
|
SNRI used for obesity – short- and long-term management
|
|
Mechanism: Propylthiouracil, Methimazole
|
Inhibit organification and coupling (iodination of tyrosil groups) of thyroid hormone synthesis. PTU also decreases peripheral T4→T3 conversion.
|
|
What decreases T4→T3 conversion peripherally?
|
PTU, Propranolol, Glucocorticoids, I-
|
|
Clinical use: Propylthiouracil, Methimazole
|
Hyperthyroidism
|
|
Clinical use: Somatotropin
|
GH. Used in GH deficiency, Turner’s syndrome (to help with height), Prader-Willi Syndrome
|
|
Clinical use: Somatostatin
|
Octreotide. Acromegaly, carcinoid, gastrinoma, glucagonoma, insulinoma, etc.
|
|
Clinical use: Oxytocin
|
Stimulates labor, uterine contractions, milk let-down. controls uterine hemorrhage
|
|
Mechanism: Glucocorticoids
|
Hydrocortisone, prednisone, triamcinolone, dexamethasone, beclomethasone, prednisolone (used for liver dz pts)
Decrease production of LTs and PGs by inhibiting Phospholipase A2 and expression of COX-2 |
|
Clinical use: Demeclocycline
|
SIADH
|
|
Tx: Malabsorption syndromes
|
Limit fat intake, replace fat-soluble vitamins, give pancreatic enzymes with meals
|
|
Tx: Crohn’s Dz
|
Corticosteroids, infliximab (anti-TNF). Don’t do surgery because dz will pop up in previously unaffected area
|
|
Tx: Ulcerative Colitis
|
Sulfasalazine, infliximab, colectomy (curative)
|
|
Tx: End Stage Liver Dz
|
Propranolol or natalol (decrease bleeding varices risk)
Vit K (help clotting factors) Lactulose (helps pull toxins out of GI wall and blood – dose to 3-4 bowel movements/day) Diuretics – for ascites (paracentesis if too much. + albumin IV) Ascites + fever? – rule out SBP HepA/B/Flu/Pneumonia vaccines |
|
Causes of hepatic steatosis
|
Didanosine (ddI), Stavudine (d4T), alcohol, non-alcoholic steatohepatitis
|
|
Mechanism: H2 blockers
|
Cimetidine, Ranitidine, Famotidine, Nizatidine
Reversible block of H2 receptors → decreased H+ secretion by parietal cells |
|
Clinical use: H2 blockers
|
Peptic ulcer, gastritis, mild esophageal reflux
|
|
Mechanism: Proton pump inhibitors
|
Omeprazole, Lansoprazole
Big guns, stronger than H2 blockers Irreversibly bind H+/K+-ATPase in stomach parietal cells |
|
Clinical use: Proton pump inhibitors
|
Omeprazole, Lansoprazole
Peptic ulcers, gastritis, esophageal reflux, Z-E syndrome, erosive esophagitis |
|
Mechanism: Bismuth, sucralfate
|
Bind to ulcer base, providing physical protection, allow HCO3- secretion to reestablish pH gradient in mucous layer
|
|
Clinical use: Bismuth, sucralfate
|
Increased ulcer healing, traveler’s diarrhea.
Sucralfate – also used to prevent gastritis and gastric ulcers. Requires acidic environment, so can’t give with antacid |
|
Prostaglandin analog used in peptic ulcer treatment
|
Misoprostol
|
|
Mechanism: Misoprostol
|
PGE1 analog. Increased production and secretion of gastric mucous barrier, decreased acid production
|
|
Clinical use: Misoprostol
|
PGE1 analog that directly antagonizes NSAID (which decrease PGs) induction of peptic ulcers. Used for maintenance of patent ductus arteriosus
Used to induce labor |
|
Mechanism: Pirenzepine
|
Blocks M1 receptors on ECL (enterochromaffin-like cells), decreasing histamine secretion, and M3 receptors on parietal cells (decreasing H+ secretion)
|
|
Clinical use: Pirenzepine
|
Muscarinic antagonist
Peptic ulcers (rarely used) |
|
Mechanism: Infliximab, Etanercept, Adalimumab
|
Monoclonal TNF Ab (etanercept = recombinant form of human TNF receptor, infliximab = mouse variable region, adalimumab = human anti-TNF variable region), blocking inflammation
|
|
Clinical use: TNF Ab
|
Infliximab, Etanercept, Adalimumab
HLA B27 diseases: Crohn’s, Rheumatoid Arthritis, Ankylosing spondylitis, psoriatic arthritis |
|
Mechanism: Sulfasalazine
|
Combination of sulfapyridine (antibacterial) and mesalamine (anti-inflammatory). Activated by colonic bacteria. Only works in distal ileum and colon because doesn’t become unbound until encounters bacteria
|
|
Clinical use: Sulfasalazine
|
=sulfapyridine AB and mesalamine (anti-inflammatory). Used in ulcerative colitis, Crohn’s (just give mesalamine if early small intestine affected)
|
|
Mechanism: 5-HT3 antagonists
|
Ondansetron, Granisetron
Powerful central-acting antiemetics, work on chemotactic trigger zone |
|
Clinical use: 5-HT3 antagonists
|
Ondansetron, Granisetron
Control vomiting post-op and in pts undergoing cancer chemo, good for morning sickness |
|
Mechanism: Metoclopramide
|
D2 receptor antagonist – increases resting tone, contractility, LES tone, motility. Does not influence colon transport time. Also stimulates 5HT receptors
|
|
Clinical use: Metoclopramide
|
5HT receptor agonist, D2 receptor antagonist
Diabetic and post-op gastroparesis |
|
Drugs and receptors involved in increased gut motility
|
Increased gut motility = Increase in Ach and 5HT (e.g. carcinoid syndrome), decrease in D2
Cholinergic agonists: bethanechol (can use for post-op neurogenic ileus), AchE-I like neostigmine Metoclopramide: stimulates 5HT, antagonizes D2 Domperidone: anti-D2 Cisapride – 5HT agonist Macrolides – Stimulate smooth mm. and motilin receptors |
|
Clinical Use: Hydroxyurea
|
Increases HbF. Used in SCD pts
|
|
Tx: SCD
|
Hydroxyurea to increase HbF
BM transplantation (ultimate Tx) |
|
Mechanism: Heparin
|
Catalyzes activation of antithrombin III, decreases thrombin and Xa. Short half-life
|
|
Clinical use: Heparin
|
Immediate anticoagulation for PE, stroke, acute coronary syndrome, MI, DVT. Used during pregnancy (doesn’t cross placenta). Follow PTT. Continuous infusion (short half-life)
|
|
Mechanism: Enoxaparin
|
Low MW heparin, acts more on Xa, has better bioavailability and 2-4 times longer half life. Can be administered SubQ and without laboratory monitoring. Not easily reversible.
|
|
Tx: HIT
|
Lepirudin, bivalirudin – hirudin derivatives. Directly inhibit thrombin. Have to give warfarin once HIT is over because pt is still hypersensitized.
|
|
Mechanism: Hirudin derivatives
|
Lepirudin, Bivalirudin
Anticoagulants – directly inhibit thrombin |
|
Mechanism: Argatrovan
|
Direct thrombin inhibitor
|
|
Mechanism: Warfarin
|
Interferes with normal synthesis and gamma-carboxylation of vit-K dependent clotting factors II, VII, IX, X, Proteins C+S. Metabolized by CYP450. Effects Extrinsic pathway more, followed by PT or INR (window = 2-3). Long half-life
|
|
Clinical use: Warfarin
|
Chronic anticoagulation. Not used in pregnant women (crosses placenta – vs. heparin). DVT, Afib, PE Hx, genetic hypercoagulability, prosthetic heart valve. Have to give heparin with Warfarin until blood level established because slow acting and action on Proteins C+S causes hypercoagulability for first 2-3 days.
|
|
Mechanism: Urokinase
|
Like tPA, it stimulates the plasminogen → plasmin conversion, leading to breakdown of Fibrin clots and fibrinogen
|
|
Mechanism: Anistreplase
|
Activates Plasmin formation and function on fibrinogen. Activates formation of plasmin from plasminogen
|
|
Mechanism: Streptokinase
|
Activates Plasminogen → plasmin conversion
|
|
Mechanism: Aminocaproic acid
|
Blocks Plasminogen → plasmin conversion
Thrombolytic antidote |
|
Mechanism: Thrombolytics
|
Streptokinase, urokinase, tPA (alteplase), APSAC (anistreplase)
Directly or indirectly aid conversion of plasminogen to plasmin, which cleaves fibrin clots, increasing PT and PTT, though not changing platelet count or bleeding time |
|
Clinical use: Thrombolytics
|
Early STEMI, early ischemic stroke (have 3 hrs if given generally, 6 if given directly)
|
|
Mechanism: Aspirin
|
Acetylates and irreversibly inhibits COX-1 and COX2 to prevent Arachidonic Acid → PGs + TxA2 conversion (Tx2 produced by activated platelets - mediates vasoconstriction, platelet aggregation/activation – by mediating expression of GPIIbIIIa for fibrinogen binding). (PGI2 → decreased platelet aggregation/uterine tone, causes vasodilation) (PGE2 → decreased vascular tone, increased pain/uterine tone, temperature, gastric mucus) Increases bleeding time. No effect on PT, PTT.
|
|
Clinical use: Aspirin
|
Low dose (<300mg/day) – decreased platelet aggregation (lasts 3-5 days)
Intermediate (300-2400) – antipyretic and analgesic High – anti-inflammatory |
|
Mechanism: Clopidogrel, Ticlopidine
|
Inhibit platelet aggregation by irreversibly blocking ADP receptors (released by activated platelets – binds to receptors to further activate platelets). Inhibits fibrinogen binding by preventing GPIIbIIIa expression
|
|
Clinical use: Clopidogrel, Ticlopidine
|
Acute Coronary Syndrome (MI), coronary stenting, decreases incidence or recurrence of thrombotic stroke
|
|
Mechanism: Abciximab, Tirofiban, Eptifibatide
|
Monoclonal Ab that binds to GP receptor IIbIIIa on activated platelets, preventing aggregation
|
|
Clinical use: Abciximab, Tirafiban, Eptifibatide
|
Acute coronary syndromes (NSTEMI – vs. tPA or streptokinase if STEMI), percutaneous transluminal coronary angioplasty
|
|
Mechanism: MTX
|
S-phase specific antimetabolite. Folic acid that inhibits dihydrofolate reductase, decreasing dTMP and therefore DNA/protein synthesis
|
|
Clinical use: MTX
|
Leukemias, lymphomas, choriocarcinoma (also use Vincristine/Vinblastine for this), sarcomas, abortion, ectopic pregnancy, rheumatoid arthritis, psoriasis, Wegener’s. Think: WBC tumors and uterine pathology
|
|
Mechanism: 5-FU
|
S-phase-specific antimetabolite. Pyrmidine analog bioactivated to 5F-dUMP, which covalently complexes folic acid. This complex inhibits thymidylate synthase, resulting in decreased dTMP and same decreased DNA/Protein synthesis
|
|
Clinical use: 5-FU
|
Colon cancer and other solid tumors (vs. Cytaraban for liquid), basal cell carcinoma (topical). Synergy with MTX. Topical for actinic keratosis – highlights all the actinic AKs – redness.
|
|
Toxicity: 5-FU
|
Myelosuppression, which is NOT reversible with leucovorin. Photosensitivity. Can rescue with thymidine
|
|
Relationship between 5-FU and MTX
|
dUMP is converted to dTMP by thymidylate synthase. This requires addition of methyl group from methyl-THF, which becomes DHF and is converted back to THF by DHF reductase. 5-FU blocks thymidylate synthase and MTX blocks DHFR. Thus, they are synergistic
|
|
Mechanism: 6-MP
|
Blocks de novo purine synthesis by blocking PRPP synthetase, which converts ribose → PRPP. Activated by HGPRTase
|
|
Clinical use: 6-MP
|
Leukemias, lymphomas (not CLL or Hodgkin’s)
|
|
Mechanism: Cytarabine (ara-C)
|
Inhibits DNA polymerase
|
|
Clinical use: Cytarabine (ara-C)
|
AML, ALL, high-grade non-Hodgkin’s lympoma. Think: liquid tumors (vs. 5-FU, Doxorubicin, Daunorubicin)
|
|
Mechanism: Cyclophosphamide, Ifosfamide
|
Alkylating agents. covalently x-link (interstrand) DNA at guanine N-7. Require bioactivation by liver
|
|
Clinical use: Cyclophosphamide, ifosfamide
|
Non-Hodgkin’s lymphoma, PAN, Wegener’s, breast and ovarian carcinomas, also immunosuppressants (e.g. SLE)
|
|
Mechanism: Nitrosureas
|
Carmustine, lomustine, semustine, streptozocin
Alkylate DNA, cross BBB → CNS |
|
Clinical use: Nitrosureas
|
Carmustine, lomustine, semustine, streptozocin
Think: brain. Brain tumors (including glioblastoma multiforme) |
|
Mechanism: Cisplatin, Carboplatin
|
Cross-link DNA
|
|
Clinical use: Cisplatin, Carboplatin
|
Testicular, bladder, ovary, and lung carcinomas
|
|
Mechanism: Busulfan
|
Alkylates DNA
|
|
Clinical use: Busulfan
|
CML. Also for ablating bone marrow in hematopoeitic stem cell transplants
|
|
Clinical use: Doxorubicin (adriamycin), Daunorubicin
|
Part of the ABVD combination regimen for Hodgkin’s lymphoma. also for myelomas, sarcomas and solid tumors (breast, ovary, lung. 5-FU also used for solid tumors, vs. cytaraban for liquid tumors)
|
|
Mechanism: Doxorubicin (adriamycin), daunorubicin
|
Generate free radicals and noncovalently intercalate in DNA (creating breaks in DNA strand to decrease replication)
|
|
Mechanism: Dactinomycin (Actinomycin D)
|
Intercalates in DNA
|
|
Clinical use: Dactinomycin (Actinomycin D)
|
Wilm’s tumor, Ewing’s Sarcoma, Rhabdomyosarcoma
Children ACT out. ACTinomycin for their tumors |
|
Mechanism: Bleomycin
|
Induces formation of free radicals, which cause breaks in DNA
|
|
Clinical use: Bleomycin
|
Testicular cancer, Hodgkin’s lymphoma (part of ABVD regimen)
|
|
Clinical use: Hydroxyurea
|
Melanoma, CML, SCD (increases HbF)
|
|
Mechanism: Etoposide (VP-16)
|
G2-phase specific agent that inhibits Topo II and increases DNA degradation
|
|
Clinical use: Etoposide (VP-16)
|
Small cell carcinoma of the lung and prostate, testicular carcinoma
|
|
Mechanism: Prednisone
|
Prototype Corticosteroid
May trigger apoptosis. May even work on nondividing cells. Inhibits synthesis of virtually all cytokines. Inactivates NF-kappaB, the TF that induces production of TNF-alpha, among other inflammatory agents. |
|
Clinical use: Prednisone
|
Most commonly used glucocorticoid in chemo-. Used in CLL, Hodgkin’s (Part of MOPP regimen). Immunosuppressant used in autoimmune diseases. First line for chronic asthma. Takes 4 hours to get started regardless of delivery
|
|
Mechanism/toxicity: Beclomethasone
|
Corticosteroid. Inhibits synthesis of virtually all cytokines. Inactivates NF-kappaB, the TF that induces production of TNF-alpha, among other inflammatory agents. Oral thrush when used for asthma (use spacer to avoid)
|
|
Clinical use: Beclomethasone
|
Antiinflammatory. First line for Asthma
|
|
Mechanism: Tamoxifen, Raloxifene
|
SERMs – receptor antagonists in breast, agonists in bone. Block binding of estrogen to estrogen receptor-positive cells
|
|
Mechanism: Clomiphene
|
SERM. Partial agonist at estrogen receptors in pituitary. Prevents normal feedback inhibition and increases release of LH and FSH, stimulating ovulation.
|
|
Clinical use: Clomiphene
|
Infertility and PCOS
|
|
Mechanism: Tamoxifen
|
Antagonist on breast tissue
|
|
Clinical use: Tamoxifen
|
SERM - Used to treat and prevent occurrence of ER+ BrCa
|
|
Mechanism: Raloxifene
|
SERM. Agonist on bone
|
|
Clinical use: Raloxifene
|
Useful in preventing/treating osteoporosis, reduce resorption of bone
|
|
Mechanism: Trastuzumab (Herceptin)
|
Monoclonal Ab against HER-2 (erb-B2). Helps kill breast cancer cells that overexpress HER-2, possibly through Ab-dependent cytotoxicity
|
|
Clinical use: Trastuzumab (Herceptin)
|
Metastatic breast cancer
|
|
Mechanism: Imatinib (Gleevac)
|
Philadelphia chromosome bcr-abl tyrosine kinase inhibitor
|
|
Clinical use: Imatinib (Gleevac)
|
CML, GI stromal tumors, Philadelphia Cr+ ALL
|
|
Mechanism: Vincristine, Vinblastine
|
M phase specific alkaloids that bind to tubulin and block polymerization of MTs so that mitotic spindles cannot form. MTs are the “vines” of your cells. Blocks chemotaxis. (Griseofulvin, colchicines, taxols [e.g. Paclitaxel] Bend-y drugs all also interfere with MTs)
|
|
Clinical use: Vincristine, Vinblastine
|
Part of the MOPP (O = Oncovin [vincristine]) regimen for Hodgkin’s lymphoma. Wilm’s tumor, choriocarcinoma (also use MTX for this), Kaposi’s sarcoma
|
|
Mechanism: Taxols
|
E.g. paclitaxel. M-phase-specific agents that bind to tubulin and hyperstabilize polymerized MTs so that mitotic spindle cannot break down (anaphase can’t occur). (Griseofulvin, colchicines, taxols [e.g. Paclitaxel] Bend-y drugs all also interfere with MTs)
|
|
Clinical use: Taxols
|
E.g. paclitaxel. Ovarian and breast carcinomas
|
|
Tx: Paget’s disease
|
Bisphosphonates to inhibit osteoclasts
|
|
Tx: Ewing’s Sarcoma
|
Dactinomycin (Actinomycin D)
Kids act up, Use Actinomycin for their tumors |
|
Tx: Osteoarthritis
|
1st line = acetaminophen (least complications). Good to schedule it vs. taking as needed
After: NSAIDS, steroid injection into joints every 3 mos, Hyaluronic acid (every 1-3 yrs), Joint replacement surgery (mainstay), Opioids – last resort, chronic. |
|
Tx: Rheumatoid Arthritis
|
1st line: NSAIDS
Anti-TNF – can’t give if pt has Tb Disease modifying drugs stop progression |
|
Tx: Gout
|
NSAIDs (e.g. indomethacin) used first, Colchicine (rarely given b/c of toxicities), probenecid (if chronic), allopurinol (if chronic, tophi). Don’t give salicylates – all but highest doses depress uric acid clearance, and even then (5-6g/day) uricosuric activity only minor. Low dose salicylates and diuretics decrease uric acid tubular secretion.
|
|
Mechanism: Colchicine
|
Depolymerizes MTs, impairing leukocyte chemotaxis and degranulation so Macrophages can’t get to uric acid crystals to phagocytise them.
|
|
Clinical use: Colchicine
|
Gout, pseudogout
|
|
Mechanism: Probenecid
|
Inhibits reabsorption of uric acid in proximal convoluted tubule.
Inhibits secretion of PCN |
|
Clinical use: Probenecid
|
Chronic gout - Should be used if uric acid is high.
Can lengthen PCN effect (blocks secretion in kidney) |
|
Mechanism: Allopurinol
|
Blocks xanthine oxidase (conversion of hypoxanthine to xanthine to uric acid)
Xanthine oxidase also metabolizes azathioprine and 6-MP |
|
Clinical use: Allopurinol
|
Chronic gout. Also used in lymphoma, leukemia to prevent tumor lysis-associated urate nephropathy
|
|
Tx: Pseudogout
|
NSAIDs, colchicines
|
|
Tx: Seronegative spondyloarthropathies
|
PAIR = Psoriatic arthritis, Ankylosing spondylitis, IBD arthritis, Reiter’s syndrome (can’t see, can’t pee, can’t climb a tree). Tx is Anti-TNF (Infliximab, Etanercept, Adalimumab)
|
|
Tx: SLE
|
Glucocorticoids, NSAIDS (these MC used)
Cyclophosphamide (if very severe), hydroxychloroquine. Primaquine (have to check 2x/year for renal damage |
|
Tx: Sarcoidosis
|
Steroids
|
|
Tx: Polymyalgia rheumatica
|
Prednisone (just as with temporal arteritis)
|
|
Tx: Polymyositis/dermatomyositis
|
Steroids
|
|
Tx: Mixed connective tissue disease
|
Responds to steroids
|
|
Tx: Fibromyalgia
|
Pregabalin, milnacipran (SNRI), amitryptiline (helps with sleep), low dose fluoxetine
|
|
Mechanism: NSAIDs
|
Ibuprofen, Naproxen, Indomethacin, Ketorolac
Reversibly inhibit COX-1/2. Block PG synthesis |
|
Clinical use: NSAIDs
|
Antipyretic, analgesic, anti-inflammatory. Indomethacin used to close PDA.
Indomethacin strongest, use for gouty arthritis but no longer than 5 days Ketorolac – very strong, can be given IM, oral |
|
Mechanism: Cox-2 inhibitor
|
e.g. Celecoxib
Reversibly inhibit Cox-2 in inflammatory cells and vascular endothelium, mediates inflammation and pain, spares Cox-1, sparing gastric mucosa |
|
Clinical use: Cox-2 inhibitor
|
e.g. celecoxib
Rheumatoid Arthritis and Osteoarthritis |
|
Mechanism: Acetaminophen
|
Reversibly inhibits COX, mostly in CNS. Inactivated peripherally (so no anti-inflammatory properties)
|
|
Clinical use: Acetaminophen
|
Antipyretic, analgesic, lacking anti-inflammation. Used instead of aspirin in children to prevent Reye’s syndrome with viral infection.
|
|
Compare Aspirin, Acetaminophen, NSAIDs
|
Acetaminophen = NSAID – anti-inflammatory activity
Aspirin = NSAID + antiplatelet activity Or Acetaminophen + anti-inflammation = NSAID NSAID + antiplatelet = Aspirin |
|
Mechanism: Bisphosphanates
|
Inhibit Osteoclast activity. reduce formation and resorption of hydroxyapatite
|
|
Clinical use: Bisphosphonates
|
Malignancy associated hypercalcemia, Paget’s disease of bone, postmenopausal osteoporosis, prophylaxis with long-term steroid users. Take on empty stomach and stay upright for 1/2 hour afterward
|
|
Tx: Osteoporosis
|
Bisphosphanates
Also, stop smoking, alcohol, steroids, PPI (b/c acid needed to absorb Ca) Give Vitamin D, exercise, hip protectors, PTH (has anabolic effect, decreases hip fractures), testosterone, estrogen, calcitonin |
|
Tx: Huntington’s Dz
|
Dopamine antagonist, e.g. haloperidol
|
|
Prophylaxis: strokes, TIA
|
Aspirin. If pt also has cardiac need, use clopidogrel
|
|
Tx: Pseudotumor cerebri
|
Acetazolamide, Prednisone. Repeat spinal taps to maintain/control pressure. If untreated, can lead to blindness
|
|
Tx: Migraine
|
Triptans, ergotamines (e.g. bromocriptine)
|
|
Tx: Tension headaches
|
NSAIDs
|
|
Tx: Cluster headache
|
Ergotamines, O2
|
|
Tx: Absence seizures
|
Ethosuxamide
|
|
Tx: Brain tumors
|
Nitrosureas (nitros on your mustang – most end in –stine)
|
|
Mechanism: Epinephrine (in glaucoma)
|
Alpha agonist – decreases aqueous humor synthesis via vasoconstriction
|
|
Mechanism: Brimonidine
|
Alpha agonist - Decreases aqueous humor synthesis
|
|
Clinical use: Brimonidine
|
Glaucoma
|
|
Mechanism: Beta blockers (in glaucoma)
|
Timolol, betaxolol, carteolol
Decrease aqueous humor secretion |
|
Mechanism: Acetazolamide (in glaucoma)
|
Decreases aqueous humor secretion due to HCO3 decrease (via inhibition of carbonic anhydrase)
|
|
Clinical use: Mannitol
|
Glaucoma – emergency Rx
Shock, drug overdose, to decrease intracranial/ocular pressure |
|
Mechanism: Mannitol
|
Osmotic diuretic. Increases TF osmolarity producing more urine. Decreasing effects, so best used in emergencies acutely.
|
|
Mechanism: Cholinomimetics (in glaucoma)
|
pilocarpine, carbachol, physostigmine, echothiophate
Increases outflow of aqueous humor, contracts ciliary muscle and opens trabecular meshwork. Very effective at opening Canal of Schlemm. Use pilocarpine for emergencies. |
|
Mechanism: Latanoprost
|
PGF-2alpha
Increases outflow of aqueous humor |
|
Clinical use: Latanoprost
|
PGF-2alpha
MC prescribed Rx in glaucoma |
|
Tx: Glaucoma (emergency)
|
Pilocarpine (cholinomimetic), Mannitol
|
|
Mechanism: Opioid analgesics
|
Morphine, fentanyl, codeine, heroin, methadone, meperidine, dextromethorphan
Opioid receptor agonists (mu = morphine, delta = enkephalin, kappa = dynorphin) to modulate synaptic transmission. Open K+ channels, close Ca channels → decreased synaptic transmission |
|
Clinical use: Opioid analgesics
|
Morphine, fentanyl, codeine, heroin, methadone, meperidine, dextromethorphan
Pain, cough suppression (DXM), diarrhea (loperamide and diphenoxylate, which slow down peristalsis and can cause constipation), acute pulmonary edema, maintenance programs for addicts (methadone). O in LMNOP for acute CHF. Increase pain threshold, decreasing need for sleep inducer in operations – less chance of waking due to pain. |
|
Mechanism: Butorphanol
|
Partial agonist at opioid mu receptors, agonist at kappa receptors
|
|
Clinical use: Butorphanol
|
Pain. causes less respiratory depression than full agonists. Indications: intranasally for migraines, pregnancy
|
|
Mechanism: Tramadol
|
Very weak opioid agonist, also blocks serotonin and NE reuptake
|
|
Clinical use: Tramadol
|
Chronic pain
|
|
Drugs that work on Simple/Complex Partial Seizures
|
Phenytoin, Carbamazepine, Lamotrigine, Gabapentin (only as adjuvant), Topiramate
Phenobarbital, Valproic acid |
|
First line drugs for Generalized Tonic-Clonic seizures
|
Phenytoin, Carbamazepine, Valproic acid
|
|
Non-First line drugs for Generalized Tonic-Clonic Seizures
|
Lamotrigine, Gabapentin, Topiramate, Phenobarbital
|
|
First line drug for Absence seizures
|
Ethosuxamide
|
|
Non-First line drug for Absence seizures
|
Valproic Acid
|
|
First line drug for prophylaxis: Status epilepticus
|
Phenytoin
|
|
First line drug for acute Status epilepticus
|
Benzodiazepines
|
|
Mechanism: Phenytoin
|
Use-dependent blockade of Na+ channels. inhibition of glutamate release from excitatory presynaptic neurons
|
|
Clinical use: Phenytoin
|
Tonic-clonic seizures (first line), Class IB antiarrhythmic. Treats simple/complex partial seizures and is first line prophylaxis for Status epilepticus
|
|
Mechanism: Barbiturates
|
Phenobarbital, pentobarbital, thiopental, secobarbital
Used as antiepileptic, anesthetic Facilitate GABAa action by binding at the receptor and INCREASING DURATION of Cl channel opening (vs. increased frequency in Benzos), thus decreasing neuron firing. “BarbiDURATes increase DURATion.” |
|
Clinical use: Barbiturates
|
Phenobarbital, pentobarbital, thiopental, secobarbital
Sedative for anxiety, seizures (phenobarbital used for simple/complex partial seizures and tonic-clonic generalized), insomnia (though long half-life = residual effects, so not commonly prescribed for insomnia), induction of anesthesia (thiopental) – high lipid solubility, rapid entry into brain, effect terminated by slower redistribution into sk. mm. and adipose, decreased cerebral blood flow. Phenobarbital first line antiepileptic in pregnancy, children |
|
Mechanism: Benzodiazepines
|
Facilitate GABAa action by acting at the binding site and INCREASING FREQUENCY (vs. Barbs – increased duration) of Cl channel opening. Decrease REM sleep (treats insomnia but less restful sleep results). Most have long half lives and active metabolites.
|
|
Clinical use: Benzodiazepines
|
Diazepam, lorazepam, triazolam, temazepam, oxazepam, midazolam, chlordiazepoxide (all have “az” in them)
Anxiety, spasticity, status epilepticus (persistent seizure - lorazepam, diazepam), detox (especially for alcohol withdrawal DTs), night terrors, sleepwalking, insomnia (temazepam), short-procedure sedation (midazolam – used with gaseous anesthetics and narcotics), trigeminal neuralgia. Also used for seizures of eclampsia (though first line is MgSO4) |
|
Benzo used in insomnia
|
Temazepam
Reduces REM, less restful sleep |
|
Benzo used in short-procedure sedation
|
Midazolam
|
|
Benzo used in alcohol withdrawal, long-acting
|
Chlordiazepoxide
|
|
Benzos used in status epilepticus (persistent seizure)
|
Diazepam, Lorazepam
|
|
GABA potentiators used for epilepsy Tx
|
Benzos, Phenobarbital, Valproic acid, Gabapentin, Topiramate
|
|
Na Channel blockers used in Epilepsy Tx
|
Carbamazepine, Phenytoin, Valproic acid, Lamotrigine, Topiramate
Prevent depolarization |
|
Mechanism: Lamotrigine
|
Blocks voltage gated Na channels
|
|
Clinical use: Lamotrigine
|
Used for Simple/Complex Partial seizures and tonic-clonic
|
|
Mechanism: Gabapentin
|
GABA potentiator (increases release)
|
|
Clinical use: Gabapentin
|
Adjuvant seizure med used for simple/complex partial seizures and tonic-clonic seizures. Also used for peripheral neuropathy.
|
|
Mechanism: Topiramate
|
Blocks Na channels, preventing neuronal depolarization. GABA potentiator (increases release)
|
|
Clinical use: Topiramate
|
Simple/Complex Partial seizures, Tonic-Clonic seizures
|
|
Mechanism: Valproic acid
|
GABA potentiator, blocks Na channels, preventing neuronal depolarization
|
|
Clinical use: Valproic acid
|
First line for tonic-clonic seizures. Used in absence seizures, simple/complex partial seizures, and myoclonic seizures
|
|
Mechanism: Ethosuximide
|
Blocks thalamic T-type Ca channels
|
|
Clinical use: Ethosuximide
|
First line for absence seizures
|
|
Mechanism: Carbamazepine
|
Blocks Na channels, preventing neuronal depolarization
|
|
Clinical use: Carbamazepine
|
First line for trigeminal neuralgia, First line for tonic-clonic seizures, also used for simple/complex partial seizures
|
|
Anesthetics: relationship between Lipid/blood solubility, MAC, potency, km
|
High lipid solubility = low MAC (minimum alveolar concentration) = high potency = low km
High blood solubility = slow induction and recovery times Give both together so as fast one wears off, slower one kicks in |
|
How do these anesthetics compare in potency and induction: Isoflurane, N2O, Halothane, Methoxyflurane, Enflurane
|
Decreasing potency/Increasing speed of induction: Methoxyflurane > Halothane + Enflurane > Isoflurane, N2O
|
|
Mechanism: Inhaled anesthetics
|
Unknown
|
|
Mechanism: Ketamine
|
Arylcyclohexylamine – PCP analog that acts as dissociative anesthetic. Blocks NMDA receptors. Cardiovascular stimulant
|
|
Clinical use: Opiates as anesthetics
|
Morphine, Fentanyl
|
|
Mechanism: Propofol
|
Potentiates GABAa (like benzos and barbs)
|
|
Clinical use: Propofol
|
rapid anesthesia induction and short procedures. Leaves system rapidly, so good for waking up rapidly.
|
|
Mechanism: Local anesthetics
|
Block Na channels by binding specific recpeptors on inner portion of channel. Preferentially bind activated Na channels, so most effective in rapidly firing neurons. Tertiary amine local anesthetics penetrate membrane in uncharged form, then bind to ion channels as charged form
|
|
How are Local anesthetics affected by infection, pH?
|
In infected (acidic) tissue, e.g. an abscess, alkaline anesthetics are charged and cannot penetrate the membrane effectively. More anesthetic is needed.
|
|
Order of nerve blockade for local anesthetics
|
Small diameter fibers > large. Myelinated fibers > unmyelinated. Size effect > myelination, so small myelinated fibers > small unmyelinated > large myelinated > large unmyelinated
Order of loss – pain (lose first) > temperature > touch > pressure (lose last) |
|
Clinical Use: Local anesthetics – Use with vasoconstrictors
|
Vasoconstrictors decrease bleeding and increase anesthesia because restricts drug to local area. All but cocaine given with vasoconstrictor (usually epinephrine).
|
|
Clinical use: Neuromuscular drugs
|
Used for muscle paralysis in surgery or mechanical ventilation. Selective for motor (vs. autonomic) nicotinic receptor
|
|
Reversal of Depolarizing neuromuscular blockade
|
Phase I – prolonged depolarization – no antidote. Block potentiated by AchE-I. Excess NT release
Phase II – repolarized by blocked – antidote consists of AchE-Is, e.g. neostigmine |
|
Reversal of Nondepolarizing neuromuscular blockade
|
Neostigmine, edrophonium, and all other AchE-Is
|
|
Mechanism: Neuromuscular blockade
|
Depolarizing – Succinylcholine – complications include hypercalcemia and hyperkalemia
Nondepolarizing – competitive inhibition of Ach receptors |
|
Mechanism: Dantrolene
|
Prevents release of Ca from SR of sk mm.
|
|
Clinical use: Dantrolene
|
Malignant hyperthermia (caused by use of inhalation anesthetics – except N2O) and succinylcholine. Also used to treat neuroleptic malignant syndrome (a toxicity of antipsychotics)
|
|
Mechanism: Bromocriptine, pramipexole, ropinirole
|
Partial dopamine agonists
|
|
Mechanism: Amantadine
|
May increase dopamine release
|
|
Clinical use: Amantadine
|
Mild, young Parkinson’s patients, used as antiviral against influenza A (not much anymore because of resistance – use oseltamavir) and rubella
|
|
Mechanism: L-dopa + Carbidopa/Tolcapone (or entacapone)
|
Increase Dopamine levels in brain. Unlike dopamine, Dopa can cross BBB into brain, where it is converted to dopamine by dopa decarboxylase. Carbidopa inhibits dopa decarboxylase peripherally. Tolcapone and entacapone block COMT conversion of L-dopa to 3-O-methyldopa, which can’t cross into CNS. These add-ons decrease necessary dose of L-dopa
|
|
Clinical use: L-dopa + Carbidopa/Tolcapone
|
Parkinsonism. L-dopa is the big gun for parkinsons Tx. Almost every Parkinsons patient is on it.
|
|
Mechanism: Selegiline
|
Selectively inhibits MAO-B, increasing availability of dopamine
|
|
Clinical use: Selegiline
|
Adjunctive agent to L-dopa in Parkinson’s Tx. Only MAOI used in Parkinson’s. Be careful not to give MAOIs and anti-depressants with L-dopa because too much increase in dopamine leads to conversion to NE → HTN crisis
Dopa → [Melanin +] Dopamine → NE → Epi |
|
Mechanism: Sumatriptan
|
5HT 1B/1D agonist. Causes vasoconstriction, inhibition of trigeminal activation and vasoactive peptide release. Half-life <2 hours
|
|
Clinical use: Sumatriptan
|
Acute migraines, cluster headache attacks
|
|
Mechanism: Memantine
|
NMDA receptor antagonist. Helps prevent excitotoxicity (mediated by Ca)
|
|
Tx: Heroin addiction
|
Naloxone and naltrexone – competitively inhibit opioids, used in OD
Methadone – long-acting oral opiate – long-acting opiate – used for heroin detox or long-term maintenance Suboxone – naltrexone + buprenorphine (partial agonist) – long acting with fewer withdrawal Sx than methadone. withdrawal symptoms if injected (lower abuse potential) |
|
Mechanism: Typical Antipsychotics (neuroleptics)
|
All typical antipsychotics block dopamine D2 receptors
|
|
Clinical use: Typical Antipsychotics
|
Schiphrenia (primarily positive symptoms), psychosis, acute mania, Tourette’s, agitated demented pt (high potency to avoid worsening dementia)
|
|
Tx: NMS
|
Antipsychotic complication
Dantrolene, agonists (e.g. bromocriptine) |
|
High Potency Typical antipsychotics + toxicities
|
Haloperidol, Fluphenazine, thiothixene
Extrapyramidal effects, not so much anticholinergic |
|
Moderate Potency Typical antipsychotics
|
Molindine, Laxopine, Trifluoperazine
|
|
Low Potency Typical antipsychotics
|
Thioridazine, Chlorpromazine
Anticholinergic side effects, not really extrapyramidal |
|
Mechanism: Atypical antipsychotics
|
Clozapine, Olanzapine, Risperidone, Aripiprazole, Quetiapine, Ziprasidone
Block 5-HT2, alpha, H1 and dopamine receptors |
|
Clinical use: Atypical antipsychotics
|
Clozapine, Olanzapine, Risperidone, Aripiprazole, Quetiapine, Ziprasidone
First line agents for Szhizophrenia (useful for both + and – symptoms) Olanzapine – also used for OCD, anxiety, depression, mania, Tourette’s |
|
Mechanism: Lithium
|
Not established. Possibly related to inhibition of phosphoinositol cascade
|
|
Clinical use: Lithium
|
Mood stabilizer for Bipolar disorder. Blocks relapse and acute manic events. Also SIADH
|
|
Mechanism: Buspirone
|
Stimulates 5HT1A receptors
|
|
Clinical use: Buspirone
|
Generalized anxiety disorder (not PTSD or panic disorder). Does not cause sedation or addiction. Does not interact with alcohol (vs. barbs and benzos)
|
|
Mechanism: TCAs
|
SNRIs
Inhibit fast sodium channels. OD can lead to blockage of phase 0 depolarization in myocytes and His-Purkinje system. Tx: hypertonic sodium bicarbonate |
|
Clinical use: TCAs
|
Imipramine, Amitriptyline, Desipramine, Nortriptyline, Chlomipramine, Doxepin, Amoxapine
(End in –pin(e), -pramine, -triptyline) Major depression, bedwetting (imipramine), OCD (clomipramine) |
|
Clinical use: SSRIs
|
Fluoxetine, paroxetine, sertraline, citalopram, fluvoxemine
Depression, OCD, anxiety, panic, PTSD, anorexia |
|
Mechanism: Bupropion
|
Increases NE and Dopamine by unknown mechanism
|
|
Clinical use: Bupropion
|
Antidepressant. Can be added to SSRI. Smoking cessation
|
|
Mechanism: Venlafaxine
|
SNRI
|
|
Clinical use: Venlafaxine
|
Depression, GAD
|
|
Clinical use: Milnacipran
|
SNRI used for Fibromyalgia
|
|
Clinical use: Sibutramine
|
SNRI used in weight loss
|
|
Mechanism: Duloxetine
|
SNRI, similar to venlafaxine, but more effect on NE
|
|
Clinical use: Duloxetine
|
Depression, diabetic peripheral neuropathy
|
|
Mechanism: Mirtazapine
|
Tetracyclic. Alpha2 antagonist (increased release of NE and 5HT) and potent 5HT2/3 receptor antagonist
|
|
Mechanism: Maprotiline
|
Tetracyclic
NE reuptake inhibitor |
|
Mechanism: Trazodone
|
Antidepressant that primarily inhibits 5HT reuptake
|
|
Clinical use: Trazodone
|
Insomnia (low dose – increases REM sleep), depression (high dose). Given as adjuvant to SSRI
|
|
Mechanism: MAOI
|
Nonselective MAO inhibition – increases levels of amine NTs
|
|
Clinical use: MAOI
|
Atypical depression, anxiety, hypochondriasis
|
|
Things that move K+ out of cells
|
Decreased insulin, beta blockers, acidosis (H/K transporter), digoxin, cell lysis (as in leukemia/treatment)
|
|
Things that move K+ into cells
|
Insulin, beta agonists (e.g. albuterol), alkalosis (give bicarb for Tx), cell creation/proliferation (e.g. cancer)
|
|
Mechanism: Acetazolamide
|
Carbonic anhydrase inhibitor. Causes self-limited NaHCO3 diuresis and reduction in total body HCO3 stores
|
|
Clinical use: Acetazolamide
|
Glaucoma, urinary alkalinization, metabolic alkalosis, altitude sickness (respiratory alkalosis. This helps compensation)
|
|
Mechanism: Loop diuretics
|
Inhibit NaK2Cl cotransport system of thick ascending limb of Loop of Henle. Abolishes hypertonicity of medulla, preventing concentrating of urine. Secretion of isotonic fluid (vs. hypertonic for thiazides). Increased Ca excretion. Loops Lose Calcium (vs. thiazides). Most potent diuretics with excellent efficacy.
|
|
Clinical use: Furosemide, Bumetanide, Torasemide
|
Most potent diuretics. Edematous states (CHF, Cirrhosis, Nephrotic syndrome, Pulmonary edema), HTN (if CHF also present), hypercalcemia
|
|
Mechanism: Ethacrynic acid
|
Essentially same as furosemide, but not a sulfonamide (so can give to pts with sulfa allergies)
|
|
Clinical use: Ethacrynic acid
|
Diuresis in patients allergic to sulfa drugs
|
|
Mechanism: Hydrochlorothiazide
|
Secretion of hypertonic fluid (vs. isotonic for loops). Inhibits NaCL reabsorption in early distal tubule, reducing diluting capacity of nephron. Decreased Ca excretion
|
|
Clinical use: Thiazides
|
HTN, CHF, Idiopathic hypercalciuria
|
|
Mechanism: K-sparing diuretics
|
Spironolactone, Triamterine, Amiloride, Eplerenone
Spironolactone – competitive aldosterone receptor antagonist in cortical collecting tubule Triamterine, Amiloride –block Na channels in CCT |
|
Clinical use: K-sparing diuretics
|
Hyperaldosteronism, K+ depletion, CHF (decrease mortality)
|
|
Diuretic effects – Urine NaCl
|
Increased by all diuretics
|
|
Diuretic effects – Urine K
|
Increased by all except K-sparing diuretics
|
|
Diuretic effects – Blood pH decrease (acidemia)
|
Carbonic anhydrase inhibitors (decreased HCO3 reabsorption), K-sparing diuretics (hyperkalemia → H/K exchange
|
|
Diuretic effects – Blood pH increase (alkalemia)
|
Loops and thiazides
1. volume contraction → increases ATII → Na/H exchange in proximal tubule → increased HCO3 (contraction alkalosis) 2. K loss → H/K exchange puts H into cells. 3. In low K state, H (instead of K) is exchanged for Na in principal cells, leading to alkalosis and “paradoxical aciduria” |
|
Diuretic effects – Urine Ca
|
Increased by loops – abolish lumen-positive potential in thick ascending limb → decreased paracellular Ca reabsorption → hypocalcemia, increased urinary Ca
Decreased by thiazides – block luminal Na/Cl cotransport in DCT → increased Na gradient → interstitial Na/Ca exchange → hypercalcemia |
|
Mechanism: ACE-I
|
Captopril, Enalapril, Lisinopril
Inhibit ACE, reducing levels of ATII, preventing inactivation of bradykinin, a potent vasodilator. Renin release is increased due to loss of feedback inhibition |
|
Clinical use: ACE-I
|
HTN, CHF, Diabetic renal disease
|
|
Tx: Menopausal symptoms
|
Estrogen replacement therapy (weigh risks of endometrial, etc. cancers), SSRI (Venlafaxine), Clonidine (Anti-HTN), Gabapentin (especially with anxiety/seizure disorder or neuropathy in addition)
|
|
Tx: Preeclampsia/eclampsia
|
Delivery of fetus as soon as viable. Otherwise, bed rest, salt restriction, monitoring and treatment of HTN. IV MgSO4 and diazepam to prevent and treat seizures of eclampsia. Benzos controversial. MgSO4 drug of choice, but it can cause hyporeflexia, pulmonary edema, decreased respiratory drive, all signs of overdosing, so check every 4 hrs
|
|
Clinical use: MgSO4
|
Eclampsia seizures. in conjunction with tocolysis to delay labor (stop contractions).
|
|
Tx: Ectopic pregnancy
|
If small, MTX to abort. If large, surgery to remove.
|
|
Tx: Leimyoma (fibroid)
|
Fibroidectomy, OCP (excess bleeding)
|
|
Tx: PCOS
|
Weight loss OCPs (makes ovaries less sensitive to LH), gonadotropin analogs (leuprolide – use pulsatile when they want to get pregnant), clomiphene (SERM - pts have decreased FSH, amenorrhea, so this can help ovulation), anti-androgens (e.g. spironolactone, ketoconazole – both prevent hirsutism and cause gynecomastia and amenorrhea) or surgery
|
|
Mechanism: Leuprolide
|
GnRH analog with agonist properties when used in pulsatile fashion, antagonistic when used in continuous fashion
|
|
Clinical use: Leuprolide
|
Infertility (pulsatile administration), prostate cancer (continuous – use with flutamide), uterine fibroids (continuous), inducing menopause. Prescribe with add back therapy – patient can take estrogen when Sx of menopause too much
|
|
Tx: BPH
|
Finasteride, alpha blockers, tamsulosin (alpha1A selective, fewer side fx, no decrease in BP). Saw Palmetto (works as finasteride does, but no negative side effects and no change to PSA)
|
|
Tx: Prostatitis
|
4 weeks fluoroquinolones or TMP-SMX
|
|
Tx: Epididymitis
|
<35 – GC/Chlamydial infection. Ceftriaxone + Doxycycline
>35 (or Hx of anal sex) – enterobacteria – Fluoroquinolones for 2 weeks (vs. 4 weeks for prostatitis because better blood flow) |
|
Mechanism: Finasteride
|
Blocks 5-alpha-reductase conversion of testosterone → DHT
|
|
Clinical use: Finasteride
|
BPH (shrinks prostate, since DHT promotes prostatic growth. Decreases PSA levels, lowering threshold for prostatic cancer screening). Promotes hair growth, treats male pattern baldness
|
|
Mechanism: Flutamide
|
Nonsteroidal competitive of androgens at the testosterone receptor
|
|
Clinical use: Flutamide
|
Prostatic carcinoma
|
|
Mechanism: Ketoconazole (anti-androgen)
|
Inhibits steroid synthesis
|
|
Mechanism: Spironolactone (anti-androgen)
|
Inhibits steroid synthesis
|
|
Mechanism: Sildenafil, Vardenafil, Tadalafil
|
Inhibit cGMP phosphodiesterase, increasing cGMP, smooth mm. relaxation in corpus cavernosum, increased blood flow, penile erection
|
|
Clinical use: Sildenafil, Vardenafil, Tadalafil
|
Treatment of ED, Pulmonary HTN, Raynaud’s syndrome
|
|
Mechanism: Mifepristone (RU-486)
|
Competitive inhibitor of progestins at progesterone receptors
|
|
Clinical use: Mifepristone (RU-486)
|
Termination of pregnancy. Administered with misoprostol (PGE1 – causes contractions).
|
|
Clinical use: Hormone replacement therapy (HRT)
|
Relief/prevention of menopausal symptoms (e.g. hot flashes, vaginal atrophy) and osteoporosis. Unopposed estrogen replacement therapy (ERT) increases the risk of endometrial cancer, so progesterone is added. Possible increased cardiovascular risk. Some will have testosterone to help with decreased libido, atrophic vaginitis
|
|
Mechanism: Dinoprostone
|
PGE2 analog that causes cervical dilation and uterine contraction
|
|
Clinical use: Dinoprostone
|
Labor induction
|
|
Mechanism: Ritodrine, terbutaline
|
B2 agonists that relax the uterus
|
|
Clinical use: Ritodrine, terbutaline
|
Delaying premature uterine contractions
|
|
Clinical use: Anastrozole, Exemestane
|
Aromatase inhibitors used for BrCa in postmenopausal women
|
|
Clinical use: Testosterone (methyltestosterone)
|
Treat hypogonadism, promote development of secondary sex characteristics. stimulation of anabolism to promote recovery after burn or injury. Treat ER+ BrCa (exemestane). Male with sexual dysfunction or osteoporosis due to decreased testosterone
|
|
Clinical use: Estrogens (ethinyl estradiol, DES, mestranol)
|
Hypogonadism orovarian failure, menstrual abnormalities, HRT in postmenopausal women. use in men with androgen dependent prostate cancer.
|
|
Mechanism: Progestins
|
Bind progesterone receptor, reduce growth and increase vascularization of endometrium
|
|
Clinical use: Progestins
|
Used in oral contraceptives and in the treatment of endometrial cancer and abnormal uterine bleeding
|
|
Tx: Neonatal respiratory distress syndrome
|
Lecithin: Sphingomyelin < 2.0 in amniotic fluid
Steroids 24 hrs before delivery – matures pneumocytes. Also artificial surfactant for infant |
|
Tx: Primary Pulmonary HTN
|
Sildenafil
|
|
Mechanism: H1-blockers
|
1st generation – Diphenhydramine, Dimenhydrinate, Chlorpheniramine, Hydroxazine
2nd Generation – Loratadine, foxofenadine, Destoratadine, Ceterizine Reversible inhibitors of H1 histamine receptors (non-stomach locations). Anti-serotonergic, anti-muscarinic, anti-alpha-adrenergic. Increase proportion of inactive H1 receptors ('reverse blockade') |
|
Clinical use: H1 Blockers
|
Can help prevent asthma exacerbations in pts with allergies
|
|
Clinical use: H1 Blockers – 1st generation
|
1st generation – Diphenhydramine, Dimenhydrinate, Chlorpheniramine, Hydroxazine
Allergy, motion sickness, sleep aid |
|
Clinical use: H1 Blockers – 2nd generation
|
2nd Generation – Loratadine, foxofenadine, Destoratadine, Ceterizine
Allergies, not sleep |
|
Mechanism: Asthma drugs
|
Bronchoconstriction is mediated by 1) inflammatory processes and 2) sympathetic tone. Tx directed at these two
|
|
Mechanism/Use/Toxicity: Salmeterol
|
Long-acting agent for asthma prophylaxis only. B2 agonist (Bronchial smooth muscle relaxer). Tremor, arrhythmia
|
|
Clinical use: Cromolyn
|
Clinical use: Cromolyn
|
|
Mechanism: Cromolyn
|
Prevents release of mediators from mast cells
|
|
Clinical use/toxicity: Methylxanthines
|
Last resort for COPD pts. Cardiotoxicity, neurotoxicity lead to narrow therapeutic window. CYP450 metabolism
|
|
Mechanism: Methylxanthines
|
Theophylline, Aminophylline
Likely cause bronchodilation by inhibiting phosphodiesterase, thereby decreasing cAMP hydrolysis |
|
Mechanism: Zileuton
|
Anti-leukotriene. 5-lipoxygenase pathway inhibitor. Blocks conversion of arachidonic acid to leukotrienes
|
|
Clinical use: Zileuton
|
Good for asthma prophylaxis. Can be given with steroids, albuterol
|
|
Clinical use: Leukotriene receptor blockers
|
allergies/asthma. Especially good for aspirin-induced asthma
Montelukast – can be given to pts under 5. Zafirlukast – only 5+ |
|
Mechanism: Guaifenesin
|
Stimulates vagus to decrease viscosity of secretions in bronchial tree
|
|
Clinical use: Guaifenesin
|
Expectorant. Removes excess sputum, but large doses necessary. Does not suppress cough reflex (need DXM, codeine [opioids] for that)
|
|
DHFR inhibitors
|
MTX, TMP, Pyrimethamine (used in eukaryotes, prokaryotes and protozoa respectively). Notice each has 'meth' in it, and that THF is used to donate methyl groups
|
|
Mechanism: Azathioprine
|
is converted to 6-MP, which blocks PRPP Amidotransferase, blocking PRPP conversion into 5-P-ribosylamine (replacement of PPi with NH2) in purine synthesis
|
|
Tx: Mucormycosis
|
surgical debridement and amphotericin B
|
|
Tx: anovulation
|
Menotropins (human menopausal gonadotropin) - act like FSH - lead to production of one dominant follicle. Followed by one large dose of HCG - simulates LH surge
|
|
Clinical use/mechanism: Menotropins
|
Used in anovulatory infertility
Human menopausal gonadotropins - act like FSH - lead to production of one dominant follicle |
|
Clinical use/mechanism: HCG
|
Used in anovulatory infertility. After menotropins create a dominant follicle, HCG is used to simulate an LH surge
|
|
Which benzo has the shortest half-life (fastest acting)?
|
Alprazolam - less than 12 hrs
Lorazepam - 10-15 hrs Chlordiazepoxide, Clonazepam, Diazepam - 25-100 hours |
|
Mechanism: Pentazocine
|
Opioid analgesic - partially agonistic and weakly antagonistic at mu receptors. Designed to be effective analgesic with little/no abuse potential. If given to pt with opioid addiction, can induce withdrawal Sx.
|
|
Mechanism: Lamivudine
|
cytosine analog NRTI. Must be phosphorylated to active lamivudine triphosphate form by intracellular kinases. Blocks HIV Reverse Transcriptase via DNA chain termination.
|
|
Mechanism: Alpha glucosidase inhibitors
|
miglitol, acarbose
Block disaccharidases, delaying carbohydrate absorption |
|
Mechanism: Digoxin
|
75% bioavailability, 20-40% protein bound, half time = 40 hours, urinary excretion
|
|
Clinical use: Digoxin
|
CHF (increased contractility), a-fib (decreased conduction at AV node and depression of SA node)
|
|
Clinical use: Bactericidal for gram+ve cocci, rods, gram-ve rods (Neisseria), spirochetes.
|
Penicillins
|
|
Mechanism of resistance against antitumor drugs
|
Human multidrug resistance (MDR1) gene codes for P-glycoprotein, a transmembrane ATP-dependent pump protein with broad specificity for hydrophobic compounds. Normally expressed in gut epithelium, also in BBB, helping keep or flush out foreign substances.
|
|
Mechanism: Zolpidem
|
GABAa receptor agonist (similar mechanism to benzos). Rapid onset (15 min), metabolized by CYP450
|
|
Clinical use: Zolpidem
|
Short-acting hypnotic agent used for short term insomnia treatment. Less risk of tolerance/addiction/withdrawal symptoms than benzos. No anticonvulsant properties in regular doses. No muscle relaxing effects, not used for anesthesia
|