Drugs COPY Flashcards
sad sad sad time
Amphotericin B
Antifungal
MOA: Combination of the polyene with cytoplasmic sterols, mainly ergosterols, results in increased cell permeability and death of the fungi.
-does not effect synthesis of ergosterols
MOR: Alteration of sterols for decreased affinity and decreased sterol concentrations in cell membranes.
Nystatin
Antifungal
MOA: Combination of the polyene with cytoplasmic sterols, mainly ergosterols, results in increased cell permeability and death of the fungi.
-does not effect synthesis of ergosterols
MOR: Alteration of sterols for decreased affinity and decreased sterol concentrations in cell membranes.
AE: -Nephrotoxicity is the major side effect.
● Adequate hydration status may decrease toxicity.
-Idiosyncratic hypotension and arrhythmias
● Test doses
-Electrolyte disturbances
● K+ , Mg++
-Fever, chills, and rigors
Clinical use: -Systemic fungal infections
Fluconazole & voriconazole
Antifungal
Azole
MOA: inhibit ergosterol synthesis;
Fluconzaole:
Drug interactions occur
Active against candida albicans
Voriconazole:
Major drug interactions through inhibition of mammalian cytochrome p450
● This is also the case with Itraconazole
Aspergillus- active against
- Very potent inhibitor of cytochrome p450
Capsofungin
Antifungal
Class: Echinocandins
MOA: beta-(1,3)-glucan inhibitor. Beta-(1,3)-glucan is an integral part of the fungal cell wall
Terbinafine
Antifungal
-blocks squalene epoxidase
AE: Liver function abnormalities, hepatitis
Isoniazid (INH)
Antituberculosis
MOA: Inhibition of synthesis of mycolic acid in cell wall
INH is a prodrug
- Catalase/peroxidase enzyme (katG) metabolizes isoniazid to active form in cell
- Strains which fail to metabolize isoniazid due to defective catalase/peroxidase are resistant to isoniazid
Metabolism:
◦ Metabolized in the liver by N-acetyl transferase. Rate of acetylation is genetically determined as an autosomal recessive trait. Does not alter therapy clinically except for weekly administration schedules.
Clinical use:
1) Treatment of latent tuberculosis (positive PPD without active disease)
2) Combination therapy for active TB at any stage
AE:
Hepatitis
◦ Can occur at any time but peak incidence is within the first 4-8 weeks. Hepatic failure can ensue and lead to death if drug is continued.
Neurotoxicity
◦ is mediated by increased excretion of pyridoxine and concomitant administration of B6 is always given when INH is used
Rifampin
Antituberculosis
MOA: Inhibits DNA dependent RNA polymerase of mycobacterial cells. Human enzyme is insensitive to effects of the drug.
(RNA-DNA polymerase= RNA reverse transcriptase)
MOR: Alteration of DNA-dependent, RNA polymerase, (rpoB).
Absorption:
◦ Excellent oral absorption; wide distribution, including CNS.
Metabolism
◦ Hepatic via cytochrome P-450 (deacylation). Induces its own increased metabolism.
AE:
Hepatotoxicity generally manifests as cholestatic changes ( increased Alk. Phos., increased bili) but can also be necroinflammatory with elevated transaminases. INH and rifampin may potentiate hepatotoxicity of the other agent.
Major major drug interactions!!!
Increased metabolism of coumarin, oral contraceptives, and phenytoin may occur. Interaction with verapamil causes marked reduction in verapamil levels.
Pyrazinamide
Antituberculosis
MOA: Inhibition of fatty acid synthesis
-converts drug to pyrazinoic acid at acid pH
-prodrug
MOR: unknown
AE:
Hepatotoxicity / Hepatitis
Gout - drug can cause elevated uric acid levels causing gout
Ethambutol
Antituberculosis
MOA:
Possibly interferes with arabinosyl transferase, an enzyme that polymerizes arabinose into arabinan
MOR:
Mutations in the gene cluster but not a specific target identified
AE: Retrobulbar neuritis(optic neuritis) ◦ Usually develops as decreased acuity and change in color vision (yellow and green).
Associated with high doses.
Peripheral neuropathy can also occur.
Acyclovir
Antivirals: Herpes
MOA:
Chain termination: removal of acyclovir triphosphate addition
-Acyclovir triphosphate is present in 40-100 fold higher concentrations in HSV infected cells. The triphosphate form inhibits DNA polymerase and is incorporated into viral DNA as function as a chain terminator.
Most commonly used:
Valacyclovir
Maraviroc
Anti HIV
MOA:
CCR5 Chemokine Receptor Antagonist
Enfuvirtide
Antiviral: HIV
-MOA:
binding a region of the HIV envelope glycoprotein gp41 and preventing viral fusion with the target cell membrane
- Formulation: Polypeptide
- SQ twice daily
Zivodudin
- Anti HIV
- Nucleoside Reverse Transcriptase Inhibitors
MOA:
Inhibition of viral RNA-dependent DNA polymerase: Nucleoside triphosphates competitively inhibit reverse transcriptase also inhibits cellular alpha-DNA polymerase 100-fold less avidly.
Incorporation of the triphosphate into the chain leads to chain termination.
MOR: Single nucleotide change can confer resistance; since low fidetly, environment is highly favorable to resistance
Zidovudine: Myeolosuppression
Abacavir: rash (fatal)
Class toxicities:
- Lactic acidosis/hepatic steatosis
- Probably responsible for lipodystrophy
Prone to fidelity
Abacavir
- Anti HIV
- Nucleoside Reverse Transcriptase Inhibitors
MOA:
Inhibition of viral RNA-dependent DNA polymerase: Nucleoside triphosphates competitively inhibit reverse transcriptase also inhibits cellular alpha-DNA polymerase 100-fold less avidly.
Incorporation of the triphosphate into the chain leads to chain termination.
MOR: Single nucleotide change can confer resistance
Abacavir: Rash (fatal) Hypersensitivity reactions Check for HLA-B*5701 Increased risk of cardiac sx
Emtricitabine: Rash (mild) [MOST COMMONLY USED]
Class toxicities:
- Lactic acidosis/hepatic steatosis
- Probably responsible for lipodystrophy
Prone to fidelity
Emtricibatine
- Anti HIV
- Nucleoside Reverse Transcriptase Inhibitors
MOA:
Inhibition of viral RNA-dependent DNA polymerase: Nucleoside triphosphates competitively inhibit reverse transcriptase also inhibits cellular alpha-DNA polymerase 100-fold less avidly.
Incorporation of the triphosphate into the chain leads to chain termination.
MOR: Single nucleotide change can confer resistance
Emtricitabine: Rash (mild) [MOST COMMONLY USED]
Class toxicities:
- Lactic acidosis/hepatic steatosis
- Probably responsible for lipodystrophy
Prone to fidelity
Tenofovir
Anti HIV
Nucleotide RTI
Already monophosphorylated
problems with renal toxicity (disoproxil»_space; alafenamide)
New tenofovir alafenamide formulation has less renal toxicity
Major toxicities include abnormalities of calcium and phosphate, increased bone fragility, and renal dysfunction.
Efavirenz
Anti HIV
Non-nucleoside Reverse Transcriptase Inhibitors:
MOA: Work on RT at a site distinct from the active site (These drugs do NOT look like nucleoside analogs)
[Inhibits reverse transcriptase]
AE: CNS effects , Variable p450 activity
Raltegravir
Anti HIV
-Integrase inhibitors
MOA: Cornerstone of therapy for HIV
AE:
Raltegravir:
First integrase inhibitor
Very few side effects - myositis
Not metabolized by CYP3A (cytochrome p450)
Better tolerated, higher CD4 counts, few adverse effects, lower lipids than efavirenz containing regimens.
Can now be recommended as first line therapy
Elvitgravir
Anti HIV
-Integrase inhibitors
MOA: Cornerstone of therapy for HIV
Elvitegravir: Part of quad pill
Dolutergravir
Anti HIV
-Integrase inhibitors
MOA: Cornerstone of therapy for HIV
Dolutegravir: can be used in less than three drug regimens; requires more than 1 mutation to receive full resistance
Dolutergravir: once daily
Ritonavir
Anti HIV:
Protease inhibitor
MOA: The major viral genes gag and gag-pol are transcribed as polyproteins requiring several proteolytic cleavages for viral proteins to be produced. l
The HIV protease is an aspartyl peptidase (Renin is an aspartyl peptidase) which has very specific cleavage site in the HIV polypeptide.
PI: Adverse effects- The agents differ individually but all share a variable and potent inhibition of the cytochrome p450 system. The drugs are also metabolized via p450.
Ritonavir:
-GI intolerance, almost exclusively used to “boost’ other drugs
-Boosting: Ritonavir is very potent CYP3A inhibitor
Given with other protease inhibitors not for its HIV protease activity, given to increase both drug level and half-life of co-administered PI
Boosting: boost serum level and half life; given in combination with other protease inhibitors
Cobicistat
Anti HIV:
Protease inhibitor
MOA: The major viral genes gag and gag-pol are transcribed as polyproteins requiring several proteolytic cleavages for viral proteins to be produced. l
The HIV protease is an aspartyl peptidase (Renin is an aspartyl peptidase) which has very specific cleavage site in the HIV polypeptide.
Cobicistat:
- protease enhancer
- A pharmacoenhancer
- An analogue of ritonavir but devoid of HIV protease activity
- Drug is metabolized by CYP3A and the metabolite irreversibly inhibits CYP3A
- NEITHER inhibit ALL
PI: Adverse effects- The agents differ individually but all share a variable and potent inhibition of the cytochrome p450 system. The drugs are also metabolized via p450.
Darunavir
MOA: The major viral genes gag and gag-pol are transcribed as polyproteins requiring several proteolytic cleavages for viral proteins to be produced. l
The HIV protease is an aspartyl peptidase (Renin is an aspartyl peptidase) which has very specific cleavage site in the HIV polypeptide.
PI: Adverse effects- The agents differ individually but all share a variable and potent inhibition of the cytochrome p450 system. The drugs are also metabolized via p450.
Adamantanes:
Amantadine
Rimantidine
MOA: Inhibit uncoating of the viral RNA by interfering with the function of the M2
-Block acidification of lysosomal fusion
Other notes: For Influenza A
Influenza B has a very different M2 and is resistant to adamantanes
MOR: Occurs easily in the laboratory through unclear mechanisms
Clinical Use: None now, but may come back in future (bc. Of resistance)
AE: 1) Anticholinergic (dry mouth,pupillary dilitation, toxic psychosis) side effects are common especially with increased age and decreased renal function.
2) GI disturbance
3) Central nervous system toxicity
4) Dehydration increases drug levels. Drug drug interaction with the diuretic triamterene and hydrochlorothiazide
Baloxavir
MOA: Inhibits the influenza specific cap endonuclease
-Effective with only a single dose of medication
Other Notes: One dose therapy for both influenza A and B
-High rates of resistant virus seen in patients treated but doesn’t seem to decrease effectiveness
Oseltamivir
Neuraminidase Inhibitors
MOA: Influenza binds to cells via the hemaglutinin which binds to sialic acid (neuraminic acid)
-Inhibition of neuraminidase activity decreases release of virus from infected cells, increases formation of viral aggregates and decreases viral spread.
Tenofovir
Nucleoside reverse transcriptase inhibitors
Other Notes: The first approved nucleoTide agent. Has excellent activity against HIV and Hepatitis B virus
AE: Major toxicities include abnormalities of calcium and phosphate, increased bone fragility, possible renal dysfunction
also used for HIV
Entecavir
Most commonly used against hepatitis B
-Nucleoside analogs; guanosine analog
Both:
No anti-HIV activity
Very potent HBV activity with low rate of selection of viral resistance
Inhibits HBV replication more effectively than lamivudine or adefovir
Generally agents of first choice with enhanced activity
Chronic Hepatitis B
- Most therapy these days with entecavir, telbivudine unless patent is HIV infected
- BE AWARE OF THE DEVELOPMENT OF RESISTANT VIRUS ESPECIALLY IN HIV AND HBV CO-INFECTED PATIENTS. Resistant mutant less virulent and sudden discontinuation may precipitate return to wild type HBV and accelerated liver disease – applies to all hep B active agents.
Telbivudine
Work against hepatitis B
-Nucleoside analogs; thymidine analogue
Both:
- No anti-HIV activity
- Very potent HBV activity with low rate of selection of viral resistance
- Inhibits HBV replication more effectively than lamivudine or adefovir
Generally agents of first choice with enhanced activity
Chronic Hepatitis B
- Most therapy these days with entecavir, telbivudine unless patent is HIV infected
- BE AWARE OF THE DEVELOPMENT OF RESISTANT VIRUS ESPECIALLY IN HIV AND HBV CO-INFECTED PATIENTS. Resistant mutant less virulent and sudden discontinuation may precipitate return to wild type HBV and accelerated liver disease – applies to all hep B active agents.
bocePRavir, telaPRavir, simePRavir
ParitaPRevir, grazoPRevir in combinations
Direct acting Antiviral
-NS3 Protease Inhibitors
Treat Hep C; used to prevent long term symptoms associated with disease
sofosBuvir
NS5B RNA-Dependent RNA polymerase inhibitor, nucleoside based
- Treat Hep C; used to prevent long term symptoms associated with disease
- NS5B inhibitors can be coupled with NS5A inhibitors inorder to treat hepatitis C
once daily nucleoside analog
dasaBuvir
NS5B RNA-Dependent RNA polymerase inhibitor, non-nucleoside based
-Treat Hep C; used to prevent long term symptoms associated with disease
NS5B inhibitors can be coupled with NS5A inhibitors inorder to treat hepatitis C
LedipAsvir, daclatAsvir
- NS5A- RNA binding and assembly replication complex inhibitors
- Treat Hep C; used to prevent long term symptoms associated with disease
Chloroquine
- long acting; given once a week
MOA: Links and inhibits haemoglobin, therefore blocking detoxification
-In chloroquine free heme accumulates in sensitive parasite → free heme accumulates in parasite which is toxic
MOR: Mutation of gene, Pfcrt, which encodes a transmembrane protein in the parasite’s food vacuole
-Pfmdr 1 mutation = compensatory mechanism
AE: Retinal degeneration with long term use
- Skin itching in West Africans
- Hypotension, heart block, cardiac arrest with overdoses
- Suicide attempts
Other Notes:Oldest, safest, synthetic antimalarial drug; Drug of choice to areas of the world with no chloroquine resistance
- Low toxicity
- SAFE IN PREGNANCY
- Must take retinal exam if taking chloroquine for more than a year
Alt. Medication: hydroxychloroquine**
Mefloquine
long acting; given once a week
MOA: Active against most strains of chloroquine-resistant P. falciparum
AE: Can trigger or worsen psychiatric disorders (depression)
-Decreased coordination or fine tremor
Important for pilots
Other notes: Avoid long term use in patients with history of depression
- Believed to be safe in pregnancy
- May use with caution in patients takin B-blocker
- Greater toxicity than chloroquine
Quinine
AE: Cinchonism: nausea, vomiting, tinnitus, disturbed vision, bizarre ideation, nightmares
Other Notes: Part of family rubiaceae: coffee, ipecac, quinine from cinchona
-NOT to be used for nocturnal leg cramp treatment or restless legs syndrome → black box warning
Primaquine
short acting for prophylaxis; given once daily
MOA: Activity against RBC stages of malaria
-Active against liver stages of P.vivax and P.ovale
MOR: Main use in malaria is to eradicate liver forms afer completing course of chloroquine
AE: Use tefinaquine if becomes unavailable
Reduce dose to 1/day
-w/ clindamycin = 2nd choice treatment for pneumonia in transplant patients
-Should be given to anyone diagnosed with P.vivax or P.ovale
Malarone/Proguanil* (atovaquone + proguanil)
-short acting for prophylaxis; given once daily
MOA: Inhibitor of electron transport, cytochrome b
AE: EXPENSIVE→ $8.60 per pill and has to be taken daily
- Antimalarial combination approved in 2000
- -> For prevention and treatment of malaria
Doxycycline*
short acting for prophylaxis; given once daily
Other Notes: Member of genus artemisia (absinthe) → sweet wormwood
- Phototoxicity (sunburn)
- Active against all strains of malaria including chloroquine resistant
CoArtem
- combination of artemether + lumefantrine (artemisinin drugs)
- Combination therapy = mandatory for P.falciparum malaria
Metronidazole (Flagyl)
-anti protozoal
Other Notes: Used to treat anaerobic bacteria (C. difficile)
Tinidazole (Tindamax)
anti-protozoal
MOA: Activity against anaerobic bacteria
-Second generation nitroimidazole
Other Notes: Alternative with metronidazole for amebic dysentery or amebic abscesses
Nitazoxanide (Alinia)
anti-protozoal
MOA: Nitrothiazolyl-salicylamide derivative
-Unknown, but thought to be related to inhibition of pyruvate:ferredoxin oxidoreductase (PFOR)
Other Notes: Active against anaerobic and microaerophilic bacteria against rotavirus, influenza, and hepatitis C
-First and only drug approved for treatment for cryptosporidiosis and to become available as a liquid
Iodoquinol
Anti-protozoal
MOA: Kills amoebic cysts in intestinal lumen
Other Notes: ALT. MED: paromomycin (poorly absorbed)
-Recommended as followup after metronidazole in patients with invasive amoebic disease
Bismuth
Anti-Protozoal
MOA: anti parasitic and anti-diarrheal drug
Other notes: Useful for self initiated treatment of travelers diarrhea
Ivacaftor
Class: CFTR Modulators
MOA: CFTR potentiators: increase CFTR activity (targets class III mutations)
- binds to CFTR channel to induce non-conventional mode of gating → increases probability of channel opening
CFTR modulators:
Therapeutic Effects:
• By restoring CFTR function, these modulators are thought to improve the airway surface liquid layer in the lungs
• Clinical trials of approved agents have demonstrated improvements in measures of lung function such as forced expiratory volume (FEV) and fewer pulmonary exacerbations
Genetic testing is always required before these drugs can be prescribed, since they are designed to correct the effects of specific mutations
Mebendazole
Antihelminthics
MOA: Inhibits microtubule function
MOR: Mutation in beta-tubulin may confer resistance
Other notes: Formerly main drug of choice for most intestinal round worms (ascaris, hookworms, whipworm (multiple doses needed to treat), pinworm)
Albendazole
Antihelminthics
Other Notes: Drug of choice for cysticercosis and echinococcal cysts
-Spectrum also includes all worms
-Single dose is enough for de-worming ascaris, hookworm, and pinworm
-Multiple doses needed to eradicated whipworm.
Lumacaftor
CFTR correctors – correct folding / trafficking (targets class II mutations)
Lumacaftor: acts as a chaperone to improve CFTR folding
CFTR modulators:
Therapeutic Effects:
• By restoring CFTR function, these modulators are thought to improve the airway surface liquid layer in the lungs
• Clinical trials of approved agents have demonstrated improvements in measures of lung function such as forced expiratory volume (FEV) and fewer pulmonary exacerbations
Genetic testing is always required before these drugs can be prescribed, since they are designed to correct the effects of specific mutations
Tezacafor
CFTR correctors – correct folding / trafficking (targets class II mutations)
Tezacafor & elexacaftor :alters CFTR protein to improve trafficking to cell surface
CFTR modulators:
Therapeutic Effects:
• By restoring CFTR function, these modulators are thought to improve the airway surface liquid layer in the lungs
• Clinical trials of approved agents have demonstrated improvements in measures of lung function such as forced expiratory volume (FEV) and fewer pulmonary exacerbations
Genetic testing is always required before these drugs can be prescribed, since they are designed to correct the effects of specific mutations
Elexacftor
CFTR correctors – correct folding / trafficking (targets class II mutations)
Tezacafor & elexacaftor :alters CFTR protein to improve trafficking to cell surface
CFTR modulators:
Therapeutic Effects:
• By restoring CFTR function, these modulators are thought to improve the airway surface liquid layer in the lungs
• Clinical trials of approved agents have demonstrated improvements in measures of lung function such as forced expiratory volume (FEV) and fewer pulmonary exacerbations
Genetic testing is always required before these drugs can be prescribed, since they are designed to correct the effects of specific mutations
Ivermectin
Anti-helminthics
MOA: Activity against arthropods (insects, ticks, mites)
Other notes: Must be used along with topical treatments for norwegian scabies
-Drug of choice for S.stercoralis and O.volvulus (river blindness) treatment
Hypertonic saline and inhaled mannitol
CF treatment:
- Airway hydrators
- they osmotically increase airway hydration, aiding expectoration
Mucolytics
- CF treatment
- Inhaled n-acetylcysteine cleaves disulfide linkages in mucus
- Inhaled dornase alfa is a DNAase endonuclease that cleaves long, sticky DNA polymers in mucus to reduce sputum viscosity & elasticity (does not affect intracellular DNA)
Praziquantel
- Opens calcium channels; results in tetanic contraction of worms and vacuolization of the integument
- Flukes become sensitized, but only adult flukes are killed
Open Notes: Kill adult tapeworms
- Treatment against adult flukes and tapeworms
- Skin- invading cercariae and larval schistosomes are not affected
Nirmatrelvir- ritonavir
MOA: nirmatrelvir inhibits the main viral protease enzyme (Mpro), preventing viral replication
AE: Warnings:
• Dose must be decreased for patients with renal dysfunction
• As CYP 3A4 inhibitor, potential for serious drug interactions
Other notes:
Antiviral
-an oral combination protease inhibitor with strong evidence for efficacy in both vaccinated and unvaccinated people
Remdesivir
MOA: active metabolite is incorporated into viral RNA, where it inhibits viral RNA polymerase, disrupting viral replication (stalling)
AE: Limitations: Requires parenteral (IV) administration over 3 days
Other notes:
- Antiviral
- a prodrug, converted to an ATP analog inside cells (a nucleotide analog)
- alternative option for symptomatic outpatients with risk of severe disease who cannot use first-line agents; is the first drug FDA approved for COVID
- unvaccinated outpatients, treated within 7 days of symptom onset; remdesivir reduced risk of hospitalization at 28 days by 87%
Molnupiravir
MOA: Active form competes with cytidine triphosphate (CTP) for incorporation into viral RNA
• Incorporation creates extensive mutations in viral RNA, resulting in viral error catastrophe
AE: Limitations:
Due to bone / cartilage toxicity, molnupiravir is not recommended for: • Children under 18 years old • Pregnancy and anyone of childbearing potential • Male partners of women of childbearing potential
Other notes:
- a prodrug, converted to an active triphosphate form
- an oral antiviral nucleoside analog – mechanism is loss of viral genetic stability (lethal mutagenesis) *not mutagenic in humans
- Efficacy Data: a reduction but not statistically significant
Sotromivab
Monoclonal Antibody
MOA: mAb binding to virus blocks fusion and prevents viral entry into host cell
(The mAb drugs in use bind to different locations on the spike protein receptor binding domain (RBD))
AE: Often low availability
• Parenteral administration (IV) • Most are not active against omicron variant
Other notes:
-Preferred option for symptomatic outpatients w risk of severe disease
-Sotrovimab: Effective against omicron
high risk unvaccinated adults treated within 5 days of symptom onset; reduced hospitalization / death at 29 days by 85%
