USMLE Pharmacology III

What type of drug is Nevirapine?

A non-nucleoside reverse transcriptase inhibitor

What is particularly beneficial about Nevirapine besides its use as part of the HAART regimen?

A one time single dose at the time of delivery DRAMATICALLY reduces the vertical transmission of HIV to baby

Drug interactions of Nevirapine?

It is an inducer of P450

Side effects of Nevirapine?

Rash

Liver damage

What is one of the main side effects of Efavirenz?

Dysphoric dreams...NIGHTMARES***

Insomnia

What type of drug is Efavirenz?

A non-nucleoside reverse transcriptase inhibitor

What type of drug is Zidovudine?

A nucleoside reverse transcriptase inhibitor

What are the other names of Zidovudine?

Azidothymidine

ZDV

AZT

What is the MOA of all nucleoside reverse transcriptase inhibitors?

They are phosphorylated nonspecifically to a triphosphate that inhibits reverse transcriptase by competing with natural nucleotides AND can be incorporated in viral DNA and cause chain termination due to their lack of a 3' OH

What is the main mode of resistance to NRTIs?

Mutation in the POL gene, which encodes RT, Integrase and Aspartate Protease

What is the most hematotoxic of all the NRTIs

Zidovudine

Is there cross resistance between different NRTIs?

No, so long as they do not represent the same nucleotide.

What nucleotide is Zidovudine and analog of?

Thymidine

What are the major side effects of Zidovudine?

Bone marrow suppression**

Headache, myalgias and peripheral neuropathy

What is the major side effect of Didanosine?

Pancreatitis***

Peripheral neuropathy

Liver dysfunction

What nucleoside is Didanosine and analog of?

Inosine, which can form A or G down the road

What is the abbreviation for Didanosine?

DDI

What type of drug is Didanosine?

A nucleoside reverse transcriptase inhibitor

What type of drug is nucleoside reverse transcriptase inhibitor Zalcitabine?

A nucleoside reverse transcriptase inhibitor... Cytosine analog?

What is the abbreviation for Zalcitabine?

DDC

What are the major side effects of Zalcitabine?

Peripheral Neuropathy***

Pancreatitis

What drug should not be used in combination with Zalcitabine?

And other Cytosine analog

and

Especially Didanosine! Both cause Pancreatitis and peripheral neuropathy.

What type of drug is Stavudine?

A nucleoside reverse transcriptase inhibitor..Thymidine analog

What is the abbreviation for Stavudine?

D4T

What are the major side effects of Stavudine?

Peripheral Neuropathy***

Bone marrow suppression, but less that Zidovudine, so commonly used in its place.

What type of drug is Lamivudine?

A nucleoside reverse transcriptase inhibitor---Cytosine analog

What is the abbreviation for Lamivudine?

3TC

What are the side effects of Lamivudine?

Some neutropenia and GI effects, but overall least toxic of any of the nucleoside reverse transcriptase inhibitors.

Use of Lamivudine besides in HIV?

Can be used to treat Hep B as this is also a uses a DNA polymerase.

What type of drug is Emtricitabine?

A nucleoside reverse transcriptase inhibitor--Cytosine analog that is the new version of Lamivudine

What type of drug is Abacavir?

A nucleoside reverse transcriptase inhibitor

What is the major side effect of Abacavir that is tested on the USMLE?

5% of people taking it develop allergies, severe enough that it must be removed from their regimen.

What is the abbreviation for Emtracitabine?

FTC

What is the abbrevation for Abacavir?

ABC

What are two common treatments for the BM suppression that comes with NRTI treatment?

GM-CSF and Erythropoeitin.

Common side effect of NRTIs in general, besides BM suppression?

Lactic Acidosis

What what CD4 count is HAART begun?

When the CD4 count drops below 500

What is the enzyme that protease inhibitors for HIV work on?

The Aspartate Protease enzyme encoded by the POL gene....

What is the normal function of the 'protease' that protease inhibitors are working on?

Cleaves precursor polypeptides in HIV so they can become active.

What is the MO Resistance to Protease inhibitors?

Mutations in the POL gene

What are the side effects of most all Protease inhibitors??

Crystalluria with Nephrotoxicity, so maintain hydration.

MAJOR DRUG INTERACTIONS as most affect P450 in some way

Disordered Lipid and CHO metabolism with central adiposity and insulin resistance...DM II type scenario

What type of drug is Indinavir?

A protease inhibitor

What type of drug is Ritonavir?

A protease inhibitor

What do ALL protease inhibitors end in?

NAVIR.... NAVIR tease a protease.

What Protease Inhibitor is least likely to cause the DM II type complications with its use in HIV pts?

Atazanavir

What protease inhibitor is most likely to cause Thrombocytopenia?

Indinavir

What type of drug is Enfuvirtide?

An HIV fusion inhibitor

What is the MOA of Enfuvirtide?

Binds gp41 on the HIV and through steric hindrance inhibits the binding of gp 120 to the CD4 receptors...This blocks HIV entry into cells

What type of drug is Maraviroc?

An HIV fusion inhibitor

What is the MOA of Maraviroc?

Binds to CCR5 protein on T-helper cells and prevents viral entry

What is the MOA of Raltegravir?

It is an integrase inhibitor that blocks the integration of HIV into host cells.

What side effect is associated with Enfuvirtide?

It leads to an increased risk of acquiring bacterial pneumonia.

What are the main drug effects of Amantidine?

Antimuscarinic

Domapine releaser

Dopamine reuptake blocker

What is the MOA of Amantidine?

Blocks viral penetration and uncoating of influenza A via the M2 protein.... Shaves a couple of days off the flu.

What is the MOA of Zanamivir?

Inhibits neuraminidase of Influenza A and B, preventing release of the viral progeny from the cell

What is the MOA of Oseltamivir?

Inhibits neuraminidase of Influenza A and B, preventing release of the viral progeny from the cell

How do you remember the Side effects and uses of Amantadine?

Amantadine blocks influenza A and rubellA, causes problems with the cerebellA! Ataxia and dizziness

What is the MOA of Ribavirin?

Inhibits IMP dehydrogenase, so guanine nucleotides cannot be made

Side effects of Ribavirin?

Hematotoxic...causes hemolytic anemia

Uses of Ribavirin?

Management of RSV in aerosolized form..

Treatment of Hep C in conjunction with Alpha interferons

Side effects of Interferon use?

Neutropenia

How do you remember the antibiotics to avoid in pregnancy and Why are they avoided??

SAFE Moms Take Really Good Care!

Sulfonamides--Kernicterus

Aminoglycosides-Ototoxicity

Fluoroquinolones-Cartilage Damage

Erythromycin-- Acute Cholestatatic Hep in mom

Metronidazole--mutagenesis

Tetracyclines- Inhibits bone/teeth growth

Ribavirin- Teratogenic

Griseofulvin--Teratogenic

Chloramphenicol- Gray Baby Syndrome

What drug may need to be added to Metronidazole when treating Amebiasis?

Diloxanide to kill the luminal form if it is in the intestine

Chloroquine is the main drug used to treat malaria but there is much resistance to it...what is the backup?

Mefloquine for prophylaxis

Quinine can be used for treatment

What are the drugs Artemether and Artesenate used for?

Block Plasmodium falciparum ER ATPase, blocking metabolism***

Side effects of Quinine antimalarials?

Cinchonism--muscarinic and alpha antagonism seen in quinine derivatives...Blurred vision, GI distress, CNS toxicity

G6PD pts---Hemolytic anemia

Pin worm...Rx?

Mebendazole

MOA of pyrantel pamoate?

Nicotinic NM agonist that paralyzes the worm and makes them fall off the gut wall

MOA of Praziquantel?

Increases Ca++ influx and causes paralysis, and vacuolization of the bug..Used in tapeworms and flukes

What actions occur with H1 receptor stimulation?

Capillary dilation via NO to decrease BP

Increased capillary permeability

Increased bronchiolar SM contraction

Increased sensation of pain/itching

DECREASE AV nodal condution

What is the effect of H2 simulation on the heart?

Increases SA nodal rate and give increased contractility

Side effects of most all H1 antagonists?

Muscarininc blockade and sedation

What antihistamine has the greatest antimotion properties of the ones tested on the USMLE?

Meclizine

Name 4 1st generation Antihistamines.

Meclizine

Diphenhydramine

Promethazine

Chlorpheniramine

Name 3 2nd generation Antihistamines?

Cetirizine

Loratidine

Fexofenadine...

Non sedative... because they have NO Muscarinic blockade...because of this they are only used for allergies, not cold meds or antimotion.

DOC for peptic ulcer disease?

Proton pump inhibitors

What is the benefit of Prostaglandins in treatment of Peptic ulcer disease? (Misoprostol PGE1 analog)

Decrease proton pump

Improve mucus secretion

Enhance bicarb secretion to neutralize acid

What is the use of Sulcralfate?

It coats ulcer pits in the stomach and protect them from further erosion as it forms a sticky gel

Name 4 H2 antagonists...

Cimetidine

Ranitidine

Famotidine

Nizatidine

What is the MOA of drugs such as Cimetidine?

Work on H2 receptors (seen on parietal cells) to antagonize HCl secretion caused by vagal or gastin stimulation induced release of histamine from enterochromaffin like cells.

What is a side effect of Cimetidine?

Antiandrogen effect...gyncomastia

Can cause confusion in the elderly.

MOA of Omeprazole?

NON competitive inhibitors of the proton pump K+/H+ pump

On the BOARDS, Misoprostol is often called a 'Antidote' to...

NSAID induced ulceration of the Stomach

What is BOARD tested about the drug Sulcrafate?

It polymerizes in the GI lumen to form a protective barrier against acid BUT IS A PRODRUG!! NEEDS AN ACID ENVIRONMENT TO BE ACTIVATED. Don't take with ANTACIDS

MOA of Bismuth Subsalycylate?

Binds to ulcers, coating and protecting them

Aluminum hydroxide can cause...

Constipation

Magnesium hydroxide can cause...

Diarrhea

What are the 3 really relevant points WRT Antacids?

DRUG ABSORPTION!

Antacids will increase the absorption of weak bases (quinidine) and decrease the absorptin of weak acids (warfarin)

As well as Cannot be take with Tetracycline as it binds Ca++ ions and makes both drugs inactive.

What type of Drug is Pirenzepine?

A muscarinic antagonist that can be used to treat peptic ulcer...

What type of Drug is Propantheline?

A muscarinic antagonist that can be used to treat peptic ulcer... Blocks M1 receptors on Enterochromaffin like cells so less histamine is release and block M3 receptors on Parietal cells thus blocking stimulation from the Vagus nerve

What type of drug is Ondansetron and what is its MOA? (and Setron drugs)

It is an antiemetic... It is a 5-HT3 antagonist...These receptors are found in the Chemoreceptor Trigger Zone in the Area Postrema in the floor of the 4th ventricle

What receptors are found in the Area Postrema, which can mediate vomiting?

D2---must block

5HT3--must block

CB1--must activate

M1 receptors that can be triggered by the vestibular system in dizziness--must block

NK1, Neurokinin 1 receptors that bind Substance P--must block

Ondansetron has been referred to on the BOARDS as an antidote to..

Cisplatin N/V from chemotherapy

What is the MOA of Metoclopramide?

DA2 receptor antagonist, which means it can act as an antiemetic...also increases LES tone and promotes motility (any of the antipsychotics will have the same effect of antinausea/antiemetic)

How is Dronabinol an antiemetic?

It binds to CB1 receptors in the CTZ of the area postrema...Since it is Gi mediated you want to activate the receptor, not block it like the other drugs used as antiemetics

What type of drug is Aprepitant?

An NK-1 receptor blocker (Neurokinin 1, like Substance P or Bradykinin, both of which can stimulate PAIN sensation...) Blocking this is useful in pain induced vomiting

What is the only Serotonin receptor that is not G-protein coupled?

5HT3...it is coupled to an ion channel***

What is the drug Sumatriptan used for and what is its MOA? (Same for other 'tryptan' drugs...

It is used to treat migraine headaches...it is a 5HT1d receptor agonist ***** Constricts cerebral vessels.

What receptor does the drug Buspirone work on?

5HT 1a partial agonist, used for anxiety without being sedative***

What is the MOA of Cyproheptadine and what is it used for?

It is a 5HT2 receptor antagonist used to treat CARCINOID syndrome but it is NOT the DOC!!!