Pharmacology Flashcards by Daniel Guck

What is the main stimulus for EPO production?

Hypoxia

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Where in the fetus and real human is EPO made?

Fetus- liver
Human- birth

(lol am i stirring some opinions)

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These are the molecules that stimulate the activity of T cells an dmacrophages.

Interleukins and interferons

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Which molecule prevents the overproduction of platelets and sensitizes them to the effects of thrombin and collagen?

Thrombopoietin (TPO)

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What are the 2 pathologies in which EPO is used?

Chronic kidney disease and cancer

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What is the sstructural difference between rhEPO and darbepoietin (NESP)?

The # of sialic acid groups attached to the protein (NESP has 2 extra)

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The extra sialic acid groups on NESP does what to the lifespan?

has a 3-fold longer 1/2 life than EPO (and thus a higher potency)

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What happens if Hb levels in EPO-treated pts exceedes 12 g/dL?

Death, serious CV evetns, and stroke

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5-azacytidine, decitabine, hydroxyurea, and butryates are all used to treat what condition?

Sickle cell anemia

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For the sickle cell drugs, what is the main MOA to treat the condition?

↑ HbF production

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Which sickle cell drug does this describe?

Relatively safe for long-term administration
Slower induction of HbF but effective in 60% of pts
↓ the frequency of painful crises by 50% and # of tranasfusions required

Hydroxyurea

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Filagastrim (recombinant human G-CSF) and PEG-filagastrim are used to treat what condition?

cancer-induced and chemo-induced neutropenia

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What is the main MOA for filagastrim?

dose-independent increase in absolute neutrophil count

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PEG-filagastrim is basically the same as filagastrin but what’s the difference?

It’s metabolized slower –> less injections

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What is the ONLY drug for chemo-induced thrombocytopenia?

rhIL-11 (oprelvekin)

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What is the major drawback to rhIL-11?

It has to be administerd prophylactically because there is a 1-2 week delay from administration to a clinically significant increase in platelet count

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What is the main immune complication to heavily bioengineered variants of TPO?

excess risk of anti-TPO autoantibodies, which could supress antural platelet production

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So if heavily engineered TPO can cause problems, what type of TPO should u use to prevent neutralzing antibodies?

Lightly bioengineered variant (rhTPO)

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What are the 2 new TPO agonists?

Eltrombopag

Romiplastim

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What condition are eltrombopag and Romiplasmin approved for?

ITP

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What are the problems with rhIL-11 (oprelvekin)?

fatigue, fluid retention, A-fib

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What is the condition that tretinoin (all-trans retinoic acid/ATRA) is used for?

Acute promyelocytic leukemia

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In acute promyelocytic leukemia, what ruses to the PML gene, which blocks differentiation?

RARa

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How does ATRA cause more normal granulocytes?

Stimulates differentiation

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However, what is the life-treatening problem with ATRA treatment?

Overproduction of WBCs

What is the most common parasitic infection in the world?

Malaria

How many species cause malaria?

5 plasmodial parasites: P. falciparum, P. vivax, P. ovale, P. malariae, and P. knowlesi. The most serious type is P. falciparum.

What is the most important Sx of malaria?

Fever

Why is fever an important manifestation of malaria?

It's caused by intravascular lysis of erythocytes and release of merozoites into the blood

What is the main problem with older agents used to treat malaria?

Resistance

Since old drugs like chrolorquine, primethamine and sulfadoxine have resistance, what is the new DOC for malaria?

Artemisinin dereivative

How does chloroquine kill the malaria parasite?

Prevents the detoxification of the a toxic product of Hb (ferriprotoporphyrin IX)

What is the main MOA of arteminisin for the Tx of malaria?

when activated by Fe, is forms a ROS --> aklylate many proteins and heme --> toxic to plasmodia (iron pulls the pin on the arteminisin grenade)

What is one advantage of artemisinin over other anti-malarial agents?

it's better tolerated than most other antimalarial agenets

What is the main CNS complication of artmisinin?

Brainstem neuropathy (potentially lethal) and auditory impairment

Since artemisinin has a short half life and resistance could occur, what should it be used with?

A secondary drug

This is the malarial drug that is an electron carrier in the respiratory chain and severely disrupt the metabolic processes of plasmodial mitochondria.

Quinone

What 2 malaria spp is primaquine used, which causes haptic malaria?

P. vivax and P. ovale

Which 2 pts should not be given primaquine as it can cause fatal hemolysis?

G6PD deficient pts | Pregnant chicks

What is the MOA of atovaquone for malaria?

Inhibits the interaction btwn reduced ubiquinone and the cytochrome bc1 complex and disrupts electron transport.

Why is stopping electron transport a good wat to kill malaria?

They require it to regenerate oxidixed DHOD --> used for DNA replication

Which subunit does doxy bind to?

30s

Can u use doxy in pregnant ladies?

Which subunit does clindamycin bind to?

50s

Can u use clindamycin in pregnant ladies?

Since sulfadoxine is a PABA analogue, which enzyme does it inhibit, which is an essential encyme in the folic acid synthesis pathway?

DHP synthase | "s"ulfa for "s"ynthase

Which drug is a folate analogue that competitively inhibits parasite DHF reductase for the Tx of malaria?

Pyrimethamine

Sulfonamide-pyrimethamine inhibit which stage of P. falciparum?

Schizont stage

Is Sulfonamide-pyrimethamine used in other strains of malaria, other than P. falciparum?

The sensitivity of Metronidazole is directly related to the activity of what?

PFOR

Which organisms is PFOR selective for?

protozoa ONLY so its used for ameba and anaerobic organisms

What is the pharmacokinetic reasons why Iodoquinol and paromomycin are effective against intraluminal amebae?

They're poorly absorbed in the Gi tract --> reach high concentrations in the lumen of the colon

Protozoa, anaerobic bacteria, and helminths are all parasites in which what drug has activity against?

Nitrazoxamide

What is the MOA for Nifurtimox to treat Chagas disease?

Creates toxic intracellular ROS in the parasite

What are the 2 first-line drugs against Leishmania?

Sodium stibogluconate and Melglumine antimonate

What do mammals have in their nervous systems that helminthes dont, which makes helminthes more susceptible to neurotoxins?

Myelin

Since Ivermectin does NOT kill adult filarial worms, what is it's MOA, which causes it to be used every 6-12 months for 5-10 years?

Prevents the production and release of new microfilariae

What is the DOC for schistosomiasis?

Praziquantel

What is the DOC for certain filarial infections, which KILLS ADULT filarial worms, and is thus a curative agent?

Diethylcarbamazine (DEC)

Which coag factors does warfarin inhibit?

VII, IX, IXa, X, and II

Which coag factors does heparin inhibit?

Xa, IIa

t-PA stimulates which reaction?

Plasminogen --> plasmin

UFH and LMWF serve as a catalytic surface to which what 2 molecules bind?

Antithrombin III | Serine proteases

Which factor does UFH and LMWH inhibit, indirectly by activating antithrombin III?

UFH is good at inhibiting Xa and what other coag factor?

thrombin

What is the MOA of lepirudin?

Direct thrombin inhibitor

What is the disease that herudin/lepirudin used to treat?

Heparin-induced thrombocytopenia

What is the drug that is also a direct trhombin inhibitor that binds to both the activa sir and exosite of thrombin, and is used in anticoagulation in pts undergoing coronary angioplasty/graphy?

Bivalirudin

What is the direct thrombin inhibitor that is used for heparin-induced thrombocytopenia, and binds ONLY to the active site of thrombin?

Argatroban

Waht is the anticoagulant that prevents the activation of vitamin K?

Warfarin

How long does it take warfarin to have its effects?

18-24hrs

Warfarin is given to prevent thrombosis in pts undergoing what other drug therapy?

Heparin

Which form of heparin is at risk for bleeding and HIT?

UFH

What is the problems with hirudin/lepirudin?

bleeding and a small percentage of patients may develop anti-hirudin antibodies, limiting the long-term effectiveness of this agent as an anticoagulant

The reactivation of what coag factor is a problem with bivalirudin?

thrombin

What pts cant u give bivalirudin?

Renal insufficiency pts

Why is argatroban super sweet?

No adverse rxns

What is the most serious and predictable toxicity for warfarin?

Bleeding

For severe hemorrhage, what is the rapid thing u should give for warfarin problems?

FFP

Should u give warfarin to pregnant ladies?

What are the drugs that diminish warfarins anticoagulant effect?

Cholestyramine Barbiturates, carbamazepine, phenytoin, rifampin Vitamin K (reduced)

What are the drugs that enhance warfarins anticoagulant effect?

Chloral hydrate Amiodarone, clopidogrel, ethanol (intoxicating dose), fluconazole, fluoxetine, metronidazole, sulfamethoxazole Broad-spectrum antibiotics Anabolic steroids (testosterone)

What is the MOA of streptokinase to degrade clots?

forms a stable complex with plasminogen --> cleavag eof palsminogen --> plasmin

What are the 2 clinical indications for streptokinase?

STEMI | PE

What are the 2 adverese effects of streptokinase?

1. capable of producing antigenic responses with repeated administration 2. systemic fibrinolysis

Waht are the 3 clinical indications for recombinant t-PA (Alteplase)?

1. STEMI 2. PE 3. CVA

What is the generitcally engineered variant of t_PA with a longer half life and increased specificity for fibrin, and can be administeres as a double bolus?

Reteplase

This variant of t-PA has an increased fibrin specificity and increases its resistance to plasminogen activator inhibitor 1, and has a long 1/2 life?

Tenecteplase

This antiplatelet agent irreversibly inhibits the ADP-pathway of platelet activation.

Clopidogrel

What are the clinical indications for using clopidogrel with ASA?

Coronary intervention | Prevention in pts with recent MI, stroke, or PVD

Is clopidogrel more or less favorable (as fase as adverse effects) than ticlopidine?

Waht are the 3 major adverse effects of ticlopidine?

Neutropenia Thrombocytopenia TTP

Which GpIIb/IIIa receptor blocker isa monoclonal Ab and reduces both logn and short-term ischemic events in pts undergoing high-risk percutaneous coronary intervention?

Abciximab

Which GpIIb/IIIa receptor blocker is a synthetic peptide, and is used to ↓ ischemic events undergoing percutaneous coronary intervention, unstable angina, and for NSTEMI?

Eptifibatide

Which GpIIb/IIIa receptor blocker is a nonpeptide tyrosine analogue that reversible antagonizes fibrinogen binding to the GpIIb/IIIa receptor, and is used for acute coronary syndromes?

Tirofiban

This is a receptor of platelet PDE, which inhibits cAMP degredation, and is used with other drugs?

Dipyridamole

Dipyridamole + warfarin are used for which pts?

inhbit thrombus formation on prosthetic heart valves

Dipyridamole + ASA are used to reduce liklihood of thrombus formation in which pts?

Thrombotic diathesis (bleeding tendency)

What are the adverse effects of Dipyridamole, as a result of the coronary steal phenomenon?

Angina in CAD pts

enoxaparin, dalterparin, and tinzaparin all belong to which anticoagulant?

UFH and LMWH

Fondapurinux belongs to which class of anticoagulants?

Xa inhibitors

Lepirudin, bivalirudin, argatroban, dabigatran belogn to which anticoagulant class?

Direct thrombin inhibitors

Which condition is recombinant activated protein C (r-APC) used in?

severe sepsis

Which factors are synthesized by vitamin K?

II, VII, IX, and X also protein C and S

What is the Moa of aminocaproic acid to reduce perioperative bleeding during coronary artery bypass grafting?

Inhibits plasminogen and plasmin

What is the MOA of Aprotinin to to decrease perioperative bleeding & erythrocyte transfusion requirement in pts treated w/ aprotinin during cardiac surgery?

Inhibiting fibrinolysis | Inhibiting thrombin to promote platelet activity by preventing hyperstimylation

Which drug increases the risk of post-op acute renal failure? Aminocaproic acid or Aprotinin

Aprotinin