Pharmacology Flashcards
Drugs causing Myalgia
Cimetidine
Cocaine, Heroin, Methadone
Cyclosporine
Danazol
Emetine
Epsilon aminocaproic acid
Statins
Gold
Labetolol
D-penicillamine
L-Tryptophan
Zidovudine
Drug causing Myopathies
Vecuronium, Suxamethanium, Rocuronium = Neuromuscular blockers
Statins, Fibrates, Niacin (anti Lipids)
Glucocorticoids - chronic proximal myopathy or acute quadriparesis
D penicillamine: Autoimmune, Polymyositis, MG,
Chloroquin, Hydroxy-chloroquin
Amiodarone (amphophillic cationic drugs)
Colchicine (anti-microtubule)
Topiramate Birth Defects
Topamax (topiramate) is an anticonvulsant drug used for the treatment of epilepsy, migraine headaches, sleeping and eating disorders, and for weight loss.
Persistent Pulmonary Hypertension of the Newborn (PPHN)
Various heart defects
Neural tube defects
Spina Bifida
Limb malformations
Lung defects
Ondansetron in First Trimester
Approximately 80 percent of women suffer from nausea and vomiting during pregnancy, and about one million take Zofran or its generic version every year. A study published in the December 2014 issue of the American Journal of Obstetrics and Gynecology discussed the risks taken by pregnant women who use Zofran. The study found a two-fold increased risk of cardiac malfunction associated with Zofran, leading to an overall 30 percent increased risk of major congenital malformations.
Codeine in Pregnancy
Links have been found between the use of codeine during the first trimester and the incidence of certain congenital heart defects, along with spina bifida, hydrocephaly, glaucoma, and gastroschisis.
Teratogenic Drugs, common
Teratogenic drugs and birth defects
Each of the following drugs or drug groups may cause birth defects in a developing fetus:
ACE (angiotensin converting enzyme) inhibitors
angiotensin II antagonist
isotretinoin (an acne drug)
alcohol
cocaine
high doses of vitamin A
lithium
male hormones
some antibiotics
some anticonvulsant medications
some cancer-fighting medications
some drugs that treat certain rheumatic conditions
some thyroid medications
thalidomide
the blood-thinning drug warfarin
the hormone diethylstilbestrol (DES).
Pregnancy Risk Classification of drugs
The classifications include:
A – Drugs that have been taken by a large number of pregnant women without any proven increase risk of birth defect.
B – Drugs that have been taken by only a limited number of pregnant women. Human data is lacking and they are further categorised based on available data from animal studies.
B1 – animal studies have not shown any increased risk.
B2 – animal studies are limited, but there does not seem to be any increased risk.
B3 – animal studies show an increased risk, but it is not clear if this risk applies to humans.
C – Drugs that, due to their effects, may cause harm to the fetus without causing birth defects. These effects may be reversible.
D – Drugs that have caused or may cause birth defects; however, the health benefit may outweigh the risk.
X – Drugs that have a high risk of birth defects and should not be used during pregnancy.
Warfarin
= Vitamin K blocker, increases INR by blocking fat soluble Vitamin K dependent clotting factors as 2, 7,9,10 synthesis
= Dose, 0.5 mg to 1/2/3/4/5 etc OD
= Cheap, needs monthly INR monitoring
= Food - drug can lower or increase effects
= Antidote in case of bleeding: Vitamin Oral/IM or IV
= Prothrombin complex concentrate in case of life threatening bleeding
= INR > 5 but no bleeding: Just stop for few days, re check INR and re start lower dose
= Always tell GP, Pharmacist if starting new medications in future
= Sit with dietician to understand what food interacts with Warfarin, increase its effect and puts you at risk
= Diarrhea, vomiting. can alter effects so watch
Rivaroxaban
Endoxaban
Apixaban
Dabigatran
Rivaroxaban, 15-20 mg OD
Endoxaban 30-60 mg OD
Apixaban 2.5-5 mg BD
= Factor Xa inhibitors
= Antidote: Adexanate alfa (Andexxa) - recombinant modified Factor Xa protein approved by the FDA in May 2018 to reverse apixaban and rivaroxaban in patients with life-threatening or uncontrolled bleeding. Start the bolus at a target rate of approximately 30 mg/min. Within two minutes following the bolus dose, administer the continuous IV infusion for up to 120 minutes.
Dabigatran: 110-150 mg BiD
Antidote: a monoclonal antibody used as a reversal agent for dabigatran. binds to dabigatran and its acyl glucuronide metabolites with higher affinity than the binding affinity of dabigatran to thrombin, neutralizing their anticoagulant effect immediately after administration. The recommended dose is 5 g idarucizumab (2 vials of 2.5 g/50 mL)
Dotrecogin alfa, Xigris
Drotrecogin alfa is a recombinant form of human activated protein C that has anti-thrombotic, anti-inflammatory, and profibrinolytic properties. Drotrecogin alpha belongs to the class of serine proteases. Drotrecogin alfa has not been found to improve outcomes in people with severe sepsis.
Xigris should be administered intravenously at an infusion rate of 24 mcg/kg/hr (based on actual body weight) for a total duration of infusion of 96 hours. Cost - 6800 $ per course of 96 Hrs.
Has been withdrawn from market.
Infliximab, Remicade
Infliximab, a chimeric monoclonal antibody, sold under the brand name Remicade among others, is a medication used to treat a number of autoimmune diseases. This includes Crohn’s disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis, and Behçet’s disease.
The recommended dosage of REMICADE® is 5 mg/kg given as an intravenous induction regimen at 0, 2, and 6 weeks, followed by a maintenance regimen of 5 mg/kg every 8 weeks thereafter for the treatment of active PsA.
Remicade belongs to a drug class called tumor necrosis factor-alpha (TNF-alpha) blockers.
Can activate TB.
C1 esterase Inhibitors
Berinert/Haegarda/ Cinryze
= Used in deficiency of them which leads to Hereditary angioedema which doesnot respond to Epinephrine. Most episodes or attacks are difficult to predict, and triggers vary from person to person. These triggers may include anxiety, surgery, dental procedures, medications and illnesses such as colds and flu.
= Human C1-esterase inhibitor concentrate (C1-INH concentrate) is derived from human plasma. Cinryze and Haegarda are indicated for routine prophylaxis in adults and adolescents. Berinert and Cinryze are administered as an intravenous infusion, whereas Haegarda is administered as a subcutaneous injection.
= C1 inhibitor is an acute phase reactant and a serine protease inhibitor (serpin). Serpins inhibit the steps in the lectin complement pathway as well as kinin-producing pathways. While C1 inhibitor has many functions, its function in the kinin pathway leads to angioedema.
= BERINERT is used in adults and children to treat swelling and/or painful attacks of hereditary angioedema (HAE) affecting the abdomen, face or throat. The safety and efficacy of BERINERT in preventing HAE attacks have not been established.
Tacrolimus
= a calcineurin-inhibitor.
= IV Dose of Prograf injection is 0.03-0.05 mg/kg/day in kidney and liver transplant and 0.01 mg/kg/day in heart transplant given as a continuous IV infusion.
= Common SE: Hyperglycemia, Infections, Nephrotoxicity, Hyperkalemia, Reversible Encephalopathy syndrome, Liver toxic etc
= Risk of NHL and skin cancers
= metabolised by the cytochrome P450 system of liver enzymes
In T-cells, activation of the T-cell receptor normally increases intracellular calcium, which acts via calmodulin to activate calcineurin. Calcineurin then dephosphorylates the transcription factor nuclear factor of activated T-cells (NF-AT), which moves to the nucleus of the T-cell and increases the activity of genes coding for IL-2 and related cytokines. Tacrolimus prevents the dephosphorylation of NF-AT.
Liver Enzyme Inhibitors
Macrolide antibiotics including erythromycin and clarithromycin, as well as several of the newer classes of antifungals, especially of the azole class (fluconazole, voriconazole), increase tacrolimus levels by competing for cytochrome enzymes.
Ciclosporin
a type of drug known as a disease-modifying anti-rheumatic drug, or DMARD.
a calcineurin inhibitor,
It slows down your immune system to prevent your body from rejecting a transplanted organ. This medication can also treat rheumatoid arthritis and psoriasis. isolated in 1971 from the fungus Tolypocladium inflatum.
SE: Gum hypertrophy, convulsions, Peptic ulcers, Hirsutism, Pancreatitis, High BP, High Lipids, Infections, Neuropathies, etc
Uses: Rheumatoid diseases, Transplants, GVHD, Psoriasis, Kerato-conjunctivitis sicca,
Can leads to Squamose cell Skin Cancers and NHL
Rituximab, anti CD 20
Rituximab is a chimeric monoclonal antibody against CD20 which is a surface antigen present on B cells. Therefore, it acts by depleting normal as well as pathogenic B cells while sparing plasma cells and hematopoietic stem cells as they do not express the CD20 surface antigen.
Rituximab is indicated to treat:
= non-Hodgkin lymphoma (NHL)
= chronic lymphocytic leukemia (CLL)
= rheumatoid having inadequate response to one or more TNF inhibitors
= vasculitis as granulomatosis with polyangiitis and microscopic polyangiitis
= moderate to severe pemphigus vulgaris
= combination with chemo for children (≥6 months to <18 years) with previously untreated, advanced stage, CD20-positive diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL), Burkitt-like lymphoma (BLL), or mature B-cell acute leukemia (B-AL).
Common SE: often occur within two hours of the medication given include rash, itchiness, low blood pressure, and shortness of breath. Infections are also common.
Severe SE: include reactivation of hepatitis B in those previously infected, progressive multifocal leukoencephalopathy, toxic epidermal necrolysis, and death. It is unclear if use during pregnancy is safe for the developing fetus or newborn baby, but it is not proven harmful.
Biphosphonates
Alendronate
Palmdronate
Zoledronate
Etidronate
Clodronate
Bisphosphonates inhibit the digestion of bone by encouraging osteoclasts to undergo apoptosis, or cell death, thereby slowing bone loss.
= Prevention and treatment of osteoporosis,
= Paget’s disease of bone, bone metastasis (with or without hypercalcemia),
= Multiple myeloma,
= Primary hyperparathyroidism,
= Osteogenesis imperfecta,
= Fibrous dysplasia, and other conditions that exhibit bone fragility.
common SE: Esophagitis, Gastritis, Flu like symptoms
Long Term SE: bisphosphonate fractures”) in the femur (thigh bone) in the shaft (diaphysis or sub-trochanteric region) of the bone, rather than at the femoral neck, which is the most common site of fracture.
Non Biphosphonate options
Strontium: = The use of strontium ranelate (strontium salt of Ranelic acid) is restricted because of increased risk of venous thromboembolism, pulmonary embolism and serious cardiovascular disorders, including myocardial infarction. Only for post menopausal women with high risk for osteoporotic fractures. It reduces osteoclast activity & also increases osteoblast activity thus leading to new bone formation.
Teriparatide: Synthetic PTH
Carbimazole
pro-drug as after absorption it is converted to the active form, methimazole. Methimazole prevents thyroid peroxidase enzyme from iodinating and coupling the tyrosine residues on thyroglobulin, hence reducing the production of the thyroid hormones T3 and T4 (thyroxine).
Treatment is usually given for 18–24 months followed by a trial withdraw. Block & replace pattern: carbimazole blocks thyroid hormone development and then needs to be given Levothyroxine while still on carbimazole.
SE: Bone marrow suppression, agranulocytosis (Watch for sore throat), flu like symptoms, Jaundice, Nausea, Headache, Pruritus, Taste disturbance
Cause cause aplasia cutis, hypothyroidism in fetus hence avoid in pregnancy.
Dose 15 mg titrate up.
propyl Thiouracil
PTU inhibits the enzyme thyroperoxidase, which normally acts in thyroid hormone synthesis by oxidizing the anion iodide (I−) to iodine (I0), facilitating iodine’s addition to tyrosine residues on the hormone precursor thyroglobulin.
PTU also acts by inhibiting the enzyme 5’-deiodinase (tetraiodothyronine 5’ deiodinase), which converts T4 to the more active form T3. (This is in contrast to methimazole, which shares propylthiouracil’s central mechanism, but not its peripheral one.
Propylthiouracil is classified as Drug Class D in pregnancy. Class D signifies there is positive evidence of human fetal risk. The maternal benefit may outweigh fetal risk in life-threatening situations.[9] PTU is preferred over methimazole (which is also a class D) only in the first trimester of pregnancy and in women who may become pregnant because of the increased risk of teratogenicity of methimazole during critical organogenesis. In the second and third trimester, this risk is diminished and methimazole is preferred to avoid the risk of liver complications from PTU in the mother.
Its notable side effects include a risk of agranulocytosis and aplastic anemia, nephritis, SLE like symptoms, Hypo-prothrombinemia
Another life-threatening side effect is sudden, severe, fulminant liver failure resulting in death or the need for a liver transplantation, which occurs in up to 1 in 10,000 people taking propylthiouracil.
Phosphodiesterase inhibitors,
11 subtypes
They relax and widens vessels
PDEi 03 = Milrinone (Heart, Vessels)
PDEi 04 = Roflumilast (Lungs)
PDEi 05 = Tadalafil (Lungs, Penis)
Pentoxyphylline- Theophylline is a non selective PDE inhibitors.
Milrinone: PDEi 3 - improved heart contraction, reduces platelet aggregation, has a role in limiting stroke
Rofflumilast: PDEi 5 = for COPD,
Crisaborole
Apremilast = for psoriasis, Ps arthritis
Insulins
Rapid-Insulins:
Actions stars in- Lasts for - Brand Name
1. Aspart: 5-15 min, 3-5 Hrs, NOVOLOG
2. Glulisine: 5-15min, 3-5 Hrs, APIDRA
3. Lispro: 5-15min, 4 Hrs, Humalog
4. inhaled: ultrarapid, AFREZZA
5. Regular: 30-60min, 6 Hrs, HUMULIN-R, NOVOLIN-R
Intermediate acting insulin:
Neutral Protamine Hagedorn insulin, also known as isophane insulin,
Insulin NPH: 3-4 Hrs, 16-24 Hrs, HUMULIN-No, NOVOLIN-N
Long acting insulins:
I. detemir: 24 Hrs action, LEVEMIR
I. Glargine: 24 Hrs action, LANTUS
Anticholinergics:
substances that block the action of the neurotransmitter called acetylcholine (ACh) at synapses in the central and peripheral nervous system.
- Anti-muscarinics: = Atropine, Scopolamine, Hyoscine, Ipratropium, Tropicamide, Cyclopentolate, Pirenzepine, Dicyclomine, Doxylamine, Hydroxyzine, Glycopyrrolate, Mebeverine, Oxybutinin, Procyclidine, Solifenacin, Tiotropium, Tolterodine, Trihexyphenydil
- Anti Nicotinics:
#Ganlionic Blocking: Hexamethonium, Mecamylamine, Trimethaphan
#Nondepolarizing neuromuscular blocking: Atracurium, Doxacurium, Mivacurium, Pancuronium, Tubocurarin, Vecuronium
#Depolarizing neuromuscular blocking: Succinylcholine
#Centrally acting nicotinic antagonists: 18-Methoxycoronaridine, Bupropion, Hydroxybupropion, Threohydrobupropion, Dextromethorphan, Dextrorphan, Methoxymorphinan
Hot as Hare - High fever
Dry as a bone - severe dehydration
Blind as a bat - blurred vision
Red as a beet - flushed skin
Mad as a hatter - Psychosis
Complications of TPN
Short term:
Bleeding, Pneumothorax due to line, Line sepsis, Vein thrombosis, Hyperglycemia, refeeding syndrome, deranged LFT (Excess Nutrition)
Long Term: Sepsis, Line thrombosis, GB Stones, Renal stones, Bone disease
Adenosine
= blocks AV node conduction
= short acting, 10-15 seconds as rapidly metabolized by peripheral esterases
= Adenosine is used as an adjunct to thallium (TI 201) or technetium (Tc99m) myocardial perfusion scintigraphy (nuclear stress test) in patients unable to undergo adequate stress testing with exercise. “stress test”, the dosage is typically 0.14 mg/kg/min, administered for 4 or 6 minutes, depending on the protocol.
SVT Dose - 6, 12, 12 mg
contra-indications: = Asthma, Sick sinus syndrome, AF+WPB together, Transplanted heart, Pt on-dipyridamole, Carbamazepine, Theophylline, and 2/3 degree CHB
Alternate SVT drug: Amiodarone, Flecainide, Verapamil, Metoprolol
Receptors with Agonist Actions
Alfa 1 = vasoconstriction
Beta 1 = inotrophic
Beta 2 = Vasidilation, Bronchodilation
Dopamine = vasodilation@ renal, splanchnic low doses, vasoconstriction high doses
GM-CSF: Granulocyte Monocyte- Colony Stimulating Factor
- Sargramostim
- Molgramostim
is a monomeric glycoprotein secreted by macrophages, T cells, mast cells, natural killer cells, endothelial cells and fibroblasts that functions as a cytokine. The pharmaceutical analogs of naturally occurring GM-CSF are called sargramostim and molgramostim.
The human gene has been localized in close proximity to the interleukin 3 gene within a T helper type 2-associated cytokine gene cluster at chromosome region 5q31, which is known to be associated with interstitial deletions in the 5q- syndrome and acute myelogenous leukemia.
GM-CSF is found in high levels in joints with rheumatoid arthritis and blocking GM-CSF as a biological target may reduce the inflammation or damage. Some drugs (e.g. otilimab) are being developed to block GM-CSF.
Filgrastim: Granulocyte Colony Stimulating Factor (Neupogen)
= is a medication used to treat low neutrophil count.
= Common SE: fever, cough, chest pain, joint pain, vomiting, & hair loss.
= Severe SE: splenic rupture & allergic reactions.
Filgrastim is a recombinant form of the naturally occurring granulocyte colony-stimulating factor (G-CSF).
Neupogen is the name for recombinant methionyl human granulocyte colony stimulating factor (r-metHuG-CSF).
Other SE: include serious allergic reactions (including a rash over the whole body, shortness of breath, wheezing, dizziness, swelling around the mouth or eyes, fast pulse, and sweating), ruptured spleen (sometimes resulting in death), alveolar hemorrhage, acute respiratory distress syndrome, and hemoptysis.
Severe sickle cell crises, in some cases resulting in death, have been associated with the use of filgrastim in patients with sickle cell disorders.
High INR with warfarin-Management
> 8 INR with minor bleeding:
= Stop warfarin
= IV Phytomenadione, 1-3/5 mg slow
= Repeat if INR still high after 24 Hrs
= re start warfarin when INR < 5
> 8 INR with major bleeding:
= Stop warfarin
= IV Phytomenadione 5 mg slow iv
= Prothrombin complex dried, 25-50 mg/kg (contains 2, 7, 9, 10) - OR FFP 15 ml/kg
> 8 INR, no bleeding:
= Stop warfarin
= PO Phytomenadione 1-3 mg using same iv solution given orally
= re start Warfarin when INR < 5
Warfarin Information
Mechanism of Action
Warfarin competitively inhibits the vitamin K epoxide reductase complex 1 (VKORC1), an essential enzyme for activating the vitamin K available in the body. Through this mechanism, warfarin can deplete functional vitamin K reserves and thereby reduce the synthesis of active clotting factors. The hepatic synthesis of coagulation factors II, VII, IX, and X, as well as coagulation regulatory factors protein C and protein S, require the presence of vitamin K. Vitamin K is an essential cofactor for the synthesis of all of these vitamin K-dependent clotting factors.
FDA-approved clinical uses for warfarin:
Prophylaxis and treatment of venous thrombosis and arising pulmonary embolisms.
= Prophylaxis and treatment of thromboembolic complications from atrial fibrillation or cardiac valve replacement
= Reduction in the risk of death, recurrent myocardial infarction, and thromboembolic events (e.g., stroke, systemic embolization) after myocardial infarction
Off-Label clinical uses of warfarin include:
= Secondary prevention of recurrent stroke and transient ischemic attacks[4]
Local Lidocaine dosing
Methyl Pred in spine trauma
