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, anti-IIa
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)
Monitoring: direct thrombin time
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 inhibitor.
Milrinone: PDEi 3 - improves 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 starts in minutes & Lasts for Hrs, 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:
#Ganglionic 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]
Warfarin Pharmacokinetics
Absorption: Rapid and complete absorption
The onset of action: The onset of action is typically 24 to 72 hours. A peak therapeutic effect is seen 5 to 7 days after initiation. However, the patient’s international normalized ratio (INR) may increase within 36 to 72 hours after initiating treatment.
Duration of Action: 2 to 5 days
Distribution: Small volume of distribution (0.14 L/kg)
Protein Binding: 99%
Metabolism: Hepatic metabolism, primarily through the CYP2C9 enzyme. Other minor enzymatic pathways for metabolism include CYP2C8, 2C18, 2C19, 1A2, and 3A4.
Genomic Variants: Research has shown that genetic variations in CYP2C9 affect an individual’s warfarin clearance. Patients who are heterozygous for the 2C9 (1/2 or 1/3) can experience an approximately 37% reduction in S-warfarin clearance. Patients who are homozygous for reduced function alleles (2/2, 2/3, or 3/3) may experience a nearly 70% reduction in clearing S-warfarin.
Elimination Half-life: The half-life of warfarin is generally 20 to 60 hours (mean: 40 hours). However, it is highly variable among individuals.
Warfarin Sideffects
=Haemorrhage,
Rare cases of purple toe syndrome, warfarin-induced skin necrosis, and there are reports of calciphylaxis with warfarin therapy.
= Purple toe syndrome is a complication characterized by cholesterol microembolization that causes purple lesions to develop on the toes and sides of the feet. Purple toe syndrome usually develops 3 to 8 weeks after the initiation of warfarin therapy.
= Warfarin-induced skin necrosis is a serious condition in which subcutaneous tissue necrosis occurs due to an acquired protein C deficiency following treatment with warfarin. The risk of necrosis increases in patients with protein C or protein S deficiency. The skin necrosis usually occurs within the first week of therapy and management strategies, including discontinuing treatment with warfarin, administering fresh frozen plasma and vitamin K, and initiating anticoagulation therapy with either unfractionated heparin or low molecular weight heparin. = Calciphylaxis or calcium uremic arteriolopathy is another rare adverse effect in patients with or without end-stage renal disease.
Warfarin and Diet
While there is no specific diet recommended for patients on warfarin, certain foods and beverages can either limit or enhance the anticoagulant effect of warfarin. Vitamin K decreases the effectiveness of warfarin in the body. Therefore, the patient should receive education on maintaining a consistent dietary intake of vitamin K-containing foods.[15] Examples of high vitamin K foods include kale, green tea leaves, Brussel sprouts, and spinach. Other dietary recommendations include limiting the consumption of cranberry juice and alcohol while on warfarin therapy. Grapefruit juice and alcohol can enhance the anticoagulant effect of warfarin, thereby leading to increased bleeding complications
Dialysable Toxins
PLASMA-TV
- Phenobarbitol
- Lithium
- Acidosis
- Salicylates
- Metformin
- Alcohols
- Theophylline
- Valproic Acid
Substances amenable to multi-dose activated charcoal.
ABCDQ:
- Aminophylline / theophylline
- Barbiturates
- Carbamazepine / concretion forming drugs (salicylates)
- Dapsone
- Quinine
Substances that do not bind to charcoal.
PHAILS:
- Pesticides
- Heavy metals
- Acids/alkalis/alcohols
- Iron
- Lithium
- Solvents
Potentially lethal toxins where early activated charcoal may be indicated.
Killer C’s:
- Cyanide
- Colchicine
- Calcium channel blockers
- Cyclic antidepressants
- Cardiac glycosides
- Cyclopeptide mushrooms
- Cocaine
- Cicutoxin (water hemlock)
- Salicylates
Substances causing a wide anion-gap acidosis
CAT MUD PILES:
- Cyanide, carbon monoxide, colchicine
- Alcohol, alcoholic ketoacidosis, acetaminophen (in large doses)
- Toluene
- Methanol, metformin
- Uraemia
- Diabetic Ketoacidosis
- Paraldehyde
- Isoniazid, iron
- Lactic acidosis
- Ethylene glycol
- Salicylates
Substances that cause hypoventilation
SLOW:
- Sedative-hypnotics (barbiturates, benzodiazepines)
- Liquor (alcohols)
- Opioids
- Weed (marijuana)
Substances that cause hyperventilation.
PANT:
- PCP, paraquat pneumonitis, phosgene
- Acetylsalicylic acid (ASA) and other salicylates
- Noncardiogenic pulmonary oedema, nerve agents
- Toxin-induced metabolic acidosis
Substances causing hypertension.
CT SCAN:
- Cocaine
- Thyroid supplements
- Sympathomimetics
- Caffeine
- Anticholinergics, amphetamines
- Nicotine
Substances that cause hypotension
CRASH:
- Clonidine, calcium channel blockers
- Rodenticides (containing arsenic, cyanide)
- Antidepressants, aminophylline, antihypertensives
- Sedative-hypnotics
- Heroin or other opioids
Substances that cause hyperthermia.
NASA:
- Neuroleptic malignant syndrome, nicotine
- Antihistamines, alcohol withdrawal
- Salicylates, sympathomimetics, serotonin syndrome
- Anticholinergics, antidepressants, antipsychotics
Substances that cause hypothermia.
COOLS:
- Carbon monoxide
- Opioids
- Oral hypoglycaemics, insulin
- Liquor (alcohols)
- Sedative-hypnotics
Substances that cause tachycardia.
FAST:
- Free Base or other forms of cocaine, Freon
- Anticholinergics, antihistamines, antipsychotics, amphetamines, alcohol withdrawal
- Sympathomimetics (cocaine, caffeine, amphetamines, phencyclidine [PCP]), solvent abuse, strychnine
- Theophylline, tricyclic antidepressants, thyroid hormones
Substances that cause bradycardia
PACED:
- Propranolol (Beta blockers), poppies (opiates), propoxyphene, physostigmine
- Anticholinesterase drugs (I.e. cholinergics like physostigmine), antiarrythmics
- Clonidine, calcium channel blockers
- Ethanol or other alcohols
- Digoxin, digitalis
Anticholinergic
Blind as a bat;
Mad as a hatter;
Red as a beet;
Hot as Hades/Hell/Desert;
Dry as a bone;
The bowel and bladder lose their tone, and the heart runs alone.
Or…
Can’t See (blurred vision);
Can’t pee (urinary retention);
Can’t spit (dry mouth);
Can’t Shit (constipated)
Cholinergic Toxidrome
DUMBELLS:
- Diarrhoea, diaphoresis
- Urination
- Miosis
- Bradycardia
- Emesis
- Lacrimation
- Lethargic
- Salivation
Seizures
OTIS CAMPBELL:
- Organophosphates, oral hypoglycaemics
- Tricyclic antidepressants
- Isoniazid, insulin
- Sympathomimetics, strychnine, salicylates
- Camphor, cocaine, carbon monoxide, cyanide, chlorinated hydrocarbons
- Amphetamines, anticholinergics
- Methylxanthines (theophylline, caffeine), methanol
- Phencyclidine (PCP), propranolol
- Benzodiazepine withdrawal, botanicals (water hemlock, nicotine), bupropion, GHB
- Ethanol withdrawal, ethylene glycol
- Lithium, lidocaine
- Lead, lindane
Agents Causing Coma or Seizures
LETHARGIC:
- Lead, lithium
- Ethanol, ethylene glycol, ethchlorvyol
- Tricyclic antidepressants, thallium, toluene
- Heroin, hemlock, hepatic encephalopathy, heavy metals, hydrogen sulphide, hypoglycaemics
- Arsenic, antidepressants, anticonvulsants, antipsychotics, antihistamines
- Rohypnol (sedative hypnotics), risperidone
- Gamma-hydroxybutyrate (GHB)
- Isoniazid, insulin
- Carbon monoxide, cyanide, clonidine
Agents Affecting Pupil Size
Miosis (COPS)
Cholinergic, clonidine, carbamates
Opioids, organophosphates
Phenothiazines (antipsychotics), pilocarpine, pontine haemorrhage
Sedative – hypnotics
Mydriasis (SAW)
Sympathomimetics
Anticholinergics
Withdrawal syndromes
Lithium Toxicity
Dose Limit < 1800 mg/Day
Signs: Tremors - fine to course, Clonus, Confusion, Coma, Death
PPT: dehydration and Co-drugs: STAND: SSRI-Theophylline - ACEi-NSAIDs-Diuretics)
It can cause nephrogenic DI with kidneys resistant to ADH action (Hyponatremia due to excess water in body retained)
Lithium to monitor 12 Hrs after first dose and twice weekly then monthly
Acute Goal: 0.8 - 1.2 mEq/Lit
Maintain: 0.8 -1 mEq/Lit
Rx: Hydration, Dialysis
Drugs that cause Gastric Ulcers
NSAIDs,
Corticosteroids
Biphosphonates
Illicit drug use
Aspirin
Potassium chloride
Mycophenolate
Non Drugs Causes:
Helicobacter pylori infection
Crohn’s disease or UC
Zollinger Ellison syn (Gastrinoma)
Radiation therapy to area
Chemotherapies
Neuhauser Syndrome: rare autosomal recessive congenital disorder that presents with megalocornea, mental retardation, hypotonia, and facial dysmorphism, peptic ulcers, tremors, mastocytosis (excess mast cells)
Drugs Causing pancreatitis
Azathioprine
Statins
Didanosine
Asparginase
Valproate
Antimonials
Pentamidine
Mercaptopurines
Thiazides, Frusemide
Co-trimoxazole
Less common:
Rifampicin, Octerotide, Carbamazepine, Acetaminophen, IFN, Enalapril, Cisplatin, Erythromycin
Drugs causing lupus
Procainamide
Hydralazine
Isoniazid
Diltiazem
Penicillamine
Radioactive Iodine, I-131
Made by John Livingston and Seaberg, 1938, California
Half Life: 8 days
High dose can induce cancers
Medical Dose: 400-600 mbg (megabequerals) capsule/liquid
Can cause initial thyroiditis symptoms
Advice:
- no sexual contacts for 1 month
- no pregnancy attempts for 6 months after
- one week isolation recommended
its byproduct of uranium/Plutonium fission
I-MIBG scan uses it for Pheochromocytoma/ Neuroblastoma diagnosis
Reacts with chlorine bleech and can release elemental iodine gas
Iodine is a chemical element with the symbol I and atomic number 53. The heaviest of the stable halogens, it exists as a semi-lustrous, non-metallic solid at standard conditions that melts to form a deep violet liquid at 114 °C (237 °F), and boils to a violet gas at 184 °C (363 °F).
Carbimazole
Prodrug of methimazole, 10 mg gives 6 mg
Inhibits thyroid peroxidase (TPO) which inhibits organification of iodine molecule into hormone
Side effects:
Agranulocytosis, Fever, Rash, Cholestasis (jaundice)
also reduces thyroid stimulating antibodies after use
takes about a month for TFT improvement
Add:
Propranolol at start of therapy 80 mg TID - taper after 4 weeks tp 40 mg TID = taper after 4 wks to 40 mg BD and then STOP
Nirmatrelvir/Ritonavir for Covid19
Nirmatrelvir/ritonavir (Paxlovid) is a combination of two protease inhibitors, nirmatrelvir and ritonavir.
Nirmatrelvir is a 3C-like protease inhibitor that interacts with the main viral protease of SARS-CoV-2, which cleaves the SARS-CoV-2 polyprotein into non-structural proteins. This represents a fundamental step in the viral replication and assembly of new viral particles.
Ritonavir is a protease inhibitor with very minimal antiviral activity. Ritonavir is a strong inhibitor of the cytochrome P450 (CYP) 3A4, and acts as a boosting agent, by increasing the concentration of nirmatrelvir.
Nirmatrelvir/ritonavir has many drug to drug interactions, mainly caused by ritonavir.
Some medications that are contraindicated with nirmatrelvir/ritonavir include: antiepileptics, anticoagulants, antibiotics (rifampicin), antiarrhythmics, antipsychotics, and immunosuppressants.
Nirmatrelvir/ritonavir is also contraindicated in patients with eGFR <30 mL/min.
Molnupivir
Molnupinavir is a synthetic ribonucleotide analogue (N4-hydroxicytidine) which binds to the viral RNA-dependent RNA-polymerase and inhibits viral replications by introducing copying errors.
Remdesivir
Remdesivir is a prodrug of an adenosine C-nucleoside, which inhibits viral replication by interacting with the RNA-dependent RNA-polymerase.
Remdesivir is contraindicated in patients with eGFR <30 mL/min. It is also contraindicated in patients with severe hepatic dysfunction or ALT >5 times the upper limit of normal.
Tocilizumab, Sarilumab, Baricitinib
Tcilizumab, sarilumab, baricitinib and other anti-inflammatory medications are used in some countries in people with severe COVID-19 in addition to dexamethasone to manage the hyperinflammatory syndrome.
Anti-inflammatory medications do not act directly against the virus, but they modulate the immune response to the virus, which is responsible for the organ damage due to the hyperinflammatory response in severe COVID-19.
Good CSF penetrating Drugs
Fluoroquinolones
Trimepthoprin-sulfamethoxazole
Metronidazole
Chloramphenicol
Fosfomycin
Isoniazid
Pyrazinamide
Voriconazole/fluconazole
Pyrimethamine
Albendazole/praziquantel
Good penetration only in inflamed meninges
Glycopeptides (vancomycin)
Macrolides (azithromycin)
Rifamp(ic)in
Ethambutol
Poor penetration of the CSF
Beta-lactams¹
Aminoglycosides
Tetracyclines (doxy, tigecycline)
Clindamycin
Daptomycin
Colistin
Amphotericin B
Echinocandins
Itraconazole/posaconazole
Drugs causing Optic neuropathy
Isoniazid, Ethambutol
Vincristine, Cisplatin
Ciclosporine
Disulfiram
Sildenaphil
Amiodarone
Diplopia causing drugs: Phenytoin, Topiramate, Carbamazepine
Other causes: B12, folate deficiency, DM, MS, Graves ophthalmopathy, Amaurosis fugax, Lead, CO exposure, Methanol blindness
Sumatriptan
used in acute attack of migraine as subcut injection, 6 mg or oral 25-100 mg. antagonist to serotonin receptors. It can cause acute chest syndrome, STEMI, Strokes as vasoconstrictor.
Do not use with complex migraine ie with neurological deficits. Also avoid Beta blockers and OCPs
Mechanisms of Anticonvulsants
Inhibition of Na dependant Action potentials: Phenytoin, Mazetol, Lamotrigine, Topiramate, Zonisamide
Inhibition of voltage gated Ca channels: Phenytoin
Decrease in Glutamate release: Lamotrigine
Increase GABA availability: Valium, Barbiturates
Modulation of Synaptic Vesicle release: through binding to the synaptic vesicle protein SV2A in the brain: = Levetiracetam (keppra)
Drugs causing convulsions
Alkylating: Busulfan, Chlorambucil
Antimalarials: Chloroquin, Mefloquin
AntiMicrobials: Ceftriaxone,
Quinolones, Acyclovir, INH
Anaesthetics: Meperedine, Tramadol, Local anaesthesia
Dietary supplements: Ephedra, Gingko
Immunomodulators: Ciclosporine, OKT3, Tacrolimus, IFN
Psychotropics: Antidepressants, Lithium, AntiPsychotics
Sedatives-Hypnotic withdrawals: Alcohol, Barbiturates, Valium
Drugs of Abuse: Cocaine, Amphetamines, Phencyclidine,
Others: Theophylline, Contrast agents, Flummazenil
Drugs causing headache
Nitrates
Calcium channel blockers
Tetracycline
Vitamin A derivatives
Analgesic overuse
Cocaine, Steroids,
Nicotine withdrawal
Acquired pendular nysagmus
may affect one or both eyes, and can occur in any axis or combination of axes. Although acquired pendular nystagmus may be idiopathic, the most common cause of secondary acquired pendular nystagmus is disorders of central myelin, namely multiple sclerosis (MS).J
Drugs causing Tremors:
Resting tremor causing drugs:
= Metoclopramide, Prochlorperazine
= Chlorpromazine, Haloperidol
Intention tremor causing drugs:
= Lithium toxicity
= Phenytoin, Valproate
Physiological tremor causing drugs:
= Salbutamol
= Theophylline
= Tricyclic antidepressants,
= Corticosteroids
= Thyroxine
Recreational drugs causing tremors:
= Cocaine, Amphetamines, Anabolics
Toxins causing Tremors:
= Heavy metals
= Organophosphates
Anti TNF drugs
for conditions:
Juvenile idiopathic arthritis, RA, Psoriatic arthropathy, Psoriasis, Ankylosing spondylitis, Crohn’s disease
Agents:
Infliximab, Etanercept, Adalimumab
Side Effects:
TB reactivation, Leukemias, Lymphomas, Nausea, Worsening CCF, Hypersensitivity reactions, Anemia, Aplastic anemia, low platelets
Contra-indications:
Pregnancy, Breast feeding, Active bacterial infections, Active TB, Latent TB, Septic arthritis, CCF, Demyelinating disease
Amiodarone Side Effects
Nausea, Metallic taste in mouth, Nightmares, Tremors, Headaches, Rashes, Phototoxicity
Optic neuritis
Peripheral neuropathy
Myopathy weakness
Hepatitis, cirrhosis
Interstitial lumb fibrosis
Hyper or Hypothyroidism
Corneal microdeposits: Night Glares
Epididymitis
Cardiac arrhythmias
Anti Arrhythmic Classification
Class 1 -
Interferes with sodium channel,
1a - Quinidine, Procainamide
1b - Lidocaine, Phenytoin, Mexilitine
1c - Flecainide, Encainide, Moricizine
Class 2 -
Anti sympathetic nerves: Beta blockers
Class 3 -
affects K efflux: Amiodarone, Sotalol, Ibutilide, Dofetilide, Dronedarone
Class 4 -
Affects Ca++ channel and AV nodes
Verapamil, Diltiazem
Class 5 - unknown or some other mechanism
Adenosine, Digoxin, Magnesium sulfate
Bismuth Subsalicylate
Bismuth subsalicylate is used to treat diarrhea in adults and teenagers. It is also used to relieve the symptoms of an upset stomach, such as heartburn, indigestion, and nausea in adults and teenagers.
You should not use bismuth subsalicylate if you have bleeding problems, a stomach ulcer, blood in your stools, or if you are allergic to aspirin or other salicylates. Using this medicine in a child or teenager with flu symptoms or chickenpox can cause a serious or fatal condition called Reye’s syndrome.
Bismuth subsalicylate is contraindicated in pregnancy because of associations with premature fetal ductus arteriosus and intrauterine growth problems.
Local Lidocaine dosing
Methyl Pred in spine trauma
Bupropion
Anti smoking medicación
Does - 150-300 mg per day
Acts - by boosting Brain levels of dopamine and norepinephrine
Mimics nicotine
Contraindicated with seizures
Evolocumab
Alirocumab
Antilipidemic monoclonal antibodies
Lowers LDL cholesterol
Binds proprotein convertase subtilisin kexin type 9 (PCSK9 inhibitors) which decreases degradation of LDL receptors thus helping their pick up and clearance
Medicacions to treat Weight Loss
- Apettite stimulants:
Corticosteroids, Progestational agents, Dronabimol, Serotonin antagonists (cyproheptadine) - Anabolic agents:
Growth hormone & testosterone derivatives - Anti catabolic agents:
Omega 3-Fatty acids, Pentoxyphylline, Hydrazine sulfate, Thalidomide
Phenazopyridine
An azo dye, a urinary analgesic, acts on urinary mucosa for local analgesia.
- 100-200 mg TDS after meals
- can cause orange ursine, tears, lenses
- can cause haemolytic anemia in G6PD deficiency
- can cause AKI, methemoglninemia
Acetylcholine esterase inhibitors
Used in moderate Dementia
Donepezil- 5 mg start, 10 mg max
Galantamine- 4 mg bd, 12 mg bd max
Rivastigmine - 1.5 mg bd, 6 mg bd max
Side effects
Diarrhea, nausea, anorexia
Weight loss
Syncope
Memantine
A NMDA antagonist
Used for dementia
Dose - 5 mg BD to 10 mg BD
Antivirals for Flu
Oseltamivir > 14 days old
Zanamivir (Relenza) - inhaled powder, > 7 days older, not in asthma/COPD
Peramivir (Rapivab) - IV only, > 6 months
Baloxavir (Xofluza) - single dose pill, not if pregnant or breastfeeding
Medications for urge incontinence
(detrusor overactivity)
Tolterodine - short/long acting
Oxybutynin - short/long acting/skinpatch
Fesoterodine
Trospium chloride
Darifenacin
Solifenacin
Mirabegron - beta 3 agonist, 25/50 mg PO OD
** Onabotulinum toxin A** injection into detrusor muscle
Anti emetic medications
Metoclopramide
Scopolamine- transdermal, 1.5mg/3days
Dexamethasone, 20 mg Divided
Diphenhydramine, 25 mg TDS
Lorazepam 0.5-1 mg
Ondansetron
Granisetron
Dolasetron
Palonosetron
Aprepitant (neurokinin-1 receptor antagonists)
Fosaprepitant
Rolapitant
Netupitant (N-receptor antagonist)
Olanzapine
Prochlorperazine
Mirtazapine
Dronabinol
Na Channel Blockers causing ECG effects
these are contra-indicated in Brugada syndrome
Tricyclic antidepressants (TCA’s)
Type Ia anti arrhythmics: Quinidine, Procainamide
Type Ic anti arrhythmics: Flecainie, Encainide
Local Anaesthetics: Bupivacaine, Ropicavaine
Antimalarials: Chloroquin, OH-chloroquin
Dextropropoxyphene (Opiod analgesics)
Propranolol
Carbamazepine
Quinine
Long acting Opioids
- Morphine - Oral Sustained release
- Hydromorphone, OD
- Oxymorphone, BID
- Oxycodone, BID, TID
- Hydrocodone, BD
- Methadone 3/4 times a day
Buprenorphine
Long acting, available as Oral, Patch, Parenteral, buccal formulations, Less addictive risk, Less risk of respiratory depression or sedation,
Skin Patch -5/10/20 mgc/Hr release
IV dose - 300 mcg, repeat after 60 min
IM dose -600 mcg once
Buccal dose - 150-450 mcg BD, max 900 mcg/Day
Subutex: sublingual tablet
Suboxone: sublingual film
Probuphine: subdermal implant
Sublocade: Subcute depot injection
Opioid induced Neuro-toxicity
occurs in patients on high dose opioids and can have manifestations as:
Hallucinations or Delirium - manage with Haloperidol
Hyperalgesia : increased pain to light touch (Allodynia), might resolve with Opioid Rotation or lowering dose but takes time.
Myoclonus: - can manage with small doses of clonazepam, baclofen, Gabapentin.
Medications to treat neuropathic pain
Neuropathic analgesic tips
- Gabapentin, Pregabalin: are Ca channel Alfa-2-delta ligands: can cause sedation, dizziness, ataxia: need renal adjustments
- Duloxetin, Venlafaxin - are Serotonin Norepinephrine reuptake inhibitors SNRIs. Duloxetine to take full stomach to avoid nausea, Venlafaxine can cause HTN & ECG changes.
- Nortryptiline & Desipramine are preferred over amitryptiline - as causes less orthostatic hypotension & less anticholinergic side effects.
- TCAs and SNRIs should not be prescribed together due to risk of serotonin syndrome
- Topical 5% Lignocaine and Capsaicin 8% patches are second line.
Managing Opioid induced nausea
Options:
1. Haloperidol: 0.5-4 mg PO/Sq/IV
2. Prochlorperazine: 10mg PO/IV or 25 rectal 6 hrly
3. Ondansetron: 4-8 mg PO or IV QDS
4. Mirtazapine
5. Medical cannabis
NOAC contra-indications
- CKD, GFR < 15 for factor Xa inhibitors
- GFR < 30 for Dabigatran, anti IIa
- Pregnancy, Lactation
- Metal cardiac valves
Heparin
Anti factor IIa and axa
Routes - IV or subcute
Monitor - aPTT, anti-Xa, anti-IIa
SideEffects - Platelet drop, bleeding
Antidote - Protamine sulfate: 1 mg neutralises 100 Unit heparin
Cryoprecipitate
Cryoprecipitate is the part of plasma that contains a number of clotting proteins (factors) that help control bleeding. It’s made by thawing fresh frozen plasma (FFP) between 1 and 6˚C and then collecting the cold-insoluble proteins (precipitate).
Contents: fibrinogen, fibronectin, clotting factors 8, 13, von willebrand factor
TNF inhibitors
Used in psoriasis treatment:
1. Infliximab- most rapid response and used in severe form like pustular or erythrodermic type
2. Etanercept: used for long term treatment as 50 mg subcute twice weekly 3 months then once weekly
3. Adalimumab (Humira):
Apremilast
Oral PDE 4 inhibitor,
Can be used long term for
Plaque type psoriasis, Needs no monitoring
Other options:
*TNF inhibitors
*IL-12/23 monoclonal antibodies: like Ustekinumab, Guselkumab
*Janus kinase JK inhibitors: Tofacitinib
*IL-17 monoclonal antibodies: Secukinumab, Brodalumab, Ixekizumab,
