Bioavailability of different routes of drug administration
| Route | Bioavailability (%) |
| Intravenous | 100 |
| Intramuscular | 80-100 |
| Subcutaneous | 80-100 |
| Oral | 5- <100 |
| Rectal | 30-100 (highly variable) |
| Inhalational | 5-100 |
| Sublingual | 30- <100% |
First-pass metabolism is avoided with all routes except oral administration.
Succinylcholine is metabolized in plasma by cholinesterase (pseudocholinesterase) into inactive forms. Inherited differences in this enzyme can slow succinylcholine breakdown, leading to prolonged neuromuscular paralysis in some patients.
The involved gene is located on chromosome 3 (gene E1). The most common mutation is a substitution of aspartic acid to glycine, which reduces enzyme binding to succinylcholine.
Slow and fast acetylators: Drugs such as isoniazid, dapsone, hydralazine, sulfa drugs, and procainamide are metabolized by acetylation reactions catalyzed by acetyltransferases. The gene is NAT2. The rate of acetylation varies by ethnicity due to polymorphisms in the enzyme. About 50% of Caucasians and African Americans are slow acetylators, while most Asians are fast acetylators.
Acetaminophen toxicity is a common cause of liver transplantation. Large doses of acetaminophen - especially in people with chronic liver disorders and in alcoholics - can saturate the usual hepatic detoxification mechanisms. This leads to excessive formation of a toxic metabolite called NAPQI (N-acetyl-p-benzoquinone imine).
Normally, NAPQI is detoxified by glutathione. In acetaminophen overdose, glutathione stores are depleted, allowing NAPQI to bind to hepatocytes and cause necrosis. Chronic alcoholism induces hepatic microsomal enzymes, increasing NAPQI formation. Alcohol also depletes glutathione.
Patients may be asymptomatic for up to 24 hours and then present with vomiting, RUQ pain, hypotension, liver failure, renal failure, coagulopathies, metabolic acidosis, and encephalopathy. Microscopically, the liver shows centrilobular necrosis.
Treatment is guided by time since ingestion:
N-acetyl cysteine also reduces NAPQI to acetaminophen, acts as a precursor to glutathione, has antioxidant and anti-inflammatory properties, increases sulphate conjugation, and increases local nitric oxide and oxygen delivery. Severe cases may also require hemodialysis and liver transplantation.
* Includes digoxin, ethanol, theophylline, cimetidine, gentamicin. Reduce loading dose.
** Includes diazepam, lidocaine, thiopental. Increase in half life.
| Type | Description |
| Primary | When chemotherapy alone can cure the cancer like in Hodgkin’s disease, Wilms tumor, small cell lung cancer, testicular cancer, Burkit’s lymphoma, large cell lymphoma, leukemias. |
| Adjuvant | Administered prior to or after other methods like surgery, to increase the effectiveness of treatment, to prolong survival or decrease the risk of recurrence. |
| Palliative | To minimize the discomfort caused by or slow progression of an incurable cancer |
| Neoadjuvant | Given prior to surgery or radiation, to shrink the size of a tumor and make it easier to resect. |
Tachyphylaxis is when a drug becomes less efficacious (or loses its effect) with continued use over a period of time. It is a type of tolerance (desensitization).
Mechanisms include:
It is seen with nitroglycerin, topical corticosteroids, local anesthetics, nicotine, etc. Temporarily withholding the drug or providing drug-free hours can restore sensitivity.
Metronidazole is commonly used to treat anaerobic and protozoal infections. It is metabolized to nitro free radicals, which cause DNA damage and inhibit protein synthesis.
It is effective against E.histolytica, Trichomonas, Giardia lamblia, Bacteroides sp, Clostridium sp, Fusobacterium sp, Gardnerella vaginalis, H.pylori etc.
Adverse effects include nausea, metallic taste, headache, diarrhea, pruritus, peripheral neuropathy, seizures, and probable carcinogenicity. It can cause an antabuse-like reaction if alcohol is consumed concurrently.
Warfarin-induced skin necrosis typically occurs 2-5 days after starting warfarin therapy. It occurs due to depletion of vitamin K-dependent anticoagulant proteins C and S.
It is due to thrombosis in blood vessels of the skin, especially in areas with abundant fat. It presents with pain, a purplish rash, blistering, blue toe syndrome, and skin necrosis (commonly in the breast, thighs, buttocks, and abdomen).
Management includes stopping warfarin and giving vit K, heparin, and protein C concentrates.
| 1st generation | Cefazolin, cephalexin, cefadroxil |
| 2nd generation | Cefaclor, cefotetan, cefoxitin, cefprozil, cefuroxime |
| 3rd generation | Cefdinir, ceftriaxone, cefotaxime, cefpodoxime, ceftazidime, cefixime |
| 4th generation | Cefepime |
| 5th generation | Ceftaroline |
| Penicillin type | Characteristics |
| Natural penicillins | Penicillin G, Penicillin V. Active against non-beta-lactamase producing Gram positive cocci like viridans streptococci, Group A streptococci, pneumococci, peptostreptococcus, Clostridia, Actinomycetes, meningococci, gonococci, Pasteurella multocida, Treponema pallidum |
| Penicillinase resistant penicillins | Methicillin (not used now, causes interstitial nephritis), nafcillin, oxacillin, dicloxacillin. Active against penicillinase producing Staphylococci but no action on MRSA, MRSE and Enterococci |
| Aminopenicillins | Ampicillin, amoxicillin; activity like natural penicillins plus also gram negative bacilli like H.influenzae, E.coli, Proteus, Salmonella, Shigella sp. Widespread resistance seen |
| Carboxypenicillins | Carbenicillin, ticarcillin; greater Gram negative spectrum including Pseudomonas aeruginosa |
| Ureidopenicillins and piperazine penicillins | Azlocillin, mezlocillin, piperacillin; coverage like carboxypenicillins plus more effective on Klebsiella, Serratia, Enterobacter, Enterococcus and P.aeruginosa; |
Colchicine binds to tubulin and blocks microtubule assembly and polymerisation. It also inhibits neutrophil chemotaxis and the release of a crystal-derived chemotactic factor (CCF) from neutrophil lysosomes, superoxide formation, and phagocytosis.
It is used to treat acute gout, familial meditteranean fever, Behcet’s disease, and inflammatory disorders.
Adverse effects include diarrhea, nausea, vomiting, neutropenia, neuropathy, and organ failure. Doses should be decreased in renal and/or hepatic failure. Colchicine has a narrow therapeutic index.
Rhabdomyolysis can occur when colchicine is given with statins. The dose should be reduced when cyt P450 inhibitors are co-prescribed.
Ultra fast acting insulin (Fiasp) is a recently FDA-approved form of insulin aspart designed to speed up absorption of subcutaneous insulin by adding vitamin B3 (niacin) and L-arginine.
It is used in type 1 and 2 DM and can be injected up to 20 minutes after starting a meal. Onset of action is within 15-20 minutes, and duration of action is 7 hours.
| Antidote | Uses |
| Activated charcoal | Typically within 1 hour and maximum within 4 hours of oral ingestion of a toxin; can be used in carbamazepine, dapsone, theophylline, phenobarbitone, quinine etc. Do not use in alcohol, acid, alkali or metal poisoning |
| Dimercaprol | Arsenic, gold, mercury and lead poisonings |
| Digi-Fab (antibody to digoxin) | Digoxin toxicity |
| Urinary alkalinization with sodium bicarbonate | TCA, salicylates, phenobarbital |
| Naloxone | Opioids, repeat doses every 2-3 minutes, onset of action <2 minutes in intravenous dosing |
| Flumazenil | Benzodiazepines |
| Fomepizole | Methanol and ethylene glycol |
| Pralidoxime and atropine | Organophosphorus |
| N acetyl cysteine | Paracetamol |
| Sodium thiosulfate | Cyanide poisoning |
| Vitamin K | Warfarin |
| Pyridoxine or Vit B6 | Isoniazid |
| Folinic acid | Methotrexate |
| Beta blockers | Theophylline |
| Octreotide | Oral hypoglycemics |
| Physostigmine | Anticholinergic poisoning |
| Protamine sulfate | Heparin |
| Glucagon, calcium, high dose insulin with glucose | Beta blockers and calcium channel blockers |
Comparison between proton pump inhibitors and H2 blockers
Treatment options for resistant bacteria
| Resistance type | Treatment |
| MRSA | Soft tissue infections: oral doxycycline, trimethoprim-sulfamethoxazole, clindamycin, minocycline, linezolid, tedizolid, delafloxacin, omadacycline; Complicated infections: Intravenous vancomycin, daptomycin or linezolid |
| VRSA and VISA | Daptomycin, telavancin, ceftaroline, linezolid, tedizolid, oritavancin |
| VRE | Ampicillin plus gentamicin/streptomycin, ceftriaxone, ampicillin-sulbactam, linezolid, daptomycin |
| MDR Pseudomonas aeruginosa | Ceftazidime-avibactam, ceftolozane-tazobactam, colistin, polymyxin B, imipenem-cilastatin, relebactam |
| ESBL | Carbapenems (imipenem, meropenem, ertapenem), piperacillin tazobactam, cefepime, fosfomycin (UTIs), temocillin |
| Carbapenem resistant Enterobacteriaceae | Avibactam plus ceftazidime, meropenem plus vaborbactam, fosfomycin (UTIs) |