Drug Names Flashcards
Name two drugs removed from the market due to drug-drug interactions:
- Sorivudine- anti-viral, inhibition of 5-fluorouracil metabolism.
- Terfenidine- anti-histamine, when coadministered with ketoconazole (and grapefruit juice), leading to cardiotoxicity.
What 1960s drug contributed to the formation of regulatory authorities of drugs?
Thalidomide- given the pregnant women to help with sleep and depression, but ended up causing bird abnormalities.
Name three drugs which were discovered from development of herbal/traditional remedies:
- Morphine from opium poppy.
- Digoxin/digitoxin from foxgloves.
- Salicyclic acid (aspirin) from willow bark.
Name two drugs which were discovered by the empirical approach, using models felt to be predictive of activity and screening a large number of compounds:
- Anti-cancer drugs.
2. Cyclosporin (immunosupressant).
Name two drugs which were discovered by the rational drug design, understanding the cellular/molecular basis of diseases (e.g. receptors), using computer technology to get the 3D structure of the receptor to design agonist drug:
- Propanolol- beta-blocker.
2. Cimetidine- H2-antagonist.
Name two drugs which are prodrugs, analogs or metabolites of existing drugs:
- Aspirin (salicyclic acid).
2. Paracetamol (phenacetin).
Name three drugs discovered by serendipity (chance):
- Penicillin.
- Valproate (anti- epilleptic).
- Sildenafil (Viagra).
Describe how drugs may be discovered from genomics- information on genes to identify drug targets:
Gene therapy, siRNA.
Describe some of the NSAID adverse reactions:
Occur due to chronic COX inhibition. This is important because some prostaglandins are cytoprotective and so initial lesion results in overt damage.
NSAID may induce lesions by interacting with phosphotidyl choline and reduce the ability of gastric mucosa to protect itself from e.g. HCl.
Describe some of the paracetamol adverse reactions:
Toxicity is due to saturation of detoxification pathways.
There is some dose dependency and predictability. Toxic metabolite is a quinoneimine that can react with sulfhydryl groups in critical cellular proteins.
Loss of intracellular calcium regulation disrupts mitochondrial function and leads to necrotic cell death.
How does 6-Mercaptopurine relate to adverse drug reactions and toxicity, and gene predisposition?
Undergoes S-methylation catalysed by the enzyme TPMT. 89% of individuals have high TMPT activity, 11% have intermediate. ~1 in 300 patients are at high risk of potentially fatal haemopoietic toxicity due to accumulation of thioguanine nucleotides in haematopoietic tissues. Suitable therapy can be achieved by using 10-15 fold reduction in dose.
Name a drug which undergoes a lack of detoxification, leading to secondary effects.
Perhexiline, an anti-angina drug that has cationic, amphiphilic properties. If it is not metabolised by CYP2D6, it will accumulate in lysosomes, resulting in hepatoxicity and neuropathy.
Describe adverse reactions to penicillin:
Nausea, vomiting, epigastrci distress, diarrhoea, and black, hairy tongue.
Haemolytic anaemia, leucopoenia, thrombocytopenia, neuropathy, and nephropathy and infrequent reactions and are usually associated with high doses of parental penicillin.
Hypersensitivity reactions include:
Skin eruptions (ranging from maculopapular to exfoliative dermatitis).
Urticaria.
Reactions resembling serum sickness, including chills, fever, oedema, arthralgia, and prostration.
Laryngeal oedema.
Anaphylaxis.
Describe the pharmacological interactions with ethanol (alcohol):
Ethanol can act at GABAa receptors. Drinking alcohol with sedatives, hypnotics and some anti-histamines can result in additive or synergistic effects. Outcome is too much sedation or come and death.
Describe the pharmacokinetic interactions of Warfarin with cimetidine:
Has a narrow therapeutic index, so patients are stabilised on a dose. Cimetidine inhibits warfarin metabolism: Blood concentrations of warfarin are increased to toxic levels.
Describe the pharmacokinetic interactions of Terfenadine with ketoconazole:
Metabolised to CYP to fexofenadine. Fatal interaction with ketoconazole, an inhibitor of CYP34A which increased plasma concentrations and revealed secondary pharmacology.
Interference with cardiac slow rectifier K+ channel, prolonging QT interval and quinidine-like effects on the heart.
Describe the pharmacokinetic interactions of alcohol with paracetamol:
Ethanol induces the enzymes that bioactivates paracetamol. Chronic alcoholics may produce more of the toxic metabolite and have greater risk of hepatotoxicity.
Describe the adverse effects and toxicitiy of Baycol/Lipobay, a statin:
Baycol (cerivastatin) lowers cholesterol, and is associated with the very rare symtoms of rhabdomyolysis, fatal cases have been reported with this brand than for other brands of statins.
Most frequently when used at higher doses, when used in elderly patients and particularly when used in combination with gemfibrozil, another lipid lowering drugs.
How is ipecac used to decrease absorption of poisons?
Vomiting agent, consits of cephaeline, which stimulates the central vomiting centre and emetine, which activates sensory receptors in the proximal small intestine. Only useful over a short timeframe. Contraindicated for substances that could cause further injury during emesis e.g. caustic substances and hydrocarbons. Will affect the absorption of other antidotes (e.g. acetyl cystein and activated charcoal).
How is activated charcoal used to deccrease absorption of poisons?
Drug may adsorb onto the charcoal and thereby prevent absorption in the first place. It may create a concentration gradient across the mesenteric vasculature, such that the drug or metabolite is eliminated faster. Useful for some drugs that undergo substantial enterohepatic recirculation, or small volume of distribution or low protein binding and are highly absorbed by charcoal. Dose usually 1-2g/kg orally or naso-gastric tube.
How may iron and deferoxamine be used to neutralise the poisonous chemical?
Ingestion of a large amount of iron overwhelms gastrointestinal regulatory mechanisms resulting in massive iron absroption. When serum iron levels exceed the capacity of the binding protein, transferrin, sever toxicity may occur secondary to deposition of iron in soft tissues. Free iron causes toxicity by directly injuring the intestinal mucosa and generating oxygen free radicals.
Deferoxamine mesylate is an anti-dote for iron poisoning, which chelates the free iron to form feroxamine but it does not remove from proteins such as transferrin, ferritin, haemoglobin and cytochromes. Feroxamine is excreted unchanged in the urine.
How may paracetamol and N-acetyl cystein be used to neutralise the chemical?
N-acetly cystein is an antidote for paracetamol overdose. NAC acts as a precursor for glutathione synthesis and so boosts the resynthesis of this vital intracellular agent and thus prevents liver damage.
How can salicylate and urinary alkalisation be used to enhance elimination?
Aspirin is readily hydrolysed to salicylate, which stimulates the medullary respiratory centre, producing hyperventilation, respiratory alkalosis and eventually metabolic acidosis. Uncouples oxidative phosphorylation increasing gluconeogenesis and lipid metabolism, produces tinnitus, nausia, vomiting, ataxia, coma and hyperthermia.
Sodium bicarbonate can be used to raise the urinary pH>7.5, weak acids with pKa<7 that undergoes significant urinary excretion become trapped in the kidney tubular fluid.
Can also be used for phenobarbital, chlorpropamide and 2,4-dichlorophenoxyacetic acid (herbicide). Used in conjunction with activated charcoal.
Describe pharmacodynamic intervention of heroin and naloxone:
Overdoses of heroin frequent when used in conjunction with alcohol, benzodiazepines, cannabis, amphetamine etc. or when a purer form is used. Many routes of administration.
Heroins typical nacrotic effects because it is converted to morphine, associated with coma, seizures and delayed encephalopathy in overdose. Letahl dose is hard to define.
Naloxone, antagonist at the mu, kappa and delta opiod recpetors, it may be necessary to administer by i.m., s.c., endotracheal or intralingual routes.
Naloxone has a shorter half life than heroin, so replase may occur. May also precipitate heroin withdrawal.
Describe how wafarin and vitamin K may be used to replace acitivity:
Warfarin is used in the prophylaxis and treatment of venous thrombosis and pulmonary embolism, inhibits vitamin K dependent coagulation factors, results in a sequential depression of ‘factors’ activity.
Vitamin K reductase and vitamin K epoxide reductase are blocked. Vitamin K therapy may be required for long time until prothrombin (coagulation) returns to normal.
Describe organophosphates toxicity:
Used extensively in agriculture, industrail and terrorism. Has nicotinic effects, CNS effects and muscarinic effects. Organophosphate inhibits acetylcholinesterase, so it cannot be readily hydrolysed and depletes cholinergic acitivity.
How may pralidoxime be used to regenerate the target affected by organophosphates?
Pralidoxime can remove the phosphate group from the cholinesterase enzyme to regenerate catalytic activity, effects at nicotinic greater than muscarinic. Effect is great at erythrocytic esterase is given soon after toxicity. Reactivation of plasma cholinestease activity is minimal.
List two types of anti-inflammatory steorids:
Steroids- e.g. endogenous steroids include cortisol, progesterone, which act via intracellular receptors to regulate gene transcription.
Glucocorticoids- e.g. adrenal steroids, have immunosupressive effects.
Describe the pro-inflammatory effects of glucocorticoids:
Pro-inflammatory genes are downregulated:
Pro-inflammatory cytokines, COX-2, phospholipase A2 (PLA2), cell-adhesion molecules, endothelins, inducible nitric oxide synthase (iNOS).
Genes that are up-regulated by gluccocorticoids:
Il-10/Il-4 (anti-inflammatory cytokines), lipocortins/annexins (PLA2 inhibitor).
What are the three types of GC preparations:
Oral- e.g. prednistone, methyl prednisone, predinsolone, dexamethasone.
Inhalable- e.g. fluticasone, beclomathasone.
Topical- e.g. prednisone, prednisolone, dexamethasone.
How do NSAIDs relate to prostaglandins?
Non-steroidal anti-inflammatory drugs, not narcotic drugs. Inhibit prostaglandin (PHG2) biosynthesis via COX enzymes.
Taken to reduce pain (analgesic), swelling, inflammation and fever (anti-pyretic).
Can have significant side-effects, rarely fatal.
List four common NSAIDs and what they are used for:
Aspirin, ibuprofen, diclofenac and naproxen. They are commonly used for post-operatively, head-ache, migraine, pyrexia (fever), menstruation pain, tooth ache.
How do NSAIDs work?
They inhibit block the enzymatic acitivity of cyclooxygenase (COX).
Describe the pathways of prostanoid biosynthesis:
Glycerophospholipids and converted into arachindonic acid by phospholipases. COX-1 and COX-2 are inhibited aspirin ibuprofin.
Describe the effects of aspirin on inflammation:
This is acetylsalicyclic acid and irreversibly inhibits COX-1. Effective inhibitor of PG-mediated pain. Also inhibits TXA2 release by platelets (anti-thrombotic).
What are some side effects of aspirin:
Associated with significant GI-side effects. Caution if prone to GI ulceration or gastritis.
Describe the effects of paracetamol on inflammation:
Good anti-pyretic and anagesic, ineffective anti-inflammatory indications. Mechanism is that it reduced prostaglandin sysnthesis and is a relatively weak inhibitors of COX.
What are some side effects of paracetamol?
Metabolised in the liver to a toxic metabolite which can cause serious liver damage. Has a low therapeutic index, so 10x adult dose can be fatal.
Describe some of the general adverse effects of NSAIDS:
Gastric upset, ulcers, GI bleeded, renal complications/impairment, increased clotting time, not for use following heart surgey, asthmatics can have an allergic type response to NSAIDs that may be fatal, hepatic toxicity, skin rashes, early pregnancy loss, fertility complications.
There are all largely associated with COX-1 inhibition.
Name some second generation COX-2 inhibitors, and explain their advantages:
Celecoxib and rofecoxib.
Reduced GI irritation and ulcer rate, with similar efficacy to non-selective NSAIDs, useful for long term use in treatment of chronic conditions, also exhibit good short-term pain relief profile.
Describe the unexpected adverse effects of COX-2 selective inhibitors:
Celecoxib associated with acute cardiovascular events. Rofecoxib increases the risk of thrombolytic events, may relate to inhibition of COX-2 derived prostacyclin, increase BP and some renal impairment.
Name two attempts to treat malaria using natural substances:
Qinghaosu plant and cinchona bark.
Describe the use of quinine as an anti-malarial:
This is the main alkaloid in the bark of the cinchona tree (quinidine also found, but not used because it causes long QT syndrome).
This is active against erythrocytic stages of the parasites, and its mode of action may involve binding to DNA, stopping synthesis of nucleic acids, inhibition of haem digestion.
Describe chloroquinine, and synthetic anti-malarial:
Based on the quinine structure, accumulates in the food vacuole of the parasite, interferes with haem digestion, effective against blood stages and is relatively safe.
Resistance is a problem.
