Pharma Flashcards
(213 cards)
Phase I reactions:
oxidation, reduction, and hydrolysis. Mainly performed by the P450 enzymes but some drugs are metabolised by specific enzymes, for example alcohol dehydrogenase and
xanthine oxidase. Products of phase I reactions are typically more active and potentially toxic
Phase II reactions:
conjugation. Products are typically inactive and excreted in urine or bile.
Glucuronyl, acetyl, methyl, sulphate and other groups are typically involved.
* The majority of phase I and phase II reactions take place in the liver.
First-Pass Metabolism
concentration of a drug is greatly ↓ before it reaches the systemic circulation due to hepatic metabolism. As a consequence much larger doses are need orally than if given by other routes. This effect is seen in many drugs, including:
* Aspirin
* Isosorbide dinitrate
* Glyceryl trinitrate
* Lignocaine
* Propranolol
* V erapamil
Zero-Order Kinetics
describes metabolism which is independent of the concentration of the reactant. This is due to metabolic pathways becoming saturated resulting in a constant amount of drug being eliminated per unit time. This explains why people may fail a breathalyser test in the morning if they have been drinking the night before
Drugs exhibiting zero-order kinetics * Phenytoin
* Salicylates * Heparin
* Ethanol
Drugs exhibiting zero-order kinetics *
Phenytoin
* Salicylates * Heparin
* Ethanol
Drugs affected by acetylator status:
- Isoniazid
- Procainamide * Hydralazine * Dapsone
- Sulfasalazine
P-450 Dependent Drugs WEPTD:
- Warfarin
- Estrogen
- Phenytoin
- Theophylline
- Digoxin
P450 inhibtors: (causing low metabolism of WEPTD → Toxicity)
Acute alcohol intake
* Allopurinol
* Amiodarone
* Cimetidine, omeprazole
* Dapsone
* Imidazoles: ketoconazole, fluconazole
* INH
* Macrolides (Azithro-Clarithro-Erythro mycins)
* Quinolones (ciprofloxacin)
* Quinupristin
* Sodium valproate
* Spironolactones
* SSRIs: fluoxetine, sertraline
* Grapefruit juice (potent inhibitor of the cytochrome P450 enzyme CYP3A4)
* Protease inhibitors (ndinavir, nelfinavir, ritonavir, saquinavir)
P450 inducers:
- Antiepileptics: phenytoin, carbamazepine (note that valporate is an inhibitor)
- Barbiturates
- Chronic alcohol intake
- Griseofulvin
- Quinidine
- Rifampicin
- Smoking (affects CYP1A2, reason why smokers require more aminophylline)
- St John’s Wort
- Sulfa drugs
- Tetracycline
- Nevirapine (NNRTI)
Drugs that can be cleared with Hemodialysis
Barbiturate
* Lithium
* Alcohol (inc methanol, ethylene glycol)
* Salicylates
* Theophyllines (charcoal hemoperfusion is
preferable)
Drugs which cannot be cleared with HD include
Tricyclics
* Benzodiazepines (diazepam,midazolam,alprazolam)
* Dextropropoxyphene (co-proxamol)
* Digoxin, β-blockers
Drugs to avoid in Renal Failure
- Antibiotics: tetracycline, nitrofurantoin
- NSAIDS
- Lithium
Drugs likely to accumulate in renal failure - need dose adjustment
Most antibiotics including penicillins, cephalosporins, vancomycin, gentamicin, streptomycin
* Digoxin, atenolol
* Methotrexate
* Sulphonylureas
* Furosemide
* Opioids
Drugs relatively safe in renal failure - use in normal dose
Antibiotics: erythromycin, rifampicin
* Diazepam
* W arfarin
Drug Induced Impaired Glucose Tolerance
Thiazides, furosemide (less common)
* Steroids
* Tacrolimus, cyclosporin
* Interferon-α
* Nicotinic acid (vitamin B3)
β-blockers cause a slight impairment of glucose tolerance. They should also be used with caution in
diabetics as they can interfere with the metabolic and autonomic responses to hypoglycemia
drugs Hepatocellular Picture
- Alcohol
- Amiodarone
- Anti-tuberculosis: isoniazid,
rifampicin, pyrazinamide - Halothane
- MAOIs
- Methyldopa
- Paracetamol
- Sodium valproate, phenytoin
- Statins
drugs Cholestasis (+/- Hepatitis)
Anabolic steroids, testosterones
* Antibiotics: flucloxacillin, co-amoxiclav,
erythromycin*, nitrofurantoin
* Fibrates
* Oral contraceptive pill
* Phenothiazines:
prochlorperazine
* Rarely: nifedipine
* Sulphonylureas
drugs Liver Cirrhosis
Amiodarone * Methotrexate * Methyldopa
Drugs Causing Visual Disturbance:
Cataracts
* Steroids
Corneal opacities
* Amiodarone * Indomethacin
Optic neuritis
* Ethambutol
* Amiodarone
* Metronidazole
Retinopathy
* Chloroquine, quinine Blue tinge in vision:
* Sildinafil Yellow-green tinge:
* Digoxin
Drugs Causing Gingival hyperplasia
- Phenytoin
- Cyclosporin
- Calcium channel blockers (especially nifedipine)
Other causes of gingival hyperplasia include - Acute myeloid leukemia (myelomonocytic and monocytic types)
Drugs Causing Urticaria:
- Aspirin
- Penicillins * NSAIDs
- Opiates
Drugs Causing Acute Intermittent Porphyria (AIP)
- Alcohol
- Barbiturates
- Benzodiazepines
- Halothane
- Oral contraceptive pill
- Sulphonamides
Acute Intermittent Porphyria (AIP) safe drugs
- Paracetamol * Aspirin
- Codeine
- Morphine
- Chlorpromazine * β-blockers
- Penicillin
- Metformin
Drug Induced Thrombocytopenia (probable immune mediated)
- Heparin
- Abciximab
- NSAIDs; ASA
- Diuretics: furosemide
- Quinine
- Antibiotics: penicillins, sulphonamides, rifampicin
- Anticonvulsants: carbamazepine, valproate