study d2 Flashcards
C. Inhibition of protein synthesis
Aminoglycosides
Aminoglycosides
* useful versus Gram – aerobic bacilli
* gentamicin, tobramycin,
* charged, therefore not well absorbed orally, rather
* administered i.v. or i.m. routes
major adverse effects:
* nephrotoxicity and ototoxicity
(auditory and vestibular)
C. Inhibition of protein synthesis
macrolides
Macrolides
* erythromycin, clarithromycin, azithromycin*
* especially useful versus Gram + bacteria
* can be used as substitute for penicillin in patients displaying hypersensitivity
* often used for respiratory infections, *chlamydia / *gonorrhea
adverse effects:
* nausea, vomiting, diarrhea
* clarithromycin inhibits hepatic enzymes … therefore risk of toxicity for any drug normally metabolized and inactivated by the the liver
Other antimicrobials that share the same mechanism of action as macrolides:
clindamycin:
* member of the lincoside family; acts like macrolides
* often used for soft tissue infections (cellulitis, bites) especially for allergy to beta-lactams; also bacterial vaginosis
telithromycin:
* member of the ketolide family
* lower resistance observed vs macrolides in S pneumoniae, as there are 2 distinct binding sites on ribosomes
* used in limited by hepatotoxicity
linezolid (class = oxazolidinones):
* member of the oxazolidinones
* use limited to infections that are otherwise difficult to treat such as VRE and MRSA
C. Inhibition of protein synthesis
tetracyclines
Tetracyclines
* tetracycline, doxycycline, minocycline
* broad spectrum; widespread resistance
* selected therapeutic uses:
* tetracycline (acne; H.pylori) doxycycline (Chlamydia)
* interactions with milk, antacids,calcium, iron (decreases absorption of drug)
* high affinity for bone and teeth discoloration (if used from ages 4 mo. to 8 y.o risk of superinfections)
* avoid during pregnancy
D. Inhibiton of DNA synthesis
fluoroquinolones, metronidazole
antimicrobials that inhibit nucleic acid replication and transcription
- fluoroquinolones:
ciprofloxacin, levofloxacin, moxifloxacin
* very active versus Gram – aerobic bacilli; newer drugs also act on many Gram + bacteria
* drug of choice to treat Bacillus anthracis (anthrax)
* avoid during pregnancy
* well tolerated; nausea, tendinopathies (tendons that swell) - metronidazole (Flagyl)
* Gram – anaerobic bacteria,
* used for trichomoniasis, bacterial vaginosis and aquatic protozoa : « beaver fever », also known as giardiasis, is a parasitic infection caused by Giardia
adverse effects:
* nausea, metallic taste, dizziness/vertigo , disulfiram effect
* nitrofurantoin (Macrobid) is also an antibiotic that affects DNA synthesis mostly used for urinary tract infections
E. Disruption of plasma membrane
polymyxins
* act like detergents (soap) to disrupt phospholipid membranes
* Spectrum: Gram – bacteria
* Due to nephrotoxicity, these drugs are only used topically (or injected with an infected body cavity)
Antimicrobial resistance
Antimicrobial Resistance
* Overuse of antibiotics is the main factor causing resistance.
* The three main mechanisms used
by bacteria to become resistant to antibiotics are:
1. reduction of bacterial permeability
2. enzymatic degradation of antibiotics
3. modification of the action site
What leads to antibiotic resistance?
* important to note that it happens naturally, by random mutations in bacteria
* overuse and misuse of antibiotics in both humans and animals
* taking antibiotics for an infection that is not caused by bacteria (e.g. viral)
* not taking antibiotics as prescribed
* self-medicating or antibiotic sharing
Antimycobacterial Drugs
tuberculosis drugs
Tuberculosis drugs
Rifampin:
* almost always used in combination
* powerful inducer of cytochromes P450
Adverse effects:
* discoloration of body fluids (urine, sweat, tears) epigastric pain, flu-like syndrome
Isoniazid:
Adverse effects:
* peripheral neuropathy
(tingling, numbness, burning, pain)
* can be reduced with vitamin B6 (pyridoxine)
Ethambutol:
Adverse effects:
* optic neuritis, reduced vision caused by inflammation of optic nerve)
* often starts as red-green color blindness
Anti-anginal Drugs -> nitrates
routes
nitrates
* drugs derived from nitroglycerin, a volatile and explosive compound (decompose when exposed to air, light or heat)
* used in the manufacturing process of dynamite
* in pharmaceutical preparations, these chemicals have been stabilized
Nitroglycerin
sublingual (tablet or aerosol):
* rapid absorption of drug and avoids 1st pass hepatic metabolism
transdermal:
* slow and continuous release of drug (tolerance)
* topical administration (ointment)
* injectable formulation (I.V.)
oral:
* would necessitate sufficient quantities to overcome the significant inactivating activity of hepatic enzymes (extensive first pass hepatic metabolism)
antifungal drugs
polynes and ESI
Antifungal drugs
* used for fungal infections (mycoses) caused by molds or yeasts
* often seen in patients with immunodeficiencies
* ergosterol: important component of fungus cell membranes
Polyenes
* amphotericin B* (iv), nystatin (topical)
* bind to ergosterol and form holes in the membrane
* poor oral absorption
adverse effects:
* Nephrotoxicity, anemia, infusion-related reaction (fever, chills), phlebitis
Ergosterol synthesis inhibitors
Azoles
* clotrimazole, miconazole (topical)
* fluconazole (po)
* many inhibit cytochromes P-450
Allylamines
* terbinafine
nitrates
Physiological mechanism of action of nitrates
Vasodilation
Veins:
* reduced venous return,
↓ preload
arterioles:
* drop in blood pressure;
↓ resistance; ↓ afterload
coronaries:
* increased coronary blood flow
Adverse effects
* orthostatic hypotension
* frequent headache, especially at the beginning of treatment
* reflex tachycardia at high doses
* tachyphylaxis or tolerance: when continuously exposed to drug
beta blockers
- are antagonists that block the stimulation of beta adrenergic receptors of the autonomic nervous system (sympathetic branch)
- They demonstrate negative chronotropic,
inotropic and dromotropic effects on the heart
1. chronotrope = heart rate
2. inotrope = force of contraction
3. dromotrope = conduction velocity - also decreases renin release by juxtaglomerular cells
- less angiotensin II (AngII)
- decrease in blood pressure
Adverse effects
* orthostatic hypotension
* frequent headache, especially at the beginning of treatment
* reflex tachycardia at high doses
* tachyphylaxis or tolerance: when continuously exposed to drug
Beta blockers
treatment of, selectivity
treatment of
* angina, hypertension, arrhythmias, heart failure
* migraines
* anxiety
* hyperthyroidism
selectivity
* some beta blockers
(metoprolol, bisprolol and atenolol) demonstrate effects that are more cardio-selective because they act mostly on beta 1 (cardiac) receptors
* Other non-specific beta blockers (propranolol) can be used but tend to demonstrate more side effects (bronchial / metabolic) as they block beta 2 receptors as well
Calcium Channel Blockers
mention adverse effects and treatment for
Subclasses
1. dihydropyridines:
amlodipine, nifedipine
2. non-dihydropyridines:
benzothiazepines: diltiazem
phenylalkylamines: verapamil
vascular effects :
* (especially amlodipine, also verapamil and diltiazem)
* arterial vasodilation leading to reduced blood pressure
* coronary artery vasodilation/reduction of vasospasms
cardiac effects (non dihydropyridines: verapamil, diltiazem)
* negative inotropic effect (decreased force of contraction)
* decreased heart rate
adverse effects:
* headaches
* flushing
* edema in lower limbs
* orthostatic hypotension
* constipation (verapamil)
therapeutic uses: treatment of
* angina
* hypertension
* arrhythmias (Non D)
