Tetracycline
Tetracycline is an antibiotic produced by the streptomyces bacterium

Mechanism and Resistance Tetracycline inhibits cell growth by inhibiting translation. It binds to the 30S  ribosomal subunit and prevents the amino-acyl tRNA from binding to the A site of the ribosome. This prevents the addition of amino acids to the elongating peptide chain, preventing synthesis of proteins. The binding is reversible in nature.

Example: Chlortetracycline, oxytetracycline, demethylchlortetracycline, rolitetracycline, limecycline, clomocycline, methacycline, doxycycline, minocycline

Source: Streptomyces spp.; some are also semi-synthetic

Spectrum of activity: Broad-spectrum. Exhibits activity against a wide range of Gram-positive, Gram-negative bacteria, atypical organisms such as chlamydiae, mycoplasmas, rickettsiae and protozoan parasites.

Effect on bacteria: Bacteriostatic

Cells become resistant to tetracyline by at least two mechanisms: efflux and ribosomal protection.

Contraindications Tetracycline use should be avoided during pregnancy and in the very young (less than 6 years) because it will result in permanent staining of teeth causing an unsightly cosmetic result.

Tetracyclines also become dangerous past their expiration dates. While most prescription drugs lose potency after their expiration dates, tetracyclines are known to become toxic over time; expired tetracyclines can cause serious damage to the kidneys.

Miscellaneous: Tetracyclines have also been used for non-antibacterial purposes, having shown properties such as anti-inflammatory activity, immunosuppresion, inhibition of lipase and collagenase activity, and wound healing.

Routes of Drug Administration

Intravenous

• No barriers to absorption since drug is put directly into the blood.
• There is a very rapid onset for drugs administered intravenously.  This can be advantagous in emergency situations, but can also be very dangerous.
• This route offers a great deal of control in respect to drug levels in the blood.
• Irritant drugs can be administer by the IV route without risking tissue injury.
• IV drug administration is expensive, inconvenient and more difficult than administration by other routes.
• Other disadvantages include the risk of fluid overload, infection, and embolism.  Some drug formulations are completely unsafe for use intravenously.

Intramuscular:

• Only the capillary wall separates the drug from the blood, so there is not a significant barrier to the drug's absorption.
• The rate of absorption varies with the drug's solubility and the blood flow at the site of injection.
• The IM route is uncomfortable and inconvenient for the patient, and if administered improperly, can lead to tissue or nerve damage.

Subcutaneous

Same characteristics as the IM route.

Oral

• Two barriers to cross: epithelial cells and capillary wall.  To cross the epithelium, drugs have to pass through the cells.

• Highly variable drug absorption influenced by many factors:  pH, drug solubility and stability, food intake, other drugs, etc.
• Easy, convenient, and inexpensive.  Safer than parenteral injection, so that oral administration is generally the preferred route.
• Some drugs would be inactivated by this route
• Inappropriate route for some patients.
• May have some GI discomfort, nausea and vomiting.
• Types of oral meds = tablets, enteric-coated, sustained-release, etc.
• Topical, Inhalational agents, Suppositories

Azithromycin

Azithromycin is the first macrolide antibiotic belonging to the azalide group. Azithromycin is derived from erythromycin by adding a nitrogen atom into the lactone ring of erythromycin A, thus making lactone ring 15-membered.

Azithromycin has similar antimicrobial spectrum as erythromycin, but is more effective against certain gram-negative bacteria, particularly Hemophilus influenzae.

azithromycin is acid-stable and can therefore be taken orally without being protected from gastric acids.

Main elimination route is through excretion in to the biliary fluid, and some can also be eliminated through urinary excretion

Dissociation constants

CARDIAC GLYCOSIDES

Cardiac glycosides (Digitalis)

Digoxin

Digitoxin

Sympathomimetics

Dobutamine

Dopamine

Vasodilators

α-blockers (prazosin)

Nitroprusside

ACE-inhibitors (captopril)

Pharmacology of Cardiac Glycosides

1. Positive inotropic effect (as a result of increase  C.O., the symptoms of CHF subside).

2. Effects on other cardiac parameters

1) Excitability

2) Conduction Velocity; slightly increased in atria & ventricle/significantly

reduced in conducting tissue esp. A-V node and His-Purkinje System

3) Refractory Period; slightly ^ in atria & nodal tissue/slightly v in ventricles

4) Automaticity; can be greatly augmented - of particular concern in ventricle

3. Heart Rate

-Decrease due to 1) vagal stimulation and 2) in the situation of CHF, due to improved hemodynamics

4 Blood Pressure

-In CHF, not of much consequence. Changes are generally secondary to improved cardiac performance.

-In the absence of CHF, some evidence for a direct increase  in PVR due to vasoconstriction.

5. Diuresis

-Due primarily to increase in  renal blood flow as a consequence of positive inotropic effect (increase CO etc.) Possibly some slight direct diuretic effect.

 Mechanism of Action of Cardiac Glycosides

Associated with an interaction with membrane-bound Na+-K+ ATPase (Na-K pump).

Clinical ramifications of an interaction of cardiac glycosides with the Na⁺ K pump.

I. Increase levels of Ca⁺⁺, Increase therapeutic and toxic effects of cardiac glycosides

II. Decrease levels of K⁺ , Increase toxic effects of cardiac glycosides

Therapeutic Uses of Cardiac Glycosides

• CHF
• CHF accompanied by atrial fibrillation
• Supraventricular arrhythmias

ISOPRENALINE

It is beta-receptor stimulant, which stimulates the heart and causes tachycardia.
It relaxes the smooth muscles particularly the bronchial and GIT. It is mainly used in bronchial asthma, in the treatment of shock and as a cardiac stimulant in heart block. 

ORCIPRENALINE
Is a potent β-adrenergic agonist.
Receptor sites in the bronchi and bronchioles are more sensitive to the drug than those in the heart and blood vessels.

AMPHETAMINE 

increases the systolic and diastolic blood pressure. Amphetamine is a potent CNS stimulant and causes alertness, insomnia, increased concentration, euphoria or dysphoria and increased work capacity.

Amphetamines are drugs of abuse and can produce behavioural abnormalities and can precipitate psychosis. 

PHENYLEPHRINE
It is used as a nasal decongestant and mydriatic agent and also in the treatment of paroxysmal supraventricular tachycardia.

UTERINE RELAXANTS (TOCOLYTICS)

ISOXSUPRINE
Isoxsuprine has a potent inhibitory effect on vascular and uterine smooth muscle and has been used in the treatment of dysmenorrhoea, threatened abortion, premature labour and peripheral vascular diseases.