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

Miconazole

Miconazole is an  imidazole antifungal agent commonly used in topical sprays, creams and ointments applied to the  skin to cure fungal infections such as Athlete's foot and Jock itch. It may also be used internally to treat vaginal  yeast infection.

When used by a person taking the anticoagulant medication warfarin, Miconazole may cause an adverse reaction which can lead to excessive bleeding or bruising.

Calcium Channel Blocking Agents 

• Act on contractile and conductive tissues of the heart and on vascular smooth muscles 
• Prevent movement of extracellular calcium into the cell 
– Coronary and peripheral arteries dilate
– Myocardial contractility decreases 
– Depress conduction system

Therapeutic Actions
• Inhibit movement of calcium ions across the membranes of myocardial and arterial muscle cells. Altering the action potential and blocking muscle cell contraction 
• Depress myocardial contractility 
• Slow cardiac impulse formation in the conductive tissues 
• Cause a fall in BP 
 

Anti-Histamines:
 
The effect of histamine can be opposed in three ways:
1. Physiological antagonism: by using a drug to oppose the effect (e.g adrenaline). Histamine constricts bronchi,
causes vasodilatation which increases capillary permeability. Adrenaline opposes this effect by a mechanism unrelated to histamine.
2. By preventing histamine from reaching its site of action (receptors), By competition with H1-H2 receptors (Drug antagonisms).
3. By preventing the release of histamine. (adrenal steroids and sodium-cromoglycate can suppress the effect on the tissues)

Types of Anti-histamine drugs

Selected H1 antagonist drugs

First-generation H1 receptor antagonists:

Chlorpheniramine (Histadin) & Dexchlorpheniramine 
Diphenhydramine (Allermine)
Promethazine (Phenergan) -  strong CNS depressants
Cyproheptadine (Periactin)

ACTION
These drugs bind to both central and peripheral H1 receptors and can cause CNS depression or stimulation.

- They usually cause CNS depression (drowsiness,sedation) with usual therapeutic doses
- Cause CNS stimulation (anxiety, agitation) 
with excessive doses, especially in children. 
They also have Anticholinergic effects (e.g. dry mouth, urinary retention, constipation, blurred vision).

Second-generation H1 receptor antagonists (non-sedating) agents

Terfenadine
Fexofenadine
Loratadine
Acravistine and Cetirizine
Astemizol

Action

They cause less CNS epression because they are selective for peripheral H1 receptors and do not cross the blood brain barrier.

Indications for use

The drugs can relieve symptoms but don’t relieve hypersensitivity.

1) Allergic rhinitis. Some relief of sneezing, rhinorrhea, nasal airway obstruction and conjunctivitis are with the use of antihistamine.
2) Anaphylaxis. Antihistamine is helpful in treating urticaria and pruritus.
3) Allergic conjunctivitis. This condition, which is characterized by redness, itching and tearing of the eyes.
4) Drug allergies. Antihistamines may be given to prevent or treat reactions to drugs (e.g, before a dignostic test that
uses an iodine preparation).
5) Transfusions of blood and blood products.
6) Dermatologic conditions. Antihistamines are the drug of choice for treatment of allergic contact dermatitis and
acute Urticaria. Urticaria often occurs because the skin has many mast cells to release histamine.
7) Miscellaneous. Some antihistamines are commonly used for non-allergic disorder such as motion sickness, nausea, vomiting, sleep, cough or add to cough mixtures.

Contraindication

hypersensitivity to the drugs, narrow-angle glaucoma, prostatic hypertroph, stenosing peptic ulcer, bladder neck obstruction, during pregnancy and lactating women

Adverse effects:

Drowsiness and sedation
Anticholinergic
Some antihistamines may cause dizziness, fatigue, hypotention, headache, epigastric distress and photosensitivity
Serious adverse reaction including cardiac arrest & death, have been reported in patients receiving high dose astemizole

H2-receptor antagonists

 Cimetidine (Tagamate), Ranitidine (Zantac), Fomatidine, Nizatidine. 

Mechanism of action

Numerous factors influence acid secretion by the stomach, including food, physiological condition and drugs. H2 receptor blockers reduce basal acid-secretion by about 95% and food stimulated acid-secretion by about 70%. Both conc. and vol. of H ions will decrease.

Pharmacokinetics:
1) They are all well absorbed after oral dose.
2) Antacids decrease their absorption in about 10-20%

Uses
Cimetidine -  reduction of gastric secretion is beneficial, these are in main duodenal ulcer, benign gastric ulcer, stomach ulcer and reflux eosophagitis.

Rantidine -used as alternative for duodenal ulcer

Adverse effects:
headache, dizziness, constipation, diarrhoea, tiredness and muscular pain. 

FUNDAMENTALS OF INJECTION TECHNIQUE

There are 6 basic techniques for achieving local anesthesia of the structures of the oral cavity:

 1. Nerve block

 2. Field block

 3. Infiltration/Supraperiosteal

 4. Topical

 5. Periodontal ligament (PDL)

 6. Intraosseous

 Nerve block- Nerve block anesthesia requires local anesthetic to be deposited in close proximity to a nerve trunk. This results in the blockade of nerve impulses distal to this point. It is also important to note that arteries and veins accompany these nerves and can be damaged. To be effective, the local anesthetic needs to pass only through the nerve membrane to block nerve conduction Field block/Infiltration/Supraperiosteal - Field block, infiltration and supraperiosteal injection techniques, rely on the ability of local anesthetics to diffuse through numerous structures to reach the nerve or nerves to be anesthetized:

  - Periosteum

 - Cortical bone

 - Cancellous bone

 - Nerve membrane

Topical - Topical anesthetic to be effective requires diffusion through mucous membranes and nerve membrane of the nerve endings near the tissue surface

PDL/Intraosseous - The PDL and intraosseous injection techniques require diffusion of local anesthetic solution through the cancellous bone (spongy) to reach the dental plexus of nerves innervating the tooth or teeth in the immediate area of the injection. The local anesthetic then diffuses through the nerve membrane

Pharmacokinetics

Pharmacokinetics is the way that the body deals with a drug - how that drug moves throughout the body, and how the body metabolizes and excretes it.  The factors and processes involved in pharmacokinetics must be considered when choosing the most effective dose, route and schedule for a drug's use.

The four processes involved in pharmacokinetics are:

Absorption:  The movement of a drug from its site of administration into the blood.

Several factors influence a drug's absorption:

• Rate of Dissolution:  the faster a drug dissolves the faster it can be absorbed, and the faster the effects will begin.
• Surface Area:  Larger surface area = faster absorption.
• Blood Flow:  Greater blood flow at the site of drug administration = faster absorption.
• Lipid Solubility:  High lipid solubility = faster absorption
• pH Partitioning:  A drug that will ionize in the blood and not at the site of administration will absorb more quickly.

Distribution:  The movement of drugs throughout the body.

Metabolism:  (Biotransformation) The enzymatic alteration of drug structure.

Excretion:  The removal of drugs from the body.

As a drug moves through the body, it must cross membranes.  Some important factors to consider here then are:

Body's cells are surrounded by a bilayer of phospholipids (cell membrane).

There are three ways that a substance can cross cell membranes:

• Passing through channels and pores: only very small molecules can cross cell membranes this way.

• Transport Systems:   Selective carriers that may or may not use ATP.

• Direct Penetration of the Cell Membrane: