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

Anesthesia agents

1. Inhalation anesthetics (volatile anesthetics)

- gases : N₂O, xenon

- Fluids (vaporisers)

2. Intravenous anesthetics

- Barbiturans : thiopental

- Others : propofol, etomidat

3. Pain killers

- Opioids: fentanyl, sufentanil, alfentanil, remifentanil, morphine

- Non Steroid Anti Inflamatory Drugs: ketonal, paracetamol

4. Relaxants

- Depolarising : succinilcholine

- Non depolarising : atracurium, cisatracurium, vecuronium, rocuronium

5. adiuvants

-benzodiazepins: midasolam, diazepam

BETA-LACTAM ANTIBIOTICS
β-lactam antibiotics are a broad class of antibiotics including penicillin derivatives, cephalosporins, monobactams, carbapenems and β-lactamase inhibitors; basically any antibiotic agent which contains a β-lactam nucleus in its molecular structure. They are the most widely used group of antibiotics available.

Mode of action All β-lactam antibiotics are bactericidal, and act by inhibiting the synthesis of the peptidoglycan layer of bacterial cell walls.β-lactam antibiotics were mainly active only against Gram-positive bacteria, the development of broad-spectrum β-lactam antibiotics active against various Gram-negative organisms has increased the usefulness of the β-lactam antibiotics.

Common β-lactam antibiotics

Penicillins

Narrow spectrum penicillins:  

benzathine penicillin
benzylpenicillin (penicillin G)
phenoxymethylpenicillin (penicillin V)
procaine penicillin

Narrow spectrum penicillinase-resistant penicillins

methicillin
dicloxacillin
flucloxacillin

Moderate spectrum penicillins : 

amoxicillin, ampicillin

Broad spectrum penicillins :      

co-amoxiclav (amoxycillin+clavulanic acid)

Extended Spectrum Penicillins:    

piperacillin
ticarcillin
azlocillin
carbenicillin
 

GENERAL ANESTHETICS

General anesthesia often involves more than one drug to get different, favourable effects.
Premedication is often used to:
1. Treat anxiety - Benzodiazapenes
2. Reduce pain - Opiod anaglesics such as morphine
3. Produce muscle paralysis -E.g. Tubocurare
4. Reduce secretions
Induction of anesthesia is often done via intravenous anesthetics, which are quick and easy to administer.
Maintenance of anesthesia involves inhalation agents.

Prototype Agents:
Volatile Anesthetics:
•    Nitrous Oxide
•    Ether
•    Halothane
•    Enflurane
•    Isoflurane

Injectable Anesthetics:
•    Thiopental 
•    Ketamine
•    Etomidate
•    Propofol 
•    Midazolam
 

Non-barbiturate sedatives

1- Chloral hydrate is trichlorinated derivative of acetaldehyde that is converted to trichlorethanol in the body. It induces sleep in about 30 minutes and last up to 6 hr. it is irritant to GIT and produce unpleasant taste sensation.

2- Ramelteon melatonin receptors are thought to be involved in maintaining circadian rhythms underlying the sleep-wake cycle. Ramelteon is an agonist at MT1 and MT2 melatonin receptors , useful in patients with chronic insomnia with no rebound insomnia and
withdrawal symptoms

3- Ethanol (alcohol) it has antianxiety sedative effects but its toxic potential out ways its benefits.
Ethanol is a CNS depressant producing sedation and hypnosis with increasing dose.

Absorption of alcohol taken orally is rapid, it is highly lipid soluble, presence of food delayed its absorption, maximal blood concentration depend on total dose, sex, strength of the solution, the time over which it is taken, the presence of food and speed of metabolism.

Alcohol in the systemic circulation is oxidized in the liver principally 90% by alcohol dehydrogenase to acetaldehyde and then by acetaldehyde dehydrogenase to products that enter the citric cycle. 

Alcohol metabolism by alcohol dehydrogenase follows first order kinetics in the smallest doses. Once the blood concentration exceeds about 10 mg/100 ml, the enzymatic processes are saturated and elimination rate no longer increases with increasing
concentration but become steady at 10-15 ml/ 1 hr. in occasional drinkers. 

Thus alcohol is subject to dose dependant kinetics i.e. saturation or zero order kinetics.

Actions

- Ethanol acts on CNS in a manner similar to volatile anesthetic.
- It also enhances GABA so stimulating flux of chloride ions through ion channels.
- Other possible mode of action involve inhibition of Ca-channels and inhibition of excitatory NMDA receptors.
- Ethanol has non selective CNS depressant activity.
- It causes cutaneous vasodilatation, tachycardia and myocardial depression

Diclofenac

Short half life (1‐2 hrs), high 1stpass metab.,  accumulates in synovial fluid after oral admn., reduce inflammation, such as in arthritis or acute injury

Mechanism of action

inhibition of prostaglandin synthesis by inhibition of cyclooxygenase (COX). There is some evidence that diclofenac inhibits the lipooxygenase pathways, thus reducing formation of the

leukotrienes (also pro-inflammatory autacoids). There is also speculation that diclofenac may inhibit phospholipase A2 as part of its mechanism of action. These additional actions may explain the high potency of diclofenac - it is the most potent NSAID on a molar basis.

Inhibition of COX also decreases prostaglandins in the epithelium of the stomach, making it more sensitive to corrosion by gastric acid. This is also the main side effect of diclofenac and other drugs that are not selective for the COX2-isoenzyme.