PLASMA FRACTIONS:

a) Fresh frozen plasma.

b) Platelets.

c) Plasma concentrates.

d) Non-plasma recombinant factor concentrates.

Fentanyl (Sublimaze)

• Related chemically to meperidine.
• Approximately 80 times more potent than morphine.
• Duration of action very short (t1/2 20 min).
• Used mainly following general anesthesia.
• Neurolept analgesia: Fentanyl & Droperidol (Innovar)
• fentanyl in analgesic (2-10 µg/kg), or anaesthetic (30-100 µg/kg) doses seldom causes significant decreases in blood pressure when given alone, even in patients with poor LV function
• hypotension following fentanyl is mostly due to bradycardia and can be prevented by the use of anticholinergics, sympathomimetics or agents such as pancuronium this is more likely to occur in patients with high pre-existing sympathetic tone
• hypertension is the commonest disturbance with high dose fentanyl anaesthesia, usually accompanying intubation, sternotomy, or aortic root dissection

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

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. 

Selective serotonin reuptake inhibitors (SSRIs)

e.g. fluoxetine, paroxetine, citalopram, and sertraline
- Most commonly used antidepressant category
- Less likely to cause anticholinergic side effects
- Relatively safest antidepressant group in overdose
- Selectively inhibits reuptake of serotonin(5-HT)

Mode of Action;
- Well absorbed when given orally
- Plasma half-lives of 18-24 h allowing once daily dosagedaily dosage
- Metabolised through CYP450 system and most SSRIs inhibit some CYP isoforms
- Therapeutic effect is delayed for 2-4 weeks

ADVERSE DRUG REACTIONS

- Insomnia, increased anxiety, irritability
- Decreased libido
- Erectile dysfunction, anorgasmia, and ejaculatory delay
- Bleeding disorders
- Withdrawal syndrome

Halothane (Fluothane) MAC 0.76%, Blood/gas solubility ratio 2.3
- Nonflammable.
- Any depth of anesthesia can be obtained in the absence of hypoxia.
- Halothane produces a marked hypotensive effect 
- accompanies hypotension.
- Halothane “sensitizes” the ventricular conduction system in the heart to the action of catecholamines. However, ventricular arrhythmias are rare if
- respiratory acidosis, hypoxia and other causes of sympathetic stimulation are avoided.
- Respiration is depressed by all anesthetic concentrations.
- Halothane is metabolized to a significant extent and some of its metabolic produces have been shown to be hepatotoxic.
- Can produce a malignant hyperpyrexia due to an uncontrolled hypermetabolic reaction in skeletal muscle. 

Halothane is generally used with nitrous oxide, an opiate and a neuromuscular blocking drug.