NEET MDS Lessons
Pharmacology
Meperidine (Demerol)
Meperidine is a phenylpiperidine and has a number of congeners. It is mostly effective in the CNS and bowel
- Produces analgesia, sedation, euphoria and respiratory depression.
- Less potent than morphine, 80-100 mg meperidine equals 10 mg morphine.
- Shorter duration of action than morphine (2-4 hrs).
- Meperidine has greater excitatory activity than does morphine and toxicity may lead to convulsions.
- Meperidine appears to have some atropine-like activity.
- Does not constrict the pupils to the same extent as morphine.
- Does not cause as much constipation as morphine.
- Spasmogenic effect on GI and biliary tract smooth muscle is less pronounced than that produced by morphine.
- Not an effective antitussive agent.
- In contrast to morphine, meperidine increases the force of oxytocin-induced contractions of the uterus.
- Often the drug of choice during delivery due to its lack of inhibitory effect on uterine contractions and its relatively short duration of action.
- It has serotonergic activity when combined with monoamine oxidase inhibitors, which can produce serotonin toxicity (clonus, hyperreflexia, hyperthermia, and agitation)
Adverse reactions to Meperidine
• Generally resemble a combination of opiate and atropine-like effects.
- respiratory depression, - tremors, - delirium and possible convulsions, - dry mouth
• The presentation of mixed symptoms (stupor and convulsions) is quite common in addicts taking large doses of meperidine.
Neurophysiology
Nerve fibers exhibit wide range of sensitivity to nerve blockade-in order of increasing resistance to block are the sensations of pain, cold, warmth, touch, pressure, proprioception and motor function
Nerve Fibers:
|
Types |
Size |
Speed |
Occurrence |
|
A (α) |
20 µm |
80 - 120 |
Myelinated (Primarily for muscular activity). |
|
β |
8 - 15 µm |
|
Myelinated (Touch and pressure) |
|
γ |
4 - 8 µm |
|
Myelinated (Muscle spindle tone) |
|
δ |
3 - 4 µm |
10-15 |
Myelinated (Pain and temperature sensation) |
|
B |
4 µm |
10-15 |
Myelinated (Preganglionic autonomic) |
|
C |
1-2 µm |
1 - 2 |
Unmyelinated (Pain and temperature sensation) |
Myelinated = faster conducting
Unmyelinated = slower conducting
- Small non-myelinated fibers (C- pain fibers) and smaller myelinated pre-ganglionic B fibers are more readily blocked than are larger myelinated fibers responsible for muscle activity and touch [A-alpha and A-beta].
- Clinically, a person would notice complete lack of sensation to a pinprick, while at the same time still be able to move their fingers.
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
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.
Diphenoxylate (present in Lomotil)
- A meperidine congener
- Not absorbed very well at recommended doses.
- Very useful in the treatment of diarrhea.
Adverse effects
Nitrates
– Headache, hypotension, dizziness, lightheadedness, tachycardia, palpitations
Beta-adrenergic blocking agents
– hypotension, bradycardia, bronchospasm, congestive heart failure
Calcium channel blockers
– hypotension, dizziness, lightheadedness, weakness, peripheral edema, headache, congestive heart failure, pulmonary edema, nausea, and constipation
Drugs that increase effects of Antianginal drugs
• Antihypertensive
• Diuretics
• Phenothiazine antipsychotic agents
• Cimetidine
• Digoxin
Drugs that decrease effects of Antianginal
• Adrenergic drugs - epinephrine
• Anticholinergic
• Calcium salts
• Phenobarbital, Phenytoin
Adjunctive Antianginal Drugs
In addition to antianginal drugs, several other drugs may be used to control risk factors and prevent progression of myocardial ischemia to myocardial infarction and sudden cardiac death.
These may include:
• Aspirin. This drug has become the standard of care because of its antiplatelet (ie, antithrombotic) effects. Recommended doses vary from 81 mg daily to 325 mg daily or every other day; apparently all doses are beneficial in reducing the possibility of myocardial reinfarction, stroke, and death. Clopidogrel 75 mg/day,
Is an acceptable alternative for individuals with aspirin allergy.
• Antilipemics. These drugs may be needed by clients who are unable to lower serum cholesterol levels sufficiently with a low-fat diet. Lovastatin or a related “statin” is often used. The goal is usually to reduce the serum cholesterol level below 200 mg/dL and lowdensitylipoprotein cholesterol to below
130 mg/dL.
• Antihypertensives. These drugs may be needed for clients with hypertension. Because beta blockers and calcium channel blockers are used to manage hypertension as well as angina, one of these drugs may be effective for both disorders.
SULPHONAMIDES
Derivative of sulphonilamide (Para-amino Benzene (PABA ) sulphonamide).
Anti-bacterial spectrum
Bacteriostatic to gram + and gram - bacteria. but bactericidal concentrations arce attained in urine. S pyogencs. H influenzae.E coli, few- Staph aureus. gonococci. pneumococci, proteus, shigella and Lymphogranuloma venereum.
Mechanism of action
Inhibits bacterial folate synthetase as they compete with PABA
Less soluble in acid urine and may precipitate to cause crystalluria.
Accumulate in patients with renal failure and can cause toxicity
Classification
Shart Acting (4-8 Hrs) sulphadiazine, sulphamethizole.
Intermediate acting(8-16 Hrs): sulphamethoxazole , sulphaphenazole
Long Acting(l-7days): sulphamethoxypyridazine.
Ultralong Acting(3-8days): sulfaline
Adverse effects
I. nausea, vomiting and epigastric pain
2. crystalluria
3. hypersensitivity-like polyarthritis nodosa. Steven-Johnson Syndrome. photosenstivity
4.hemolysis in G-6PD deficiency
5. kernicterus
They inhibit metabolism of phenytoin. tolbutamide. methotrexate
Therapeutic Use
UTI Meningitis, Streptococcal pharyngitis, Bacillary Dysentery