NEET MDS Lessons
Pharmacology
Beta - Adrenoceptor blocking Agents
These are the agents which block the action of sympathetic nerve stimulation and circulating sympathomimetic amines on the beta adrenergic receptors.
At the cellular level, they inhibit the activity of the membrane cAMP. The main effect is to reduce cardiac activity by diminishing β1 receptor stimulation in the heart. This decreases the rate and force of myocardial contraction of the heart, and decreases the rate of conduction of impulses through the conduction system.
Beta blockers may further be classified on basis of their site of action into following two main classes namely
cardioselective beta blockers (selective beta 1 blockers)
non selective beta 1 + beta 2 blockers
Classification for beta adrenergic blocking agents.
A. Non-selective (β1+β2)
Propranolol Sotalol Nadolol Timolol Alprenolol Pindolol
With additional alpha blocking activity
Labetalol Carvedilol
B. β1 Selective (cardioselective)
Metoprolol Atenolol Bisoprolol Celiprolol
C. β2 Selective
Butoxamine
Mechanisms of Action of beta blocker
Beta adrenoceptor Blockers competitively antagonize the responses to catecholamines that are mediated by beta-receptors and other
adrenomimetics at β-receptors
Because the β-receptors of the heart are primarily of the β1 type and those in the pulmonary and vascular smooth muscle are β2 receptors, β1-selective antagonists are frequently referred to as cardioselective blockers.
β-adrenergic receptor blockers (β blockers)
1. Used more often than α blockers.
2. Some are partial agonists (have intrinsic sympathomimetic activity).
3. Propranolol is the prototype of nonselective β blockers.
4. β blocker effects: lower blood pressure, reduce angina, reduce risk after myocardial infarction, reduce heart rate and force, have antiarrhythmic effect, cause hypoglycemia in diabetics, lower intraocular pressure.
5. Carvedilol: a nonselective β blocker that also blocks α receptors; used for heart failure.
Excretion
Routes of drug excretion
The most important route of drug elimination from the body is via the kidney
Renal Drug Excretion
- Glomerular Filtration
- Passive Tubular Reabsorption: drugs that are lipid soluble undergo passive reabsorption from the tubule back into the blood.
- Active Tubular Secretion
Factors that Modify Renal Drug Excretion
- pH Dependent Ionization: manipulating urinary pH to promote the ionization of a drug can decrease passive reabsorption and hasten excretion.
- Competition for Active Tubular Transport
- Age: Infants have a limited capscity to excrete drugs.
Nonrenal Routes of Drug Excretion
Breast Milk
Bile, Lungs, Sweat and Saliva
The kidney is the major organ of excretion. The lungs become very important for volatile substances or volatile metabolites.
Drugs which are eliminated by the kidney are eliminated by:
a) Filtration - no drug is reabsorbed or secreted.
b) Filtration and some of the drug is reabsorbed.
c) Filtration and some secretion.
d) Secretion
By use of the technique of clearance studies, one can determine the process by which the kidney handles the drug.
Renal plasma clearance = U x V ml/min U / Cp = conc. of drug in urine
Cp = conc. of drug in plasma
V = urine flow in ml/min
Renal clearance ratio = renal plasma clearance of drug (ml/min) / GFR (ml/min)
Total Body Clearance = renal + non-renal
Pharmacology is the study of drugs and the way they interact with living systems. Clinical pharmacology is the study of drugs in humans.
A drug is any chemical that can effect living processes.
Therapeutics: the medical use of drugs.
An ideal drug has several important properties. Three of these properties are of utmost importance: effectiveness, safety and selectivity.
Effectiveness: This is the most important quality that a drug can have. Effectiveness refers to the drug's ability to do what it is supposed to do.
Safety: Although no drug can be totally safe, proper usage can lessen the risks of adverse effects.
Selectivity: A truly selective drug would have no side effects, and would effect only the body process' for which it is designed and given. Therefore, there is no such thing as a selective drug.
Pharmacokinetics: The way the body deals with a drug. Pharmacokinetics is concerned with the processes of absorption, distribution, metabolism and excretion.
Pharmacodynamics: What a drug does to the body.
Pharmacokinetics and pharmacodynamics are two of the processes that determine how a person will respond to a drug. Other factors include how a drug is administered (dose, route, and timing of administration), interactions with other drugs, and individual physiological variables (weight, age, function of body systems).
Example calculations of maximum local anesthetic doses for a 15-kg child
Articaine
5 mg/kg maximum dose × 15 kg = 75 mg
4% articaine = 40 mg/mL
75 mg/(40 mg/mL) = 1.88 mL
1 cartridge = 1.8 mL
Therefore, 1 cartridge is the maximum
Lidocaine
7 mg/kg × 15 kg = 105 mg
2% lidocaine = 20 mg/mL
105 mg/(20 mg/mL) = 5.25 mL
1 cartridge = 1.8 mL
Therefore, 2.9 cartridges is the maximum
Mepivacaine
6.6 mg/kg × 15 kg = 99 mg
3% mepivacaine = 30 mg/mL
99 mg/(30 mg/mL) = 3.3 mL
1 cartridge = 1.8 mL
Therefore, 1.8 cartridges is the maximum.
Prilocaine
8 mg/kg × 15 kg = 120 mg
4% prilocaine = 40 mg/mL
120 mg/(40 mg/mL) = 3 mL
1 cartridge = 1.8 mL
Therefore, 1.67 cartridges is the maximum
Loperamide
- Similar chemically and pharmacologically to Diphenoxylate.
- Slows gastrointestinal motility by effects on the circular and longitudinal muscles of the intestine.
- Not well absorbed following oral administration.
- Useful in the treatment of diarrhea.
Propoxyphene
- A methadone analog.Used orally to relieve mild to moderate pain.
- A typical opiate, it does not possess anti-inflammatory or antipyretic actions, but has little or no antitussive activity.
- Cannot be used parenterally because of irritant properties.
- Has a low addiction potential primarily due to its lack of potency as an opiate.
- The most common adverse side effects are:• dizziness, drowsiness, and nausea and vomiting. • these effects are more prominent in ambulatory patients.
- Withdrawal symptoms have occurred in both adults and in neonates following use of the drug by the mother during pregnancy.
- CNS depression is additive with other CNS depressants.
Cells of the Nervous System
1-Neurons (Nerve Cells):function units of the nervous system by conducting nerve impulses, highly specialized and amitotic. Each has a cell body (soma), one or more dendrites, and a single axon.
• Cell Body: it has a nucleus with at least one nucleolus and many of the typical cytoplasmic organelles, but lacks centriolesfor cell division.
• Dendrites:Dendrites and axons are cytoplasmic extensions (or processes), that project from the cell body. They are sometimes referred to as fibers. Dendrites (afferent processes) increase their surface area to receive signals from other neurons, and transmit impulses to the neuron cell body.
• Axon: There is only one axon (efferent process) that projects from each cell body.
It carries impulses away from the cell body.
2-Glial cells: do not conduct nerve impulses, but support, nourish, and protect the neurons. They are mitotic, and far more numerous than neurons.
Astrocyte: A glialcell that provides support for neurons of the CNS, provides nutrients regulates the chemical composition of the extracellularfluid.
• Oligodendrocyte: A type of glialcell in the CNS that forms myelin sheaths.
• Microglia:The smallest glialcells; act as phagocytes (cleaning up debris) and protect the brain from invading microorganisms.
• Schwann cell:A cell in the PNS that is wrapped around a myelinatedaxon, providing one segment of its myelin sheath.