NEET MDS Lessons
Pharmacology
Heroin (diacetyl morphine)
Heroin is synthetically derived from the natural opioid alkaloid morphine
Largely owing to its very rapid onset of action and very short half-life, heroin is a popular drug of abuse
It is most effective when used intravenously
Heroin is rapidly deacetylated to 6-monoacetyl morphine and morphine, both of which are active at the mu opioid receptor
More lipid soluble than morphine and about 2½ times more potent. It enters the CNS more readily.
Fluconazole: an antifungal used orally, intravenously or vaginally to treat yeast and fungal infections. Side-effects of systemic administration include hepatotoxicity (liver damage).
- For vaginal candidiasis (vaginal thrush), a once-only oral dose is often sufficient.
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
Valdecoxib
used in the treatment of osteoarthritis, acute pain conditions, and dysmenorrhoea
Etoricoxib new COX-2 selective inhibitor
Organic Nitrates
Relax smooth muscle in blood vessel
Produces vasodilatation
– Decreases venous pressure and venous return to the heart Which decreases the cardiac work load and oxygen demand.
– May have little effect on the coronary arteries CAD causes stiffening and lack of
– responsiveness in the coronary arteries
– Dilate arterioles, lowering peripheral vascular resistance Reducing the cardiac workload
Main effect related to drop in blood pressure by
– Vasodilation- pools blood in veins and capillaries, decreasing the volume of blood that the heart has to pump around (the preload)
– relaxation of the vessels which decreases the resistance the heart has to pump against (the afterload)
Indications
- Myocardial ischemia
– Prevention
– Treatment
Nitroglycerin (Nitro-Bid)
• Used
– To relive acute angina pectoris
– Prevent exercise induced angina
– Decrease frequency and severity of acute anginal episodes
Type
• Oral - rapidly metabolized in the liver only small amount reaches circulation
• Sublingual – Transmucosal tablets and sprays
• Transdermal – Ointment s
– Adhesive discs applied to the skin
• IV preparations
Sublingual Nitroglycerine
• Absorbed directly into the systemic circulation, Acts within 1-3 minutes , Lasts 30-60 min
Topical Nitroglycerine
• Absorbed directly into systemic circulation, Absorption at a slower rate. , Longer duration of action
Ointment - effective for 4-8 hours
Transdermal disc - effective for 18-24 hours
Isosorbide dinitrate
• Reduces frequency and severity of acute anginal episodes
• Sublingual or chewable acts in 2 min. effects last 2-3 hours
• Orally, systemic effects in about 30 minutes and last about 4 hours after oral administration
Tolerance to Long-Acting Nitrates
• Long-acting dosage forms of nitrates may develop tolerance
– Result in episodes of chest pain
– Short acting nitrates less effective
Prevention of Tolerance
• Use long-acting forms for approximately 12-16 hours daily during active periods and omit them during inactive periods or sleep
• Oral or topical should be given every 6 hours X 3 doses allowing a rest period of 6 hours
Isosorbide dinitrate (Isordil, Sorbitrate) is used to reduce the frequency and severity of acute anginal episodes.
When given sublingually or in chewable tablets, it acts in about 2 minutes, and its effects last 2 to 3 hours. When higher doses are given orally, more drug escapes metabolism in the liver and produces systemic effects in approximately 30 minutes. Therapeutic effects last about 4 hours after oral administration
Isosorbide mononitrate (Ismo, Imdur) is the metabolite and active component of isosorbide dinitrate. It is well absorbed after oral administration and almost 100% bioavailable. Unlike other oral nitrates, this drug is not subject to first-pass hepatic metabolism. Onset of action occurs within 1 hour, peak effects occur between 1 and 4 hours, and the elimination half-life is approximately 5 hours. It is used only for prophylaxis of angina; it does not act rapidly enough to relieve acute attacks.
Ofloxacin : It is a quinolone antibiotic and similar in structure to levofloxacin. It is an alternative treatment to ciprofloxacin for anthrax.
ANTICHOLINERGIC DRUGS
Blocks the action of Ach on autonomic effectors.
Classification
Natural Alkaloids - Atropine. Hyoscine
Semi-synthetic deriuvatives:- Homatropine, Homatropine methylbromide, Atropine methonitrate.
Synthetic compounds
(a) Mydriatics - Cyclopentolate. Tropicamide.
(b) Antisecretory - Antispasmodics - Propantha1ine. Oxy-phenonium, Pirenzipine.
c) Antiparkinsonism- Benzotopine, Ethopropazine, Trihexyphenidyl, Procyclidine, Biperiden
Other drugs with anticholinergic properties • Tricyclic Antidepressants • Phenothiazines • Antihistaminics • Disopyramide
MUSCARINIC RECEPTORS SUBTYPES & ANTAGONISTS
• M 1 Antagonists – Pirenzepine, Telenzepine, dicyclomine, trihexyphenidyl
• M 2 Antagonists – Gallamine, methoctramine
• M 3 Antagonists – Darifenacin, solifenacin, oxybutynin, tolterodine
Pharmacological Actions
CNS - stimulation of medullary centres like vagal. respiratory. vasomotor and inhibition of vestibular excitation and has anti-motion sickness properties.
CVS - tachycardia.
Eye - mydriasis
Smooth muscles - relaxation of the muscles receiving parnsympathetic motor innervation.
Glands - decreased secretion of sweat and salivary glands
Body Temperature - is increased as there is stimulation of temperature regulating centre.
Respiratory System- Bronchodilatation & decrease in secretions. For COPD or Asthma - antimuscarinic drugs are effective
GIT - Pirenzepine & Telenzepine - decrease gastric secretion with lesser side effects.