NEET MDS Lessons
Pharmacology
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
ISOPRENALINE
It is beta-receptor stimulant, which stimulates the heart and causes tachycardia.
It relaxes the smooth muscles particularly the bronchial and GIT. It is mainly used in bronchial asthma, in the treatment of shock and as a cardiac stimulant in heart block.
ORCIPRENALINE
Is a potent β-adrenergic agonist.
Receptor sites in the bronchi and bronchioles are more sensitive to the drug than those in the heart and blood vessels.
AMPHETAMINE
increases the systolic and diastolic blood pressure. Amphetamine is a potent CNS stimulant and causes alertness, insomnia, increased concentration, euphoria or dysphoria and increased work capacity.
Amphetamines are drugs of abuse and can produce behavioural abnormalities and can precipitate psychosis.
PHENYLEPHRINE
It is used as a nasal decongestant and mydriatic agent and also in the treatment of paroxysmal supraventricular tachycardia.
UTERINE RELAXANTS (TOCOLYTICS)
ISOXSUPRINE
Isoxsuprine has a potent inhibitory effect on vascular and uterine smooth muscle and has been used in the treatment of dysmenorrhoea, threatened abortion, premature labour and peripheral vascular diseases.
Prostaglandines:
Every cell in the body is capable of synthesizing one or more types of PGS. The four major group of PGs are E, F, A, and B.
Pharmacological actions:
stimulation of cyclicAMP production and calcium use by various cells
CVS
PGE2 acts as vasodilator; it is more potent hypotensive than Ach and histamine
Uterous
PGE2 and PGF2α Contract human uterus
Bronchial muscle
PGF2α and thromboxan A2 cause bronchial muscle contraction.
PGE2 & PGI2 cause bronchial muscle dilatation
GIT: PGE2 and PGF2α cause colic and watery diarrhoea
Platelets
Thromboxan A2 is potent induce of platelets aggregation
Kidney
PGE2 and PGI2 increase water, Na ion and K ion excretion (act as diuresis) that cause renal vasodilatation and inhibit
tubular reabsorption
USE
PGI2: Epoprostenol (inhibits platelets aggregation)
PGE1: Alprostadil (used to maintain the potency of arterioles in neonates with congenital heart defects).
PGE2: Dinoproste (used as pessaries to induce labor)
Synthetic analogue of PGE1: Misoprostol (inhibit the secretion of HCl).
Sympatholytics (Antiadrenergic Agents)
PHENOXYBENZAMINE
It is a potent alpha-adrenergic blocking agent
It effectively prevents the responses mediated by alpha receptors and diastolic blood pressure tends to decrease.
It interferes with the reflex adjustment of blood pressure and produces postural hypotension.
It increases the cardiac output and decreases the total peripheral resistance.
It is used in the management of pheochromocytoma and also to treat peripheral vasospastic conditions e.g. Raynaud’s disease and shock syndrome.
Phentolamine, another alpha blocker is exclusively used for the diagnosis of pheochromocytoma and for the prevention of abrupt rise in blood pressure during surgical removal of adrenal medulla tumors.
ERGOT ALKALOIDS
Ergotamine is an important alkaloid that possesses both vasoconstrictor and alpha-receptor blocking activity. Both ergotamine and dihydroergotamine are used in the treatment of migraine.
METHYSERGIDE
It is a 5-hydroxytryptamine antagonist ). It is effective in preventing an attack of migraine.
SUMATRIPTAN
It is a potent selective 5-HT 1D receptor agonist used in the treatment of migraine.
PRAZOSIN
It is an piperazinyl quinazoline effective in the management of hypertension. It is highly selective for α1 receptors. It also reduces the venous return and cardiac output. It is used in essential hypertension, benign prostatic hypertrophy and in Raynaud’s syndrome.
Prazosin lowers blood pressure in human beings by relaxing both veins and resistance vessels but it dilates arterioles more than veins.
TERAZOSIN
It is similar to prazosin but has higher bioavailability and longer plasma t½
DOXAZOSIN
It is another potent and selective α1 adrenoceptor antagonist and quinazoline derivative.
It’s antihypertensive effect is produced by a reduction in smooth muscle tone of peripheral vascular beds.
TAMSULOSIN
It is uroselective α1A blocker and has been found effective in improving BPH symptoms.
Other drugs used for erectile dysfunction
Sildenafil: It is orally active selective inhibitor of phosphodiesterase type 5 useful in treatment of erectile dysfunction.
Distal (Potassium Sparing) Diuretics
Agents:
spironolactone
triamterene
Mechanism of action
Inhibition of Na/K exchange at aldosterone dependent distal tubular site
Spironolactone - competes with aldosterone for regulatory site
Triamterene - decreases activity of pump directly
• Either mechanism decreases potassium wasting
• Either mechanism produces poor diuresis (when used alone)
o relatively unimportant Na recovery site
Diurectic activity increased if:
• sodium load (body) is high
• aldosterone concentrations are high
• sodium load (tubule) is high - secondary to diuresis
Other electrolytes unaffected
Toxicity
• spironolactone may produce adrenal and sex hormone effects with LONG-TERM use
• Both drugs may produce electrolyte imbalance
Mechanism of Action
When a local anesthetic is injected, it is the ionized [cation] form of the local anesthetic that actually binds to anionic channel receptors in the sodium channel, thus blocking the influx of sodium ions which are responsible for lowering the -70mv resting potential towards the firing threshold of -55mv which then results in depolarization of the nerve membrane. However, only the lipid soluble nonionized [base] form of the local anesthetic can penetrate the various barriers [e.g., nerve membrane, fibrous tissue] between the site of injection and the targeted destination which is the sodium channel.
Ibuprofen
used to relieve the symptoms of arthritis, primary dysmenorrhoea, fever; and as an analgesic, especially where there is an inflammatory component.
Indications
rheumatoid arthritis, osteoarthritis, juvenile rheumatoid arthritis, primary dysmenorrhoea
fever, relief of acute and/or chronic pain states in which there is an inflammatory component
MOA
inhibition of cyclooxygenase (COX); thus inhibiting prostaglandin synthesis.